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What changed in Protalix BioTherapeutics, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Protalix BioTherapeutics, Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+462 added−537 removedSource: 10-K (2026-03-18) vs 10-K (2025-03-17)

Top changes in Protalix BioTherapeutics, Inc.'s 2025 10-K

462 paragraphs added · 537 removed · 354 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

168 edited+56 added−121 removed129 unchanged
Biggest changeIf we are unable to attract and retain key personnel, it could adversely affect our ability to develop and market our products. ” Company Background We were originally incorporated in the State of Florida in April 1992, and reincorporated in the State of Delaware in March 2016.
Biggest changeIf we are unable to attract and retain key personnel, it could adversely affect our ability to develop and market our products .” Set forth below is a chart showing the number of people we employed at the times indicated: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ As of December 31, ​ ​ 2023 ​ 2024 ​ 2025 Total Employees ​ ​ 208 ​ ​ 213 ​ ​ 226 Research and Development ​ ​ 47 ​ ​ 48 ​ ​ 62 General and Administrative ​ ​ 14 ​ ​ 14 ​ ​ 14 Operations ​ ​ 147 ​ ​ 151 ​ ​ 150 ​ Company Background We were originally incorporated in the State of Florida in April 1992, and reincorporated in the State of Delaware in March 2016.
Uncontrolled gout is when serum urate (sUA) levels are above the maximum medically appropriate level (6.8 mg/dL), as well as tophi formation and/or flares that cannot be treated with available urate lowering therapies. Currently available ULTs can be effective in treating gout.
Uncontrolled gout is when serum urate (sUA) levels are above the maximum medically appropriate level (6.8 mg/dL), as well as tophi formation and/or flares that cannot be treated with available urate lowering therapies. Currently available Urate-lowering therapies (ULTs) can be effective in treating gout.
The submission of an NDA or BLA is subject to the payment of substantial user fees which may be waived under certain limited circumstances. The testing and approval processes require substantial time and effort, and may not result in an approval on a timely basis, if at all.
The submission of an NDA or BLA is subject to the payment of substantial user fees which may be waived under certain limited circumstances. The testing and approval processes require substantial time and effort, and may not result in approval on a timely basis, if at all.
Gout leads to substantial morbidity, severe pain, reduced quality of life, decreased physical function, increased healthcare costs, and lost economic productivity. Furthermore, gout is strongly associated with a number of comorbidities, including hypertension, cardiovascular disease, renal impairment, diabetes, obesity, hyperlipidaemia and frequently occurs in a combination known as the metabolic syndrome.
Gout leads to substantial morbidity, severe pain, reduced quality of life, decreased physical function, increased healthcare costs, and lost economic productivity. Furthermore, gout is strongly associated with a number of comorbidities, including hypertension, cardiovascular disease, renal impairment, diabetes, obesity, hyperlipidaemia and frequently occurs in a combination known as metabolic syndrome.
The process required by the FDA before a biological product or drug may be marketed in the United States generally involves the following: ● Completion of preclinical laboratory tests, animal studies and formulation studies , with certain studies conducted in accordance with Good Laboratory Practice regulations, or GLPs, and other applicable regulations ; ● Submission to the FDA of an investigational new drug application, or IND, which must become effective before human clinical trials may begin; ● Approval by an independent institutional review board, or IRB, or ethics committee at each clinical site before each trial may be initiated; ● Performance of adequate and well-controlled clinical trials according to Good Clinical Practices, or GCPs, to establish the safety and efficacy of a proposed drug candidate, and the safety, purity and potency of a proposed biological product candidate, for its intended use ; ● Submission to the FDA of a BLA for a new biological product or a new drug application, or NDA, for a new drug; ● Satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with cGMP to assure that the facilities, methods and controls are adequate to preserve the drug’s or biologic’s identity, strength, quality and purity; ● satisfactory completion of potential inspection of selected clinical investigation sites to assess compliance with GCPs; and ● FDA review and approval of the BLA or NDA.
The process required by the FDA before a biological product or drug may be marketed in the United States generally involves the following: ● Completion of preclinical laboratory tests, animal studies and formulation studies , with certain studies conducted in accordance with Good Laboratory Practice regulations, or GLPs, and other applicable regulations ; ● Submission to the FDA of an investigational new drug application, or IND, which must become effective before human clinical trials may begin; ● Approval by an independent institutional review board, or IRB, or ethics committee at each clinical site before each trial may be initiated; ● Performance of adequate and well-controlled clinical trials according to Good Clinical Practices, or GCPs, to establish the safety and efficacy of a proposed drug candidate, and the safety, purity and potency of a proposed biological product candidate, for its intended use ; ● Submission to the FDA of a BLA for a new biological product or a new drug application, or NDA, for a new drug; ● Satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with cGMP to assure that the facilities, methods and controls are adequate to preserve the drug’s or biologic’s identity, strength, quality and purity; 18 Table of Contents ● satisfactory completion of potential inspection of selected clinical investigation sites to assess compliance with GCPs; and ● FDA review and approval of the BLA or NDA.
