Company Quick10K Filing
Evogene
20-F 2019-12-31 Filed 2020-04-27
20-F 2018-12-31 Filed 2019-04-29
20-F 2017-12-31 Filed 2018-03-30
20-F 2016-12-31 Filed 2017-04-28
20-F 2015-12-31 Filed 2016-04-25
20-F 2014-12-31 Filed 2015-04-30
20-F 2013-12-31 Filed 2014-04-08

EVGN 20F Annual Report

Item 17 ☐ Item 18 ☐
Part I
Item 1. Identity of Directors, Senior Management and Advisers
Item 2. Offer Statistics and Expected Timetable
Item 3. Key Information
Item 4. Information on The Company
Item 4A. Unresolved Staff Comments
Item 5. Operating and Financial Review and Prospects
Item 6. Directors, Senior Management and Employees
Item 7. Major Shareholders and Related Party Transactions
Item 8. Financial Information
Item 9. The Offer and Listing
Item 10. Additional Information
Item 11. Quantitative and Qualitative Disclosures About Market Risk
Item 12. Description of Securities Other Than Equity Securities
Part II
Item 13. Defaults, Dividend Arrearages and Delinquencies
Item 14. Material Modifications To The Rights of Security Holders and Use of Proceeds
Item 15. Controls and Procedures
Item 16. [Reserved]
Item 16A. Audit Committee Financial Expert
Item 16B. Code of Ethics
Item 16C. Principal Accountant Fees and Services
Item 16D. Exemptions From The Listing Standards for Audit Committees
Item 16E. Purchases of Equity Securities By The Issuer and Affiliated Purchasers
Item 16F. Change in Registrant's Certifying Accountant
Item 16G. Corporate Governance
Item 16H. Mine Safety Disclosure
Part III
Item 17. Financial Statements
Item 18. Financial Statements
Item 19. Exhibits
Note 1: - General
Note 2: - Significant Accounting Policies
Note 3: - Significant Accounting Judgments, Estimates and Assupmtions Used in The Preparation of The Financial Statements
Note 4: - Disclosure of New Standards in The Period Prior To Their Adoption
Note 5: - Collaboration and Research Agreements -
Note 6: - Cash and Cash Equivalents
Note 7: - Marketable Securities
Note 8: - Other Receivables and Prepaid Expenses
Note 9: - Leases
Note 10: - Property, Plant and Equipment, Net
Note 11: - Intangible Assets
Note 12: - Liabilities in Respect of Government Grants
Note 13: - Financial Instruments
Note 14: - Severance Pay Liability
Note 15: - Taxes on Income
Note 16: - Shareholders' Equity
Note 17: - Share - Based Compensation
Note 18: - Statements of Profit or Loss - Additional Information
Note 19: - Loss per Share
Note 20: - Operating Segments
Note 21: - Balances and Transactions with Key Officers and Certain Shareholders
Note 22: - Subsequent Events
EX-2.1 exhibit_2-1.htm
EX-4.7 exhibit_4-7.htm
EX-8.1 exhibit_8-1.htm
EX-12.1 exhibit_12-1.htm
EX-12.2 exhibit_12-2.htm
EX-13.1 exhibit_13-1.htm
EX-13.2 exhibit_13-2.htm
EX-15.1 exhibit_15-1.htm

Evogene Earnings 2019-12-31

Balance SheetIncome StatementCash Flow

20-F 1 zk2024279.htm 20-F


UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

FORM 20-F
 
 
REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934

OR
   
 
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, 2019

OR
 
 
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

OR
 
 
SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

Commission file number 001-36187

EVOGENE LTD.
(Exact name of Registrant as specified in its charter)

N/A
(Translation of Registrant's Name Into English)

Israel
(Jurisdiction of incorporation or organization)

13 Gad Feinstein Street, Park Rehovot, Rehovot
P.O.B 4173, Ness Ziona, 7414002, Israel
(Address of principal executive offices)

Ofer Haviv
President and Chief Executive Officer
Telephone: +972-8-931-1900
Facsimile: +972-8-946-6724
Email: Ofer.Haviv@evogene.com
13 Gad Feinstein Street, Park Rehovot, Rehovot
P.O.B 4173, Ness Ziona, 7414002, Israel

 (Name, Telephone, E-mail and/or Facsimile number and Address of Company Contact Person)


Securities registered or to be registered pursuant to Section 12(b) of the Act:

Title of each class
 
Trading symbol(s)
 
Name of each exchange on which registered
Ordinary shares, par value NIS 0.02 per share
 
EVGN
 
Nasdaq Stock Market LLC

Securities registered or to be registered pursuant to Section 12(g) of the Act: None.

Securities for which there is a reporting obligation pursuant to Section 15(d) of the Act: None.

Indicate the number of outstanding shares of each of the issuer’s classes of capital or common stock as of the close of the period covered by the annual report: As of December 31, 2019, the registrant had outstanding 25,754,297 ordinary shares, par value NIS 0.02 per share.

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.

Yes No ⌧

If this report is an annual or transition report, indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934.

Yes No ⌧

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.

Yes ⌧ No

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§229.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).

Yes ⌧ No

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer
Accelerated filer
Non-accelerated filer ⌧
Emerging Growth Company

If an emerging growth company that prepares its financial statements in accordance with U.S. GAAP, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards† provided pursuant to Section 13(a) of the Exchange Act.

† The term “new or revised financial accounting standard” refers to any update issued by the Financial Accounting Standards Board to its Accounting Standards Codification after April 5, 2012.
Indicate by check mark which basis of accounting the registrant has used to prepare the financial statements included in this filing:

U.S. GAAP
International Financial Reporting Standards as issued by the
International Accounting Standards Board ⌧
Other

If “Other” has been checked in response to the previous question, indicate by check mark which financial statement item the registrant has elected to follow.

Item 17 Item 18

If this is an annual report, indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).

Yes No ⌧

2

 
EVOGENE LTD.


FORM 20-F
ANNUAL REPORT FOR THE FISCAL YEAR ENDED DECEMBER 31, 2019


TABLE OF CONTENTS
 
5
     
   
6
6
6
28
56
57
70
84
88
89
89
97
98
   
98
98
98
99
99
99
100
100
100
100
101
101
   
101
101
102

103
F-1

3


 CERTAIN TERMS AND CONVENTIONS

In this annual report, unless the context otherwise requires:


references to “Evogene,” “we,” “us,” “our,” “our company” and “the company” refer to Evogene Ltd. and its consolidated subsidiaries, consisting of AgPlenus Ltd., Biomica Ltd., Canonic Ltd., Casterra Ag Ltd. (formerly known as Evofuel Ltd.), Evogene Inc., Lavie Bio Ltd., and their consolidated subsidiaries;


references to “U.S. dollars,”, “USD”, “$” or “dollars” are to United States dollars;


references to “NIS” or “shekels” are to New Israeli Shekels;


References to “U.S.” are to the United States;


references to “ordinary shares”, “our shares” and similar expressions refer to our Ordinary Shares, par value NIS 0.02 per share;


references to the “articles of association” are to our Amended and Restated Articles of Association, which became effective upon the closing of the U.S. initial public offering, as subsequently amended;


references to the “Companies Law” are to the Israeli Companies Law, 5759-1999, as amended;


references to the “Securities Act” are to the Securities Act of 1933, as amended;


references to the “Exchange Act” are to the Securities Exchange Act of 1934, as amended;


references to the “NYSE” are to the New York Stock Exchange;


references to the “Nasdaq” are to the Nasdaq Stock Market LLC;


references to the “TASE” are to the Tel Aviv Stock Exchange; and


references to the “SEC” are to the United States Securities and Exchange Commission.

Unless derived from our financial statements or otherwise noted, amounts presented in this annual report are translated at the rate of NIS 3.456 = USD 1.00, the exchange rate between the NIS and the U.S. dollar reported by the Bank of Israel as of December 31, 2019.

This annual report includes other statistical, market and industry data and forecasts which we obtained from publicly available information and independent industry publications and reports that we believe to be reliable sources. Some data is also based on our good faith estimates, which are derived from management’s knowledge of the industry and independent sources. These publicly available industry publications and reports generally state that they obtain their information from sources that they believe to be reliable, but they do not guarantee the accuracy or completeness of the information. Although we believe that these sources are reliable and are not aware of any misstatements regarding the industry data presented in this annual report, we have not independently verified the information contained in such publications. Certain estimates and forecasts involve uncertainties and risks and are subject to change based on various factors, including those discussed under the headings “—Special Note Regarding Forward-Looking Statements” and “Item 3. Risk Factors—D. Risk Factors” in this annual report.

Throughout this annual report, we refer to various trademarks, service marks and trade names that we use in our business. The “Evogene” design logo, “Evogene” and other trademarks or service marks of Evogene Ltd. appearing in this annual report are the property of Evogene Ltd. We have several other registered trademarks, service marks and pending applications relating to our computational technologies. Other trademarks and service marks appearing in this annual report are the property of their respective holders. Solely for convenience, the trademarks and trade names in this annual report are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto. We do not intend the use or display of other companies’ trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

4

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

In addition to historical facts, this annual report contains forward-looking statements within the meaning of Section 27A of the Securities Act, Section 21E of the Exchange Act, and the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. We have based these forward-looking statements on our current expectations and projections about future events. Forward-looking statements include information concerning our possible or assumed future results of our business, financial condition, results of operations, liquidity, anticipated growth strategies, anticipated trends in our industry, market size, our potential growth opportunities, plans and objectives. Forward-looking statements include all statements that are not historical facts and can be identified by terms such as “anticipates,” “believes,” “could,” “seeks,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “will,” “would” or similar expressions that convey uncertainty of future events or outcomes and the negatives of those terms.

Our actual future results, performance or achievements may differ materially from what is expressed or implied by those forward-looking statements due to a variety of factors, some of which are beyond our control, including the following factors:


the extent of our continuing to maintain our holdings in our subsidiary companies;


the extent to which our discoveries and product candidates will have the desired effect so as to reach the stage of commercialization;


whether we and our collaborators are able to allocate the resources needed to develop commercial products from our discoveries and product candidates;


the length and degree of complexity of the process of our developing commercial products based on our discoveries and product candidates and the probability of our success, and the success of our collaborators, in developing such products;


the degree of success of third parties upon whom we rely to conduct certain activities, such as field-trials and pre-clinical studies;


whether we are able to comply with regulatory requirements;


whether we and our subsidiaries are able to meet expected timelines in the performance of our activities (or are delayed, including as a result of the effect of the Coronavirus);


the extent of the future growth of the agriculture, human health and industrial application industries in which we operate;


whether we can maintain our current business models;


the actual commercial value of our key product candidates;


whether we or our collaborators receive regulatory approvals for the product candidates developed by us or our collaborators;


whether products and product candidates containing or based on our discoveries are commercialized and earn us revenues or royalties;


whether we are able to maintain and recruit knowledgeable or specialized personnel to perform our research and development work;


the degree of our success at adapting to the continuous technological changes in our industries;


whether we can maintain our collaboration agreements with our current collaborators or enter into new collaboration agreements and expand our research and development to new fields;

5


whether we can improve our existing, or develop and launch new, computational technologies and screening and validation systems;


whether we can patent our discoveries and protect our trade secrets and proprietary know-how; and


the effect of the spread and resulting government actions implemented to limit coronavirus.

A number of additional important factors could cause our actual results to differ materially from those indicated by our forward-looking statements, including, but not limited to, those factors described in “Item 3. Key Information—D. Risk Factors,” “Item 4. Information on the Company” and “Item 5. Operating and Financial Review and Prospects.”

You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in our forward-looking statements are reasonable, we cannot guarantee that future results, levels of activity, performance and events and circumstances reflected in the forward-looking statements will be achieved or will occur. All of the forward-looking statements that we have included in this annual report are based on information available to us on the date of this annual report. Except as required by law, we undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changes in our expectations or otherwise.

PART I

ITEM 1.
IDENTITY OF DIRECTORS, SENIOR MANAGEMENT AND ADVISERS

Not applicable.

ITEM 2.
OFFER STATISTICS AND EXPECTED TIMETABLE

Not applicable.

ITEM 3.
KEY INFORMATION

A.          Selected Financial Data

The following tables set forth our selected consolidated financial data. You should read the following selected consolidated financial data in conjunction with “Item 5. Operating and Financial Review and Prospects” and our consolidated financial statements and related notes included in this annual report. Historical results are not necessarily indicative of the results that may be expected in the future. Our financial statements have been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board, or IASB.

The selected consolidated statements of profit or loss and other comprehensive income (loss) data for each of the years in the three-year period ended December 31, 2019 and the consolidated statements of financial position data as of December 31, 2018 and December 31, 2019 are derived from our audited consolidated financial statements appearing in this annual report. The consolidated statements of profit or loss and other comprehensive income (loss) data for each of the years ended December 31, 2015 and December 31, 2016 and the consolidated statements of financial position data as of December 31, 2015, 2016 and 2017 are derived from our audited consolidated financial statements that are not included in this annual report.

   
2015
   
2016
   
2017
   
2018
   
2019
 
Consolidated Statements of Profit or Loss and Other Comprehensive Income (Loss):
                             
Revenues:
                             
Research and development payments, including up-front payments
 
$
10,956
   
$
6,500
   
$
3,369
   
$
1,747
   
$
753
 
Share purchase related revenues
   
173
     
40
     
12
     
-
     
-
 
Total Revenues
   
11,129
     
6,540
     
3,381
     
1,747
     
753
 
Cost of revenues          
   
8,255
     
5,639
     
2,845
     
1,452
     
334
 
Gross profit          
   
2,874
     
901
     
536
     
295
     
419
 
Operating expenses:
                                       
Research and development, net          
   
14,449
     
16,405
     
16,987
     
14,686
     
15,791
 
Business development          
   
1,964
     
1,696
     
1,686
     
2,084
     
2,029
 
General and administrative          
   
4,382
     
3,889
     
3,810
     
3,514
     
3,765
 
Total operating expenses          
   
20,795
     
21,990
     
22,483
     
20,284
     
21,585
 
Operating loss          
   
(17,921
)
   
(21,089
)
   
(21,947
)
   
(19,989
)
   
(21,166
)
Financing income          
   
2,571
     
2,424
     
2,125
     
1,413
     
2,630
 
Financing expenses          
   
(1,863
)
   
(891
)
   
(1,005
)
   
(2,206
)
   
(555
)
Loss before taxes on income          
   
(17,213
)
   
(19,556
)
   
(20,827
)
   
(20,782
)
   
(19,091
)
Taxes on income          
   
-
     
36
     
11
     
30
     
24
 
Loss          
   
(17,213
)
   
(19,592
)
   
(20,838
)
   
(20,812
)
   
(19,115
)
Other comprehensive income (loss):
                                       
Loss from cash flow hedges
   
(45
)
   
-
     
-
     
-
     
-
 
Amounts transferred to the statement of profit or loss for cash flow hedges
   
267
     
-
     
-
     
-
     
-
 
 Total comprehensive loss
 
$
(16,991
)
 
$
(19,592
)
 
$
(20,838
)
 
$
(20,812
)
 
$
(19,115
)
Attributable to:
                                       
Equity holders of the Company
   
-
     
-
     
-
     
(20,758
)
   
(18,112
)
Non-controlling interests
   
-
     
-
     
-
     
(54
)
   
(1,003
)
   
$
(16,991
)
 
$
(19,592
)
 
$
(20,838
)
 
$
(20,812
)
 
$
(19,115
)
Basic and diluted loss per share, attributable to equity holders of the Company
 
$
(0.68
)
 
$
(0.77
)
 
$
(0.81
)
 
$
(0.81
)
 
$
(0.70
)
Weighted average number of ordinary shares used in computing basic and diluted loss per share (1)
   
25,378,325
     
25,444,733
     
25,673,276
     
25,753,411
     
25,754,297
 

6

 
   
2015
   
2016
   
2017
   
2018
   
2019
 
Selected Consolidated Statements of Financial Position Data:
                             
Cash and cash equivalents          
 
$
10,221
   
$
3,236
   
$
3,435
   
$
5,810
   
$
34,748
 
Marketable securities          
   
71,807
     
71,738
     
59,940
     
26,065
     
2,128
 
Short-term bank deposits
   
18,603
     
13,137
     
8,380
     
22,592
     
10,000
 
Trade receivables          
   
2,675
     
169
     
132
     
160
     
72
 
Total current assets          
   
104,376
     
89,490
     
72,791
     
55,488
     
49,027
 
Total assets
   
112,595
     
95,986
     
77,602
     
58,694
     
71,364
 
Net assets
   
103,752
     
87,289
     
69,378
     
50,306
     
60,217
 
Deferred revenues and other advances          
   
858
     
1,105
     
605
     
440
     
395
 
Total liabilities          
   
8,843
     
8,697
     
8,224
     
8,388
     
11,147
 
Working capital (2)          
   
98,737
     
84,265
     
68,127
     
50,057
     
43,298
 
Shareholders’ equity          
   
103,752
     
87,289
     
69,378
     
50,306
     
60,217
 
 
The issued and outstanding share capital of the company is composed of 25,754,297 ordinary shares as of December 31, 2019.
_____________________
 
(1)
Basic and diluted loss per share is computed based on the weighted average number of ordinary shares outstanding during each period, in accordance with International Accounting Standard 33, “Earnings per Share.”
(2)          Working capital is defined as total current assets less total current liabilities.

B.           Capitalization and Indebtedness

Not applicable.

C.           Reasons for the Offer and Use of Proceeds

Not applicable.

7

D.          Risk Factors

Our business faces significant risks. You should carefully consider all of the information set forth in this annual report and in our other filings with the SEC, including the following risk factors which we face and which are faced by the industries in which we operate. Our business, financial condition or results of operations could be materially adversely affected by any of these risks. This report also contains forward-looking statements that involve risks and uncertainties. Our results could materially differ from those anticipated in those forward-looking statements, as a result of certain factors, including the risks described below and elsewhere in this report and our other SEC filings. See “Special Note Regarding Forward-Looking Statements” on page 4.

Risks Related to Our Business and Industry

If our equity holdings in our subsidiary companies are diluted, the benefit recognized by our shareholders from value that may be created in such subsidiary companies may be substantially reduced.
 
We initiated a new corporate strategy and structure at the beginning of 2018, with the intent to make product development more efficient and to better reflect the individual value of each of our market focused business units. Under the new corporate structure, the Evogene group operates with Evogene as a technology hub and a growing group of divisions and subsidiaries that benefit from the unique capabilities of Evogene’s CPB platform. Each such subsidiary is responsible for advancing its product development and pipeline, establishing its “go-to-market” strategy via direct sales or through existing and new collaborations, and securing additional financial resources, if and when required. Due to our limited financial resources and other investment considerations, our subsidiaries may obtain financing from external sources. External financing may result in a decrease of our percentage shareholdings in our subsidiaries, which, in turn, may reduce the benefit we (and, indirectly, our shareholders) recognize from value established in such subsidiaries, and potentially negatively affect our results of operations, financial condition, our long-term growth strategy and the value of our shares.
 
Our discoveries and product candidates may not achieve the desired effect required in order to create commercially-viable products.

Our success depends on our ability to develop products that have the desired effect: in our agriculture activity, on plants, in our human health activity, on humans, and in our industrial applications activity, on the relevant industrial inputs. Research and development in these industries entails considerable uncertainty. We may spend many years developing product candidates that will never be commercialized. The science underlying the development of our product candidates is highly complex and, although we use innovative approaches, there is no certainty that our discoveries will result in product candidates that satisfy market requirements. Except in our castor oil activity, none of our discoveries has completed the development process and become commercially available so far, and may never reach commercialization. If our discoveries and product candidates will not have the desired effect, we and our collaborators may not develop commercial products that are based on them, which could materially and adversely affect our results of operations and our long-term growth strategy.

Various factors may delay or prevent commercialization of our product candidates.

Our success depends in part on our ability to identify discoveries that will improve crop performance, in our agriculture activity, obtain clinical benefits, in our human health activity, or improve industrial inputs, in our industrial applications activity. To develop these discoveries and product candidates into commercial products, we either license them to collaborators or develop them independently. Pursuant to our collaboration agreements in our agriculture activity, we are usually entitled, subject to certain conditions, to receive royalties on products that are based on, or integrate, these discoveries. In addition, certain of our agreements in our agriculture activity entitle us to upfront fees, research and development payments and milestone payments in the event that specified milestones are met. Except for Casterra’s castor varieties, none of our product candidates has completed the development process and become commercially available, and there can be no guarantee that any of our current or future product candidates will ever reach commercialization. Therefore, we currently do not earn royalties, nor do we have significant sales revenues from the sale of products based on our discoveries and product candidates. Nevertheless, our long-term growth strategy is based in large part on the expectation that such royalties and revenues from product sales will comprise a significant portion of our revenues in the future. If we or our collaborators never commercialize products based on our discoveries, we will not realize revenues from royalties and may not earn a profit on our discoveries, which could materially and adversely affect our results of operations, financial condition and our long-term growth strategy and could cause us to cease operations.

8

The manner in which we and our collaborators develop our product candidates in our various fields of activity affects the period that will pass until such products are commercialized, if ever. Product candidates based on our discoveries may never become commercialized for any of the following reasons:


our discoveries may not be successfully validated or may not have the desired effect required in order to become, or to be incorporated into, commercial products;


the process of developing product candidates based on our discoveries is lengthy and expensive, and we or our collaborators may not be able to allocate the resources needed to complete such development within the desired timeline;


we or our collaborators may decide to discontinue, pause, reduce, or alter the scope of the development efforts for our product candidates;


we may fail to satisfy, in a timely manner or at all, relevant milestones under our agreements with our collaborators;


regulatory conditions related to our product candidates may change in different territories, thus negatively affecting the relevant development processes and extending their length or limiting the commercialization of such product candidates;


we or our collaborators may be unable to obtain the requisite regulatory approvals for product candidates based on our discoveries;


our competitors may launch competing or more effective products;


we or our collaborators may be unable to fully develop and commercialize product candidates containing our discoveries or may decide, for whatever reason, not to commercialize, or to delay the commercialization of, such product candidates;


a market may not exist for products containing our discoveries or such products may not be commercially successful or relevant; and


we may be unable to protect the intellectual property underlying our discoveries in the necessary jurisdictions.

Our product development cycle is lengthy and uncertain, and we may never sell or earn royalties on the sale of commercial products based on our discoveries.

Research and development in our fields of activity is expensive and prolonged and entails considerable uncertainty. We may spend many years and dedicate significant financial and other resources developing product candidates that will never be commercialized. The process of discovering, developing and commercializing seed traits, ag-chemicals, ag-biologicals, castor varieties, human microbiome-based therapeutics or medical cannabis products involves several phases and a long development period. The timelines for development of product candidates by ourselves or by our collaborators may extend beyond our expectations for many reasons, such as:


we or our collaborators may not be able to allocate the resources needed to develop product candidates based on our discoveries;


we or our collaborators may revise the process of product development or make other decisions regarding their product development pipelines that may extend the development period;


we or our collaborators may prioritize other development activities ahead of development activities with respect to the product candidates on which we collaborate;


our discoveries may not be successfully validated or may not have the desired effect sought by us or by our collaborators; and


we or our collaborators may be unable to obtain the requisite regulatory approvals for the product candidates based on our discoveries within expected timelines or at all.

9

Most of the product candidates we or our collaborators are developing are in early development stages. We have little to no certainty as to which and when, if any, any of these product candidates will eventually reach commercialization. Because of the long product development cycle and the complexities and uncertainties associated with research in our fields of activity, there is significant uncertainty as to whether we will ever generate significant revenues or royalties, if any, from the product candidates that we or our collaborators are developing. For more information on the product development cycle of the product candidates we develop and a description of the phases of development, see the ‘Product Development Cycle’ paragraph under the description of each of our activity divisions and subsidiaries in “Item 4. Information on the Company—B. Business Overview”.

Due to mergers and consolidations, there is a reduced number of companies in the agriculture industry with which we might establish strategic partnerships, and we rely on a limited number of collaborators to develop and commercialize product candidates containing our seed trait, ag-chemical and ag-biological product candidates.

The agriculture markets are highly consolidated and dominated by a relatively small number of large companies. In our agriculture operations, we are currently undertaking collaborations with several of these companies to develop improved seed traits, ag-chemical and ag-biological product candidates. Due to the small number of major companies in this industry, there are limited opportunities for us to grow our business with new collaborators. In addition, if we fail to develop or maintain our relationships with any of our current collaborators, we could not only lose our opportunity to work with that collaborator, but we could also suffer a reputational risk that could impact our relationships with other collaborators in what is a relatively small industry community.

In our agriculture operations, we are currently working either with collaborators or on independent projects to research and develop our different seed trait, ag-chemical and ag-biological product candidates. While we seek to expand our portfolio of product candidates in the future, the research and development required to discover and develop new product candidates is costly, time-intensive and requires significant infrastructure resources. If we are unable to enter into new collaborations, or if we do not have the resources to develop the capabilities or resources necessary to discover and develop such product candidates independently, we may not be able to expand our portfolio of these product candidates, which could have a material adverse effect on our business prospects.

A decrease in research expenditures by the major companies in our target markets may jeopardize the continuation, or scope, of our collaborations with such companies and adversely impact our ability to continue or extend existing collaborations or enter into new collaborations on favorable financial terms.

The research and development expenditures of our existing and potential collaborators in the agriculture, human health, and industrial applications markets we operate in may be reduced for reasons beyond our control. For example, a global crisis or economic recession, a decrease in the prices of agricultural commodities, or the consolidation trend in the seeds and ag-chemicals industries may result in decreased research and development expenditures in the markets relevant for our seed trait, ag-biological and ag-chemical product candidates. Such developments may, in turn, adversely impact our ability to maintain or extend our existing collaborations or enter into new collaborations on favorable financial terms. For example, we may not be able to enter into new collaborations under which our collaborators cover our expenses through research and development payments.

