Part I [Business](index=4&type=section&id=Item%201.%20Business) Protalix BioTherapeutics develops and commercializes recombinant therapeutic proteins using its proprietary ProCellEx® plant cell-based system, with Elelyso® marketed and PRX-102 under FDA Priority Review [Our ProCellEx Platform](index=6&type=section&id=Our%20ProCellEx%20Platform) ProCellEx is a proprietary plant cell-based protein expression system, FDA-approved for Elelyso®, offering scalable manufacturing and no viral contamination risk - ProCellEx is a proprietary platform for manufacturing recombinant proteins using plant cell-based expression in suspension, which avoids the use of mammalian components and the associated risk of viral contamination[17](index=17&type=chunk)[18](index=18&type=chunk) - The system utilizes genetically engineered plant cells, such as carrot and tobacco, grown in custom-designed, sterile, disposable polyethylene bioreactors, allowing for rapid and low-cost horizontal scale-up[21](index=21&type=chunk)[22](index=22&type=chunk) [Our Marketed Product and Clinical Pipeline](index=8&type=section&id=Our%20Marketed%20Product%20and%20Clinical%20Pipeline) The company's portfolio includes Elelyso® for Gaucher disease and a clinical pipeline led by PRX-102 for Fabry disease, currently under FDA Priority Review Product Pipeline Status | Product Candidate | Indication | Development Stage | | :--- | :--- | :--- | | **Elelyso®** | Gaucher Disease | Marketed | | **pegunigalsidase alfa (PRX-102)** | Fabry Disease | BLA Submitted (FDA Priority Review) | | **alidornase alfa (PRX-110)** | Respiratory Diseases | Phase IIa completed; Licensed to SarcoMed | | **uricase (PRX-115)** | Refractory Gout | Preclinical | | **Long Acting DNase (PRX-119)** | NETs Related Diseases | Preclinical | - Elelyso® is approved and marketed in 23 countries for Gaucher disease. Sales in Brazil, marketed as BioManguinhos alfataliglicerase, generated **$8.0 million in 2020**[23](index=23&type=chunk)[47](index=47&type=chunk) - The FDA accepted the Biologics License Application (BLA) for PRX-102 for Fabry disease, granting it **Priority Review** with a PDUFA action date of **April 27, 2021**. However, FDA inspections of manufacturing facilities may be delayed due to COVID-19 travel restrictions[24](index=24&type=chunk)[38](index=38&type=chunk)[54](index=54&type=chunk) - The company entered an exclusive worldwide license agreement with SarcoMed for alidornase alfa (PRX-110) for use in human respiratory diseases, including sarcoidosis and pulmonary fibrosis[29](index=29&type=chunk)[34](index=34&type=chunk) [Intellectual Property](index=26&type=section&id=Intellectual%20Property) The company holds over 90 global patents and 35 pending applications protecting its ProCellEx technology and products, serving as collateral for 2021 convertible notes - The company holds a global portfolio of over **90 patents** and has more than **35 pending patent applications** to protect its technology, products, and methods of use[97](index=97&type=chunk) - In **2020**, the company secured new patents in Europe for its "Large Scale Disposable Bioreactor" and in Israel and the U.S. for "Stabilized Alpha-Galactosidase and Uses Thereof" (related to PRX-102)[98](index=98&type=chunk) - The company's material assets, primarily its intellectual property, are pledged as collateral to secure its outstanding **7.50% convertible promissory notes due in 2021**[101](index=101&type=chunk) [Agreements and Partnerships](index=32&type=section&id=Agreements%20and%20Partnerships) Protalix maintains strategic partnerships with Pfizer for Elelyso® and Chiesi for PRX-102, involving significant upfront payments, potential milestones, and royalties - Pfizer holds the exclusive global rights to Elelyso (excluding Brazil) under an amended agreement where Pfizer covers **100% of costs** and retains **100% of revenue**, while Protalix serves as the drug substance manufacturer for a **10-year period**[116](index=116&type=chunk)[117](index=117&type=chunk) - The company has two exclusive global agreements with Chiesi for PRX-102, covering ex-U.S. and U.S. markets. These agreements include **$50 million in upfront payments**, up to **$45 million in development cost reimbursements**, over **$1.0 billion in potential milestones**, and tiered royalties ranging from **15% to 40%**[120](index=120&type=chunk)[121](index=121&type=chunk)[122](index=122&type=chunk) - The