If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same treatment for the same indication for seven years, except in limited circumstances, such as (i) the drug’s orphan designation is revoked; (ii) its marketing approval is withdrawn; (iii) the orphan exclusivity holder consents to the approval of another applicant’s product; (iv) the orphan exclusivity holder is unable to assure the availability of a sufficient quantity of drug; or (v) a showing of clinical superiority to the product with orphan exclusivity by a competitor product.
If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not 20 Table of Contents approve any other applications to market the same treatment for the same indication for seven years, except in limited circumstances, such as (i) the drug’s orphan designation is revoked; (ii) its marketing approval is withdrawn; (iii) the orphan exclusivity holder consents to the approval of another applicant’s product; (iv) the orphan exclusivity holder is unable to assure the availability of a sufficient quantity of drug; or (v) a showing of clinical superiority to the product with orphan exclusivity by a competitor product.
The Brazil Agreement provides for a staged technology transfer which is intended to transfer to Fiocruz the capacity and skills required for the Brazilian government to construct its own manufacturing facility, at its sole expense, and to produce a sustainable, high-quality, and cost-effective supply of BioManguinhos alfataliglicerase. Fiocruz has not satisfied certain purchase commitments under the Brazil Agreement.
The Brazil Agreement provides for a staged technology transfer that is intended to transfer to Fiocruz the capacity and skills required for the Brazilian government to construct its own manufacturing facility, at its sole expense, and to produce a sustainable, high-quality, and cost-effective supply of BioManguinhos alfataliglicerase. Fiocruz has not satisfied certain purchase commitments under the Brazil Agreement.
In both the United States and foreign markets, our ability to commercialize our product and product candidates successfully, and to attract commercialization partners, depends in significant part on the availability of adequate financial coverage and reimbursement from third party payors, including, in the United States, governmental payors such as Medicare, Medicaid and the Veterans Affairs Health programs, and private health insurers.
Commercialization of drug products in both the United States and foreign markets, our ability to commercialize our product and product candidates successfully, and the ability to attract commercialization partners, depends in significant part on the availability of adequate financial coverage and reimbursement from third party payors, including, in the United States, governmental payors such as Medicare, Medicaid and the Veterans Affairs Health programs, and private health insurers.
The designation includes all of the fast track program features, as well as more intensive FDA interaction and guidance beginning as early as phase I and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers. Accelerated Approval; Breakthrough Therapy Designation Section 901 of the U.S.
The designation includes all of the fast track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers. Accelerated Approval; Breakthrough Therapy Designation Section 901 of the U.S.
Based on market research we have commissioned, we estimate that approximately 25% of the gout population in the US and Western Europe do not have their gout controlled. Some of those patients cannot be treated with existing therapies; others stop treatment with existing therapies due to adverse events.
Based on market research we have commissioned, we estimate that approximately 25% of the gout population in the US and Western Europe does not have their gout controlled. Some of those patients cannot be treated with existing therapies; others stop treatment with existing therapies due to adverse events.
In addition, such research shows that there are gout patients treated with existing therapies that continue to suffer from tophi despite having reached urate target levels. The risk of gout increases with age, and is more common in males. Gout results from sustained elevation of serum urate levels (hyperuricaemia).
In addition, such research presents that there are gout patients treated with existing therapies that continue to suffer from tophi despite having reached urate target levels. The risk of gout increases with age, and is more common in males. Gout results from sustained elevation of serum urate levels (hyperuricaemia).
Phase III clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical trial sites. These trials are intended to establish the overall risk/benefit ratio of the product and provide an adequate basis for regulatory approval and product labeling.
Phase 3 clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical trial sites. These trials are intended to establish the overall risk/benefit ratio of the product and provide an adequate basis for regulatory approval and product labeling.
The ProCellEx reactors are easy to use and maintain, allow for rapid horizontal scale-up and do not involve the risk of mammalian viral contamination. Our bioreactors are well-suited for plant cell growth using a simple, inexpensive, chemically defined growth medium.
Unlike these bioreactors, the ProCellEx reactors are easy to use and maintain, allow for rapid horizontal scale-up and do not involve the risk of mammalian viral contamination. Our bioreactors are well-suited for plant cell growth using a simple, inexpensive, chemically defined growth medium.