We or our collaborators may fail to perform obligations under the collaboration agreements.

We are obligated under our collaboration agreements to perform research activities over a particular period of time. If we fail to perform our obligations under these agreements, in some cases our collaborators may terminate our agreements with them and in other cases our collaborators’ obligations may be reduced and, as a result, our anticipated revenues may decrease. In addition, any of our collaborators may fail to perform their obligations, which may hinder development and commercialization of products containing the product candidates we develop and materially and adversely affect our future results of operations. Furthermore, the various payments we receive from our collaborators are currently our primary source of revenues. If our collaborators do not make these payments, either due to financial hardship, disagreement under the relevant collaboration agreement or for any other reason, our results of operations and business could be materially and adversely affected. If disagreements with a collaborator arise, any dispute with such collaborator may negatively affect our relationship with one or more of our other collaborators and may hinder our ability to enter into future collaboration agreements, each of which could negatively impact our business and results of operations.

10

We are operating in multiple industries, each of which consist of multiple companies with much greater resources than us. Competition in our industries is intense and requires continuous technological development. If we are unable to compete effectively, our financial resources will be diluted and our financial results will suffer.

We currently face significant competition in the markets in which we operate. The agriculture, human health and industrial applications markets in which we operate are intensely competitive and rapidly changing. Many companies engage in research and development of products in such markets, and speed in getting a new product candidate to market can be a significant competitive advantage. In most segments of our operations, the number of products available to the consumer is steadily increasing as new products are introduced. At the same time, an increasing number of products are coming off patent and are thus available to generic manufacturers for production. We may be unable to compete successfully against our current and future competitors, which may result in lower prices and margins and the inability to achieve market acceptance for products containing our discoveries. In addition, many of our competitors have substantially greater financial, marketing, sales, distribution and technical resources than us and some of our collaborators are significantly larger than us and have more experience in research and development, regulatory matters, manufacturing and marketing. We anticipate increased competition in the future as new companies enter these markets and new technologies become available. Our technologies may be rendered obsolete or uneconomical by technological advances or entirely different approaches developed by one or more of our competitors or collaborators, which will prevent or limit our ability to receive any associated research and development payments or generate revenues from the commercialization of our product candidates.

We are working to develop and commercialize novel ag-biological products, and our efforts may be unsuccessful.

Our majority-owned subsidiary, Lavie Bio, is developing ag-biological product candidates, currently focused mainly on microbial-based bio-stimulants and bio-pesticides, through a novel approach, focused on plant-microbiome relationship. In certain of our ag-biological product programs, Lavie Bio funds its early stages of research and development efforts in order to potentially capture more value, while in others it funds the entire development program towards launch of a commercial product. Lavie Bio’s efforts to develop novel ag-biological product candidates may fail for a variety of reasons, including:


failure to establish the requisite infrastructure to enable the discovery and development of microbial bio-stimulants;


failure to identify and develop microbial candidates that enhance plant performance at the desired efficacy and stability;


failure to successfully complete development of microorganisms to achieve cost-effective and commercially viable products;


failure to meet regulation requirements in case significant changes occur in the future; and


failure to establish cost-effective go-to-market models for selling our products.

If Lavie Bio’s efforts to develop ag-biological product candidates are unsuccessful, our results of operations could be negatively impacted.

We are working to develop and commercialize novel ag-chemical products, and our efforts may be unsuccessful.

Our subsidiary, AgPlenus, is currently developing solutions for crop protection through chemistry, or ag-chemistry. AgPlenus is developing these product candidates through a novel approach, focused on biologically significant proteins called “targets”. AgPlenus’ efforts to develop novel ag-chemical product candidates may fail for a variety of reasons, including:


failure of its relatively novel target-based approach to lead to an effective product candidate or failure to identify chemical compounds that will display required level of performance;


inability to obtain sufficient funding to fully execute its ag-chemical business plan; and


failure to meet regulation requirements.

If AgPlenus’ efforts to develop ag-chemical product candidates are unsuccessful, our results of operations could be negatively impacted.

11

We are working to develop and commercialize seed-trait products, and our efforts may be unsuccessful.

We are developing seed trait and insect control product candidates in our internal Ag-Seeds division. Our efforts to develop novel product candidates may fail for a variety of reasons, including:


failure to identify and develop candidate genomic elements having the desired effect on the target trait in the plant of interest;


failure to identify and develop toxin candidates having the desired effect on the target insects when inserted into the plants of interest;


failure to successfully complete development of our seed trait product candidates; and


our failure to meet regulation requirements for seed trait and insect control product candidates.

Furthermore, even if we are able to discover and begin to develop effective product candidates, we may not be successful if we are unable to find collaborators for further development and commercialization of the product candidates. If our efforts to develop seed trait product candidates are unsuccessful, our results of operations could be negatively impacted.

We are working to develop human microbiome-based therapeutic product candidates, and our efforts may be unsuccessful.

Our subsidiary, Biomica, is developing microbiome-based therapeutic product candidates. Biomica’s efforts to develop its product candidates and develop marketable products may be unsuccessful for a variety of reasons, including the following:


failure to complete pre-clinical studies and clinical trials with positive results;


failure to finance the development and commercialization of its product candidates;


failure to receive marketing approvals from applicable regulatory authorities;


failure to obtain and maintain patent and trade secret protection and regulatory exclusivity for its product candidates;


failure to making arrangements with third-party manufacturers for, or establishing its own, commercial manufacturing capabilities;


failure to launch commercial sales of its products, if and when approved, whether alone or in collaboration with others;


failure to enter into new collaborations throughout the development process as appropriate, from pre-clinical studies through to commercialization;


failure to achieve acceptance of its products, if and when approved, by patients, the medical community and third-party payors;


failure of its products, if approved, to compete effectively with other therapies;


failure to obtain and maintain coverage and adequate reimbursement by third-party payors, including government payors, for its products, if approved;


failure to protect its rights in its intellectual property portfolio;


failure to operate without infringing or violating the valid and enforceable patents or other intellectual property rights of third parties;


failure to maintain a continued acceptable safety profile of the products following approval; and


failure to maintain and develop an organization of scientists and business people who can develop and commercialize its products and technology.

If Biomica’s efforts to develop microbime-based human therapeutics are unsuccessful, our results of operations could be negatively impacted.

We are working to develop and commercialize medical cannabis products, and our efforts may be unsuccessful.

Canonic, our subsidiary, is developing medical cannabis product. Canonic’s efforts to develop and commercialize medical cannabis products may fail for a variety of reasons, including:


failure to develop cannabis varieties having desired efficacy and stability;


failure to establish the agro-technical knowledge and expertise for cultivating cannabis;


failure to meet regulation requirements;


failure to engage with, and successfully operate, contractors, in Israel and abroad, for performing cultivation and production services;


failure to establish successful distribution channels, in Israel and abroad, for our medical cannabis products;


failure to secure our cannabis cultivation facilities; and


the market for medical cannabis products is relatively new and suffers from high uncertainty in many aspects, including demand, supply, pricing, regulation, customer preferences, etc.

If Canonic’s efforts to develop and commercialize medical cannabis products are unsuccessful, our results of operations could be negatively impacted.

12

We are working to develop and commercialize castor seeds for industrial applications, and our efforts may be unsuccessful in achieving a commercial presence in this market.

Our subsidiary, Casterra, is currently developing improved, high-yield castor bean seeds for use as a source of non-edible feedstock for the existing industrial uses of castor oil. The supply chain in the market of castor oil for industrial uses is not well established and is evolving. In order for Casterra’s castor bean seeds to be an attractive feedstock for oil for industrial uses, we will need to demonstrate on a commercial scale that our castor beans can reliably be used as a cost-efficient feedstock for castor oil production. Casterra’s efforts to develop castor been seeds for industrial uses may fail for a variety of reasons, including:


failure to reach desired yields of its castor seed varieties on a commercial scale to secure economic viability as bio-based oil feedstock;


failure to establish an efficient mechanical harvest solution;


failure to establish a cost-effective production of castor bean grains, allowing grower profitability;


failure to reach large scale adoption of castor by growers, including the successful management of diseases, and pests;


failure to address the health and environmental risks posed by castor bean seeds, which contain a naturally occurring poison called ricin;


failure to comply with any regulatory requirement related to sales of castor beans, and in particular those related to the import of such beans and the potential effects of ricin; and


failure to establish sustainable production of castor seeds.

We are operating in a new industry, with limited understanding of the dynamics involved in producing and selling castor seeds. We have made initial commercial sales of castor seeds; however, we are unable to foresee as to when significant sales will commence. If we are unable to adequately address any of these issues, we may not find a market for our castor bean seeds and our results of operations could be materially and adversely affected.

If Lavie Bio is unable to establish successful distribution and retail channels for the commercialization of its products, it will not be able to meet its commercialization plans.
 
Our majority-owned subsidiary, Lavie Bio, intends to commercialize part of its future ag-biological products through distribution and retail channels. We have little experience in establishing such channels and may be unsuccessful in doing so. In addition, we will be dependent on our distributers in introducing our products to the market. If we or our distributors are unsuccessful in our efforts to penetrate the market, our revenues and financial results will be adversely affected.
 
Even if we are entitled to royalties from our collaborators, we may not actually receive these royalties, or we may experience difficulties in collecting the royalties that we believe we are entitled to.

If and when our collaborators launch commercial products containing our licensed discoveries, we will rely on our collaborators to report to us the sales they earn from these products and to accurately calculate the royalties we are entitled to, a process that will involve complicated calculations. Although we seek to address these concerns in our collaboration agreements, such provisions may not be effective. Additionally, we may not be able to achieve our long-term goal of generating revenues from royalties, and in the coming years our revenues will be entirely dependent on fees we earn for our research and development services and milestone payments from our collaborators.

Each of us and our subsidiaries depends on our key personnel and, if we are not able to attract and retain qualified scientific and business personnel, we may not be able to grow our business or develop and commercialize our product candidates.

The vast majority of our workforce is involved in research and development. Our business is therefore dependent on our ability to recruit and maintain a highly skilled and educated workforce with expertise in a range of disciplines, including biology, chemistry, plant genetics, agronomics, entomology, mathematics, computer science and other subjects relevant to our operations. For example, of our staff, 38 employees hold a Ph.D. The number of qualified and highly educated personnel in the fields upon which our business focuses in Israel, where most of our operations are located, is limited and competition for the services of such persons is intense. Although we have employment agreements with all of our employees, most of these agreements may be terminated upon short notice. The failure to hire and retain skilled and highly educated personnel could limit our growth and hinder our research and development efforts.

13

We develop certain discoveries independent of our collaborators, and we may need to finance the cost of the development of such technologies ourselves.

In recent years we have begun to develop certain discoveries and product candidates independent of our collaborators, with a goal of making such discoveries available to collaborators in later phases, including the final product development stage in certain cases. While we believe this will allow us to negotiate more favorable license or commercialization terms with respect to such discoveries and product candidates, the up-front cost to us of developing programs without a collaborator (and therefore without external funding for the research and development expenditures we incur) in these early phases involves higher risks, since we need to fund the research and development of such programs ourselves. If we are unsuccessful in discovering promising product candidates after having invested significant funds, or if we are unable to find collaborators who are interested in such results and willing to fund subsequent phases of development and commercialization, such failures could have a material and adverse effect on our business, financial condition and results of operations. Traditional financing sources such as bank financing or public debt or equity financing, if available to us, could carry with them certain drawbacks, such as imposition of covenants restricting our ability to operate, or substantial dilution to our existing shareholders.

Our business is subject to various government regulations and, if we or our collaborators are unable to obtain the necessary regulatory approvals, we may not be able to continue our operations.

Our business is generally subject to two types of regulations: regulations that apply to how we operate and regulations that apply to products containing our discoveries and product candidates. Typically, we apply for and maintain the regulatory approvals necessary for our operations, while our collaborators apply for and maintain regulatory approvals necessary for the commercialization of products containing our discoveries. We may fail to comply with all currently applicable regulations, and we may become subject to new or revised regulations or approvals in the future. Furthermore, any violation of these regulations could expose us to civil and criminal penalties.

The relevant regulatory regimes may be particularly onerous; for example, the U.S. federal government’s regulation of biotechnology is divided among the United States Environmental Protection Agency, which regulates activity related to the invention of plant pesticides and herbicides, the United States Department of Agriculture, which regulates the import, field testing and interstate movement of specific technologies that may be used in the creation of transgenic plants, and the United States Food and Drug Administration, or the FDA, which regulates foods derived from new plant varieties. If we or our collaborators are unable to obtain the requisite regulatory approvals or there is a delay in obtaining such approvals as a result of negative market perception or heightened regulatory standards, such product candidates will not be commercialized, which would negatively impact our business and results of operations.

Our medical cannabis activity exposes us to legal and reputational risks associated with the cannabis industry.

          Although Canonic, our subsidiary that develops medical cannabis products currently has limited operations, our current and potential involvement in cannabis-related activity may expose us to legal and reputational risks. Such risks include:


activities in the field of cannabis are subject to enhanced regulation in Israel and worldwide. For example, Israeli regulation requires that we obtain a specific permit for each of the following activities: research, propagation, cultivation, production, marketing and distribution, use, etc.;


changes in laws, regulations and guidelines related to cannabis may result in significant additional compliance costs for us or limit our ability to operate in certain jurisdictions;


certain banks will not accept deposits from or provide other bank services to businesses involved with cannabis; and


third parties with whom we do business may perceive that they are exposed to reputational risk as a result of our cannabis-related business activities and may ultimately elect not to do business with us.

          Any of the foregoing factors could adversely affect our business and results of operations

The cost we incur in procuring a directors and officers, or D&O, liability insurance has substantially increased during the last years. If this trend continues, it will have an adverse effect on our results of operations.

D&O liability insurance is intended to cover the liability of the individuals serving as our directors and management, from losses incurred as a result of such service, our liability to indemnify such individuals for such losses and to protect us from certain securities claims. During the last years, there has been a significant increase in the cost of D&O insurance for smaller, dual-listed public companies such as our Company. The increases have been tied to perceived heightened levels of risk for D&O insurers. For example, the year 2018 set a 20-year record high for securities class actions filed against issuers of common or preferred stock listed in the United States. In parallel, there has been an increase in the amounts of the deductibles payable by public companies in situations in which an insurable event occurs. If this trend continues, it will increase our operational expenses and have a negative effect on our financial results.

14

Disruption to our information technology, or IT, system could adversely affect our reputation and have a material adverse effect on our business and results of operations.

Our computational technologies rely on our IT system to collect and analyze the biological and chemical data we collect and discover. We store significant amounts of data, and to date, have compiled several petabytes of data. There can be no assurance that our back-up storage arrangements will be effective if it becomes necessary to rely on them. Furthermore, we can provide no assurance that our current IT system is fully protected against third-party intrusions, viruses, hacker attacks, information or data theft or other similar threats. Disruption or failure of our IT system due to technical reasons, cyberattacks, natural disasters or other unanticipated catastrophic events, including power interruptions, storms, fires, floods, earthquakes, terrorist attacks and wars could significantly impair our internal development efforts and materially and adversely affect our collaborations, our business and our results of operations.

As we continue to develop our computational technologies and expand our datasets, we may need to update our IT system and storage capabilities. However, if our existing or future IT system does not function properly, or if the IT system proves incompatible with our new technologies, we could experience interruptions in data transmissions and slow response times, preventing us from completing routine research and business activities, which could adversely affect our business and results of operations.

Development of our product candidates, particularly during our validation and testing activities, may be adversely affected by circumstances caused by us or those beyond our control.

The industries we are engaged in are subject to various factors that make our operations relatively unpredictable from period to period. For example, the testing of our product candidates may be adversely affected by circumstances both caused by us and those that are beyond our control. Factors caused by us include any failure by us or our collaborators to follow proper agronomic practice or suggested protocols for conducting our experiments, and failure to successfully complete such experiments. Factors beyond our control include weather and climatic variations, such as droughts or heat stress, or other factors we are unable to identify. For example, if there was prolonged or permanent disruption to the electricity, climate control or water supply operating systems in our greenhouses or laboratories, the plants and pests on which we test our discoveries and product candidates and the samples we store in freezers, both of which are essential to our research and development activities, would be severely damaged or destroyed, adversely affecting our research and development activities and thereby our business and results of operations. We have experienced these kind of failures in the past for unknown reasons, causing delays in our achievement of milestones and delivery of results, and necessitating that we re-start the trials. Any test failure we may experience is not covered by our insurance policy, and therefore could result in increased cost of the trials and development of our product candidates, which may negatively impact our business and results of operations.

The COVID-19 pandemic, or any other pandemic, epidemic or outbreak of an infectious disease in the United States, Israel or elsewhere, may hurt our business in many ways, and, if prolonged, could adversely impact our operating results and financial condition in a significant manner.

The COVID-19 pandemic, and any other pandemic, epidemic or outbreak of an infectious disease that occurs in the United States, Israel or elsewhere, may adversely affect our business and, if prolonged, could adversely impact our operating results and financial condition in a significant manner. In December 2019, a novel strain of coronavirus, COVID-19, was identified in Wuhan, China. This virus continues to spread globally and, as of April 2020, has spread to over 100 countries, including the United States, Israel and Latin America. The spread of COVID-19 from China to other countries has resulted in the World Health Organization declaring the outbreak of COVID-19 as a “pandemic,” or a worldwide spread of a new disease, on March 11, 2020. Many countries around the world have imposed quarantines and restrictions on travel and mass gatherings to slow the spread of the virus. Since March 2020, the Government of Israel imposed multiple precautionary measures, such as quarantine restrictions for foreign travelers arriving from any country, avoiding gatherings, and restrictions on work places. Employers (including us) are also required to prepare and increase as much as possible the capacity and arrangement for employees to work remotely. In addition, since March, 2020, the President of the United States issued a proclamation to restrict travel to the United States from certain foreign nationals  and governors of many U.S. states have enacted temporary measures seeking to limit the spread of COVID-19, including in the State of Missouri, where our U.S. research and development site is located. We are still assessing and will continue to assess the effect on our business, from the spread of COVID-19 and the actions implemented by the governments of the State of Israel, the United States and elsewhere across the globe.
 
15

These actions have disrupted the ordinary course of operations for us, our collaborators and contractors, causing operational delays, labor shortages, travel disruption and shutdowns, thus restricting our, our collaborators’ and contractors’ ability to ensure the continuous development of our product candidates, which could have an adverse effect on our development programs.

In addition, regulatory bodies may reduce or postpone meetings with us or internally if resources are pushed away from our industries in response to the spread of an infectious disease. Such events may result in a period of business disruption, and in reduced operations, any of which could materially affect our business, financial condition and results of operations.
 
The COVID-19 outbreak and mitigation measures also have had and may continue to have an adverse impact on global economic conditions which could have an adverse effect on our business and financial condition, including impairing our ability to raise capital if and when needed. The extent to which COVID-19 impacts our business will depend on future developments, which are highly uncertain and cannot be predicted, including new information which may emerge concerning the severity of COVID-19 and the actions to contain COVID-19 or treat its impact, among others.

Consumer and government resistance to genetically modified organisms may negatively affect our public image and reduce sales of plants containing our traits.

A certain part of our seed traits activity includes research and development of genetically modified, or GM, seeds. Foods made from such seeds are not accepted by many consumers and in certain countries production of certain GM crops is effectively prohibited, including throughout the European Union, due to concerns over such products’ effects on food safety and the environment. The high public profile of biotechnology agriculture, especially in food production, and lack of consumer acceptance of products to which we have devoted substantial resources could negatively affect our public image and results of operations. For example, the prohibition on the production of certain GM crops in select countries and the current resistance from consumer groups, particularly in Europe, to GM crops not only limits our access to such markets but also has the potential to spread to and influence the acceptance of products developed through biotechnology in other regions of the world and may also influence regulators in other countries to limit or ban production of GM crops, which could limit the commercial opportunities to exploit biotechnology.

GM crops are grown principally in the United States, Brazil and Argentina where there are fewer restrictions on the production of GM crops. If these or other countries where GM crops are grown enact laws or regulations that ban the production of such crops or make regulations more stringent, we could experience a longer product development cycle for our product candidates and may even have to abandon projects related to certain crops or geographies, both of which would negatively affect our business and results of operations and could cause us to have to cease operations. Furthermore, any changes in such laws and regulations or consumer acceptance of GM crops could negatively impact our collaborators, who in turn might terminate or reduce the scope of their collaborations with us or seek to alter the financial terms of our agreements with them.

We have a history of operating losses and negative cash flow, and we may never achieve or maintain profitability.

We have a history of losses, and incurred operating losses of $21.1 million, $20.0 million and $21.9 million for the years ended December 31, 2019, 2018, and 2017, respectively. There is no assurance that our efforts in developing our product candidates will result in commercially successful products. We expect to continue to incur losses in future periods, until we begin earning revenues or royalties on the product candidates we are currently developing and any new product candidates we develop in the future, if at all. Because we will incur significant costs and expenses for these efforts before we obtain any incremental revenues from them, our losses in future periods could be significant. In addition, we may find that these efforts are more expensive than we anticipate or that they do not result in profitability in the time period we anticipate, which would further increase our losses. For example, if governments across the globe continue to implement actions that limit movement and activity, as a result of the COVID-19 pandemic or otherwise, we could face increased costs in order to meet our product development timeline. If we are unable to adequately control the costs associated with operating our business, including our costs of development and sales, we may deplete our cash resources and may be unable to continue to finance our business from our existing cash resources, and, our business, financial condition, operating results and prospects will suffer. For more information concerning our cash resources, please see “Liquidity and Capital Resources” in Item 5.B below.

16

The licenses we grant to our collaborators to use our discoveries are in most cases exclusive with respect to a specified discovery, product type or market area. This may limit our opportunities to enter into additional licensing or other arrangements with respect to such discoveries, product types or market areas.

Most of the licenses we grant our collaborators to our product candidates or to use specific discoveries we have made are exclusive in the area of the license. That means that once these discoveries are licensed to a collaborator, we are generally prohibited from licensing those discoveries to any third party for use in such area. The limitations imposed by these exclusive licenses could prevent us from expanding our business and increasing our exposure to new licensees, both of which could adversely affect our business and results of operations.

We may be required to pay substantial damages as a result of uninsured product liability claims.

Once products integrating our discoveries and product candidates reach commercialization, if ever, product liability claims will be a commercial risk for our business, particularly as some of the products that we develop can be harmful to humans or the environment. Courts have levied substantial damages in the United States and elsewhere against a number of companies in the agriculture and human health industries in past years based upon claims for injuries allegedly caused by the use of their products. Product liability claims against us or our collaborators selling products that contain our product candidates or allegations of product liability relating to products containing our discoveries could damage our reputation, harm our relationships with our collaborators, and materially and adversely affect our business, results of operations, financial condition and prospects. We currently do not have product liability insurance coverage. Any such insurance we may obtain in the future may be expensive and may not cover our potential liability in full. Furthermore, while our collaboration agreements typically require that our collaborators indemnify us for the cost of product liability claims brought against us, such indemnification provisions may not always be enforced, and we may receive no indemnification if our own misconduct led to the claims.

Our facilities, in Israel and in the U.S., are located on leased properties. Termination of any of the leases, changes in lease terms, and long-term leases that may not be terminated at will may jeopardize our activity and materially affect our financial condition or results of operations.

Our office spaces, labs, facilities, and farm are all situated on properties that we lease pursuant to lease agreements, in Israel and in the U.S. Once a lease agreement ends, we may not be able to renew it on favorable terms, or not at all, which may require us to increase our lease payments or take a new lease in another property, adversely affecting our business and results of operations. In addition, a long-term lease may mean no or limited possibility to terminate the lease at will before the completion of the lease period, which may lead to continued holding of an un-needed space or entry into a sub-lease, which may adversely affect our results of operations. For more information regarding our facilities, please see “Item 4. Information on the Company—D. Property, Plants and Equipment.”

Lavie Bio’s research and development facility in the U.S., our contracts with foreign businesses and any other current or future operations outside of Israel expose us to additional market and operational risks, and failure to manage these risks may adversely affect our business and operating results.

Lavie Bio’s research and development facility in St. Louis, Missouri may expose us to some of such operational risks, including:


fluctuations in foreign currency exchange rates;


potentially adverse tax consequences;


difficulties in staffing and managing foreign operations;


hiring and retention of employees and/or consultants under foreign employment laws which are not familiar to us;


laws and business practices that sometimes favor local business;


compliance with foreign legislation, being subject to laws, regulations and the court systems of multiple jurisdictions; and


tariffs, trade barriers and other regulatory or contractual limitations on our ability to develop (and, when applicable in the future, sell) our solutions in certain foreign markets.

Failure to manage the market and operational risks associated with international operations effectively could limit the future growth of our business and adversely affect our operating results.

17

Our operations are subject to various health and environmental risks associated with our use, handling and disposal of potentially toxic materials.

Our operations involve various health and environmental risks. As part of our seed traits operations, we assist in the development of GM crops by inserting new genes into the genomes of certain plants. Though we introduce these genes in order to improve plant traits, we cannot always predict the effect that these genes may have on the plant. In some cases, the genes may render the plant poisonous or toxic, or they may cause the plant to develop other dangerous characteristics that could harm the plant’s surrounding environment. Furthermore, while we comply with relevant environmental laws and regulations, there is a risk that, when testing genetically modified plants, the seeds of these plants may escape the greenhouse or field in which they are being tested and contaminate nearby fields. Poisonous or toxic plants may therefore be inadvertently introduced into the wild, or possibly enter the food production system, harming the people and animals who come in contact with them.