company commercializes Elelyso in Brazil as BioManguinhos alfataliglicerase through an agreement with Fiocruz. However, Fiocruz has not met certain purchase commitments, and discussions are ongoing to address this[118](index=118&type=chunk)[119](index=119&type=chunk) [Manufacturing and Government Regulations](index=36&type=section&id=Manufacturing%20and%20Government%20Regulations) The company operates an FDA-approved cGMP manufacturing facility in Israel and is subject to extensive global regulations, benefiting from Israeli government tax and R&D programs - The manufacturing facility in Carmiel, Israel, is **FDA-approved** as a multi-product facility and has sufficient capacity for current and expected commercial and clinical needs, including the anticipated launch of PRX-102[123](index=123&type=chunk)[124](index=124&type=chunk) - The company is subject to extensive regulation by the FDA and other global authorities, covering preclinical studies, clinical trials (Phase I-III), manufacturing (cGMP), and post-approval requirements[129](index=129&type=chunk)[132](index=132&type=chunk)[135](index=135&type=chunk) - The company's Israeli facility has "Approved Enterprise" status, making it eligible for a **10-year tax exemption period** once it generates taxable income. It also receives R&D grants from NATI, which require royalty payments on future sales of funded products[126](index=126&type=chunk)[182](index=182&type=chunk)[192](index=192&type=chunk) [Risk Factors](index=61&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks including PRX-102 approval delays, clinical and regulatory uncertainties, dependence on key products and partners, financial instability, and geopolitical risks in Israel - A key risk is the potential delay or failure to obtain FDA approval for PRX-102 by the **April 27, 2021 PDUFA date**, as COVID-19 travel restrictions may prevent the FDA from conducting required pre-license inspections of manufacturing facilities[213](index=213&type=chunk) - The company's financial stability is at risk due to its history of net losses, significant indebtedness from **$57.9 million in convertible notes due 2021**, and the need to raise additional capital to fund operations and clinical trials[278](index=278&type=chunk)[285](index=285&type=chunk) - Heavy reliance on the commercial success of PRX-102 and the performance of collaboration partners like Chiesi and Pfizer creates significant business risk. Failure in these areas would materially harm the company's financial condition[238](index=238&type=chunk)[243](index=243&type=chunk) - Operations are concentrated in Israel, exposing the company to risks from political, economic, and military instability, as well as restrictions tied to Israeli government R&D grants that limit the transfer of technology and manufacturing outside of Israel[327](index=327&type=chunk)[334](index=334&type=chunk) [Properties](index=110&type=section&id=Item%202.%20Properties) The company's primary operations, including manufacturing and R&D, are in a leased Carmiel, Israel facility, with a corporate office in Hackensack, New Jersey - The main facility in Carmiel, Israel, houses manufacturing, R&D labs, and offices, totaling approximately **58,900 sq/ft** of utilized space, with an additional **14,500 sq/ft** available for future expansion[357](index=357&type=chunk) [Legal Proceedings](index=110&type=section&id=Item%203.%20Legal%20Proceedings) The company is not currently involved in any material legal proceedings - As of the report date, the company is not a party to any material legal proceedings[358](index=358&type=chunk) Part II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=111&type=section&id=Item%205.%20Market%20for%20Registrant%27s%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock trades on NYSE American and TASE, with details on equity compensation plan securities and outstanding options Equity Compensation Plan Information (as of Dec 31, 2020) | Plan Category | Securities to be Issued Upon Exercise of Outstanding Options | Weighted Average Exercise Price of Outstanding Options | Securities Remaining Available for Future Issuance | | :--- | :--- | :--- | :--- | | Approved by Stockholders | 2,551,650 | $5.30 | 1,493,626 | [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=112&type=section&id=Item%207.