Once an IND is in effect, each new clinical protocol and any amendments to the protocol must be submitted to the FDA for review, and to the IRBs for approval. Human clinical trials are typically conducted in three sequential phases that may overlap or be combined: ● Phase I.
Once an IND is in effect, each new clinical protocol and any amendments to the protocol must be submitted to the FDA for review, and to the IRBs for approval. Human clinical trials are typically conducted in three sequential Phases that may overlap or be combined: ● Phase 1.
The following corporate tax benefits, among others, are available to Industrial Companies: ● amortization of the cost of purchased know-how and patents over an eight-year period for tax purposes; ● accelerated depreciation rates on equipment and buildings; ● under specified conditions, an election to file consolidated tax returns with other related Israeli Industrial Companies; and ● expenses related to a public offering are deductible in equal amounts over three years.
The following corporate tax benefits, among others, are available to Industrial Companies: ● amortization of the cost of purchased know-how and patents over an eight-year period for tax purposes; ● accelerated depreciation rates on equipment and buildings; 28 Table of Contents ● under specified conditions, an election to file consolidated tax returns with other related Israeli Industrial Companies; and ● expenses related to a public offering are deductible in equal amounts over three years.
In the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing may be conducted in patients having the specific disease. ● Phase II.
In the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing may be conducted in patients having the specific disease. ● Phase 2.
Compliance with Environmental, Health and Safety Laws In addition to FDA regulations, we are also subject to evolving federal, state and local environmental, health and safety laws and regulations. In the past, compliance with environmental, health and safety laws and regulations has not had a material effect on our capital expenditures.
Compliance with Environmental, Health and Safety Laws In addition to FDA regulations, we are also subject to evolving federal, state and local environmental, health and safety laws and regulations. Compliance with environmental, health and safety laws and regulations has not had a material effect on our capital expenditures.
The agrobacterium-mediated transformed cells are then able to produce specific proteins, which are extracted and purified and can be used as therapies to treat a variety of diseases. Our ProCellEx technology can be utilized to express complex therapeutic proteins belonging to different drug classes, such as enzymes, hormones, monoclonal antibodies, cytokines and vaccines.
The agrobacterium-mediated 5 Table of Contents transformed cells are then able to produce specific proteins, which are extracted and purified and can be used as therapies to treat a variety of diseases. Our ProCellEx technology can be utilized to express complex therapeutic proteins belonging to different drug classes, such as enzymes, hormones, monoclonal antibodies, cytokines and vaccines.
Elfabrio was approved by the FDA with a boxed warning for hypersensitivity reactions/anaphylaxis, consistent with Enzyme Replacement Therapy (ERT) class labeling, and Warnings/Precautions providing guidance on the signs and symptoms of hypersensitivity and infusion-associated reactions seen in the clinical studies as well as treatments to manage such events should they occur.
Elfabrio was approved by the FDA with a boxed warning for hypersensitivity reactions/anaphylaxis, consistent with ERT class labeling, and warnings/precautions providing guidance on the signs and symptoms of hypersensitivity and infusion-associated reactions seen in the clinical studies as well as treatments to manage such events should they occur.
The three basic criteria for the registration of pharmaceuticals in Israel is quality, safety and efficacy of the 27 Table of Contents pharmaceutical product and the Israeli Ministry of Health requires pharmaceutical companies to conform to international developments and standards. Regulatory requirements are constantly changing in accordance with scientific advances as well as social and ethical values.
The three basic criteria for the registration of pharmaceuticals in Israel is quality, safety and efficacy of the pharmaceutical product and the Israeli Ministry of Health requires pharmaceutical companies to conform to international developments and standards. Regulatory requirements are constantly changing in accordance with scientific advances as well as social and ethical values.
If the dividend is distributed within 12 years after the end of the benefits period (or, in the case of a foreign investor’s company, without time limitation), the dividend recipient is taxed at the reduced withholding tax rate of 20% applicable to dividends from approved enterprises, or at the lower rate under an applicable tax treaty.
If the dividend is distributed within 12 years after the end of the benefits period (or, in the case of a foreign investor’s company, without time limitation), the dividend recipient is taxed at the reduced withholding tax rate of 20% applicable to dividends from approved enterprises, or at the 26 Table of Contents lower rate under an applicable tax treaty.
The Commission maintains an Internet site that contains reports, proxy and information statements and other information regarding issuers that file electronically with the Commission at www.sec.gov . Additionally, from time to time, we provide notifications of material news including press releases and conferences on our website.