As part of Lavie Bio’s operations, it develops novel product candidates based on microbes in order to improve plants traits. Although microbes exist naturally in the environment, we cannot always predict the effect that microbes have on the plant and its environment. There may be cases where the microbes render the plant poisonous or toxic, or they may cause the plant to develop other dangerous characteristics that could harm the plant’s surrounding environment.

Changes in laws and regulations to which we are subject, or to which we may become subject in the future, may materially increase our costs of operation, decrease our operating revenues and disrupt our business.

Laws and regulatory standards and procedures that impact our business are continuously changing. Responding to these changes and meeting existing and new requirements may be costly and burdensome. Changes in laws and regulations may occur that could:


impair or eliminate our ability to research and develop our product candidates, including validating our product candidates through field or clinical trials;


increase our compliance and other costs of doing business through increases in the cost to patent or otherwise protect our intellectual property or increases in the cost to our collaborators to obtain the necessary regulatory approvals to commercialize and market the product candidates we develop with them;


require significant product redesign or systems redevelopment;


render our product candidates less profitable, obsolete or less attractive compared to competing products;


affect our collaborators’ willingness to do business with us;


reduce the amount of revenues we receive from our collaborators through milestone payments or royalties; and


discourage our collaborators from offering, and consumers from purchasing, products that incorporate our discoveries.

Any of these events could have a material adverse effect on our business, results of operations and financial condition. For example, legislators and regulators have increased their focus on plant biotechnology in recent years, with particular attention paid to GM crops as well as on ag-chemicals.

While none of our product candidates are currently available for sale, other than Casterra’s castor seeds, our future growth relies on our ability and the ability of our collaborators to commercialize and market our product candidates, and any restrictions on such activities could materially and adversely impact our business and results of operations. Any changes in regulations in countries where our product candidates are used could result in our collaborators being unable or unwilling to develop, commercialize or sell products that incorporate our discoveries. In addition, we rely on patents and other forms of intellectual property protection. Legislation and jurisprudence on patent protection in the key target markets where we seek patent protection, such as the United States and the European Union, is evolving and changes in laws could affect our ability to obtain or maintain patent protection for our product candidates. Any changes to these existing laws and regulations may materially increase our costs of operation, decrease our operating revenues and disrupt our business. For more information please see ‘Government Regulation of our Operations’ and ‘Government Regulation of Product Candidates’ paragraphs under the description of each of our activity divisions and subsidiaries under “Item 4. Information on the Company—B. Business Overview.”

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Risks Related to Our Intellectual Property Rights

Our success depends on our ability to protect our intellectual property and our proprietary technologies.

Our commercial success depends in part on our ability to obtain and maintain patent protection and trade secret protection for our proprietary computational technologies, our discoveries and their uses, as well as our ability to operate without infringing upon the proprietary rights of others. If we do not adequately protect our intellectual property, competitors may be able to use our technologies and erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.

While we expect our patent applications to receive approval, we cannot be certain that we will obtain such results. Despite our efforts to protect our proprietary rights, unauthorized third parties may attempt to use, copy or otherwise obtain and market or distribute our intellectual property rights or technology or otherwise develop products or solutions with the same functionality as our solutions. In addition, the laws of some foreign countries provide less protection for proprietary rights than U.S. law. We face the occasional risk, moreover, that third parties may assert copyright, trademark and other intellectual property rights against us. Such claims may result in direct or indirect liability as we have contractually agreed to indemnify certain parties for any damages suffered as a result of infringement by us of any third-party intellectual property rights.

If we are unable to protect the confidentiality of our trade secrets, the value of our technology could be materially adversely affected and our business would be harmed.

We treat our proprietary computational technologies, including unpatented know-how and other proprietary information, as trade secrets. We seek to protect these trade secrets, in part, by entering into non-disclosure and confidentiality agreements with any third parties who have access to them, such as our consultants, independent contractors, advisors, corporate collaborators and outside scientific collaborators. We also enter into confidentiality and invention or patent assignment agreements with employees and certain consultants. Any party with whom we have executed such an agreement may breach that agreement and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable. In addition, if any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent such third party, or those to whom it communicates that technology or information, from using that technology or information to compete with us. If any of our trade secrets were to be disclosed to or independently developed by a competitor, or if we otherwise lose protection for our trade secrets or proprietary know-how, the value of this information may be greatly reduced and our business and competitive position could be harmed.

We may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting, maintaining and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States are less extensive than those in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we are unable to prevent third parties from using our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the jurisdictions in which we do not have patent protection. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products, and we may be unable to prevent such competitors from importing those infringing products into territories where we have patent protection but enforcement is not as strong as in the United States. These products may compete with our product candidates and our patents and other intellectual property rights may not be effective or sufficient to prevent them from competing in those jurisdictions. Moreover, farmers or others in the chain of commerce may raise legal challenges against our intellectual property rights or may infringe upon our intellectual property rights, including through means that may be difficult to prevent or detect. For example, the practice by some farmers of saving seeds from non-hybrid crops (such as soybeans, canola and cotton) containing biotechnological traits may prevent us from realizing the full value of our intellectual property in countries outside of the United States.

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Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions, including China, where we have filed patent applications. The legal systems of certain countries, including China, have not historically favored the enforcement of patents or other intellectual property rights, which could hinder us from preventing the infringement of our patents or other intellectual property rights and result in substantial risks to us. Proceedings to enforce our patent rights in the United States or foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert patent infringement or other claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license from third parties.

If we or one of our collaborators are sued for infringing the intellectual property rights of a third party, such litigation could be costly and time consuming and could prevent us or our collaborators from developing or commercializing our product candidates.

Our ability to generate significant revenues from our product candidates depends on our and our collaborators’ ability to develop, market and sell our product candidates and utilize our proprietary technology without infringing the intellectual property and other rights of any third parties. In the United States and abroad there are numerous third party patents and patent applications that may be applied toward our proprietary technology, business processes or product candidates, some of which may be construed as containing claims that cover the subject matter of our product candidates or intellectual property. Because of the rapid pace of technological change, the confidentiality of patent applications in some jurisdictions, and the fact that patent applications can take many years to issue, there may be currently pending applications that are unknown to us that may later result in issued patents upon which our product candidates or proprietary technologies infringe. Similarly, there may be issued patents relevant to our product candidates of which we are not aware. These patents could reduce the value of the product candidates we develop or, to the extent they cover key technologies on which we have unknowingly relied, require that we seek to obtain licenses or cease using the technology, no matter how valuable to our business. We may not be able to obtain such a license on commercially reasonable terms. There is a substantial amount of litigation involving patent and other intellectual property rights in the biotechnology industry generally. If any third party patent or patent application covers our intellectual property or proprietary rights and we are not able to obtain a license to it, we and our collaborators may be prevented from commercializing products containing our discoveries.

As the biotechnology industry continues to develop, we may become party to, or threatened with, litigation or other adverse proceedings regarding intellectual property or proprietary rights in our technology, processes or product candidates. Third parties may assert claims based on existing or future intellectual property rights and the outcome of any proceedings is subject to uncertainties that cannot be adequately quantified in advance. Any litigation proceedings could be costly and time consuming and negative outcomes could result in liability for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. There is also no guarantee that we would be able to obtain a license under such infringed intellectual property on commercially reasonable terms or at all. A finding of infringement could prevent us or our collaborators from developing, marketing or selling a product candidate or force us to cease some or all of our business operations. Even if we are successful in these proceedings, we may incur substantial costs and the time and attention of our management and scientific personnel may be diverted as a result of these proceedings, which could have a material adverse effect on us. Claims that we have misappropriated the confidential information or trade secrets of third parties could similarly have a negative impact on our business.

We may be required to pay royalties to employees who develop inventions that have been or will be commercialized by us, even if the rights to such inventions have been assigned to us and the employees have waived their rights to royalties or other additional compensation.

A significant portion of our intellectual property has been developed by our employees in the course of their employment for us. Under the Israeli Patent Law, 5727-1967, or the Patent Law, inventions conceived by an employee in the course and as a result of or arising from his or her employment with a company are regarded as “service inventions,” which belong to the employer, absent a specific agreement between the employee and employer giving the employee proprietary rights. The Patent Law also provides under Section 134 that if there is no agreement between an employer and an employee as to whether the employee is entitled to consideration for service inventions, and to what extent and under which conditions, the Israeli Compensation and Royalties Committee, or the Committee, a body constituted under the Patent Law, shall determine these issues. Section 135 of the Patent law provides criteria for assisting the Committee in making its decisions. According to decisions of the Committee, an employee’s right to receive consideration for service inventions is a personal right and is entirely separate from the proprietary rights in such invention. Therefore, this right must be explicitly waived by the employee. A decision handed down in May 2014 by the Committee clarifies that the right to receive consideration under Section 134 can be waived and that such waiver can be made orally, in writing or by behavior like any other contract. The Committee will examine, on a case by case basis, the general contractual framework between the parties, using interpretation rules of the general Israeli contract laws. Further, the Committee has not yet determined one specific formula for calculating this remuneration, nor the criteria or circumstances under which an employee’s waiver of his right to remuneration will be disregarded. Similarly, it remains unclear whether waivers by employees in their employment agreements of the alleged right to receive consideration for service inventions should be declared as void being a depriving provision in a standard contract. All of our employees execute invention assignment agreements upon commencement of employment, in which they assign their rights to potential inventions and acknowledge that they will not be entitled to additional compensation or royalties from commercialization of inventions. Although our employees have agreed to assign to us service invention rights and have specifically waived their right to receive any special remuneration for such service inventions beyond their regular salary and benefits, we may face claims demanding remuneration in consideration for assigned inventions.

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Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.

As is the case with other biotechnology companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing biotechnology patents involves technological and legal complexity, and is costly, time consuming, and inherently uncertain. In addition, the U.S. Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained. Depending on decisions by the U.S. Congress, the federal courts, and the U.S. Patent and Trademark Office, the laws and regulations governing patents could change in unpredictable ways that may weaken or undermine our ability to obtain new patents or to enforce our existing patents and patents we might obtain in the future.

We and our collaborators may disagree over our right to receive payments under our collaboration agreements, potentially resulting in costly litigation and loss of reputation.

Our ability to generate royalty payments from our collaboration agreements depends on our ability to clearly delineate our intellectual property rights under those agreements. We often license patented genes or other intellectual property to our collaborators, who use or will use such intellectual property to develop and commercialize products with our discoveries. However, a collaborator may use our intellectual property without our permission, dispute our ownership of certain intellectual property rights or argue that our intellectual property does not cover their marketed product. If a dispute arises, it may result in costly litigation, and our collaborator may refuse to pay us royalty payments while the dispute is ongoing. Furthermore, regardless of any resort to legal action, a dispute with a collaborator over intellectual property rights may damage our relationship with that collaborator, and may also harm our reputation in the industry.

Our employment agreements with our employees and other agreements with our collaborators and third parties may not adequately prevent disclosure of trade secrets, know-how and other proprietary information.

A substantial portion of our technologies and intellectual property is protected by trade secret laws. We rely on a combination of patent and other intellectual property laws as well as our employment agreements with our employees and other agreements with our collaborators and third parties to protect and otherwise seek to control access to, and distribution of, our proprietary information. These measures may not prevent disclosure, infringement or misappropriation of our confidential information. Our confidentiality, nondisclosure and assignment agreements or covenants may be breached, and we may not have adequate remedies for such a breach that would effectively prevent the further dissemination of our confidential information. We have limited control over the protection of trade secrets used by our collaborators and could lose future trade secret protection if any unauthorized disclosure of such information occurs. In addition, others may independently discover our trade secrets and proprietary information, and in such cases we could not assert any trade secret rights against such parties. Laws regarding trade secret rights in certain markets where we operate may afford little or no protection of our trade secrets. Failure to obtain or maintain trade secret protection could adversely affect our business, sales and competitive position.

We may not be able to fully enforce covenants not to compete with our key employees, and therefore we may be unable to prevent our competitors from benefiting from the expertise of such employees.

Our employment agreements with key employees, which include executive officers, contain non-compete provisions. These provisions prohibit our key employees, if they cease working for us, from competing directly with us or working for our competitors for one year. Under applicable U.S. and Israeli laws, we may be unable to enforce these provisions. If we cannot enforce the non-compete provisions with our key employees, we may be unable to prevent our competitors from benefiting from the expertise of such employees. Even if these provisions are enforceable, they may not adequately protect our interests. The defection of one or more of our employees to a competitor could materially adversely affect our business, results of operations and ability to capitalize on our proprietary information.


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Risks Relating to Our Incorporation and Location in Israel

Conditions in Israel could adversely affect our business.

We are incorporated under Israeli law and our principal offices and research and development facilities are located in Israel. Accordingly, political, economic and military conditions in Israel directly affect our business. Since the State of Israel was established in 1948, a number of armed conflicts have occurred between Israel and its Arab neighbors. In recent years there has been an increase in unrest and terrorist activity, and several times since 2005 (when Israel withdrew from the Gaza Strip) conflicts arose due to Hamas’ rocket attacks against Israeli civilian targets, during which Israel responded to rocket attacks by engaging in an armed conflict with Hamas in the Gaza Strip. Our principal place of business is located in Rehovot, Israel, which is approximately 30 miles from the nearest point of the border with the Gaza Strip. There can be no assurance that attacks launched from the Gaza Strip will not reach our facilities, or that hostilities will not otherwise cause a significant disruption to our operations, such as preventing our employees from reaching our facilities and limiting our ability to monitor and otherwise conduct the crop and other experiments we conduct at the facilities.

Several countries, still restrict doing business with Israel and Israeli companies, and additional countries may impose restrictions on doing business with Israel and Israeli companies if hostilities in Israel or political instability in the region continues or increases. These restrictions may limit materially our ability to sell our product candidates to companies in these countries. Any hostilities involving Israel or the interruption or curtailment of trade between Israel and its present trading partners, or significant downturn in the economic or financial condition of Israel, could adversely affect our operations and research and development, cause our revenues to decrease and adversely affect the share price of publicly traded companies having operations in Israel, such as ours. Further, the political and security situation in Israel may result in parties with whom we have agreements involving performance in Israel claiming that they are not obligated to perform their commitments under those agreements pursuant to force majeure provisions in such agreements. In addition, there have been increased efforts by activists to cause companies and consumers to boycott Israeli goods for political reasons. Such actions, particularly if they become more widespread, may adversely impact our ability to conduct business.

Furthermore, our business insurance does not cover losses that may occur as a result of events associated with the security situation in the Middle East. Although the Israeli government currently covers the reinstatement value of direct damages that are caused by terrorist attacks or acts of war, we cannot assure that this government coverage will be maintained. Any losses or damages incurred by us could have a material adverse effect on our business and financial condition.

On Israel’s domestic front there is currently a level of unprecedented political instability. The Israeli government has been in a transitionary phase since December of 2018, when the Israeli Parliament, or the Knesset, first resolved to dissolve itself and call for new general elections. In 2019, Israel held general elections twice – in April and September – and a third general election was held in March of 2020. The Knesset, for reasons related to this extended political transition, has failed to pass a budget for the year 2020, and certain government ministries, which may be critical to the operation of our business, are without necessary resources and may not receive sufficient funding moving forward. Given the uncertainty with respect to when the current political stalemate will be resolved, our ability to conduct our business effectively may be adversely affected.

Our operations may be disrupted by the obligations of personnel to perform military service.

Many Israeli citizens are obligated to perform several days, and in some cases more, of annual military reserve duty each year until they reach the age of 40 (or older, for reservists who are military officers or who hold certain military positions) and, in the event of a military conflict, may be called to active duty. In response to increases in terrorist activity, there have been periods of significant call-ups of military reservists. It is possible that there will be military reserve duty call-ups in the future. Our operations could be disrupted by such call-ups, which may include the call-up of our key employees and members of our management. Such disruption could materially adversely affect our business, financial condition and results of operations.

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Exchange rate fluctuations between the U.S. dollar and the NIS may negatively affect our financial results.

The Company’s reporting currency is U.S. dollars. In view that a substantial part of our expenses is in NIS, any appreciation of the NIS relative to the U.S. dollar would adversely impact our financial results. If we enter into hedging contracts in the future, we may be unsuccessful in protecting against currency exchange rate fluctuations. See “Item 11. Quantitative and Qualitative Disclosure About Market Risk—Foreign Currency Risk.”

Interest rate fluctuations may devalue our investments and could have an adverse impact on our financial condition.

Included on our balance sheet are corporate bonds and government treasury notes denominated in New Israeli Shekels and in U.S. dollars having an aggregate value of approximately $2.1 million as of December 31, 2019. These investments expose us to the risk of interest rate fluctuations. An increase in Israeli or in U.S. interest rates could cause the fair value of these investments to decrease. As of December 31, 2019, we did not have any hedge arrangements in place to protect our exposure to interest rate fluctuations. See “Item 11. Quantitative and Qualitative Disclosure About Market Risk—Foreign Currency Risk.”

We have received Israeli government grants for certain of our research and development activities. The terms of these grants may require us to satisfy specified conditions in order to manufacture products and transfer technologies supported by such grants outside of Israel. In addition, in some circumstances, we may be required to pay penalties in addition to repaying the grants.

 Our research and development operations have been partly financed through certain governmental grants, which impose certain restrictions on the transfer outside of Israel of the underlying know-how and the manufacturing or manufacturing rights of the underlying products and technologies. As of December 31, 2019, we had received from Israeli National Authority for Technological Innovation, or the IIA, approximately $7.4 million (including accrued interest). We may not receive the required approvals should we wish to transfer the know-how, technology or manufacturing rights related to such government grants outside of Israel in the future or, if we receive such required approvals, they may be subject to certain conditions and payment obligations. See “Item 5. Operating and Financial Review and Prospects—B. Liquidity and Capital Resources—Government Grants.”

It may be difficult to enforce a U.S. judgment against us, our officers and directors and the Israeli experts named in this annual report in Israel or the United States, or to assert U.S. securities laws claims in Israel or serve process on our officers and directors and these experts.

We are incorporated in Israel. The majority of our directors and executive officers reside outside the United States and the majority of our assets are located outside the United States. Therefore, it may be difficult for an investor, or any other person or entity, to enforce a U.S. court judgment based upon the civil liability provisions of the U.S. federal securities laws against us or any of these persons in a U.S. or Israeli court, or to effect service of process upon these persons in the United States. Additionally, it may be difficult for an investor, or any other person or entity, to assert U.S. securities law claims in original actions instituted in Israel. Israeli courts may refuse to hear a claim based on a violation of U.S. securities laws on the grounds that Israel is not the most appropriate forum in which to bring such a claim. Even if an Israeli court agrees to hear a claim, it may determine that Israeli law and not U.S. law is applicable to the claim. If U.S. law is found to be applicable, the content of applicable U.S. law must be proved as a fact, which can be a time-consuming and costly process. Certain matters of procedure will also be governed by Israeli law. There is little binding case law in Israel addressing the matters described above.

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Your rights and responsibilities as our shareholder will be governed by Israeli law, which may differ in some respects from the rights and responsibilities of shareholders of U.S. corporations.

Since we are incorporated under Israeli law, the rights and responsibilities of our shareholders are governed by Israeli law and by our articles of association. These rights and responsibilities differ in some respects from the rights and responsibilities of shareholders of U.S.-based corporations. In particular, a shareholder of an Israeli company has a duty to act in good faith and in a customary manner in exercising its rights and performing its obligations towards the company and other shareholders and to refrain from abusing its power in the company, including, among other things, in voting at the general meeting of shareholders on certain matters, such as an amendment to the company’s articles of association, an increase of the company’s authorized share capital, a merger of the company and approval of related party transactions that require shareholder approval. A shareholder also has a general duty to refrain from discriminating against other shareholders. In addition, a controlling shareholder or a shareholder who knows that it possesses the power to determine the outcome of a shareholders’ vote or to appoint or prevent the appointment of an office holder in the company has a duty to act in fairness towards the company. However, Israeli law does not define the substance of this duty of fairness. See “Item 6. Directors, Senior Management and Employees—C. Board Practices—Shareholder Duties.” Since Israeli corporate law underwent extensive revisions approximately 18 years ago, the parameters and implications of the provisions that govern shareholder behavior have not been clearly determined. These provisions may be interpreted to impose additional obligations and liabilities on our shareholders that are not typically imposed on shareholders of U.S. corporations.

Provisions of Israeli law may delay, prevent or make undesirable an acquisition of all or a significant portion of our shares or assets.

Certain provisions of Israeli law and our articles of association could have the effect of delaying or preventing a change in control and may make it more difficult for a third party to acquire us or for our shareholders to elect different individuals to our board of directors, even if doing so would be beneficial to our shareholders, and may limit the price that investors may be willing to pay in the future for our ordinary shares. For example, Israeli corporate law regulates mergers and requires that a tender offer be effected when certain thresholds of percentage ownership of voting power in a company are exceeded (subject to certain conditions). Further, Israeli tax considerations may make potential transactions undesirable to us or to some of our shareholders whose country of residence does not have a tax treaty with Israel granting tax relief to such shareholders from Israeli tax. With respect to mergers, Israeli tax law allows for tax deferral in certain circumstances but makes the deferral contingent on the fulfillment of numerous conditions, including a holding period of two years from the date of the transaction during which certain sales and dispositions of shares of the participating companies are restricted. Moreover, with respect to certain share swap transactions, the tax deferral is limited in time, and when such time expires, the tax becomes payable even if no actual disposition of the shares has occurred. See Exhibit 2.1 to this annual report.

Furthermore, under the Encouragement of Research, Development and Technological Innovation in the Industry Law, 5744-1984 (formerly known as the Law for the Encouragement of Research and Development in Industry 5744-1984), and the regulations, guidelines, rules, procedures and benefit tracks thereunder, collectively, the Innovation Law, to which we are subject due to our receipt of grants from the IIA, a recipient of IIA grants such as our company must report to the IIA regarding any change in the holding of any means of control of our company which transforms any non-Israeli citizen or resident into an “interested party”, as defined in the Israeli Securities Law 5728-1968, and that such non-Israeli citizen or resident shall execute an undertaking in favor of IIA, in a form prescribed by IIA.

Risks Related to Our Ordinary Shares and the Ownership and Trading of Our Ordinary Shares

The price of our ordinary shares may fluctuate significantly.

Our ordinary shares were first offered publicly in the United States after our public offering in the United States in November 2013, at a price of $14.75 per share, and our ordinary shares have subsequently traded on the NYSE (until December 2016) and on the Nasdaq (since December 2016) as high as $19.80 per share and as low as $0.91 and as of April 23, 2020 were trading at $1.11 per share.

The market price of our ordinary shares could be highly volatile and may fluctuate substantially as a result of many factors, including:


our inability to obtain additional funding
 

any delay in filing a regulatory submission for any of our product or product candidates and any adverse development or perceived adverse development with respect to the review of that regulatory submission by the applicable regulatory body


actual or anticipated fluctuations in our results of operations;

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variance in our financial performance from the expectations of market analysts;


announcements by us or our competitors of significant business developments, changes in relationships with our collaborators, acquisitions or expansion plans;


our involvement in litigation;


our sale, or the sale by our significant shareholders, of ordinary shares or other securities in the future;


failure to publish research or the publishing of inaccurate or unfavorable research;


market conditions in our industry and changes in estimates of the future size and growth rate of our markets;


changes in key personnel;


the trading volume of our ordinary shares; and


general economic and market conditions, including as a result of the scope and duration of the COVID-19 pandemic.

Although our ordinary shares are listed on Nasdaq, an active trading market on Nasdaq for our ordinary shares may not be sustained. If an active market for our ordinary shares is not sustained, it may be difficult to sell ordinary shares in the U.S.

In addition, the stock markets have recently experienced extreme price and volume fluctuations, including as a result of the COVID-19 pandemic. Broad market and industry factors may materially harm the market price of our ordinary shares, regardless of our operating performance. In the past, following periods of volatility in the market price of a company’s securities, securities class action litigation has often been instituted against that company. If we were involved in any similar litigation, we could incur substantial costs and our management’s attention and resources could be diverted.

Any inability to meet the Nasdaq listing requirements may have an adverse effect on our share price and lead to our delisting from Nasdaq.

We are required to meet the continued listing requirements of Nasdaq, including those regarding minimum share price. In particular, we are required to maintain a minimum bid price for our listed ordinary shares of $1.00 per share. If we do not meet Nasdaq’s continued listing requirements, Nasdaq could initiate delisting proceedings and our ordinary shares could be delisted.

If Nasdaq initiates delisting proceedings or delists our ordinary shares from trading on its exchange, we could face significant material adverse consequences including: reduced liquidity with respect to our ordinary shares; limited amount of news and analyst coverage for our company; reputational damage; diminished investor, supplier and employee confidence; and decreased ability to issue additional securities or obtain additional financing in the future.

Our ordinary shares are traded on more than one market and this may result in price variations.

Our ordinary shares have been traded on the TASE since 2007, and are currently listed on Nasdaq. Trading in our ordinary shares on these markets will take place in different currencies (U.S. dollars on Nasdaq and NIS on the TASE), and at different times (resulting from different time zones, trading days and public holidays in the United States and Israel). The trading prices of our ordinary shares on these two markets may differ due to these and other factors. Any decrease in the price of our ordinary shares on the TASE could cause a decrease in the trading price of our ordinary shares on Nasdaq or vice versa.

We could become subject to parallel reporting obligations in Israel and the United States, which could increase compliance costs and divert management attention.