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Total revenues increased to $62.9 million in 2020, net loss narrowed to $6.5 million, and recent financing activities strengthened liquidity for future operations and debt repayment Financial Performance Summary (Years ended Dec 31) | Metric (in millions) | 2020 | 2019 | Change | | :--- | :--- | :--- | :--- | | Total Revenue | $62.9 | $54.7 | +15.0% | | - Revenues from Selling Goods | $16.2 | $15.9 | +1.9% | | - Revenues from License and R&D | $46.7 | $38.8 | +20.4% | | R&D Expenses, Net | $38.2 | $44.6 | -14.3% | | Net Loss | $(6.5) | $(18.3) | +64.5% improvement | - The increase in **2020 revenue** was primarily due to a **$7.9 million** rise in license and R&D service revenue from the Chiesi agreements, reflecting an updated cost estimation for completing clinical trials[411](index=411&type=chunk) - R&D expenses decreased by **$6.4 million** in 2020 compared to 2019, mainly because two of the three Phase III trials for PRX-102 were completed and costs for the ongoing BALANCE study were reduced[413](index=413&type=chunk) - As of December 31, 2020, the company had **$38.5 million** in cash and short-term deposits. Subsequent financing activities in early 2021, including a public offering and ATM sales, raised gross proceeds of approximately **$49.0 million**[418](index=418&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=127&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is currency exchange rate fluctuations, as 43% of costs are in NIS while its functional currency is USD - The company's main market risk is currency fluctuation, as approximately **43% of its costs** are in New Israeli Shekels (NIS) while its functional currency is the U.S. dollar[429](index=429&type=chunk)[432](index=432&type=chunk) [Financial Statements and Supplementary Data](index=129&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section presents audited consolidated financial statements and the independent auditor's report, highlighting revenue recognition for Chiesi agreements as a critical audit matter Consolidated Balance Sheet Data (as of Dec 31) | Metric (in thousands) | 2020 | 2019 | | :--- | :--- | :--- | | **Assets** | | | | Cash, cash equivalents, and short-term deposits | $38,545 | $17,792 | | Total Current Assets | $55,723 | $32,479 | | Total Assets | $67,934 | $45,392 | | **Liabilities & Capital Deficiency** | | | | Total Current Liabilities | $86,474 | $40,175 | | Total Liabilities | $94,971 | $115,714 | | Total Capital Deficiency | $(27,037) | $(70,322) | - The independent auditor, Kesselman & Kesselman (PwC), identified revenue recognition for the license and R&D services performance obligation as a critical audit matter, citing the significant management judgment required to estimate total costs to completion[487](index=487&type=chunk)[489](index=489&type=chunk) [Controls and Procedures](index=129&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2020, with no material changes reported - The CEO and CFO concluded that the company's disclosure controls and procedures were effective as of **December 31, 2020**[440](index=440&type=chunk) - Management assessed internal control over financial reporting based on the COSO framework and concluded that it was effective as of **December 31, 2020**[443](index=443&type=chunk) Part III [Directors, Executive Officers, Corporate Governance, Compensation, and Principal Accountant Fees](index=134&type=section&id=Item%2010%2C%2011%2C%2012%2C%2013%2C%20and%2014) Information on directors, executive officers, corporate governance, compensation, and principal accountant fees is incorporated by reference from the 2021 Proxy Statement - Information regarding directors, executive officers, corporate governance, executive compensation, security ownership, and principal accountant fees is incorporated by reference from the registrant's **2021 Proxy Statement**[451](index=451&type=chunk)[452](index=452&type=chunk)[453](index=453&type=chunk)[454](index=454&type=chunk)[455](index=455&type=chunk) Part IV [Exhibits and Financial Statement Schedules](index=135&type=section&id=Item%2015.%20Exhibits%20and%20Financial%20Statement%20Schedules) This section provides an index of exhibits and financial statement schedules filed with the 10-K report, including key corporate and contractual documents - This section contains the index to the Consolidated Financial Statements and a list of all exhibits filed with the **10-K report**[457](index=457&type=chunk)[458](index=458&type=chunk)