The Commission maintains an Internet site that contains reports, proxy and information statements and other information regarding issuers that file electronically with the Commission at 29 Table of Contents www.sec.gov . Additionally, from time to time, we provide notifications of material news including press releases and conferences on our website.
PRX-119 PRX-119 is our plant cell-expressed PEGylated recombinant human DNase I product candidate which we are designing to have an elongated half-life in the circulation for the potential treatment of NETs-related diseases. NETs, or Neutrophil extracellular traps, are web-like structures released by activated neutrophils that trap and kill a variety of microorganisms.
Our Pipeline – Preclinical and Research Programs PRX-119 PRX-119 is our plant cell-expressed PEGylated recombinant human DNase I product candidate which we are designing to have an elongated half-life in the circulation for the potential treatment of NETs-related diseases. NETs, or Neutrophil extracellular traps, are web-like structures released by activated neutrophils that trap and kill a variety of microorganisms.
The FDA impose other conditions, including distribution restrictions or other risk management mechanisms, including a risk evaluation and mitigation strategy, or REMS, which can materially affect the potential market and profitability of the product.
The FDA imposes other conditions, including distribution restrictions or other risk management mechanisms, including a risk evaluation and mitigation strategy, or REMS, which can materially affect the potential market and profitability of the product.
As of December 31, 2024, NATI approved grants in respect of Protalix Ltd.’s continuing operations totaling approximately $53.2 million (before interest, as described below), measured from inception.
As of December 31, 2025, NATI approved grants in respect of Protalix Ltd.’s continuing operations totaling approximately $53.2 million (before interest, as described below), measured from inception.
The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the product candidate, proposed labeling and other relevant information, are 24 Table of Contents submitted to the FDA as part of an NDA or BLA, requesting approval to market the product.
The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the product candidate, proposed labeling and other relevant information, are submitted to the FDA as part of an NDA or BLA, requesting approval to market the product.
An intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality. The FDA bases its decision on whether to accept the proposed surrogate or intermediate clinical endpoint on the scientific support for that endpoint.
An intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality. The FDA bases its decision on whether to accept the proposed surrogate or 21 Table of Contents intermediate clinical endpoint on the scientific support for that endpoint.
The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and 25 Table of Contents the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.
The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.
Japanese RISE Study Chiesi is currently enrolling patients in its clinical trial entitled “A Multicenter Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Pegunigalsidase Alfa (PRX-102) in Japanese Patients With Fabry Disease,” or the RISE study (NCT05710692).
Japanese RISE Study Chiesi is currently recruiting patients for its clinical trial entitled “A Multicenter Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Pegunigalsidase Alfa (PRX-102) in Japanese Patients With Fabry Disease,” or the RISE study (NCT05710692).
We seek to protect our competitive position by filing United States, European Union, Israeli and other foreign patent applications covering our technology, including both new technology and improvements to existing technology. Our patent strategy includes obtaining patents on methods of production, compositions of matter and methods of use.
We seek to protect our competitive position by filing United States, EU, Israeli and other foreign patent applications covering our technology, including both new technology and improvements to existing technology. Our patent strategy includes obtaining patents on methods of production, compositions of matter and methods of use.
Protalix Ltd. may not receive the required approvals for any proposed transfer and, if received, Protalix Ltd. may be required to pay NATI a portion of the consideration that it receives upon any sale of such technology by a non-Israeli entity.
Protalix Ltd. may not receive the required approvals for any 27 Table of Contents proposed transfer and, if received, Protalix Ltd. may be required to pay NATI a portion of the consideration that it receives upon any sale of such technology by a non-Israeli entity.
Our ProCellEx technology allows for many unique advantages, including: biologic optimization; an ability to handle complex protein expressions; flexible manufacturing with improvements through efficiencies, enhancements and/or rapid horizontal scale-ups; a simplified production process; elimination of the risk of viral contaminations from mammalian components; and intellectual property advantages.
Our ProCellEx technology allows for many unique advantages, including: biologic optimization; an ability to handle expression of complex proteins; flexible manufacturing with improvements through efficiencies, enhancements and/or rapid horizontal scale-ups; a simplified production process; elimination of the risk of viral contaminations from mammalian components; and intellectual property advantages.
Orphan drug designation in the European Union is granted to medicinal products intended for the diagnosis, prevention and treatment of life-threatening diseases and very serious conditions that affect not more than five in 10,000 people in the European Union.
Orphan drug designation in the EU is granted to medicinal products intended for the diagnosis, prevention and treatment of life-threatening diseases and very serious conditions that affect not more than five in 10,000 people in the EU.
Some parts of this discussion are based on new tax legislation that has not been subject to judicial or administrative interpretation. Therefore, the views expressed in the 29 Table of Contents discussion may not be accepted by the tax authorities in question.