On July 28, 2013, our shareholders approved our plan to transition solely to U.S. reporting standards under the rules and regulations of the SEC. However, should this change in the future, we may become subject to parallel reporting obligations in Israel and the United States. While similar in many respects, certain differences between Israeli and U.S. reporting schemes may impose on us disclosure obligations that are more stringent than those generally applied to foreign private issuers whose securities are listed only in the United States. In addition, a requirement to comply with the separate reporting obligations under U.S. and Israeli securities laws would require additional management attention and could burden us with additional costs.

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The requirements of being a public company in the United States and Israel may strain our resources and distract our management, which could make it difficult to manage our business.

Changing laws, regulations and standards, in the United States or Israel, relating to corporate governance and public disclosure and other matters, may be implemented in the future, which may increase our legal and financial compliance costs, make some activities more time consuming and divert management’s time and attention from revenue-generating activities to compliance activities. If our efforts to comply with new laws, regulations and standards differ from the activities intended by regulatory or governing bodies due to ambiguities related to practice, regulatory authorities may initiate legal proceedings against us and our business may be harmed. Being a publicly traded company in the United States and Israel and being subject to U.S. and Israeli rules and regulations make it more expensive for us to obtain director and officer liability insurance, and we may be required to accept reduced coverage or incur substantially higher costs to obtain coverage. These factors could also make it more difficult for us to attract and retain qualified members of our board of directors, particularly to serve on our audit committee, and qualified executive officers.

As a public company whose ordinary shares are listed in the United States, we will continue to incur significant accounting, legal and other expenses, including costs associated with our reporting requirements under the Exchange Act. We also incur additional costs associated with corporate governance requirements, including requirements under Section 404 and other provisions of the Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act, rules implemented by the SEC and the Nasdaq, and provisions of Israeli corporate and securities laws applicable to public companies. The Exchange Act requires that we file annual and certain other reports with respect to our business and financial condition. The Sarbanes-Oxley Act requires, among other things, that we maintain effective disclosure controls and procedures and internal control over financial reporting. These rules and regulations could continue to increase our legal and financial compliance costs, such as the cost of hiring consultants or testing compliance processes, and make some activities more time-consuming and costly. These activities may divert management’s attention from other business concerns, which could have a material adverse effect on our business, financial condition, results of operations and cash flows.

If we fail to maintain effective internal control over financial reporting, the price of our ordinary shares may be adversely affected.
 
Our internal control over financial reporting may have weaknesses and conditions that could require correction or remediation, the disclosure of which may have an adverse impact on the price of our ordinary shares. We are required to establish and maintain appropriate internal control over financial reporting. Failure to establish those controls, or any failure of those controls once established, could adversely affect our public disclosures regarding our business, prospects, financial condition or results of operations. In addition, management’s assessment of internal control over financial reporting may identify weaknesses and conditions that need to be addressed in our internal control over financial reporting or other matters that may raise concerns for investors.  In addition, as a “non-accelerated filer,” we are exempt from the provisions of Section 404(b) of the Sarbanes-Oxley Act requiring that independent registered public accounting firms provide an attestation report on the effectiveness of internal control over financial reporting. Decreased disclosures in our SEC filings due to our status as a “non-accelerated filer” may make it harder for investors to analyze our results of operations and financial prospects and may make our ordinary shares a less attractive investment. Any actual or perceived weaknesses and conditions that need to be addressed in our internal control over financial reporting or disclosure of management’s assessment of our internal control over financial reporting may have an adverse impact on the price of our ordinary shares.

As a foreign private issuer we are not subject to the provisions of Regulation FD or U.S. proxy rules and are exempt from filing certain Exchange Act reports.

As a foreign private issuer, we are exempt from compliance with the rules and regulations under the Exchange Act related to the furnishing and content of proxy statements, and our officers, directors, and principal shareholders are exempt from the reporting and short-swing profit recovery provisions contained in Section 16 of the Exchange Act. In addition, we are not required under the Exchange Act to file annual and certain other reports and financial statements with the SEC as frequently or as promptly as U.S. domestic companies whose securities are registered under the Exchange Act, we are permitted to disclose limited compensation information for our executive officers on an individual basis and we are generally exempt from filing quarterly reports with the SEC under the Exchange Act. Moreover, we are not required to comply with Regulation FD, which restricts the selective disclosure of material nonpublic information to, among others, broker-dealers and holders of a company’s securities under circumstances in which it is reasonably foreseeable that the holder will trade in the company’s securities on the basis of the information. These exemptions and leniencies will reduce the frequency and scope of information and protections to which you may otherwise have been eligible in relation to a U.S. domestic issuer.

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As a foreign private issuer, we have elected to follow home country corporate governance practices instead of certain Nasdaq corporate governance requirements, which may result in less protection than is accorded to investors under rules applicable to domestic U.S. issuers.

As a foreign private issuer whose shares are listed on the Nasdaq Global Market, we are permitted to follow certain home country corporate governance practices instead of those otherwise required under the corporate governance standards for U.S. domestic issuers listed on Nasdaq. We currently follow Israeli home country practices, rather than the requirements under the Nasdaq corporate governance rules, with regard to the (i) quorum requirement for shareholder meetings, (ii) executive sessions for independent directors and non-management directors and (iii) the requirements to obtain shareholder approval for certain dilutive events (such as for the establishment or amendment of certain equity-based compensation plans, issuances that will result in a change of control of the company, certain transactions other than a public offering involving issuances of a 20% or more interest in the company and certain acquisitions of the stock or assets of another company). See “Item 16G. Corporate Governance.” Furthermore, we may in the future elect to follow Israeli home country practices with regard to other matters such as the requirement to have a majority independent board of directors, have a compensation committee and have a nominating committee. Accordingly, our shareholders may not be afforded the same protection as provided under Nasdaq corporate governance rules. Following our home country governance practices as opposed to the requirements that would otherwise apply to a United States company listed on Nasdaq may provide less protection than is accorded to investors of domestic issuers. For further discussion, see “Item 16G. Corporate Governance.”

We may lose our status as a foreign private issuer, which would increase our compliance costs and could thereby negatively impact our results of operations.

We would lose our foreign private issuer status if (a) a majority of our outstanding voting securities were either directly or indirectly owned of record by residents of the United States and (b)(i) a majority of our executive officers or directors were United States citizens or residents, (ii) more than 50 percent of our assets were located in the United States, or (iii) our business were administered principally outside the United States. Our loss of foreign private issuer status would make U.S. regulatory provisions mandatory. The regulatory and compliance costs to us under U.S. securities laws as a U.S. domestic issuer may be significantly higher. If we are not a foreign private issuer, we will be required to file periodic reports and registration statements on U.S. domestic issuer forms with the SEC, which are more detailed and extensive than the forms available to a foreign private issuer. We would also be required to follow U.S. proxy disclosure requirements, including the requirement to disclose, under U.S. law, more detailed information about the compensation of our senior executive officers on an individual basis. We may also be required to modify certain of our policies to comply with accepted governance practices associated with U.S. domestic issuers. Such conversion and modifications will involve additional costs. In addition, we would lose our ability to rely upon exemptions from certain corporate governance requirements on U.S. stock exchanges that are available to foreign private issuers, as described in the previous risk factor above.

If a United States person is treated as owning at least 10% of our ordinary shares, such holder may be subject to adverse U.S. federal income tax consequences.

If a United States person is treated as owning (directly, indirectly or constructively) at least 10% of the value or voting power of our ordinary shares, such person may be treated as a “United States shareholder” with respect to each “controlled foreign corporation” in our group (if any). If our group includes one or more U.S. subsidiaries, certain of our non-U.S. subsidiaries could be treated as controlled foreign corporations (regardless of whether we are or are not treated as a controlled foreign corporation). A United States shareholder of a controlled foreign corporation may be required to annually report and include in its U.S. taxable income its pro rata share of “Subpart F income”, “global intangible low-taxed income” and investments in U.S. property by controlled foreign corporations, whether or not we make any distributions. An individual that is a United States shareholder with respect to a controlled foreign corporation generally would not be allowed certain tax deductions or foreign tax credits that would be allowed to a United States shareholder that is a U.S. corporation. A failure to comply with these reporting obligations may subject you to significant monetary penalties and may prevent the statute of limitations with respect to your U.S. federal income tax return for the year for which reporting was due from starting. We cannot provide any assurances that we will assist investors in determining whether any of our non-U.S. subsidiaries are treated as a controlled foreign corporation or whether such investor is treated as a United States shareholder with respect to any of such controlled foreign corporations or furnish to any United States shareholders information that may be necessary to comply with the aforementioned reporting and tax paying obligations. A United States investor should consult their own advisors regarding the potential application of these rules to its investment in the ordinary shares.

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We believe we were a passive foreign investment company, PFIC, for U.S. federal income tax purposes in 2019, and there is significant risk we will be a PFIC in 2020 as well. U.S. shareholders who held our ordinary shares at any time during a taxable year in which we are a PFIC may suffer adverse tax consequences.

Generally, if for any taxable year 75% or more of our gross income is passive income, or at least 50% of the average quarterly value of our assets (which may be determined in part by the market value of our ordinary shares, which is subject to change) are held for the production of, or produce, passive income, we would be characterized as a passive foreign investment company, or PFIC, for United States federal income tax purposes. According to these rules, a publicly traded non-U.S. corporation may treat the aggregate fair market value of its assets as being equal to the sum of the aggregate value of its outstanding shares, or Market Capitalization, and the total amount of its liabilities. We intend to take the position that the excess of our Market Capitalization plus liabilities over the book value of all of our assets may generally be treated as attributable to non-passive assets. Based on the book value of our assets and liabilities and our Market Capitalization in 2019, we believe that we met the PFIC asset test described above for 2019 and, as a result, we were classified as a PFIC in 2019. Furthermore, because we currently hold, and expect to continue to hold, a substantial amount of cash and cash equivalents and other passive assets used in our business, and because our Market Capitalization is currently below the level necessary to avoid PFIC status for 2020, there is substantial risk we will be classified as a PFIC for the 2020 taxable year as well. However, because PFIC status is determined after the close of each taxable year, we will not be able to determine whether we will be a PFIC for the 2020 taxable year or for any future taxable year until after the close of such year.

U.S. shareholders who held our ordinary shares at any time in 2019 or during any other taxable year in which we are a PFIC may suffer adverse tax consequences, including having gains realized on the sale of our ordinary shares treated as ordinary income, rather than capital gain, the loss of the preferential rate applicable to dividends received on our ordinary shares by individuals who are U.S. Holders (as defined in “Item 10. Additional Information—E. Taxation—United States Federal Income Taxation”), and having interest charges apply to distributions by us and the proceeds of share sales. Certain elections may be available that would alleviate some of the adverse consequences of PFIC status and result in an alternative treatment (such as mark-to-market treatment) of our ordinary shares; however, we do not intend to provide the information necessary for U.S. holders to make qualified electing fund elections. See “Item 10. Additional Information—E. Taxation—United States Federal Income Taxation—Passive Foreign Investment Company Considerations.”

ITEM 4.
INFORMATION ON THE COMPANY

A.          History and Development of the Company

Our History

We are a leading biotechnology company aiming to revolutionize the development of novel products for life-science based industries, including human health, agriculture, and industrial applications, by utilizing cutting edge computational biology technologies.

Our company was founded on October 10, 1999 as Agro Leads Ltd., a division of Compugen Ltd. In 2002, our company was spun-off as an independent corporation under the laws of the State of Israel, and changed its name to Evogene Ltd. In 2018 and early 2019, we reorganized certain of our divisions into wholly-owned subsidiaries of the Company, as described elsewhere in this annual report. In addition, in April 2019 we established a new subsidiary, Canonic Ltd., or Canonic, for developing next generation medical cannabis products.

Our shares have been listed for trading on the TASE since 2007, and were listed for trading on the NYSE commencing with our U.S. initial public offering in November 2013, until December 2016, when we transferred the listing to Nasdaq.

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We are registered with the Israeli Registrar of Companies in Jerusalem. Our registration number is 51-283872-3. Our purpose as set forth in our articles of association is to engage in any lawful business. Our principal executive offices are located at 13 Gad Feinstein Street, Park Rehovot, Rehovot P.O.B 4173 Ness Ziona, 7414002, Israel, and our telephone number is +972-8-931-1900.

Our authorized representative in the United States and agent for service of process in the United States, Puglisi & Associates, is located at 850 Library Avenue, Suite 204, Newark, Delaware 19711. Information contained on, or that can be accessed through, our website does not constitute a part of this annual report and is not incorporated by reference herein.

The SEC maintains an internet site, http://www.sec.gov that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC. Our internet address is www.evogene.com. Neither such internet addresses is a part of this annual report.

Principal Capital Expenditures

Our capital expenditures for fiscal years 2019, 2018 and 2017 amounted to $0.9 million, $0.4 million and $0.6 million, respectively. Our capital expenditures during those years consisted of investments in property, plant and equipment. We anticipate our capital expenditures in fiscal year 2020 to include payments for maintenance and improvements of our facilities in Israel in order to support our activities, which we anticipate we will finance with our currently available cash.

B.          Business Overview

Overview

 We are a leading biotechnology company aiming to revolutionize the development of novel products for life-science based industries, including human health, agriculture, and industrial applications, by utilizing cutting edge computational biology technologies. To achieve this mission, we established our unique Computational Predictive Biology, or CPB, platform, leveraging the revolutions in big data and artificial intelligence and incorporating a deep understanding of biology. Our CPB platform aims to disrupt conventional life-science product development methodology, currently challenged by inefficiencies, by computationally designing the most relevant core components for life-science products such as microbes, small molecules and genes.

Business Model

To capture the value of the diverse applicability of our computational platform, our business model consists of two main pathways, both based primarily on the utilization of the CPB Platform: (i) The establishment of market-focused subsidiaries to develop and commercialize product pipelines, meeting unmet needs in selected industries, and (ii) in certain other cases, engaging directly with strategic partners for the development of specific products.

Each of the subsidiaries we established under the first pathway is an independently managed company, fully supported by the capabilities and corporate management of Evogene Ltd.  Evogene provides each of the subsidiaries with initial funding as well as a long-term exclusive right to use the CPB platform in order to develop products in a defined field of activity, and, at least initially certain corporate functions. Under this pathway, Evogene expects its income to include: (i) ongoing license and research fees from its subsidiaries and (ii) income based on our equity holdings in its subsidiaries, namely dividends and revenues from sales of equity.

In addition, pursuant to the second pathway of the business model, Evogene intends to collaborate directly with strategic partners for the development of products, as we have done over the past years in our ag-seeds activity. Under this pathway, Evogene expects its income to include: (i) on-going license and research fees from its partners and (ii) success-based payments, including milestone payments and revenue sharing.

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Currently, we apply our technology and approach for the development of products based on microbes, small molecules and genes in three general industries:


(i)
Agriculture, focusing on the following target markets:

a.
Agriculture biologicals, via our subsidiary Lavie Bio Ltd. or Lavie Bio,

b.
Agro chemicals, via our subsidiary AgPlenus Ltd., or AgPlenus, and

c.
Seed traits, via our Ag-Seeds division;


(ii)
Human health, focusing on the following target markets:

a.
Human microbiome-based therapeutics, via our subsidiary Biomica Ltd., or Biomica, and

b.
Medical cannabis products, via our subsidiary Canonic Ltd., or Canonic; and


(iii)
Life-science based industrial applications, currently focusing on castor seed varieties and agro-technical capabilities, through our subsidiary Casterra Ag Ltd. (formerly Evofuel Ltd.), or Casterra.

Each subsidiary pursues its individual mission, focusing on the following objectives: (i) advancing its product development and pipeline, (ii) establishing its “go-to-market”, and (iii) securing additional financial resources, if and when required.

We continuously evaluate new substantial industries with well-recognized development road-blocks for which we can leverage our capabilities and assets for the development of next-generation products. We select the most suitable markets to focus on, based on a number of criteria, including: (i) market size; (ii) a well-recognized, unmet need for next-generation products; (iii) an understanding of the scientific or technical road-blocks that prevent others from developing next-generation products; and, most importantly; and (iv) the expectation that our CPB platform and unique approach provide a significant competitive advantage in addressing these roadblocks.

Except for initial seed sales under our Casterra activity, our activities are still in the development stages and no products have been commercialized based on our discoveries. Our revenues consist primarily of research and development payments under our strategic collaborations in the field of seed traits and ag-chemical products. A breakdown of our revenues by business activity and geographic markets for each of the last three financial years is provided in “Item 5. Operating and Financial Review and Prospects—Key Measures of Our Performance—Revenues.” In the future, we expect that we and our subsidiaries will receive, milestone payments and royalty revenues under such collaborations, as well as revenues from the sale of end-products or commercialization of product candidates.

In 2020, through our subsidiaries, we expect to continue to develop our product pipelines and initiate new collaborations with an increased focus on strategic relationships for joint product development. We also expect to continue to evolve our organization, and to continue to examine new areas in which additional value can be created in a relatively short time.

The precautionary measures undertaken by many governmental authorities worldwide, including in Israel and the U.S., in order to limit the spread of the ongoing Coronavirus outbreak, and its negative impact on economies and financial markets worldwide, may affect the implementation of our business plan and objectives by: (i) disruption of ordinary course of operations for us, our collaborators and contractors, causing operational delays, labor shortages, travel disruption and shutdowns, which could have an adverse effect on our development programs, (ii) adversely impacting our ability to maintain or extend our existing collaborations or enter into new collaborations on favorable financial terms, (iii) negatively impacting on our ability to raise additional funds for our operations, if and when needed.

The following are major occurrences and developments in the Company during 2019 and until the date of this annual report, reflecting advancement in all areas of activity:

Evogene


-
In February 2019 – we announced that Evogene’s Ag-Biologicals activities are being transferred to a new subsidiary – Lavie Bio Ltd., or Lavie Bio.


-
In April 2019 – we announced that we will develop next generation medical cannabis products through a new subsidiary, Canonic Ltd.


-
In August 2019 – Corteva AgriScience, or Corteva, invested in Lavie Bio. The investment included $10 million in equity funding and the contribution by Corteva to Lavie Bio of its shares in Taxon Biosciences, Inc., or Taxon Biosciences, in exchange for shares in Lavie Bio. Taxon Biosciences is a company focused on microbiome discovery to develop biological crop products.

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Lavie Bio


-
In July 2019 – Lavie Bio announced positive 2nd-year field results in its bio-stimulant program for wheat.


-
In November 2019 – Lavie Bio announced advancement in the product development pipeline for wheat bio-stimulants.

AgPlenus


-
In March 2020 – AgPlenus announced entering a collaboration with Corteva for the development of novel herbicides.

Ag-Seeds division


-
In July 2019 – we amended our corn disease resistance research collaboration agreement with Bayer (previously with Monsanto) to include genome editing targets.

Biomica


-
In April 2019 – Biomica announced initiation of pre-clinical studies in its Immuno-Oncology Program.


-
In October 2019 – Biomica announced advancement to pre-clinical studies in its Inflammatory Bowel Disease program.


-
In October 2019 – Biomica announced a collaboration with the Weizmann Institute of Science to develop a selective treatment against antibiotic-resistant bacteria.


-
In November 2019 – Biomica reported positive preliminary results in animal studies in its Immuno-Oncology program.


-
In January 2020 – Biomica announced entering a new agreement with Biose Industrie for scale-up and GMP production of drug candidates BMC121 & BMC127 for its immuno-oncology program to support the preparation towards the anticipated first in man proof of concept clinical trials.

Canonic


-
In November 2019 - Canonic announced initiation of cultivation and breeding of cannabis varieties with unique genomic profiles for the development of medical cannabis products.


-
In January 2020 - Canonic announced an agreement with Hadassah Medical Center for pre-clinical studies to support the development of Canonic’s medical cannabis products.

Casterra (formerly Evofuel)


-
In May 2019 – our subsidiary Evofuel Ltd. was rebranded as Casterra Ltd. to better reflect its change in business focus from the alternative fuel industry to the market of castor oil for industrial uses.

Approach, Science & Technology

Approach

The mission of the CPB platform is to revolutionize the product development approach in life science industries by decoding the biological world. This platform is a result of a decade long, multidisciplinary effort to integrate scientific concepts with semi-structured big data and the most advanced computational analytics in order to develop predictions of potential products that later undergo experimental validation.

The CPB platform aims to disrupt conventional life-science product development methodology, currently challenged by inefficiencies, by computationally designing the most relevant core components for life-science products such as microbes, small molecules and genes. The uniqueness of our computational design approach stems from our ability to successfully address multiple product attributes at the beginning of the discovery process, rather than one at a time during the development phase. This is expected to reduce both time and cost, but more importantly, increase the probability of reaching a successful product launch.

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These efforts have been enabled by two parallel revolutions: (i) the data revolution – allowing the creation of enormous amounts of biological and chemical data in a cost-effective manner, and (ii) the computational processing revolution – allowing the integration and analysis of data with advanced algorithms such as machine learning and other artificial intelligence.

The CPB platform represents a revolutionary approach for the design and prediction of novel products, based on four pillars: first, computationally modeling the specific biological challenges in the discovery and development of each product into pre-defined criteria, based on profound scientific understanding and know-how; second, designing genomic, chemical and microbial databases holding diverse types of curated data specifically aimed at addressing the biological challenges identified; third, developing state of the art computational tailored analytics, including artificial intelligence algorithms, designed to provide more accurate predictions to those challenges; and fourth, screening and validation systems comprised of multiple tailored bioassays.

This approach enables the CPB platform to first predict the most relevant candidates from our comprehensive databases to begin the candidate selection, validation and product development process, and thereafter to guide the process. The ability to make and evaluate candidate selection and prioritization according to these pre-defined criteria upon the initiation of a program significantly increases the probability of successful product development while decreasing time and cost.

This approach is broadly applicable to various life science industries. We continuously evaluate new substantial markets with well-recognized development roadblocks where we can leverage our capabilities and assets for the development of next generation products.

Science and Know-how

The underlying driver of the CPB platform’s unique approach is deep scientific understanding of the life sciences combined with computer sciences and tailored experimental tools. Our multidisciplinary scientific teams play a pivotal role in our unique product development approach.

As of December 31, 2019, our research and development activities involve 86 employees amounting to approximately 67% of our total full-time workforce, of which 49 are employed at Evogene and 37 are employed via our subsidiaries. Our staff possesses multidisciplinary and wide-ranging expertise, with employees specializing in biology, chemistry, plant genetics, agronomics, mathematics, computer science and other related fields. 38 of our employees hold a Ph.D.

Furthermore, we have a Scientific Advisory Board composed of representatives from the Faculty of Agriculture of The Hebrew University in Jerusalem, the Weizmann Institute of Science in Rehovot and other global academic institutions, as well as experienced scientists from the industry.

Computational Technologies

Our computational technologies, utilized for data integration and analysis, are comprised of two main proprietary components: (i) our databases generated via data integration capabilities; and (ii) our computational analysis platforms, utilized to mine these databases within our ongoing activities.

Proprietary Databases

To date, Evogene’s databases leverage multiple sources and types of tailored “big data” in order to support the different research and development activities across the company. Specifically, we focus on four different entities: microbial organisms, microbial genes, small molecules and plant genes. Our information databases on these different entities are rich and highly interconnected, enabling our analysis platforms to maximize their predictive power.

Our databases draw in part from the public domain (primarily from academic institutions and research publications), and in part compile increasing amounts of proprietary data, generated either in-house or received from our collaborators.

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Our current database framework consists of the following:


Plant and microbial gene databases – These databases are focused on the gene entity, linking available data relevant to a gene in a single assembled database.


o
Our plant gene databases cover over 16 million genes from more than 200 plant species, and account for various data types, including phenotypic data (i.e., data related to a plant’s observable characteristics, morphology, development and physiological properties) and genotypic data (i.e., data from the molecular level, derived from DNA, RNA or other sources).


o
Our microbial gene database incorporates more than 250 million microbial genes. In our pursuit to expand our databases to include novel genetic material, we established a pipeline for assembling gene models from samples containing bacterial populations, or metagenomics. Utilizing this approach, we have unveiled millions of genes, some of which have never been observed before, as well as a multitude of bacteria never previously cultured.


Microbial strain database (microbial organisms) – This database comprises data on microbial strains isolated from plant and human sources. It includes several tens of thousands of microbial strains that are key to plant and human life cycles.


Chemical database (small molecules) – This database is structured as molecule-centric, covering broad chemical collections and derived from publicly available sources of synthetic and natural chemistry. This database currently comprises over 400 million chemicals, integrating multiple layers of data describing the chemicals' properties.

Computational Analysis Platforms

We have developed advanced proprietary computational analysis platforms, comprised of novel algorithms and methodologies designed to handle immense amounts of data. Our computational analysis platforms are designed to deliver innovative solutions to key bottlenecks in the product development process. In recent years, we have increasingly focused on artificial intelligence, machine learning driven approaches to provide effective predictions for key questions. As our predictions undergo validation via dedicated validation systems, this allows us to continuously improve our predictions by feeding back these results into our systems.

Currently, we operate and develop the following computational analysis platforms, for the prediction of genetic elements (ATHLETE, GEDAI, BiomeMiner and PointTar), small molecules (PointHit and PointLead) and microbes (MicrobeMiner and PRISM):

Genetic elements:

ATHLETE

The ATHLETE computational analysis platform that is our central computational analysis platform for plant gene identification is comprised of unique algorithmic tools and novel data-mining concepts that allow generation of rapid and reliable lists of genes relevant to a target trait.

GEDAI

GEDAI is our central computational analysis platform for plant gene editing. It is comprised of deep learning-based analysis (artificial intelligence) and a novel approach that allows predicting the desired editing in regulatory elements to be implemented in order to achieve a desired pattern of expression.