Protalix BioTherapeutics, Inc. (NYSE:PLX) Q3 2020 Results Conference Call October 29, 2020 8:30 AM ET Company Participants Chuck Padala - LifeSci Advisors, Investor Relations Dror Bashan - President & Chief Executive Officer Eyal Rubin - Chief Financial Officer Conference Call Participants Boobalan Pachaiyappan - H.C. Wainwright Operator Greetings and welcome to the Protalix Biopharmaceuticals Third Quarter 2020 Financial Results and Business Update. At this time all participants are in a listen-only mode. ...

Protalix BioTherapeutics, Inc. (NYSE:PLX) Q2 2020 Results Earnings Conference Call August 10, 2020 8:30 AM ET Â Company Participants Chuck Padala - LifeSci Advisors, Investor Relations Dror Bashan - President and CEO Eyal Rubin - Chief Financial Officer Conference Call Participants Boobalan Pachaiyappan - H.C. Wainwright Operator Good morning, ladies and gentlemen. And welcome to the Protalix BioTherapeutics Second Quarter 2020 Earnings Call. As a reminder, this conference is being recorded. I would now lik ...

Protalix Bio Therapeutics (NYSE:PLX) Q1 2020 Earnings Conference Call June 1, 2020 8:30 AM ET Company Participants Dror Bashan - President, Chief Executive Officer Eyal Rubin - Senior Vice President, Chief Financial Officer Chuck Padala - Investor Relations Conference Call Participants Boobalan Pachaiyappan - HC Wainwright Philippa Gardner - Jefferies Walter Goering - private investor Operator Greetings and welcome to the Protalix Bio Therapeutics first quarter 2020 earnings conference call. At this time, a ...

Protalix BioTherapeutics, Inc. (NYSE:PLX) Q4 2019 Earnings Conference Call March 12, 2020 8:30 AM ET Company Participants Monique Kosse - IR, LifeSci Advisors Dror Bashan - President & CEO Eyal Rubin - CFO Conference Call Participants Boobalan Pachaiyappan - H.C. Wainwright Peter Welford - Jefferies Operator Greetings and welcome to the Protalix Biopharmaceuticals reports Fourth Quarter and Full-Year 2019 Financial and Business Results Conference Call. At this time, all participants are in a listen-only mod ...

Protalix BioTherapeutics, Inc. CORPORATE UPDATE | FEBRUARY 2020 Note Regarding Forward-Looking Statements This presentation (the "Presentation") contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements, including, among others, statements regarding expectations as to regulatory approvals, market opportunity for, and potential sales of, the Company's product and product candid ...

Investment Highlights - Protalix has a revenue-generating marketed drug for Gaucher disease[4] - The company's pipeline includes products in active clinical phase development, such as pegunigalsidase alfa (PRX-102) for Fabry disease, tulinercept for Inflammatory Bowel Disease, and alidornase alfa (PRX-110) for multiple indications[4] - A BLA submission for Fabry disease is anticipated by Q2 2020[4] - Protalix utilizes an advantageous proprietary ProCellEx® platform for recombinant protein expression and cGMP manufacturing, successfully inspected and audited by multiple regulatory agencies, including the US FDA and EU EMA[4] Commercial Performance & Partnerships - Sales in Brazil provide a consistent revenue stream for 5+ years, validating the company's ability to bring a treatment from concept to market and support long-term production[11] - In 2019, sales to the Brazilian Ministry of Health amounted to approximately $91 million[11] - Approximately 20% of Gaucher patients in Brazil are treated with alfataliglicerase (Elelyso®)[11] - Protalix has a global partnership with Chiesi Farmaceutici S·p·A, including a $50 million upfront payment and potential milestone payments of over $1 billion, plus tiered royalties of 15-35% (ex-US) and 15-40% (US)[22] Product Pipeline & Milestones - The Fabry disease market is estimated to be over $14 billion and growing at a CAGR of approximately 10%[15] - Final results from the BRIDGE trial are expected in Q2 2020, and final results from the BRIGHT trial are expected in Q4 2020[34] - Protalix anticipates FDA approval of pegunigalsidase alfa in Q4 2020 and a launch in Q1 2021[34]