BiomeMiner

BiomeMiner is a computational analysis platform for identifying microbial insecticidal toxins, i.e. microbial genes that can be specifically toxic to insects that lead to substantial crop damage. This unique computational technology platform consists of a newly developed vast proprietary microbial-based gene centric database, the underlying data assembly pipelines, as well as a dedicated analysis platform, BiomeMiner. The BiomeMiner platform utilizes advanced machine learning methods in order to identify toxins with novel modes of action in order to overcome the rising resistance to current products’ modes of action.

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PoinTar

PoinTar specializes in the identification of plant targets (proteins) for development of ag-chemicals such as herbicides, and examines data aimed to indicate the potential impact that a target, when inhibited, would have on a weed. Both our gene-centric database and its integrated chemical-centric database are mined by PoinTar to achieve this goal. PoinTar addresses the structural characteristics of a target in order to predict the target’s likelihood of binding to a small chemical molecule for use as a herbicide.

Small molecules:

PointHit

PointHit, is a computational analysis platform for identifying chemical molecules that are predicted to be potential inhibiting chemicals. This analysis platform leverages biological rationale, discovering chemical molecules by optimizing among three key considerations: (i) predicted binding to molecular targets, (ii) compliance with product desired attributes such as low cost of production, low toxicity and others, and (iii) mainly for ag-applications – potential for activity, namely probability to be absorbed by the plant and transported within the plant to reach a specific molecular target within it. Overall, relying on “big data” computational approaches, the PointHit platform is capable of prioritizing tens of millions of chemicals to a selected library of candidate hits.

PointLead

PointLead is a computational platform that supports the Hit-to-Lead phase in the development of ag-chemical products, as described under “—Fields of Activity—Agriculture—AgPlenus—Product—Development Programs—Product Development Cycle.”  The platform includes computational tools addressing various challenges common to the drug and herbicide development processes, such as toxicity, efficacy, metabolic stability, resistance and others. In addition, PointLead includes a computational molecule generator that suggests compounds for synthesis based on an initial hit, thus assisting the chemist to think “outside the box”. This tool is combined with machine-learning models for focusing on the most relevant molecules as well as a proprietary tool for innovative analog search within Evogene’s database of synthetically feasible small molecules.

Microbes:

MicrobeMiner

MicrobeMiner is a computational platform addressing key challenges in the discovery and development of microbial products. The core of the analysis platform relies on the ability to identify the genetic functions within the microbe responsible for important aspects of product development including, efficacy, stability of effect across conditions and shelf life. This platform leverages the vast digital catalog of microbial functions within our microbial gene database along with our proprietary plant-microbe phenotypic data in our microbial strain database.

PRISM

PRISM (Predictive high-Resolution Integrative Selection of Microbes) is a computational analysis platform that combines a high-resolution profiling of the microbiome, based on accurate strain-level taxonomy and comprehensive functional analyses, and the efficient correlation of the microbiome to host physiological and genomic profiles.

Screening and validation systems

Our screening and validation systems support two key aspects of our unique research and development approach: (i) generating data sets to enable development of tailored computational modules and their prediction performance evaluation; and (ii) screening, validating and characterizing selected product candidates by the division’s/subsidiary’s scientific teams.

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Our experimental technologies include bioassays as well as screening and validation pipelines (set of bioassays organized in a cascade of tests). They relate to diverse scientific fields including plant tissue culture, plant pathology greenhouse and field activities, molecular biology, microbiology, organic chemistry and insect biology.

Market Segments

Agriculture

Ag-Business Market

Background

The global population is projected to reach 10 billion inhabitants by 2050, which is expected to lead to a necessary 50% expansion in food, feed and biofuel production1. Moreover, changing diets in BRIC countries (Brazil, Russia, India and China) to more protein and dairy heavy diets, are leading to a rising need for grain for animal feed. On the supply side, 17% of harvest is lost to climate change, while 12 million hectares of agricultural land is lost, annually. This results in the need to increase in food production by increasing yields and cropping intensity as there is limited arable land left to expand planting.2

In light of historical and current needs to improve crop productivity, technological inventions have been incorporated into agriculture since the dawn of humanity. The most advanced and recent technological tool available is biotechnology, which aims to enhance crop performance and productivity. During the last decade, the biological world has witnessed a dramatic increase in the availability of data, which is used to drive agricultural product innovation. This increase in the availability of biological and chemical data has primarily been a result of the introduction of new technologies that facilitate the rapid generation of quality data at a significantly lower cost. As a result, the key opportunity, and challenge, for enhancing crop productivity has shifted from the generation of quality data to data integration and the analysis of large volumes of data.

Lavie Bio Ltd.

Overview

In 2015, we initiated our activity for developing ag-biological products as a division within Evogene and early in 2019 it was organized under Lavie-Bio Ltd., a separate company that is wholly owned by Evogene. Lavie Bio aims to improve food quality, sustainability and agricultural productivity through the introduction of microbiome-based ag-biologicals. Ag-biologicals are externally-applied products from biological sources, such as microbial (micro-organisms) and naturally derived biochemistries, designed to improve crop productivity. A sub-segment within the microbial biologicals is the “microbiome”, the microbial population living close or within the plant or other organisms, such as pests, which is a promising source for novel ag-biologicals.

Lavie Bio is focused on developing two main types of products: (i) bio-stimulants, which are ag-biologicals for crop enhancement, directly impacting crop yield or abiotic stress tolerance and (ii) bio-pesticides, which are ag-biologicals for crop protection, addressing biotic stresses such as insects, diseases and weeds.

Investment by Corteva

In August 2019, we announced that Corteva Agriscience had invested in Lavie Bio. The transaction included the exchange of all shares of Corteva’s wholly owned subsidiary Taxon Biosciences along with a US$10 million equity investment by Corteva in Lavie Bio in consideration of approximately 28% of Lavie Bio’s equity. The assets of Taxon Biosciences include, among others, a large microbial collection and product candidate pipeline, which are integrated into Lavie Bio’s pipeline.

Corteva and Lavie prioritized certain product programs to be executed by Lavie Bio, and Lavie Bio committed to allocate a certain part of its research and development budget to these programs. In addition, Corteva’s investment in Lavie Bio was accompanied by the provision to Corteva of certain rights to obtain in the future commercial licenses to Lavie Bio’s candidate products, mainly in corn and soy.


1 Source: FAO 2017, The Future of Food and Agriculture
2 Source: Piper Jaffray, Industry Note August 27, 2013, Agriculture
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Market

The market for ag-biological products was estimated at $7.0 billion in 20193 and is a growing segment in the approximately $250 billion agricultural input market which includes the seed, crop protection and fertilizers segments. The sales of ag-biological products significantly grew in past years, expanding from a market size of $3.2 billion in 2015 to its current size following a shift in growers and consumer preferences to more sustainable and healthier practices, while driving agriculture productivity. According to market estimates, this market is forecasted to reach sales of $13.4 billion in 20243, anticipated to be driven by improvement of the product attributes of ag-biologicals, such as efficacy, stability and commercial viability.

Companies in this market can be generally divided into three groups: (i) major seed and ag-chemical companies, such as BASF, Bayer, ChemChina and Corteva others, with internal research and development units dedicated to development of ag-biological products, (ii) small to mid-size biotech companies specializing in ag-biologicals with their own product development programs, and (iii) academic and agricultural research institutions that pursue research activities in the field, typically focusing on early stage activities.

Business Model

Lavie Bio has defined two main models for market access, upon commercialization:


(i)
Direct market access – in fragmented markets we expect to complete product development independently and then establish a tailored market access strategy per specific product and territory (such as certain fruits and vegetables), and


(ii)
Indirect market access – in markets in which Lavie Bio identifies strategic partners that can drive its go-to-market, it will aim to gain market access through collaborations with such partners, either through co-development or through royalty-bearing commercialization agreements.

To date, Lavie Bio has not commenced commercialization and has not yet generated any revenues. In the longer term, as its product candidates advance through development and to the extent that they are commercialized, Lavie Bio expects revenues from direct sales as well as milestone payments and royalty payments from products developed and commercialized indirectly through partners. Lavie Bio expects its first product launch, of a spring wheat bio-stimulant product, by 2022.

Product Development Programs

Scientific Approach

Lavie Bio's approach is focused on 'Biology Driven Design' for the discovery, optimization and development of effective, stable and cost-effective microbial-based ag-biologicals. Lavie Bio’s approach is based on converging the plant, microbial and environmental factors to decode their complex interactions in order to enable the amplification of the positive, elimination of the negative and retrieval of lost interactions within the biological system.

Lavie Bio’s technological platform includes end-to-end capabilities for product discovery, optimization and development. This approach harnesses the power of genomics, employing a combination of computational and biological assets including a broadly diverse microbial collection, a proprietary validation platform and formulation and fermentation technologies. The computational aspects of Lavie Bio’s platform are empowered by Evogene’s CPB platform and by the Taxon Biosciences technology platform, acquired in August 2019, as part of the Corteva investment in Lavie Bio.

Product Development Cycle

We estimate that developing an ag-biological product based on microbial sources takes, on average, between six to eight years. The length of the process may vary depending on several factors, such as product type, target market and applicable regulatory or registration regime, type of application, type of natural source serving as active ingredient, as well as number of active ingredients within the final products, which impacts the development activities required to reach a commercially viable product.


3 According to industry publications.
 
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The development process for microbial-based ag-biologicals is divided into four steps, or phases, which generally include discovery, pre-development, development, pre-commercialization, and ending with registration approval and commercial launch. As this is a relatively young industry, the process is not yet well established and standardized and the below outline was structured based on our experience and estimations.


Discovery: The identification of a candidate microbial strain, or microbial strain teams, having the potential to improve the target trait. A collection of selected microbial candidates is typically tested on the crop(s) of choice in greenhouse screens or limited field experiments for various efficacy, stability and commercial viability criteria. Candidates that meet the testing criteria are referred to as “Hits”. Discovery phase typically lasts approximately 12-18 months.


Pre-development: Promising Hits are advanced to pre-development phase, in order to further assess and optimize performance criteria such as shelf life, efficacy and stability. Successfully performing microbial candidates are referred to as “Advanced Hits”. This stage typically lasts approximately 12-18 months.


Development: This phase is usually divided into Development Stage 1, resulting with a “Lead”, and Development Stage 2, resulting with a “Pre-Product”. In this phase, the fermentation and formulation procedures are further optimized to allow for further testing and validation of efficacy and stability in the field as well as for commercial scale production, addressing cost of good targets and compatibility with other agricultural inputs. Based on industry benchmarks and our estimates, this stage typically lasts approximately 24 months.


Pre-commercialization: In this phase, extensive field tests are undertaken to demonstrate the effectiveness of product candidates in enhancing the target trait, including production of data to support product positioning. Additional activities towards launch are performed, including packaging development, upscale manufacturing protocol, registration and regulation. Based on industry benchmarks and our estimates, in the U.S. we expect this stage to last approximately 24 months for bio-stimulants and 36-48 months for bio-pesticides due to longer regulation processes.

Product Development Pipeline

The following table sets forth Lavie Bio’s main product development programs:

Program
 
Ag-biological product
 
Crop/Target
 
Development phase (1)
1
 
Bio-stimulants – Yield & abiotic stress tolerance (2)
 
Corn
 
Pre-Development
2
 
Bio-stimulants – Yield & abiotic stress tolerance
 
Wheat
 
Development stage 2
3
 
Bio-pesticides – Seedling disease resistance
 
Row crops, seed treatment
 
Pre-development
4
 
Bio-pesticides – Mildew and fruit rots resistance
 
Row and specialty Crop, foliar application
 
Development stage 1
5
 
Bio insecticides – Western corn rootworm
 
Corn, soil and foliar
 
Pre-development

(1) Please see “—Product Development Cycle” for a description of the product development cycle of ag-biological products.

(2) Part of our bio-stimulants program for yield and abiotic stress tolerance in Corn is conducted in collaboration with Corteva (originally with ‘DuPont-Pioneer’), pursuant to a multiyear collaboration initiated in 2017. For more information on such collaboration, see “—Key Collaborations—Corteva.”

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In respect to its Bio-stimulants for Wheat program, in November 2019, Lavie Bio announced that it had advanced its leading product candidate LAV211 into development stage 2, having exhibited consistent positive results across commercial varieties in target locations, with advanced product formulation for extended shelf life. Overall, the fields treated with LAV211 showed significant yield improvement compared with controls and industry benchmarks with a ‘win rate’ in over 75% of the locations.

Key Collaboration

Corteva (originally with DuPont-Pioneer)

In July 2017, Evogene entered into a multiyear collaboration with DuPont Pioneer (now Corteva, following the merger of Dow Chemicals and DuPont in September 2017 and the establishment of Corteva as the agriculture division of the merged DowDuPont entity), for the research and development of novel microbial bio-stimulant seed treatments for the improvement of corn productivity globally. Under the agreement, Lavie Bio is entitled to milestone payments for advancement of candidate strains, and royalties from products sales. This collaboration helped in establishing the relationship with Corteva, which matured into Corteva’s investment in Lavie Bio.

Intellectual Property

Lavie Bio files for patents to cover the use of microbial strains, or strain teams, that are the core active ingredients of the products we develop. Other innovative and proprietary technologies that we develop (such as computational predictive and design technologies), are typically protected as ‘trade secrets’.

Raw Materials

We do not significantly rely upon any sources of raw materials for our operations.

Seasonality

As field trials are highly dependent on crop seasonality and the time windows for conducting such trials are rigid, Lavie Bio's research and development activities are dependent on crop seasonality. Although Lavie Bio currently does not have any commercialized products, our expectation is that in the future, sales cycles of the products Lavie Bio develops will be dependent on crop seasonality.

Government Regulation of our Operations and of Product Candidates

In general, the regulatory landscape in the evolving field of ag-biological products is still developing. As a result, it may face additional changes in the next few years. Complexity of regulatory processes varies between bio-stimulants and bio-pesticides and between regulatory organizations.

In the U.S., the key focus market for the ag-biological products Lavie Bio is currently developing, the Animal and Plant Health Inspection Service within the Department of Agriculture, or USDA APHIS, is responsible for importation and field release permits for ag-biological products, and the U.S. Environmental Protection Agency, or EPA, is in charge of the registration of plant protection products. Most U.S. states also require certain registration processes for such products, which vary among states. Both U.S. and European regulators are in the process of establishing a more defined regulation process for bio-stimulants. Under current EPA guidance, bio-stimulants are regarded as plant inoculants, which currently does not require any regulatory action at the federal level, but requires registration at the state level. Bio-pesticides require registration at both federal and the state level.

In the European Union, bio-stimulants are currently regulated as fertilizers, and bio-pesticides are regulated and registered as plant protection products.

AgPlenus Ltd.

Overview

In 2015, we initiated our activity for developing ag-chemical products as a division within Evogene and in 2018, we announced that it had been organized under AgPlenus Ltd., a separate company, wholly owned by Evogene. AgPlenus aims to design effective and sustainable crop protection products (crop protection refers to the science and practice of managing risks of weed, plant diseases, and insects that damage agricultural crops and forestry) by leveraging predictive biology. AgPlenus’ activities focus on herbicides, with a strong focus on novel modes-of-action, or MoAs, and on insecticides, focusing on new sites-of-action, or SoAs. AgPlenus is also active in fungicides and crop enhancers.

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Market

According to industry publications, the ag-chemicals market was estimated at approximately $57.5 billion in 2018, out of which approximately 42%, 28% and 27% were attributable to herbicides, insecticides and fungicides, respectively, and is expected to grow to over $70 billion by 2022. Lack of available solutions for pest control and increasing resistance to existing crop protection solutions lead to a pressing need for novel crop protection products. However, due to current technological limitations and increasing regulatory requirements, the development of crop protection products is lengthy, complicated and expensive.

Competition

The ag-chemical market, as described above, can be classified into four key groups of companies: (i) leading innovative players – multi-billion dollar companies (such as Bayer, Syngenta and Corteva) that invest substantial resources in the discovery and development of novel molecules for crop protection, (ii) small innovative players – companies with revenues in the range of tens to hundreds of millions of dollars, developing innovative molecules. These are mainly Japanese companies which are mostly focused on the Japanese market. Such players are investing resources in the development of novel crop protection molecules, (iii) small to mid-size biotech companies – companies that undertake new approaches to research and development of novel molecules for crop protection, and (iv) Academic and agricultural research institutions that grant licenses to third parties to use their ag-chemical discoveries.

Business Model

AgPlenus’ business model is based on three commercialization avenues: (i) reach high-value, revenue-sharing deals based on its internal product development pipeline, (ii) sales of product candidates that have reached the 'Pre-Development' stage (described below under —Product Development Cycle); and (iii) in parallel, early stage collaborations providing a tailored product offering per partner and market.

High value revenue sharing deals – based on AgPlenus’ internal pipeline of novel MoA herbicides and new SoA insecticides.

Sale of Product candidates that have reached the ‘Pre-Development’ stage – when product candidates advance to what is referred to in the industry as a ‘Lead’ or ‘Optimized Lead’, these product candidates gain significant commercialization value.

Early collaborations – AgPlenus aims to enter such collaborations in order to build long-term relationships in the industry and to mitigate the risk associated with building an independent pipeline.

Currently, AgPlenus’ revenues are derived from research and development payments under early collaborations. In the longer term we expect that: (i) as AgPlenus’ product candidates advance through development in our partner’s pipelines, and to the extent that they are commercialized by its collaboration partners, revenues will include milestone payments and royalty payments, or to the extent that they are sold, revenues may include significant one-time payments; and (ii) as its internal pipeline product candidates further advance, AgPlenus will be able to reach higher value revenue-sharing deals.

Product Development Programs

Scientific Approach

AgPlenus' approach is based on the disruption of the traditional methods of ag-chemical discovery and optimization by implementing a target-based approach for identifying and developing novel herbicides and insecticides with new MoAs or SoAs to address the growing resistance of weeds and insects to existing products. AgPlenus utilizes Evogene’s CPB platform’s capabilities, namely the expertise in plant and insect genomics, as well as advanced technologies and know-how, to drive chemical discovery with the target of ultimately developing new herbicides and insecticides that display new MoAs or SoAs.

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AgPlenus' approach begins with the computational identification of protein ‘targets’, which are proteins that are essential to the function of performance of the relevant weed or insect. Following the identification and validation of such targets, we identify candidate Hits, which are chemical compounds that potentially inhibit these targets. We screen candidate hits to identify those displaying effect on weeds or insects of focus. Hits displaying confirmed activity in the initial validation screens enter the Hit-to-Lead process, which includes computational optimization and additional, more advanced, validation experiments. In addition, these capabilities are also used independently of each other to discover new Hits for known targets, optimize an existing Hit-to-Lead and optimize a commercial molecule.

Product Development Cycle

The product development cycle for the development of ag-chemical products is generally comprised of several stages, described as follows:

Discovery stage


Identification of Targets – Identification and validation of vital targets or proteins that when inhibited (for instance by a chemical), lead to plant or insect death.


Identification of Hits – Screening of chemical compounds for the identification of candidate Hits that potentially inhibit identified vital targets and are capable of achieving the desired impact on the plants or insects of interest. The development process includes in-silico as well as biological screening and validation activities.


Hit-to-Lead process – Hits displaying confirmed activity in the initial validation screens will enter the Hit-to-Lead process, including several optimization cycles, each constructed of compound design (in our case focusing on computational optimization), synthesis of compounds and validation experiments. This stage ends with a Lead compound.


Lead – A lead is a validated hit that has confirmed activity in advanced validation screens proving commercial level efficacy.

Pre-development stage


In this stage different types of regulatory experiments are conducted, and the chemistry may be further modified to address specific challenges. This stage ends with an Optimized Lead compound.

Development, Regulation & Registration


In the final development phases, new chemical products are registered with the proper regulatory authorities and then launched for commercialization. According to publications of key industry players, such development processes are likely to last 5-8 years. We expect that these last stages of development will be conducted by our current and future collaboration partners or by our customers.

Product Development Pipeline


(i)
internal product development pipeline

Program
 
Product
 
Target Organism / Crop
 
Stage
1
 
Non-selective & selective herbicides (novel MoAs)
 
Key crops
 
Discovery – Hit-to-Lead process
2
 
Broad spectrum insecticides (novel SoAs/MoAs)
 
Lepidoptera, Coleoptera and Hemiptera
 
Discovery– Identification of Hits

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(ii)
Product development under collaborations:

Program
 
Product
 
Target Organism / Crop
 
Collaborator
 
Stage
1
 
Non-selective & selective herbicides
 
Key crops
 
BASF
 
Undisclosed
2
 
Non-selective & selective herbicides
 
Key crops
 
Corteva
 
Undisclosed
3
 
Broad spectrum insecticides
 
Lepidoptera, Coleoptera and Hemiptera
 
BASF
 
Undisclosed
4
 
Crop enhancers
 
Key crops
 
ICL
 
Undisclosed

Key Collaborations

BASF SE (BASF) – Herbicides

Overview

In December 2015, Evogene entered into a multi-year collaboration with BASF for the discovery and development of novel herbicides. Under the terms of the collaboration agreement, we utilize our biology-driven computational discovery approach to identify potential candidate chemicals for novel herbicides while BASF uses its proprietary advanced plant platform to screen the candidate chemicals in order to experimentally validate their biological effects on weeds. Successful candidates from this collaboration will be further developed by BASF. Following the establishment of AgPlenus, the collaboration was assigned from Evogene to AgPlenus.

License & Consideration

Pursuant to the agreement, BASF obtains a worldwide, royalty-bearing, exclusive license to use and modify chemical compounds that we identify under the collaboration to develop and commercialize weed control products containing such compounds. Under the terms of the agreement, AgPlenus is entitled to milestone payments upon achievement of certain development milestones as well as royalty payments from sales of products developed under the collaboration.

BASF SE (BASF) – Insecticides

Overview

In May 2018, Evogene announced that we entered into a two-year collaboration with BASF for the development of novel insecticides based on new binding areas (SoAs). Following the establishment of AgPlenus, the collaboration was assigned from Evogene to AgPlenus. Under the terms of the agreement, in the initial phase of the collaboration, we utilized our biology-driven computational methods to identify potential novel compounds that act on new proteins binding sites. Compounds we discover enter BASF’s proprietary insecticides discovery platform for efficacy screening and testing and to validate the chemistry’s ability to modulate the respective target proteins.

License & Consideration

Pursuant to the agreement, BASF obtains a worldwide, royalty-bearing, exclusive license to use and modify chemical compounds that we identify under the collaboration to develop and commercialize weed control products containing such compounds. Under the terms of the agreement, we are entitled to milestone payments upon achievement of certain development milestones. Commercial arrangements concerning further development and commercialization are subject to further agreement between the parties.

Corteva – Herbicides

Overview

In March 2020, AgPlenus entered into a multi-year collaboration with Corteva for the discovery and development of novel herbicides. Under the terms of the collaboration agreement, AgPlenus and Corteva will work together to optimize herbicide product candidates originating from AgPlenus’ pipeline. Successful candidates from this collaboration are expected to be further developed by Corteva.

License & Consideration

Pursuant to the agreement, Corteva obtained a worldwide, royalty-bearing, exclusive license to use and modify chemical compounds identified under the collaboration to develop and commercialize weed control products containing such compounds. Under the terms of the agreement, AgPlenus is entitled to research and development payments, milestone payments upon achievement of certain development milestones as well as royalty payments from sales of products developed under the collaboration.

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Intellectual Property

AgPlenus expects to file patent applications with respect to its discoveries, either alone or together with its collaborators, in later stages of maturity of its product candidates. AgPlenus’ ongoing operations take into consideration various aspects of such future filings, and our filing policy follows industry standards with respect to the preferred timing for filing.

Government Regulation of our Operations

AgPlenus' activities are performed at labs in Israel and are regulated by the provisions of several Israeli governmental agencies. Violation of these regulations may expose us to criminal or civil actions and may impose liability on us.

Government Regulation of Product Candidates

Regulatory approvals are required prior to the commercialization and importation of ag-chemical products in most countries. Most of the key target markets where AgPlenus anticipates its collaborators to sell products containing its compounds, including the U.S., the European Union, Brazil and Argentina, will require such regulatory approvals prior to the commercialization of such products. Pursuant to AgPlenus’ collaboration agreements, its collaborators are responsible for product regulation.

Among other regulatory requirements, our collaborators may need to test new active ingredients for assessment of potential effects on mammals. These include tests on acute toxicity, carcinogenicity, mutagenicity and reproduction. The results of these tests may impact the chemistry and formulation development stages.

In order to sell a crop protection ag-chemical product in most countries, both the product and its active ingredient first need to be registered. This process may require the submission of over 100 toxicology and ecotoxicology studies, as well as detailed information on the chemistry of the active ingredient and the product. In the United States, collaborators may need to seek regulatory approval from the EPA, which regulates the marketing and use of new plant pesticides and herbicides. In addition, in Brazil, the commercialization of ag-chemical products is regulated by Anvisa, the federal agency in charge of evaluating pesticide health risks. The approval process involves data collection and analysis, environmental impact assessments and public hearings on certain products, and is similarly costly and time-intensive.

Raw Materials

AgPlenus does not significantly rely upon any sources of raw materials for its operations.

Seasonality

At this stage of development, AgPlenus’ business in general, and revenues in particular, are not subject to variations based on seasonality. In more advanced stages of product development its activities are expected to include field trials, which are highly dependent on crop seasonality. Although AgPlenus currently does not have any commercialized products, its expectation is that, in the future, sales cycle of the products it develops will be dependent on crop seasonality.

Ag-Seeds Division

Overview

Initiated in 2004, our seed traits activity is focused on the development of products improving seed traits that have a direct impact on crop productivity through the use of GM (genetically modified) and non-GM approaches. We mainly target key commercial crops such as corn, soy, wheat, rice and cotton.