Financial Data and Key Metrics Changes - Protalix recorded revenues from selling goods of $12.1 million during the nine-month period ended September 30, 2019, an increase of $4.9 million, or 67%, compared to the revenues of $7.2 million for the same period of 2018, primarily due to higher sales of Elelyso in Brazil [16] - Research and development expenses, net, were $35 million for the nine months ended September 30, 2019, an increase of $11.3 million, or 47%, compared to $23.8 million for the same period of 2018, mainly due to increased clinical trial costs [17] - Selling, general and administrative expenses for the nine months ended September 30, 2019, were $6.9 million, a decrease of $1.9 million, or 21%, compared to $8.7 million for the same period in 2018 [18] - Net loss for the nine months ended September 30, 2019, was $18.6 million, or $0.13 per share, compared to a net loss of $21 million, or $0.14 per share, for the same period in 2018 [19] - As of September 30, 2019, the company had $21.4 million in cash and cash equivalents [20] Business Line Data and Key Metrics Changes - The ongoing clinical studies for PRX-102 continue to show outstanding data, with the BALANCE Phase III study designed to evaluate the safety and efficacy of PRX-102 on renal function in Fabry patients [7][8] - Interim results from the BRIDGE study indicate a mean improvement in kidney function for patients switched from Replagal to PRX-102, with the switch being well tolerated [12] Market Data and Key Metrics Changes - In Brazil, Protalix has achieved approximately 23% market share for taliglucerase, with an average growth of about 15% year-over-year expected in the next few years [52] Company Strategy and Development Direction - The company plans to submit a Biologics License Application (BLA) for PRX-102 by April 2020 under an accelerated approval pathway, based on data from completed and ongoing clinical studies [10] - A reverse stock split is proposed to regain compliance with the NYSE American, which is seen as essential for attracting institutional investors [35] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the outcome of ongoing studies and the potential of PRX-102 to address unmet medical needs in Fabry patients [10][11] - The company is making significant progress and is committed to its goals, thanking patients, investigators, and shareholders for their support [22] Other Important Information - The company has convened a special meeting with stockholders to approve amendments to its certificate of incorporation, including a reverse stock split and a reduction in the total number of authorized shares [14] Q&A Session Summary Question: Has the pre-BLA meeting with the FDA taken place? - Yes, the pre-BLA meeting with the FDA took place in October, and the company will share the minutes publicly once received [28] Question: What are the usage patterns and government ordering in Brazil for taliglucerase? - The company sees alignment between orders and production, achieving around 23% market share and expecting steady growth [52] Question: What are the gating items remaining for the completion of the FDA submission for PRX-102? - Protalix and Chiesi are working closely together on the submission, with responsibilities shared between both companies [56] Question: What feedback has Chiesi provided regarding its commercial preparations for the potential future US launch of PRX-102? - While specific details were not disclosed, preparations have started, and the company is pleased with Chiesi's progress [58]

Protalix Biotherapeutics, Inc. (NYSE:PLX) Q2 2019 Earnings Conference Call August 8, 2019 8:30 AM ET Company Participants Dror Bashan - President & CEO Conference Call Participants Edward Marks - H.C. Wainwright & Co. Peter Welford - Jefferies Operator Good morning ladies and gentlemen and welcome to the Protalix Second Quarter 2019 Financial Results and Corporate Conference Call. At this time all participants are in a listen-only mode. Later we will conduct a question and answer session and instructions wi ...

Protalix Biotherapeutics, Inc. (NYSE:PLX) Q1 2019 Earnings Conference Call May 6, 2019 8:30 AM ET Company Participants Yossi Maimon - CFO, VP, Treasurer & Secretary Moshe Manor - CEO, President & Director Conference Call Participants Edward Marks - H.C. Wainwright & Co. Peter Welford - Jefferies Operator Good day, ladies and gentlemen, and welcome to the Protalix First Quarter 2019 Financial Results and Corporate Conference Call. [Operator Instructions]. As a reminder, this call will be recorded. I would no ...