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The activities of this division are divided into three categories: (i) yield & abiotic stress tolerance – increase crop performance and productivity by enhancing yield, tolerance to abiotic stresses such as drought, heat and salinity and fertilizer use efficiency; (ii) disease resistance – increase crop resistance to diseases such as fungi and nematodes; and (iii) insect control – increase crop tolerance to pests.

In general, we utilize several biotechnology approaches with the goal of improving seed traits, including: (i) genetic modification of plants, which involves the direct manipulation of a plant’s genome by inserting a gene into the plant’s DNA, (ii) genome editing technologies, enabling deletion or modification of specific genomic regions in the crop's genome without inserting foreign DNA to the plant, and (iii) advanced breeding methods, whereby plants with favorable characteristics are selectively crossed through genomic-guided breeding schemes.

Market

According to industry publications, in 2015 the seeds market size was estimated at approximately $37 billion, out of which approximately 53% was attributed to GM seeds4. The market potential for traits addressing plant insects and diseases was estimated to be between $7.5 billion to $8.5 billion, out of which the commercial value of insect control products was approximately $4.5 billion.5 We estimate that the potential value of improving non-existent commercial seed traits such as yield, drought or fertilizer utilization in the major crops of corn and soybean alone could be significant.

Business Model

In the Ag Seeds activity, we collaborate with seed companies in the development of improved seed traits. Our partners include world-leading seed companies, including Bayer and Corteva, as well as regional seed companies such as Tropical Melhoramento & Genética S/A, or TMG, and Instituto Mato-grossense do Algodão, or IMAmt. Typically, under these collaborations we perform the discovery phase, during which we discover and validate candidate trait-improving genetic elements, and subsequently our collaborators, under license from us, test and further develop these discoveries in their product development pipelines, starting Phase I, with the goal of introducing them into commercial crop seeds. For more information on the product development pipeline, please see “—Product Development Pipeline.”

In most cases, we expect to generate revenue from our collaboration agreements at two different points: first, we expect to receive milestone payments when certain specified results are achieved, such as when a product candidate containing our traits is submitted for regulatory approval; second, we expect to receive royalty payments once a commercial product containing our traits is launched into the market. Under several collaboration agreements, we also receive research and development service payments to cover the costs of our research.

In the Ag-Seeds division, we currently generate revenues from research and development payments for our activities. All of our product development programs under our Ag-Seeds activity are currently either in the Discovery or in Phase I stages. For more information on our product development programs in this field, see “—Product Development Programs.”

Product Development Programs

Scientific Approach

The division uses our expertise in plant science and genomics to improve commercial seed traits. Evogene’s proprietary CPB platform, validation techniques and other capabilities enable us to identify and optimize promising genetic elements that have the potential to improve our traits of interest in target crops.

We have accumulated substantial scientific knowledge on plant, diseases and insect mechanisms associated with yield, abiotic stress, fertilizer use efficiency, disease resistance traits and insect control traits. We maintain a large proprietary genomic data from over 200 different plant species as well as large microbial data tailored for insect and disease control. We have also established proprietary plant, disease and insect validation systems.


4 According to Industry publications.
5 According to Industry publications.
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Product Development Cycle

 Developing and integrating seed traits into commercial seeds may take, based on estimations, between eight and sixteen years. The length of the process may vary depending on the technology being applied, the complexity of the trait and the type of crop involved. The development process for seed traits is divided into five discrete steps, or phases, as follows:


Discovery: The identification of candidate genetic elements for enhancing specified plant traits. We usually test these elements in model systems to determine whether they will enhance the specified trait. In our experience, the Discovery phase typically lasts approximately 18-24 months. In our collaborations, we typically undertake this phase.


Phase I, or “Proof of Concept”: Validated candidate genetic elements are advanced to Phase I. In this phase, they are tested in target plants through greenhouse trials, field trials, or both, for their efficacy in improving plant performance. During this phase, the genetic elements are also optimized to improve their efficacy. Phase I may be conducted by us or by our collaborators, and in our experience, may last up to six years.


Phase II, or “Early Development”: In this phase, the field tests are expanded, and our collaborators evaluate the genetic elements on multiple geographical locations and varieties, to reach commercially viable success rates. By the end of this phase, a specific product candidate is being selected to advance to Phase III. We estimate Phase II to last between two to four years.


Phase III, or “Advanced Development and Regulation”: Extensive field trials are performed to test the effectiveness of the selected product candidate across locations, and regulatory approvals are obtained, including potential environmental impact assessments, toxicity and allergenicity. We estimate Phase III to last between one to two years.


Phase IV, or “Pre-Launch”: Involves preparation for commercial launch. The range of activities here includes preparing the seeds for commercial sales, formulation of a marketing strategy and preparation of marketing materials. We estimate Phase IV to last between one to two years.

As indicated, the estimated timeframes of phase duration and probability of success are mainly based on our experience and estimates according to available information. The total development time for a particular product may be longer or shorter than the duration presented above depending on a range of factors.

Product Development Pipeline

The following table sets forth our key product development programs in the segment of yield & abiotic stress tolerance seed traits under development with our collaborators:

Program
   
Crop
 
Technology
 
Collaborator
 
Development Phase
1
   
Corn
 
GM
 
Bayer
 
Phase I
2
   
(1)

Advanced breeding
 
A consumer goods company (1)
 
Development with Collaborator
__________
 

(1)
Crop and collaborator name not disclosed.

The following table sets forth our key product development programs in the segment of disease resistance traits, under development with our collaborators:

Program
 
Crop
 
Trait
 
Technology
 
Collaborator
 
Development Phase
1
 
Corn
 
Fusarium
 
GM & genome editing
 
Bayer
 
Undisclosed
2
 
Soybean
 
Asian Soybean Rust
 
GM
 
Corteva
 
Undisclosed
3
 
Soybean
 
Nematodes
 
Genome editing
 
TMG
 
Discovery
4
 
Banana
 
Black Sigatoka
 
GM
 
Rahan Meristem
 
Phase I

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The following table sets forth our key product development programs in the segment of insect control traits, under development with our collaborators or as internal product development programs:

Program
 
Trait
 
Crop
 
Technology
 
Collaborator and Collaboration Phase
 
Phase
1
 
Coleoptera / Lepidoptera
 
Cotton
 
GM
 
IMAmt
 
Undisclosed
2
 
Lepidoptera
 
Corn, Soybean, Cotton
 
GM
 
Internal program
 
Phase I
3
 
Coleoptera
 
Corn, Cotton
 
GM
 
Internal program
 
Phase I
4
 
Hemiptera
 
Soybean
 
GM
 
Internal program
 
Phase I

Key Collaborations

Bayer (originally with Monsanto)

Background

In August 2008, we entered into a Collaboration and License Agreement with Monsanto (now Bayer, following the completion of the acquisition of Monsanto by Bayer in June 2018), which we refer to as the Monsanto Collaboration Agreement. This agreement was amended in November 2011 and again in October 2013, in both cases extending and expanding the original agreement. As part of the October 2013 amendment and restatement, we further apply our computational technologies in the field of biotic stress in corn.

Yield and abiotic stress tolerance program

Pursuant to the Monsanto Collaboration Agreement, Monsanto funded a research program under which we identified and optimized genes with the potential to improve yield and abiotic stress tolerance in corn, soybean, cotton and canola, and candidate genes have entered Phase I in Monsanto's product development pipeline. In July 2017, we announced completion of candidate gene discovery stage in this collaboration.

Biotic stress program - Fusarium

As part of the October 2013 amendment of the Monsanto Collaboration Agreement, we applied our computational technologies in the field of biotic stress to identify genes providing resistance to Fusarium, a type of fungi that is a main pathogen responsible for Stalk Rot disease in corn (a widespread, yield-reducing disease). In July 2017, we announced that we have reached an important milestone in the collaboration with the demonstration of positive Fusarium resistance results with Evogene-discovered genes. In July 2019, we announced that the collaboration is being refocused on the identification of genome editing targets for evaluation against a broad range of corn diseases.

License & Consideration

We have granted Monsanto an exclusive, royalty-bearing, worldwide license under our patents and know-how to commercially exploit and conduct research on the genes we discovered under the collaboration, in the specified crops.

Monsanto provided us with research and development payments, and undertook to provide us with development milestone payments, if and when our product candidates reach significant milestones in its product development pipeline, as well as royalty payments on any sales or other transfers of products it develops containing our licensed genes. 

A Multinational Consumer Goods Company

Background

In October 2014, we entered a Collaboration Agreement with a multinational consumer goods company, focusing on improving yield in a certain field crop through non-GM methods. The agreement significantly limits the parties' freedom to disclose information on the nature of, and the parties to, the agreement. In the framework of the collaboration, we identified genes with the potential to improve the desired trait in the target crop when the expression of such genes in the plant is modified. We generated new varieties of the target crop using molecular methods, and further tested the performance of these new varieties. These activities were performed over a period of approximately four years before we delivered these varieties to our partner for further development as part of their product development pipeline.

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License & Consideration

We granted the partner an exclusive worldwide license to the genes we identified and the varieties we delivered under the collaboration. The agreement provided for research and development payments, as well as milestone payments by the partner upon achievement of certain development milestones. The agreement does not provide for payment of royalties to us.

Corteva (originally with DuPont-Pioneer)

Background

In 2011, we entered a multi-year research and development collaboration with DuPont-Pionner (now Corteva, following the merger of Dow Chemicals and DuPont in September 2017), to improve resistance to Asian Soybean Rust, or ASR, a devastating fungal disease in soybean. We amended and expanded the agreement in October 2013. Pursuant to this collaboration, we identified relevant genes having the potential to improve in-plant resistance to ASR.

License & Consideration

DuPont holds a worldwide, royalty-bearing, exclusive license to develop and commercialize soybean products containing our licensed genes. Our compensation under the 2011 agreement with DuPont is in the form of milestone payments and royalty payments based on the sales of resulting products. According to the agreement, each party funds its expenses in performing its activities using its own resources and a grant from the Israel-U.S. Binational Industrial Research and Development Foundation, or BIRD. We hold a contractual option to co-invest in the development costs for greater royalty percentages downstream if a product is successfully commercialized.

Rahan Meristem

Background

In 2007, we entered into a multi-year collaboration with Rahan Meristem, or Rahan, with the target of developing banana varieties expressing tolerance to Black Sigatoka, the most damaging disease threatening commercial banana plantations. The agreement focuses on identifying and developing genes targeting this trait in bananas. Together with Rahan, we have identified candidate genes, while transformation to banana plants and further validation in infected areas is conducted by Rahan.

In 2013, we announced that, in field trials conducted by Rahan, banana crops consisting of Evogene-discovered genes demonstrated a lower infection rate than banana crops which did not contain the selected genes. In September 2017, we announced positive results in 2nd year field trials.
 
License and Consideration

Pursuant to the agreement, Rahan holds an exclusive license to develop and commercialize banana products containing genes identified under the collaboration. Each of Rahan and us bears its costs in performing its activities under the program, using its own resources. Under the terms of the agreement, we are entitled to royalty payments from sales by Rahan of commercial products containing genes identified under the collaboration.

TMG

Background

In December 2018, we entered into a multi-year collaboration and license agreement with TMG, a major Brazilian developer and marketer of soybean varieties, for the development of nematode-resistant soybean varieties using genome editing technologies. Under the agreement, we identify genomic elements for editing to attribute nematode resistance in soybean and perform such edits on TMG’s commercial soybean germplasm. In turn, TMG validates the efficacy of the edited soybean varieties in greenhouse assays and field trials in Brazil and for incorporation in its breeding pipeline.

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License and Consideration

Under the collaboration and license agreement, TMG obtained a worldwide, royalty-bearing license to incorporate genome edits originating from the collaboration in its soybean varieties. Evogene, on the other hand, obtains a non-exclusive, royalty-bearing license to commercialize such genome edits and soybean lines, subject to certain exclusivity restrictions. According to the agreement, each party is entitled to receive royalty payments from the other party when the products of the collaboration are commercialized. In addition, Evogene received from TMG an up-front payment in consideration for its R&D costs and is entitled to success-based payments upon achievement of pre-defined development milestones.

IMAmt

Background

In July 2018, we entered into a research and testing agreement with IMAmt, a crop research company, owned by Mato Grosso Cotton Grower Association, a leading developer and marketer of cotton seeds, with the objective of discovering and testing toxins against major cotton pests, such as the Boll Weevil and the Fall Armyworm, which threaten the viability of the cotton industry in Brazil. According to the agreement, we selected insecticidal genes predicted to have desired insecticidal activity against Boll Weevil and Fall Armyworm, and IMAmt will validate their activity in lab assays against the target pests.

Consideration

Under the terms of the agreement, we are entitled to R&D funding from IMAmt for the initial discovery phase. Commercial arrangements for development and commercialization of the genes are subject to further agreement between the parties.

Intellectual Property

Our intellectual property rights are important to our business. In certain cases they determine our eligibility to receive royalties for seed traits under the licenses we grant our collaborators. We actively seek to protect the intellectual property and proprietary technology that we believe is important to the development of our business. To date, we have sought and obtained patent protection for hundreds of plant and bacterial genes linked to desired traits.

Government Regulation of Product Candidates

Regulatory approvals are required prior to the commercialization and importation of biotechnologically enhanced seeds in most countries. Most of the key target markets where we anticipate our collaborators will sell seeds containing our traits, including the United States, the European Union, Brazil and Argentina, will require such regulatory approvals prior to the commercialization of such products. Additional regulatory approvals will be required for countries importing grain produced from seeds containing our traits, such as China, India and certain countries in the European Union. Pursuant to our collaboration agreements in the field of seed traits, our collaborators will apply for all requisite regulatory approvals prior to commercialization of the product candidates we are developing with them.

The regulatory status of products developed via genome editing technologies is currently unclear. In the United States, approvals are required by the USDA prior to field testing of genomic edited seeds. A ‘non-regulated organism’ approval has been issued by the USDA for some products currently under development; however, the regulatory status of all changes this technology allows has yet to be determined.

Government Regulation of our Operations

Our business is subject to regulation related to agriculture, health and the environment. To operate, we must obtain various permits and licenses from government authorities and municipalities in our active jurisdictions, and we must maintain our compliance with the terms of those permits, licenses and other government standards as necessary. These laws and regulations, particularly in relation to biotechnology, are not fully settled, but continue to evolve in order to keep pace with technological advances.

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As an Israeli company, our activities in the fields of biotechnology and plant genomics are regulated by the Israel Ministry of Agriculture and Rural Development, or ISARD, and more specifically by the ISARD’s Plants Protection and Inspection Services. Our activities are subject to various laws, regulations, orders and procedures, which require us, among other things, to obtain permits for conducting experiments on genetically enhanced plants and to satisfy special conditions determined by the ISARD regarding the growing procedures of such seeds and plants. Violation of these regulations may expose the company to criminal penalties. Pursuant to these regulations, we are also obligated to obtain separate permits to own and operate our greenhouses and testing fields in Israel and we are routinely inspected by ISARD.

Raw Materials

We do not significantly rely upon any sources of raw materials for our operations.

Seasonality

Our seed traits business in general, and our revenues in particular, are not subject to variations based on crop seasonality. Our revenues from our seed traits business are generated from our strategic collaborations, based on research and development and milestone payments as the seed traits we discover advance in the product development pipeline of our collaborators, and are therefore not season-dependent.

Human Health

Background

In 2017, we decided to leverage our capabilities in computational biology towards the area of human health with the establishment of Biomica. In 2019, we expanded our activity in this area with the establishment of Canonic.

Biomica Ltd.

Overview

In 2017, we established Biomica, a subsidiary focused on the discovery and development of innovative human microbiome-based therapeutics. The human microbiome is an array of more than 100 trillion microorganisms that live on and in our bodies, creating a community of symbiotic, commensal and pathogenic bacteria, all of which call the human body home. These microbes have numerous beneficial functions relevant to supporting life, such as digesting food, preventing disease-causing pathogens from invading the body, and synthesizing essential nutrients and vitamins. Numerous studies have shown the connection between the human microbiome and various medical disorders, and the search for microbiome therapies and treatments is a rapidly growing focus for biotherapeutics research and development.

Biomica focuses on the development of human-microbiome based therapies utilizing either rationally-designed microbial consortia or small molecule approaches for (i) immuno-oncology and (ii) GI related disorders (iii) MDRO (Multi Drug resistant organisms) - antibiotic resistant bacteria.

Market

Biomica’s product development is currently focused in three main markets:

Immune-Oncology – In oncology, checkpoint inhibitor antibodies, including those targeting the programmed cell death protein/ligand 1, or PD-1/PD-L1 pathways, block the tumor’s ability to suppress the immune response. They have significantly improved the treatment of many cancers. The cancer immunotherapy market size was estimated at $84 billion in 2018 and is expected to reach a market size of $243 billion by 20266


6 https://www.globenewswire.com/news-release/2019/07/17/1884118/0/en/Cancer-Immunotherapy-Market-To-Reach-USD-242-86-Billion-By-2026-Reports-And-Data.html
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Even in cancers, where checkpoint inhibition is considered the frontline standard of care, a significant percentage of the patients do not respond to PD-1 + CTLA-4 inhibitor combination and part of responders relapse within a few years. In all approved cancer indications, agents with differentiated immune mechanisms of action may be complementary to checkpoint inhibitors by both augmenting existing effects and testing alternative pathways of immunotherapy in checkpoint inhibitor non-responsive tumor types and patients.

Given a growing body of literature, it is becoming increasingly clear that modulation of the gut microbiota may represent a novel and important adjunct to current anti-cancer therapeutic modalities.

GI related disorders –

-          Irritable Bowel Syndrome (IBS) is a common disorder that affects the large intestine. Signs and symptoms include cramping, abdominal pain, bloating, gas, and diarrhea or constipation, or both. It is estimated that the total market for IBS reached $1.5 billion in 2018, with 45 million patients in the U.S. alone and is expected to reach $3.3 billion in 20267. Existing drugs for IBS mainly treat the symptoms of the condition, leaving patients exposed to cycles of remission and relapse that characterize this chronic condition.

-         Inflammatory Bowel Disease (IBD) is a group of gastrointestinal inflammatory diseases, mainly comprised of Ulcerative colitis and Crohn’s disease. IBDs cause long term chronic as well as severe inflammation in the gastrointestinal tract without any known cause. According to the Centers for Disease Control and Prevention, or CDC, in 2015 an estimated 3.1 million people (1.3% of the entire population) in the United States were diagnosed either with Crohn’s disease or with Ulcerative Colitis. The global IBD drug market is estimated to grow from $15.9 billion in 2018 to $22.4 billion in 2026.8

MDRO (Multi Drug resistant organisms) -

-          Clostridium Difficile Infection (CDI) – The CDC has identified CDI as one of the top three most urgent antibiotic-resistant bacterial threats in the United States. CDI is most often caused by the use of broad spectrum antibiotics which induce dysbiosis of the microbiome causing susceptibility to infection by C. difficile, a spore forming bacterium. It is the most common cause of hospital acquired infection in the United States.

CDI is responsible for the deaths of approximately 29,000 Americans each year. Based on an epidemiological study conducted by the CDC, the incidence of CDI in the U.S. was estimated to be over 600,000. CDI space across the seven major markets of the U.S., France, Germany, Italy, Spain, the UK and Japan is set to grow from just under $630 million in 2016 to almost $1.7 billion by 2026, representing a compound annual growth rate of 10.2%. The global CDI market is expected to approach $1.7 billion by 2026.9

-          Methicillin-resistant Staphylococcus aureus (MRSA) - One of the most common Staphylococcus aureus infections is caused by MRSA, which is a multi-drug resistant bacterium, responsible for several difficult-to-treat infections in humans, leading to tens of thousands of annual cases of mortality in the U.S. MRSA is the leading causative agent for hospital acquired infections and has recently been documented as community-acquired as well as livestock-acquired. Current medical treatments include broad spectrum antibiotics that are becoming increasingly ineffective. The current MRSA market was valued at approximately $922 million in 2018 and is projected to reach over $1.3 billion by 202610.


7 https://www.grandviewresearch.com/industry-analysis/irritable-bowel-syndrome-ibs-treatment-market
 
8 https://www.prnewswire.com/news-releases/the-global-inflammatory-bowel-diseases-ibd-drug-market-is-estimated-at-6-7bn-in-2017-and-7-6bn-in-2023--300688523.html
 
9 https://www.globaldata.com/global-clostridium-difficile-infections-market-approach-1-7-billion-2026/
 
10 https://www.prnewswire.com/news-releases/global-methicillin-resistant-staphylococcus-aureus-mrsa-drugs-market-to-reach-over-us-39-billion-by-2025-upsurge-in-the-consumption-of-antibiotics-across-the-globe-to-fuel-market-growth-observes-transparency-market-research-676949593.html

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Competition

The biotechnology and pharmaceutical industries are characterized by rapid growth and a dynamic landscape of proprietary therapeutic candidates. The development and commercialization of new drug and biologic products is highly competitive and is characterized by rapid and substantial technological development and product innovations. While we believe that our computational platform and microbial drug candidates, coupled with our resources and industry expertise, give us a competitive advantage in the field, we face competition from a variety of institutions, including larger pharmaceutical companies with more resources. Specialty biotechnology companies, academic research institutions, governmental agencies, as well as public and private institutions are also potential sources of competitive products and technologies.

In both inflammatory diseases and oncology, we anticipate intensifying competition as new therapies are approved and advanced technologies become available. Many of our competitors, either alone or with strategic partners, have considerably greater financial, technical, and human resources than we do.

Significant competition exists in the immuno-oncology and inflammatory diseases field, where we are developing our first product candidates in oncology and IBD. Although our rationally-designed microbial consortium approach is unique relative to most other existing or investigational therapies in immuno-oncology, we will need to compete with all currently or imminently available therapies within the indications where our development is focused. Although there is a wide range of potentially competitive mechanisms, possible synergies between these and rationally-designed microbial consortia will also be evaluated.

Business Model

Our goal (through Biomica) is to become a leading biopharmaceutical company developing and commercializing microbiome therapeutics to address significant unmet medical needs, through strategic collaborations with world-leading pharmaceutical companies.

Product Development Programs

Scientific Approach

Biomica aims to identify unique microbiome-based therapeutic entities through multilayered analysis and integration of high resolution big-data originating from the human gut microbiome. Employing a holistic approach, we combine a profound understanding of the microbiome and its functions and their intricate relations with the human host.

Biomica’s approach relies on a multi-layered analysis of omic and clinical / phenotypic data using an extensive nexus of modules in four key areas: (i) creation of microbial classifications – enabling high-resolution taxonomy analysis of the microbial community down to the strain level, (ii) identification of microbial functions – functional-level microbial community analysis profiling microbial genes, pathways and metabolites, (iii) identification of host genomics – profiling of patients' genomic information (genetics and expression patterns), and (iv) clinical data – integrate relevant phenotypic and physiological information manifested in patient.

Biomica’s discovery and development efforts are powered by the PRISM platform, a facet of Evogene’s CPB platform. PRISM is a proprietary metagenomics analysis platform for functional genomics profiling, utilizing internal comprehensive databases. These databases have been specifically developed to allow the processing of large amounts of sequencing data, obtain high-resolution profiling of microbial communities both at the taxonomic and the functional levels, and correlate them with specific clinically relevant host expression and phenotypic profiles, enabling us to achieve the following:


At the taxonomic level our analysis allows strain-level resolution and relies on an extensive proprietary strain database.


At the functional level, our proprietary resources rely on a comprehensive catalog of microbial genes enabling mapping of an average of 90% of the functions of the human gut microbiome obtained through metagenomics sequencing.

In addition to its comprehensive computational solutions to profile the microbiome, Biomica utilizes Evogene's PointHit platform for virtual screening of small molecular inhibitors to specifically target bacterial proteins of interest. This platform combines the physiochemical requirements for binding a specific protein target and utilizes a comprehensive proprietary database of roughly 200 million small-molecules for the discovery of potential therapeutics.

50

Product Development Pipeline

Biomica expects to continue to promote its discovery stage programs to pre-clinical and Proof-of-Concept studies in 2020.

Immune-Oncology – rationally-designed microbial consortia, BMC121 and BMC127, with potential to enhance immunologic therapeutic responses and facilitate anti-tumor immune activity, were identified using our computational analysis and predictive capabilities. During 2019, Biomica initiated pre-clinical studies wherein anti-tumor activity was tested in mice following treatment with Biomica’s rationally designed bacterial consortia BMC121 & BMC127 and achieved positive preliminary results from animal studies.

GI disorders

For IBD - using our computational predictive biology capabilities Biomica identified BMC321 & BMC322, two rationally-designed microbial consortium with potential anti-inflammatory activity in IBD. During 2019, pre-clinical studies were initiated for the development of a novel microbiome-based drug for IBD that triggers multiple mechanisms for the reduction of intestinal inflammation.

For IBS, we utilize proprietary data from several clinical trials conducted in the U.S. to develop a novel microbiome based drug. Biomica aims to push the barriers posed by existing therapies and address the underlying cause of the disorder, rather than the symptoms, using bacteria/bacterial-associated factors affecting symptoms and underlying pathophysiology.

MDRO (Multi Drug Resistant Organisms) -

CDI – Using our microbiome therapeutics platform, we are developing a small-molecule drug candidate (BMC201), designed to target the main toxin secreted by the bacterium and hence repair dysbiosis in the colonic microbiome in the setting of primary or recurrent CDI. BMC201 is being developed as an orally available drug.

MRSA – Biomica initiated a collaboration with the Weizmann Institute of Science to develop a selective treatment against antibiotic resistant strains of Staphylococcus aureus infection, in a microbiome focused approach. The company has in-licensed Prof. Ada Yonath’s, Nobel Prize laureate, work and discoveries in high-resolution crystal structure of the large ribosomal subunit of the pathogenic Staphylococcus aureus for the design and development of new types of selective, narrow spectrum antibiotics agents.

Intellectual Property

We aim to protect the proprietary intellectual property that we believe is important to our Biomica business, including seeking international patent protection for our product candidates and promptly file patent applications for new commercially valuable inventions of our Biomica business. We also rely on trade secrets to protect aspects of our Biomica business that we do not consider appropriate for patent protection. Our success with Biomica will depend on our ability to obtain and maintain patent and other proprietary protection for commercially important technology, inventions and know-how related to our business, as well as defend and enforce any patents that we may obtain.

Raw Materials

Biomica does not significantly rely upon any sources of raw materials for its operations.

Seasonality

Biomica’s business in general is not subject to variations based on seasonality.

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Government Regulation of our Operations

The FDA and other regulatory authorities at federal, state and local levels, as well as in other countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of drugs and biologics such as those Biomica is developing. We, along with our contract manufacturers, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval for our product candidates. The process of obtaining regulatory approvals and ensuring subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

Government Regulation of Product Candidates

The development of therapeutic products targeting the underlying biology of the human microbiome is an emerging field, and it is possible that the FDA and other regulatory authorities could issue regulations or new policies in the future affecting our microbiome therapeutics that could adversely affect our product candidates. All of our product candidates are based on microbiome therapy, a therapeutic approach that is designed to treat disease by restoring the function of a dysbiotic microbiome. We have not, nor to our knowledge has any other company, received regulatory approval for a therapeutic based on this approach.

Canonic Ltd.

Overview

In April 2019, we announced the establishment of a new subsidiary, Canonic Ltd., focusing on the development of precise and stable medical cannabis products for better therapeutic performance.

Market

The global legal cannabis market is forecasted to reach $103.9 billion in 202411. In North America alone, the size of this market increased to greater than $11 billion in 2018 and is estimated to reach $30 billion in 202412. This overall market is rapidly growing due to changes in regulatory acceptance and can be divided into recreational and medical products. For more information on the regulatory environment of cannabis activities and products, please see “⸺Government Regulation of our Operations and Product Candidates” below. The market segment attributed to medical cannabis products is projected to reach $62 billion in 202412.

Canonic has identified three main challenges in this market:


-
Cannabinoid specificity – the lack of clinical data demonstrating the correlation between medical indications and the genomic and cannabinoid profile of the cannabis plant.


-
Cannabinoid yields – with the increasing legalization of cannabis in more and more countries, the price per gram of cannabis is decreasing. The decreasing selling price of cannabis has made this product increasingly sensitive to the cost of production, making yield of cannabinoid per square foot a significant factor.


-
Genetic stability – there is high genetic variability in currently available cannabis lines, which directly reflects on product consistency, or lack thereof.

Competition

In view of Canonic’s current stage of operations, companies that are in direct competition to Canonic are plant genomics companies aiming to improve the properties of medical cannabis varieties, such as Arcadia Biosciences, Benson Hill and KeyGene. When Canonic reaches commercialization of its products, its competitors will include companies developing and marketing medical cannabis products.

Business Model

Canonic intends to develop its products by conducting in-house the core elements relating to cannabis genetics, such as advanced breeding and seed and seedling production, while outsourcing other production activities, such as cannabis cultivation, extraction, and formulation. With respect to commercialization, Canonic intends to access the markets through distributors.


11 The global cannabis report, Nov. 2019, Prohibition Partners
52

Scientific Approach

Canonic is focused on the development of precise and stable medical cannabis products based on proprietary cannabis varieties with unique genomic profiles. Leveraging Evogene's CPB platform, Canonic utilizes advanced breeding technologies in order to improve the properties of cannabis varieties. Canonic is currently establishing a unique cannabis data base, which is based on its diverse genetic collection, and is identifying specific genomic elements in order to enhance either specific active compounds in the plant or the plant’s total active compounds.

In addition, Canonic integrates pre-clinical data collected from trials performed with its genetic collection. These trials are conducted in parallel to the breeding program and support the company product development to achieve unique genomic profile for better therapeutic effects.

Product Development

Canonic's product development efforts include the following main activities:


-
Development of varieties – This stage includes pre-breeding and breeding activities of tailored cannabis varieties (i.e., selective crossing of cannabis lines) to achieve desired properties. In addition, during this stage Canonic also performs pre-clinical trials in order to support and direct its medical product development pipeline.


-
Pre-production and pre-commercialization – During this stage, Canonic performs several activities that are intended to support future production and commercialization of its product. These activities include the establishment of business agreements with manufacturers and distributers, introduction of cannabis varieties to cultivators and provision of agro-technical support, as well as upscale through seed and seedling multiplication.


-
Production and Commercialization – This stage will include the production of Canonic’s products as well as their commercialization through local distributors.

Product Development Pipeline

Canonic has two product lines under development, which are both at the stage of development of varieties:


-
MetaYield, for enhancement of total active compounds in the plant, and


-
Precise, for the enhancement of specific active compounds in the plant, targeting anti-inflammatory and pain management properties.

Intellectual Property

We expect Canonic's intellectual property to be composed of three layers: (i) Evogene's existing patent portfolio regarding the use of plant genes for the improvement of plant traits and the development of genetic markers, which is licensed exclusively to Canonic for cannabis; (ii) plant variety protection rights for cannabis varieties that will be developed by Canonic; and (iii) intellectual property relating to the therapeutic attributes of active compounds within the cannabis plant, resulting from pre-clinical and clinical trials to be conducted by Canonic.

Raw Materials

Canonic does not significantly rely upon any sources of raw materials for its operations.

Seasonality

While outdoor cultivation of cannabis varieties is impacted by seasonality, cultivation under controlled environments is not. Currently, all of Canonic’s cultivation activities are performed under controlled environments.

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Government Regulation of our Operations and Product Candidates

All cannabis related activities in Israel (including R&D, cultivation, manufacturing and distribution) are regulated by the Israeli Medical Cannabis Agency, or IMCA. Every company with cannabis-related activity in Israel is subject to the IMCA’s regulation and is required to obtain the relevant annually IMCA certifications for such activities. Relevant certifications may include one or more of the following: (i) Good Security Practice, or GSP, (ii) Good Agriculture Practice, or GAP, (iii) Good Manufacturing Practice, or GMP, (iv) Good Distribution Practice, or GDP, (v) Good Consumption Practice, or GCP, and (vi) Good Waste Disposal Practice, or GWDP12, depending on the specific activity undertaken by Canonic. In order to be eligible for a certain certification, a company may be required to obtain certain preliminary approvals or licenses. Canonic operates under the IMCA’s guidelines and has received a GSP certification, a possession license, approval for its R&D work plan and an import permit for cannabis seeds.

Under the guidelines of the IMCA, medical cannabis can be manufactured and marketed in Israel for local use. Export has been approved by the government but regulation for cannabis export has yet to be set. Potential end markets include Europe and North America. In Europe, regulation is on a country by country basis. In North America, Canada has legalized cannabis for both medical and recreational use and in the United States, regulation is carried out on a state by state basis, while under federal law, cannabis is illegal.

Industrial Applications

Casterra Ag Ltd.

Overview

In 2007, we initiated our activities related to castor beans, which were in 2012 organized under Evofuel, a wholly owned subsidiary, which changed its name to Casterra Ag, or Casterra, in 2019. Casterra focuses on the development of an integrated solution – agricultural-technical growth protocols for castor cultivation for the production of castor oil to be used for industrial uses, such as bio-polymers and lubricants. Casterra’s integrated agricultural solution includes breeding of advanced high-yielding castor bean varieties that are non-GM and agricultural growth protocols compatible with a mechanical harvesting solution exclusively available to Casterra’s customers. Our target market is Brazil, where large scale castor agriculture and industry are well established.

Market

Castor beans are grown today for their high-quality oil, which is used for the production of bio-polymers and lubricants for various industries such as the cosmetics, electronics, automotive and aerospace industries, to name a few. Currently treated as a “low-tech” crop in its key production areas around the world (for example, in India the castor bean is grown using traditional techniques such as hand picking), according to industry estimations, the castor oil extracted from the castor bean plant may hold great promise as an input for industrial markets. The market for castor oil and its derivatives is rapidly growing and according to market publications, is expected to reach $2.3 billion by 202413. The growth in this market is expected to be further supported by the conversion of the castor bean plant to a modernized commercial crop.

Competition

Casterra’s competition includes a few other relatively small companies that supply castor seeds to growers worldwide. Casterra differentiates itself by providing rain-fed varieties (while its competitors offer irrigation-based varieties) and by providing a unique, mechanical harvesting solution for modernized commercial crop.

Business Model & Products

Business Model

Casterra’s business model is to sell proprietary improved castor seed varieties, together with targeted agro-technical growth protocols, to castor growers. These seed varieties and growth protocols are adapted and targeted to localized characteristics. Casterra’s offering includes: (i) high yielding varieties with plant structure suitable for mechanized harvest; (ii) best practices and recommendations to growers for growing castor efficiently in large scale; and (iii) advanced compatible mechanical harvest solution.


12 For more info see https://www.health.gov.il/UnitsOffice/HD/cannabis/Pages/default.aspx
13 Grand View Research, August 2016, http://www.grandviewresearch.com/industry-analysis/castor-oil-derivatives-industry.

54

Product development

Casterra develops proprietary castor seed varieties and growth protocols adapted to specific target markets. During 2018, Casterra completed semi-commercial field trials of certain castor varieties with partners in multiple target locations. In 2019, Casterra completed semi commercial field trials in multiple locations in South America and decided to focus its commercialization efforts to Brazil.

The castor seeds product development process includes three main steps: (i) research and pre-breeding, which we typically undertake in Israel and which takes between one to two years, resulting in experimental varieties for market location trials; (ii) yield field trials in the target markets, which take between two to three years and yield varieties for pre-commercial field trials; and (iii) semi-commercial field trials, which take approximately two years in the target markets.

Key Collaborations

Fantini s.r.l.

In October 2018, Casterra announced a breakthrough achieved in the mechanical harvesting of castor beans with Fantini s.r.l., a leading manufacturer and distributor of agricultural equipment. The lack of an available solution for mechanical harvesting has been a major challenge in the conversion of castor to a fully modernized commercial crop, and the combination of the Fantini s.r.l Harvester with Casterra’s proprietary varieties demonstrated significant improvement in yield loss in field trials.

The harvester is commercialized by Fantini s.r.l to Casterra’s global partners.

Intellectual Property

Our policy is to register relevant castor varieties in the destination territories. To date we have registered several of our varieties in several Latin America countries including Brazil.

Government Regulation of our Operations

Casterra’s activities in Israel in the field of seeds are regulated by the Israeli Ministry of Environmental Protection. Pursuant to these regulations, we are required, among other things, to (i) obtain toxins permits, which allow us to conduct experiments using “hazardous materials,” as such term is defined in the applicable regulations, and (ii) follow specific rules regarding waste disposal. Violation of these regulations may expose the company to criminal penalties, administrative sanctions and responsibility to compensate those injured for any environmental damages.

Government Regulation of Product Candidates

All seed production designated for export to our partners is subject to field and warehouse inspection by the regulator in the country of destination for compliance with the local regulations, including sampling and inspection for pests and diseases.

Raw Materials

We do not significantly rely upon any sources of raw materials for our operations.

Seasonality

Casterra’s castor seed business in general, and our revenues in particular, generated from our collaborations with castor growers, are subject to variations based on crop seasonality. The timing of our seed production field trials, as well as the delivery of castor seeds to our partners and revenue recognition with respect to such seed sales, derive substantially from the seasonality of castor growing in the locations where we produce seeds and in our target markets.

55

C.          Organizational Structure

As of the date of this report, we held directly and indirectly the percentage indicated of the outstanding capital stock of the following significant subsidiaries:


Name of Subsidiary
 
Jurisdiction
 
Ownership Interest
AgPlenus Ltd.
 
Israel
 
100%
Biomica Ltd.
 
Israel
 
90.9% (1)
Canonic Ltd.
 
Israel
 
100%
Casterra Ag Ltd. (formerly known as Evofuel Ltd.).
 
Israel
 
100%
Lavie Bio Ltd.
 
Israel
 
72.2% (2)


(1)
Remaining 9.1% of Biomica Ltd.’s outstanding share capital is held by Biomica's Chief Technology Officer.

(2)
Remaining 27.8% of Lavie Bio Ltd.’s outstanding share capital is held by Pioneer Hi-Bred International, Inc. (also known by the name Corteva).

D.          Property, Plants and Equipment

Our principal facility is located in Rehovot, Israel and consists of 3,209 square meters (approximately 34,500 square feet) of leased office space accommodating our corporate offices and our molecular, microbial and crop protection labs. The lease for these offices will expire on December 31, 2021, and we hold an option to renew such lease for an additional 36 months.

We perform most of our testing in plants, or in-planta testing, at our “Evogene Farm,” located on two adjacent lots that we lease outside Rehovot. The first lease covers approximately 13,500 square meters (or approximately 145,000 square feet) of land, and expires on July 21, 2025, and we hold an option to renew such lease for an additional 36 months. The second lease covers approximately 10,000 square meters (approximately 108,000 square feet) of land and expires on May 14, 2021, and we hold an option to renew such lease for an additional 60 months.

The Evogene Farm contains greenhouses, which are used for various in-planta experiments of the company and its subsidiaries. During 2019, we converted part of the Evogene Farm to a designated area for cannabis greenhouse as part of the activities of Canonic, our subsidiary which is focused on the area of medicinal cannabis. In addition, the Evogene Farm contains warehouses, office facilities and seed banks. During 2018 and 2019, we subleased a portion of the Evogene Farm to an agriculture-tech start-up company.

In 2015, we established a research and development facility in the Bio-Research and Development Growth (BRDG) Park, developed by Wexford Science & Technology, a BioMed Realty Company, at the campus of the Donald Danforth Plant Science Center in St. Louis, Missouri. We signed a six year lease, expiring November 1, 2021 and covering approximately 5,745 square feet lab facility. Starting March 2020, the facility accommodates the activities of Lavie Bio Inc., a wholly owned subsidiary of our subsidiary Lavie Bio. A portion of the leased space, comprising approximately 1,200 square feet of lab and office space, is subleased to a biotech company since December 2017, under a three-year sublease agreement.

Unless otherwise stated, all of our facilities are fully utilized. We have no material tangible fixed assets apart from the leased properties described above.

ITEM 4A.
UNRESOLVED STAFF COMMENTS

There are no unresolved staff comments.

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ITEM 5.
OPERATING AND FINANCIAL REVIEW AND PROSPECTS

The information contained in this section should be read in conjunction with our consolidated financial statements as of, and for the year ended, December 31, 2019 and related notes and the information contained elsewhere in this annual report. Our financial statements have been prepared in accordance with IFRS as issued by the IASB. This discussion contains forward-looking statements that are subject to known and unknown risks and uncertainties. As a result of many factors, such as those set forth under “Item 3. Key Information—D. Risk Factors” and “Special Note Regarding Forward-Looking Statements,” our actual results may differ materially from those anticipated in these forward-looking statements.

Summary

We are a leading biotechnology company aiming to revolutionize the development of novel products for life-science based industries, including human health, agriculture, and industrial applications, by utilizing cutting edge computational biology technologies. To achieve this mission, we established our unique Computational Predictive Biology, or CPB, platform, leveraging the revolutions in big data and artificial intelligence and incorporating a deep understanding of biology. Our CPB platform aims to disrupt conventional life-science product development methodology, currently challenged by inefficiencies, by computationally designing the most relevant core components for life-science products such as microbes, small molecules and genes.

Currently, we apply our technology and approach for the development of products based on microbes, small molecules and genes in three general industries:


(iv)
Agriculture, focusing on the following target markets:

a.
Agriculture biologicals, via our subsidiary Lavie Bio Ltd.,

b.
Agro chemicals, via our subsidiary AgPlenus Ltd., and

c.
Seed traits, via our Ag-Seeds division;


(v)
Human health, focusing on the following target markets:

a.
Human microbiome-based therapeutics, via our subsidiary Biomica Ltd., or Biomica, and

b.
Medical cannabis products, via our subsidiary Canonic Ltd.; and


(vi)
Life-science based industrial applications, currently focusing on castor seed varieties and agro-technical capabilities, through our subsidiary Casterra Ltd. (formerly Evofuel Ltd.), or Casterra.

Each subsidiary pursues its individual mission, focusing on the following objectives: (i) advancing its product development and pipeline, (ii) establishing its “go-to-market”, and (iii) securing additional financial resources, if and when required.

To capture the value of the diverse applicability of our computational platform, our business model consists of two main pathways, both based primarily on the utilization of the CPB Platform: (i) The establishment of market-focused subsidiaries to develop and commercialize product pipelines, meeting unmet needs in selected industries, and (ii) in certain other cases, engaging directly with strategic partners for the development of specific products.

Key Measures of Our Performance

Revenues

Our revenues are principally derived from research and development payments under our collaboration agreements and related arrangements with our collaborators. Most of our agreements with collaborators also provide for success-based payments, such as milestone payments paid by our collaborators upon the occurrence of certain specified events and royalty revenues based on the sales or transfer of products our collaborators develop that contain, or are based on, our discoveries, which we license to them. We have not yet generated revenues from royalty payments.

Share Purchases

We have entered into share purchase agreements with Monsanto (now Bayer) and Bayer, which were signed in contemplation of our collaboration agreements with them. We attribute the proceeds from arrangements under these agreements to the value of our ordinary shares issued to Monsanto and Bayer at the time of the investments as well as to the services we perform under the collaboration agreements. As a result, we recognized in 2018 and 2017 as revenues the excess payment, which is the consideration these investors paid for our ordinary shares over the market value of our ordinary shares traded on the TASE at the time of the investment. We did not record such revenues for the year ended December 31, 2019.

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Breakdown of Revenues by Operating Segment:

The following table presents a breakdown of net revenues by operating segment for the periods indicated.

   
Year ended December 31,
 
Operating Segment:
   2019      
2018
    2017  
   
(U.S. dollars, in thousands)
 
Agriculture
 
$
651
   
$
1,641
   
$
3,247
 
Industry
   
26
     
106
     
134
 
Human
   
-
     
-
     
-
 
Unallocated
   
76
     
-
     
-
 
Total
 
$
753
   
$
1,747
   
$
3,381
 

Geographical Breakdown of Net Revenues

The following table presents net revenues by geographic breakdown of customers as a percentage of our total net revenues for the periods indicated. This data refers to the location of the customer and does not take into consideration the location of the end-user (to the extent it is different).

   
Year ended December 31,
 
Geographical Region:
 
2019
   
2018
   
2017
 
United States
   
33
%
   
57
%
   
76
%
Germany
   
2
%
   
13
%
   
10
%
Israel
   
35
%
   
12
%
   
6
%
Brazil
   
28
%
   
6
%
   
-
 
Other
   
2
%
   
12
%
   
8
%
Total
   
100
%
   
100
%
   
100
%

Cost of Revenues

Cost of revenues primarily consists of development costs incurred in conjunction with our collaborations, which include: salaries and related personnel costs (including share-based compensation) for our research and development employees working on the collaborations; payments to third party suppliers that assist us in producing genomic data; and the cost of disposable materials (such as seeds, laboratory supplies, fertilizer, water and soil). Cost of revenues also includes operational overhead costs such as: depreciation of our property, plant and equipment; costs related to leasing and operating our office and laboratory facilities and greenhouses; and expenses related to retaining advisors, who primarily consist of biological experts.

Operating Expenses

Research and Development Expenses, net: Research and development expenses primarily consist of costs related to our internal or independent research and development activities, as opposed to development costs incurred in connection with our collaborations (which are included in cost of revenues). These independent activities of ours consist of developing and improving our computational, scientific and validation technologies, know-how and capabilities used by our subsidiaries and product divisions. Research and development costs include: salaries and related personnel costs (including share-based compensation); payments to third party suppliers, mainly with respect to producing genomic data, field-trials and pre-clinical studies carried out by third parties; cost of disposable materials; expenses associated with participation in professional conferences; operational overhead costs, which include costs related to leasing and operating our office, laboratory facilities and greenhouses; depreciation of property, plant and equipment; and amortization of intangible assets. Expenses related to our intellectual property, such as legal and other costs associated with patent applications, are also included as research and development expenses.

58

In view of the COVID-19 outbreak, which has disrupted our operations starting March 2020, we adjusted our work plans and budget, reducing and delaying certain activities originally planned for the second quarter and second half of 2020. Accordingly, we expect that our research and development expenses during 2020 will decrease from those of 2019.

Business Development Expenses: Business development expenses consist of costs primarily related to maintaining our relationships with our collaborators and establishing new collaborations. These costs include: salaries and related personnel costs (including share-based compensation); expenses incident to business travel; and expenses related to legal and professional services. We expect our business development expenses will remain at the current level during 2020.

General and Administrative Expenses: General and administrative expenses mainly consist of: salaries and related personnel costs (including share-based compensation) for our general and administrative employees; expenses related to HR activities and employee benefits and welfare; expenses for consulting, insurance, legal, Directors’ and officers’ insurance, and professional services; and other expenses associated with being a U.S. publicly listed company. We expect that our general and administrative expenses will remain at the current level during 2020.

Financing Income and Expenses

Financing income primarily consists of: interest income on our cash bank deposits and securities; income related to a revaluation of the marketable securities we hold, which consist of money market funds, corporate bonds and government treasury notes; and foreign currency exchange income. Financing expenses primarily consist of: expenses related to bank charges and commissions; expenses related to a revaluation of the marketable securities we hold; interest expense for our operating lease liability; and foreign currency exchange expense. The interest due on government grants is also considered a financial expense and is recognized beginning on the date on which we receive the grant until the date on which the grant is expected to be repaid.

Taxes on Income

We do not generate taxable income in Israel, as we have historically incurred operating losses resulting in carryforward tax losses totaling approximately $119 million as of December 31, 2019, to be carried forward indefinitely to future tax years. Accordingly, we do not expect to pay taxes in Israel for the foreseeable future, until we have taxable income after the full utilization of our carryforward tax losses.

Our U.S. subsidiary, Evogene Inc., is subject to U.S. income taxes. In 2019, the weighted tax rate applicable to Evogene Inc. was approximately 27.25% (federal tax and state tax where the company operates).

Segment Data

We divide our operations into three operating segments – Agriculture, Human Health and Industrial applications, as follows:


Agriculture: our agriculture segment includes our division and subsidiaries engaged in agricultural activities, including seed traits activity, ag-chemicals activity (now through our subsidiary AgPlenus) and ag-biologicals activity (now through our subsidiary Lavie Bio).


Human Health: our human health segment focuses on discovery and development of human microbiome-based therapeutics (through our subsidiary Biomica) and cannabis activity (through our subsidiary Canonic).


Industrial Applications: our industrial applications segment focuses on the development and commercialization of improved castor bean seeds for industrial uses (through our subsidiary Casterra).

The following table presents our revenues and operating loss by segment for the periods presented:

 
 
Agriculture
   
Industry
   
Human
   
Unallocated
   
Total
 
 
 
(in thousands)
 
Year ended December 31, 2019
                             
Revenues
 
$
651
   
$
26
   
$
   
$
76
   
$
753
 
Operating loss
   
(10,062
)
   
(419
)
   
(3,219
)
   
(7,466
)
   
(21,166
)
Year ended December 31, 2018
                                       
Revenues
 
$
1,641
   
$
106
   
$
   
$
0
   
$
1,747
 
Operating loss
   
(7,674
)
   
(456
)
   
(1,608
)
   
(10,251
)
   
(19,989
)
Year ended December 31, 2017
                                       
Revenues
   
3,247
     
134
     
     
3,381
     
3,381
 
Operating loss
   
(8,347
)
   
(344
)
   
(502
)
   
(12,754
)
   
(21,947
)

59

A.          Operating Results

Comparison of Period-to-Period Results of Operations

The following table sets forth our overall results of operations (on an unsegmented basis) for the years ended December 31, 2017, 2018 and 2019. The below discussion of our results of operations omits a comparison of our results for the years ended December 31, 2017 and 2018. In order to view that discussion, please see “Item 5. Operating and Financial Review and Prospects—A. Operating Results—Comparison of Period-to-Period Results of Operations” in our Annual Report on Form 20-F for the year ended December 31, 2018, which we filed with the SEC on April 29, 2019. 
   
2017
   
2018
   
2019
 

 
(U.S. dollars, in thousands)
 
Consolidated Statements of Comprehensive loss:
                 
Total Revenues
 
$
3,381
   
$
1,747
   
$
753
 
Cost of revenues          
   
2,845
     
1,452
     
334
 
Gross profit          
   
536
     
295
     
419
 
Operating Expenses:
                       
Research and development, net          
   
16,987
     
14,686
     
15,791
 
Business development          
   
1,686
     
2,084
     
2,029
 
General and administrative          
   
3,810
     
3,514
     
3,765
 
Total operating expenses          
   
22,483
     
20,284
     
21,585
 
Operating loss          
   
(21,947
)
   
(19,989
)
   
(21,166
)
Financing income
   
2,125
     
1,413
     
2,630
 
Financing expenses          
   
(1,005
)
   
(2,206
)
   
(555
)
Loss before taxes on income
   
(20,827
)
   
(20,782
)
   
(19,091
)
Taxes on income
   
11
     
30
     
24
 
Loss          
 
$
(20,838
)
 
$
(20,812
)
 
$
(19,115
)

Year Ended December 31, 2019 Compared to Year Ended December 31, 2018

Revenues

Our total revenues decreased by $0.9 million, or 56.9%, to $0.8 million for the year ended December 31, 2019 from $1.7 million for the year ended December 31, 2018. This decline was mainly due the completion of our gene discovery and optimization activities under our collaboration agreement with Monsanto (from which we had recognized revenues).

Cost of Revenues

Cost of revenues decreased by $1.1 million, or 77.0%, to $0.3 million for the year ended December 31, 2019 from $1.4 million for the year ended December 31, 2018. The decrease primarily related to the decrease in revenues from R&D cost reimbursement, due to the completion of our gene discovery and optimization activities under our collaboration agreement with Monsanto.

Gross Profit

Gross profit increased by $0.1 million, or 42.0%, to $0.4 million for the year ended December 31, 2019 from $0.3 million for the year ended December 31, 2018, due to the combined impact of changes in our revenues and cost of revenues, as described above.

60

Operating Expenses

Research and Development Expenses, Net. Research and development expenses increased by $1.1 million, or 7.5%, to $15.8 million for the year ended December 31, 2019 from $14.7 million for the year ended December 31, 2018. This increase in R&D expenses during 2019 was attributable to (a) payments made to third parties for (i) pre-clinical studies conducted for Biomica, (ii) field trials conducted in target locations for Lavie Bio and (iii) the acquisition of a genomic-unique seed collection for Canonic, as well as (b) amortization of intangible assets.

Business Development Expenses. Business development expenses decreased by $0.1 million, or 2.6%, to $2.0 million for the year ended December 31, 2019 from $2.1 million for the year ended December 31, 2018, constituting a non-material decrease.

General and Administrative Expenses. General and administrative expenses increased by $0.3 million, or 7.1%, to $3.8 million for the year ended December 31, 2019 from $3.5 million for the year ended December 31, 2018, constituting an insignificant increase.

Financing Income and Expenses

Financing Income. Financing income increased by $1.2 million, or 86.1%, to $2.6 million for the year ended December 31, 2019 from $1.4 million for the year ended December 31, 2018. This increase was mainly due to exchange rate differences between the U.S. dollar and the New Israeli Shekel during the two years.

Financing Expenses. Financing expenses decreased by $1.6 million, or 74.8%, to $0.6 million for the year ended December 31, 2019 from $2.2 million for the year ended December 31, 2018. This decrease was mainly due to profit from marketable securities in 2019 as compared to loss from marketable securities in 2018.

Taxes on Income

For the year ended December 31, 2019, we recorded insignificant amounts for taxes on income in Israel due to advances on excess expenses and an insignificant amount of taxes with respect to Evogene Inc. We did not record or pay taxes on income for the year ended December 31, 2018 in Israel due to our loss for the year. We recorded an insignificant amount of taxes with respect to Evogene Inc.

Loss

The amount of our overall loss decreased by 8.2% to $19.1 million for the year ended December 31, 2019, from $20.8 million for the year ended December 31, 2018. That decrease reflected the cumulative effect of all of the above-described line items from our consolidated statements of comprehensive loss.

Application of Critical Accounting Policies and Estimates

Our accounting policies affecting our financial condition and results of operations are more fully described in our consolidated financial statements included elsewhere in this annual report. The preparation of our financial statements requires management to make judgments, estimates and assumptions that affect the amounts reflected in the consolidated financial statements and accompanying notes, and related disclosure of contingent assets and liabilities. We base our estimates upon various factors, including past experience, where applicable, external sources and on other assumptions that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions, and could have a material adverse effect on our reported results.

In many cases, the accounting treatment of a particular transaction, event or activity is specifically dictated by accounting principles and does not require management’s judgment in its application, while in other cases, management’s judgment is required in the selection of the most appropriate alternative among the available accounting principles, that allow different accounting treatment for similar transactions.

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We believe that the accounting policies discussed below are critical to our financial results and to the understanding of our past and future performance as these policies relate to the more significant areas involving management’s estimates and assumptions. We consider an accounting estimate to be critical if: (1) it requires us to make assumptions because information was not available at the time or it included matters that were highly uncertain at the time we were making our estimate; and (2) changes in the estimate or different estimates that we could have selected may have had a material impact on our financial condition or results of operations.

Revenue Recognition

We recognize revenues when the control over the goods or services is transferred to the customer. The transaction price is the amount of the consideration that is expected to be received based on the contract terms, excluding amounts collected on behalf of third parties (such as taxes).

We have entered into collaboration agreements under which we grant to our collaborators an exclusive license to intellectual property rights for the development and commercialization of our proprietary product candidates. The agreements contain multiple performance obligations, including funding from periodic payments for research and development services, payments based on achievement of specified milestones and royalties on sales of products sold by our collaborators that include the licensed traits.

Revenues from research and development services as part of the Company's collaboration agreements are recognized over time, during the period the customer simultaneously receives and consumes the benefits provided by the Company's performance. Recognition of the service is throughout the services period and is determined based on the proportion of actual costs incurred for each reporting period to the estimated total costs, subject to the enforceable rights. The Company charges its customers based on payment terms agreed upon in specific agreements. When payments are made before or after the service is performed, the Company recognizes the resulting contract asset or liability.
 
Revenues from milestone events stipulated in the agreements are recognized upon the occurrence of event or achievement of the milestone specified in the agreement.

Share-Based Compensation

We account for share-based compensation in accordance with the fair value recognition provision of IFRS guidance on share-based compensation. Under these provisions, share-based compensation is measured at the grant date based on the fair value of the award and is recognized as an expense, net of estimated forfeitures, over the requisite service period, which is generally the vesting period of the respective award. Share-based compensation expense was $1.6 million, $1.7 million and $2.2 million in 2019, 2018 and 2017, respectively. We selected the binomial option-pricing model as the most appropriate method for determining the estimated fair value of our share-based compensation. The determination of the grant date fair value of options using an option-pricing model is affected by estimates and assumptions regarding a number of complex and subjective variables. These variables include the estimated period of time that we expect employees to hold their options, the expected volatility of our share price over the expected term of the options (estimated using historical data from prior years, including historical forfeiture rates), share option exercise and cancellation behaviors, risk-free interest rates, expected dividend yields (assumed to be zero as we have historically not paid and do not intend to pay dividends on our ordinary shares) and the price of our ordinary shares. In addition, our compensation expense is affected by our estimate of the number of awards that will ultimately vest. In the future, if the number of equity awards that are forfeited by employees is lower than expected, the expense recognized in future periods will be higher.

Government Grants

Government grants received from the IIA, BIRD and Canada-Israel Industrial Research and Development Foundation, or CIIRDF, are recognized as a liability if future economic benefits are expected from the projects that will result in royalty-bearing sales.

A liability for the grant is first measured at fair value using a discount rate that reflects a market rate of interest. The difference between the amount of the grant received and the fair value of the liability is accounted for as a government grant and recognized as a reduction of research and development expenses. After initial recognition, the liability is measured at amortized cost using the effective interest method. Royalty payments we make to repay the grant are treated as a reduction of the liability. If no economic benefits are expected from the research activity, the grant receipts are recognized as a reduction of research and development expenses, in which case, the royalty obligation is treated as a contingent liability.

62

There is uncertainty regarding the estimates of future cash flows and the estimate of the capitalization rate that is used for determining the amount of the liability recognized. At the end of each reporting period, we evaluate whether there is reasonable assurance that the liability recognized, in whole or in part, will not be repaid (since we will not be required to pay royalties) based on the best estimate of future sales, and if so, the appropriate amount of the liability is recognized as a reduction of research and development expenses.

Leases
 
We cannot readily determine the interest rate implicit in our operating lease for our principal facility in Rehovot, Israel.  We therefore, it use our incremental borrowing rate, IBR, to measure lease liabilities. The IBR is the rate of interest that we would have to pay to borrow over a similar term, and with a similar security, the funds necessary to obtain an asset of a similar value to the right-of-use asset in a similar economic environment. The IBR therefore reflects what we ‘would have to pay’, which requires estimation when no observable rates are available or when they need to be adjusted to reflect the terms and conditions of the lease.
 
We estimate the IBR using observable inputs (such as market interest rates) when available and we are required to make certain entity-specific estimates (such as the Company's stand-alone credit rating).

Intangible assets

On August 6, 2019, Corteva Inc. invested in the Company's agriculture biologicals subsidiary, Lavie Bio, by way of a contribution of all Corteva’s holdings in its wholly owned subsidiary Taxon Biosciences, which included several intangible assets, and payment of an amount of $10 million in cash.

The fair value of intangible assets received through the Corteva investment is determined upon initial recognition by either one of three traditional methods in valuating an asset. These methods include the market approach, the income approach and the cost approach. The pipeline products and potential products were valued by applying the income approach and the Microorganisms collection was valued using the cost approach.

The Company’s significant estimates in this analysis included, but were not limited to, future cash flow projections, the weighted average cost of capital, the terminal growth rate, and the tax rate. The Company believes the current assumptions and estimates utilized were both reasonable and appropriate.  Future cash flow estimates are, by their nature, subjective and actual results may differ materially from the Company’s estimates.  If the Company’s ongoing estimates of future cash flows are not met, the Company may have to record impairment charges in future periods.  The Company’s estimates of future cash flows are based on current regulatory and economic climates, recent operating results, and planned business strategy.  These estimates could be negatively affected by changes in federal, state, or local regulations or economic downturns.

The useful economic life of the intangible assets acquired by us in this transaction was determined through years of development until final year of projected sales. When applying the income approach, the cash flows expected to be granted by intangible assets are discounted to their present value equivalent using a rate of return that reflects the relative risk of the investment, as well as the time value of money. For each intangible asset a specific discount rate was valuated using “Modified CAPM Build-Up Method”.

Impact of Israeli Tax Policies and Government Programs on our Operating Results

Tax regulations have a material impact on our business, particularly in Israel where we have our headquarters. The following summary describes the current tax structure applicable to companies in Israel, with special reference to its effect on us.

General Corporate Tax Structure in Israel

Israeli companies are generally subject to corporate tax on their taxable income. In 2018 and 2019, the corporate tax rate was 23%. Capital gains derived by an Israeli company are generally subject to tax at the prevailing regular corporate tax rate.

63

Law for the Encouragement of Industry (Taxes), 5729-1969

The Law for the Encouragement of Industry (Taxes), 5729-1969, generally referred to as the Industry Encouragement Law, provides several tax benefits for an “Industrial Company”.

The Industry Encouragement Law defines an “Industrial Company” as an Israeli resident company which was incorporated in Israel, of which 90% or more of its income in any tax year, other than income from certain government loans, is derived from an “Industrial Enterprise” owned by it and located in Israel. An “Industrial Enterprise” is defined as an enterprise that is held by an Industrial Company whose principal activity in a given tax year is industrial production.

The following tax benefits, among others, are available to Industrial Companies:


amortization over an eight-year period of the cost of purchased know-how and patents and rights to use a patent and know-how which are used for the development or advancement of the Industrial Enterprise, commencing in the year in which such rights were first exercised;


under limited conditions, an election to file consolidated tax returns together with Israeli Industrial Companies controlled by it; and


expenses related to a public offering are deductible in equal amounts over a three-year period, commencing in the year of the offering.

Eligibility for benefits under the Industry Encouragement Law is not contingent upon the approval of any governmental authority. We believe that we currently qualify as an Industrial Company within the meaning of the Industry Encouragement Law. There can be no assurance that we will continue to qualify as an Industrial Company or that the benefits described above will be available in the future.

Law for the Encouragement of Capital Investments, 5719-1959

The Law for the Encouragement of Capital Investments, 5719-1959, generally referred to as the Investment Law, provides certain incentives for capital investments in production facilities (or other eligible assets) by “Industrial Enterprises” (as defined under the Investment Law).

The Investment Law was significantly amended effective April 1, 2005 (which we refer to as the 2005 Amendment), further amended as of January 1, 2011 (which we refer to as the 2011 Amendment) and further amended as of January 1, 2017 (which we refer to as the 2017 Amendment). Pursuant to the 2005 Amendment, tax benefits granted in accordance with the provisions of the Investment Law prior to its revision by the 2005 Amendment remain in force but any benefits granted subsequently are subject to the provisions of the 2005 Amendment. Similarly, the 2011 Amendment introduced new benefits to replace those granted in accordance with the provisions of the Investment Law in effect prior to the 2011 Amendment. However, companies entitled to benefits under the Investment Law as in effect prior to January 1, 2011 were entitled to choose to continue to enjoy such benefits, provided that certain conditions are met, or elect instead irrevocably to forego such benefits and have the benefits of the 2011 Amendment apply. The 2017 Amendment introduced new benefits for Technological Enterprises, alongside the existing tax benefits.

On October 24, 2010, we received a tax ruling from the Israel Tax Authority, according to which, among other things, our activity has been qualified as an “industrial activity”, as defined in the Investment Law and is also eligible to tax benefits as a Beneficiary Enterprise, which will apply to the turnover attributed to such enterprise. The benefit period under this tax ruling ended in 2018, and since we did not generate any taxable income in tax year 2018, we were not entitled to any tax benefits under this tax regime.

In addition, we have reviewed and evaluated the implications and effect of the benefits under the 2011 and 2017 Amendments, and, while potentially eligible for such benefits, we have not yet chosen to be subject to the tax benefits introduced by the 2011 or the 2017 Amendments.

B.          Liquidity and Capital Resources

Our working capital requirements generally reflect the growth in our business and have historically been provided by cash raised from our investors, payments from our collaborators and government grants. As of December 31, 2019, we had cash, marketable securities and short term bank deposits of $46.9 million, of which $10 million were contributed in the transaction with Corteva, and working capital of $43.3 million, which is calculated by subtracting our current liabilities from our current assets. As of December 31, 2019, we had $3.3 million of outstanding long-term indebtedness related to government grants.

64

We expect that our working capital and capital investment needs will be funded for the foreseeable future mainly by our cash and cash equivalents, marketable securities and bank deposits we hold as well as from payments from our collaborators. Currently, our principal uses of cash are to fund our operations. In the future, cash may serve us in effecting M&A transactions for achieving inorganic growth in our different segments of operation. We believe that our existing cash and cash equivalents, marketable securities and short-term bank deposits as of December 31, 2019 will be sufficient to meet our projected cash requirements for at least 12 months.

To the extent that existing cash, and cash equivalents, marketable securities and short-term bank deposits are insufficient to fund our future activities, we may need to raise additional funding through debt and equity financing. Additional funds may not be available when we need them on terms that are acceptable to us, or at all. The negative impact of the ongoing Coronavirus outbreak on economies and financial markets worldwide may adversely impact on our ability to raise additional funds for our operations, if and when needed.

If adequate funds are not available to us on a timely basis, we may be required to delay, limit, scale back or cease our research and development activities, establishment and maintenance of sales and marketing capabilities or other activities that may be necessary to commercialize our product candidates.

Cash Flows

The following table presents the major components of net cash flows used in or provided by (as applicable) operating, investing and financing activities for the periods presented. For a discussion of our net cash flows for the year ended December 31, 2017, please see “Item 5. Operating and Financial Review and Prospects— B. Liquidity and Capital Resources— Cash Flows” in our Annual Report on Form 20-F for the year ended December 31, 2018, which we filed with the SEC on April 29, 2019:

   
2017
   
2018
   
2019
 
   
(U.S. dollars, in thousands)
 
Net cash used in operating activities
 
$
(15,929
)
 
$
(15,161
)
 
$
(17,666
)
Net cash provided by investing activities
   
15,245
     
17,353
     
37,139
 
Net cash provided by financing activities
   
814
     
297
     
9,306
 
Exchange rate differences - cash and cash equivalents
   
69
     
(114
)
   
159
 
Net increase (decrease) in cash and cash equivalents
 
$
199
   
$
2,375
   
$
28,938
 

Cash Used in Operating Activities

Cash used in operating activities for the year ended December 31, 2019 was $17.7 million and primarily reflects our overall loss of $19.1 million, as reduced, in part, by the elimination of certain non-cash items that were taken into account in calculating, and that increased, our overall loss, including $2.4 million of depreciation expenses, $1.6 million of share-based compensation expenses, increase in other payables of $0.4, and $0.4 million of expense due to the amortization of intangible assets; which reduction was partially offset by the elimination non-cash items that were taken into account in calculating, and that reduced, that loss amount, including the increase in other receivables of $1.3 million and net financing income of $2.4 million.

Cash used in operating activities for the year ended December 31, 2018 was $15.1 million and primarily reflects our overall loss of $20.8 million, as reduced, in part, by the elimination of certain non-cash items that were taken into account in calculating, and that increased, our overall loss, including $1.7 million of share-based compensation expenses, $2.0 million of depreciation expenses and $0.7 million of net financing expenses, as well as by $1.4 million interest received; which reduction was partially offset by the elimination of non-cash items that were taken into account in calculating, and that reduced, that loss amount, including a decrease of $0.2 million in deferred revenues and other advances.
 
65

Cash Provided by Investing Activities

Cash provided by investing activities was $37.1 million for the year ended December 31, 2019. That primarily reflects $25.4 million of net cash proceeds from the sale of marketable securities and $12.6 million of cash withdrawn from bank deposits, partially offset by $0.9 million of cash used for the purchase of property, plant and equipment.

Cash provided by investing activities was $17.4 million for the year ended December 31, 2018. That primarily reflects $31.9 million of net cash proceeds from the sale of marketable securities, partially offset by $14.2 million of cash invested in bank deposits and $0.4 million of cash used for the purchase of property, plant and equipment.

Cash Provided by Financing Activities

Cash provided by financing activities was $9.3 million for the year ended December 31, 2019. That was primarily attributable to $10 million of cash provided by the issuance and sale of ordinary shares of subsidiaries to third parties, offset, in part, by the use of $0.1 million for net repayments in respect of government grants and $0.6 million for the repayment of an operating lease liability.

Cash provided by financing activities was $0.3 million for the year ended December 31, 2018, which was primarily attributable to net proceeds from government grants.

Government Grants

Our research and development efforts have been financed, in part, through grants from IIA, BIRD, CIIRDF and the EU. From our inception through 2019, we received grants totaling $7.4 million (including accrued interest) from the IIA, and repaid $3.4 million, in respect of refundable projects. We also received an additional $1.85 million from the IIA in respect of a non-refundable project. We have received grants totaling approximately $1 million (linked to the U.S. Consumer Price Index) from BIRD and have repaid $0.6 million, whereas the remaining $0.4 million of grants from BIRD have been cancelled, as we decided to withdraw from the relevant project, as detailed in Note 12 to the financial statements included in this annual report under Item 18. We have received grants totaling $0.8 million from the EU, which are not required to be repaid. As of December 31, 2019, we had four active research grants under which we have received funding: three from the IIA and one from the EU.

See “Item 3. Key Information—D. Risk Factors—Risks Relating to Our Incorporation and Location in Israel—We have received Israeli government grants for certain of our research and development activities. The terms of these grants may require us to satisfy specified conditions in order to manufacture products and transfer technologies supported by such grants outside of Israel. We may be required to pay penalties in addition to repayment of the grants.”

IIA Grants

Under the Innovation Law, research and development programs that meet specified criteria and are approved by a committee of the IIA are eligible for grants. The grants awarded are typically up to 50% of a project’s expenditures, as determined by the IIA committee and subject to the benefit track under which the grant was awarded. A company that receives a grant from the IIA is typically required to pay 3% royalties to the IIA on income generated from products incorporating know-how developed using that grant (including income derived from services associated with such products), until 100% of the U.S. dollar-linked grant, plus interest at the annual London Interbank Offered Rate, or LIBOR, is repaid. Certain benefit tracks do not require payment of royalties.

The obligation to pay royalties is contingent on actual income generated from such products and services. In the absence of such income, no payment of royalties is required. It should be noted that the restrictions under the Innovation Law, including restrictions on the sale, transfer or assignment outside of Israel of know-how developed as part of the programs under which the grants were given will continue to apply even after the repayment of such royalties in full.

The terms of the grants under the Innovation Law also require that the products developed as part of the programs under which the grants were given be manufactured in Israel and that the know-how developed thereunder may not be transferred outside of Israel, unless prior written approval is received from the IIA (such approval is not required for the transfer of a portion of the manufacturing capacity which does not exceed, in the aggregate, 10% of the manufacturing (in which case only notification is required)), and additional payments are required to be made to the IIA, as described below. It should be noted that this does not restrict the export of products that incorporate the funded know-how.

Ordinarily, as a condition to obtaining approval to manufacture outside Israel, we may be required to pay royalties at an increased rate, and up to an increased cap amount of up to three or six times the total amount of the relevant IIA grant, plus interest accrued thereon, depending on the manufacturing volume to be performed outside of Israel.

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The Innovation Law restricts the ability to transfer know-how funded by the IIA. Transfer of IIA-funded know-how outside of Israel requires prior approval and is subject to payment of a redemption fee to the IIA calculated according to a formula provided under the Innovation Law. A transfer for the purpose of the Innovation Law is generally interpreted very broadly and includes, inter alia, any actual sale of the IIA-funded know-how, any license to develop the IIA-funded know-how or the products resulting from such IIA-funded know-how or any other transaction, which, in essence, constitutes a transfer of the IIA-funded know-how.

 The IIA approval to transfer know-how created, in whole or in part, in connection with an IIA-funded project to a third party outside Israel is subject to payment of a redemption fee to the IIA calculated according to a formula provided under the Innovation Law that is based, in general, on the value of the transferred know-how, multiplied by the amount of grants received from the IIA (including the accrued interest), divided by the total amounts expended by the grant recipient on R&D. To the extent any royalties were paid on account of the grants, such royalties will be deducted from the calculation. The redemption fee is subject to a cap of six times the total amount of the IIA grants, plus interest accrued thereon, namely the total liability to the IIA, including the accrued interest, multiplied by six. If the grant recipient undertakes that for a period of not less than three years, at least 75% of its relevant R&D positions will remain in Israel, then the cap will be reduced to three times (rather than six times) the total liability to the IIA, calculated as set out above.

Subject to prior approval of the IIA, we may transfer the IIA-funded know-how to another Israeli company. If the IIA-funded know-how is transferred to another Israeli entity, the transfer would still require IIA approval but will not be subject to the payment of the redemption fee (although there will be an obligation to pay royalties to the IIA from the income of such sale transaction as part of the royalty payment obligation). In such case, the acquiring company would have to assume all of the selling company’s restrictions and obligations towards the IIA (including the restrictions on the transfer of know-how and manufacturing capacity outside of Israel) as a condition to IIA approval.

We are required to pay up to 100% of the amount of grants received by us from the IIA, plus interest at the LIBOR. In addition to paying any royalty due, we must abide by other restrictions associated with receiving such grants under the Innovation Law. Those restrictions may impair our ability to outsource development of products containing our traits, engage in change of control transactions or otherwise transfer our know-how outside of Israel and may require us to obtain the approval from the IIA for certain actions and transactions and pay additional royalties and other amounts to the IIA. We cannot be certain that any approval of the IIA will be obtained on terms that are acceptable to us, or at all. We may not receive the required approvals should we wish to transfer IIA-funded know-how, manufacturing and/or development outside of Israel in the future. Furthermore, in the event that we undertake a transaction involving the transfer to a non-Israeli entity of know-how developed with IIA-funding pursuant to a merger or similar transaction, the consideration available to our shareholders may be reduced by the amounts we are required to pay to IIA. Any approval, if given, will generally be subject to additional financial obligations. Failure to comply with the requirements under the Innovation Law may subject us to mandatory repayment of grants received by us (together with interest and penalties), as well as expose us to criminal proceedings. In addition, the IIA may from time to time conduct royalties audits and such audits may lead to additional royalties being payable on additional products. Such grants may be terminated or reduced in the future, which would increase our costs. IIA approval is not required for the marketing of products resulting from the IIA-funded research or development in the ordinary course of business.

In January 2018, we announced participation in a three-year IIA-sponsored Phenomics Consortium to develop tools and systems for precision agriculture and innovative development of agriculture products. In addition to Evogene, the Phenomics Consortium consists of several Israeli industrial companies and academic institutions. The goal of the consortium is to develop plant phenotyping technologies, including the generation of comprehensive agricultural ‘Big-Data’ and the development of artificial intelligence algorithms for real time analysis of phenotypic data. The grant for the consortium was originally approved for calendar year 2018 in an amount of approximately $5 million, of which approximately $1.4 million was granted to Evogene. By the end of 2018, the grant was extended by an additional six months to a total period of 18 months until mid-2019, and the grant amount was updated to approximately $7.6 million total, of which approximately $2.1 million was granted to Evogene. In June 2019, the IIA approved the continuation of the consortium following such 18-month period, until the end of 2020, which would complete a three-year workplan, and granted an additional amount of approximately $7.5 million, of which approximately $1.8 million was granted to Evogene.

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BIRD Grants

We have received two BIRD grants, covering the following programs: (i) a joint development program with DuPont-Pioneer (now Corteva) of research and development improvements to soybean rust resistance; and (ii) a joint research and development program with Marrone Bio Innovations, or MBI, for discovery of novel modes of biological action for insect control.

Under these two BIRD programs, the grant for the joint development will be repaid: (a) from revenues received for the licensing of products developed under the project; (b) from revenues generated from sales of products developed under the project; (c) from proceeds received from the outright sale of the technology developed under the project; (d) if we and our partner have concluded the development of a product within the period of development defined under each of the programs; or (e) if within 66 months from the original grant date, in the case of our program with DuPont, or 60 months, in the case of our program with MBI, we and our partner to the development program did not conclude the development of a product but nevertheless decide to continue the project. In each such case, the repayment will be in an amount of up to 150% of the total grant received, depending on the timing of the repayment.

As alluded to in this section above and as described in Note 12 to our financial statements that appear in Item 18 of this annual report, the grant received for the joint development program with DuPont-Pioneer (now Corteva) has been repaid in full, whereas our liability for grants received for our joint research and development program with MBI has been cancelled.