Some parts of this discussion are based on new tax legislation that has not been subject to judicial or administrative interpretation. Therefore, the views expressed in the discussion may not be accepted by the tax authorities in question.
Post-Approval Requirements Any drugs for which we receive FDA approval are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse effects with the product, reporting of changes in distributed products which would require field alert reports (FARs), drugs and biological product deviation reports (BPDRs) providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements and complying with FDA promotion and advertising requirements.
Post-Approval Requirements Drugs approved by the FDA are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse effects with the product, reporting of changes in distributed products which would require field alert reports (FARs), drugs and biological product deviation reports (BPDRs) providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements and complying with FDA promotion and advertising requirements.
It can have a significant impact on quality of life due to presence of serious, chronic and debilitating complications, including cardiovascular and renal complications, and comorbid conditions such as pain can have a significant impact on the psychological well-being of Fabry patients and their social functioning. Fabry disease involves substantial reduction in life expectancy.
It can have a significant impact on quality of life due to presence of serious, chronic and debilitating complications, including cardiovascular and renal complications, and comorbidities such as pain can have a significant impact on the psychological well-being of Fabry patients and their social functioning. Fabry disease often involves substantial reduction in life expectancy.
Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity. Orphan drug status in the European Union has similar but not identical benefits in the European Union.
Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity. Orphan drug status in the EU has similar but not identical benefits in the EU.
Under the F/F Agreement, we agreed to supply Chiesi with drug substance for PRX-102 and, following relevant technology and technical information transfer activities, Chiesi has agreed, among other things, to provide us with commercial fill/finish services for PRX-102, including to support the anticipated global launch of PRX-102.
Under the F/F Agreement, we agreed to supply Chiesi with drug substance for pegunigalsidase alfa and, following relevant technology and technical information transfer activities, Chiesi has agreed, among other things, to provide us with commercial fill/finish services for pegunigalsidase alfa, including to support the anticipated global launch of pegunigalsidase alfa.
Global Pending Jurisdictions Granted Jurisdictions Nominal Expiry Production of High Mannose Proteins in Plant Culture/PCT/ Il2004 000181 N/A Russian Federation, Australia, USA 2025(1) (3) Plant Cell/Tissue Culturing Device, System and Method/PCT/Il2005/000228 N/A Israel 2025 Large Scale Disposable Bioreactor/PCT/Il2008/000614 N/A Australia, Canada, China, Europe, Hong Kong, India, Israel, Republic of Korea, Russian Federation, Singapore, South Africa, USA, Brazil 2028(2) Stabilized Alpha-galactosidase and uses thereof/PCT/Il2011/ 000209 Brazil Canada, South Africa, Russian Federation, Singapore, Israel, India, New Zealand, Republic of Korea, Australia, China, Japan, USA, Europe, Hong Kong, India, Brazil 2031(3) Nucleic Acid Construct for Expression of Alpha-galactosidase in Plants and Plant Cells/PCT/ Il2011/000719 N/A India, China, Republic of Korea, Japan, Israel, Europe, Hong Kong, USA, Brazil 2031(2) Therapeutic Regimen For The Treatment of Fabry Using Stabilized Alpha-galactosidase/ PCT/Il2018/050018 Europe, Brazil, Japan, Canada, Israel, Republic of Korea, China, Hong Kong South Africa, New Zealand, Russian Federation, USA, Chile, Mexico, Australia 2038 18 Table of Contents Dry Powder Formulations of DNase 1/PCT/Il2013/050094 N/A Israel, USA 2033 DNase I Polypeptides, Polynucleotides Encoding Same, Methods of Producing DNase I and uses thereof in Therapy/PCT/ Il2013/050097 N/A Europe, Israel, Brazil 2033 Inhalable Liquid Formulations of DNase I/PCT/Il2013/050096 N/A Israel, USA 2033 Modified DNase and uses thereof/ PCT/Il2016/050003 Europe, Canada, China, Hong Kong USA, Australia, Mexico, Israel, New Zealand, South Africa 2036 Removal of Constructs from Transformed Cells/PCT/IL2019/ 051266 USA, Israel, New Zealand, Australia Japan, 2040 Long-Acting DNase/PCT/IL2021/051207 Canada, Israel, USA, Japan, Europe, Hong Kong, Republic of Korea, China N/A 2041 Dicer-Like Knock-Out Plant Cells/ PCT/IL2021/051194 Israel, USA, Japan, Europe, Hong Kong, Republic of Korea, China N/A 2041 Modified Uricase and Uses Thereof/PCT/IL2021/051305 Japan, Canada, Brazil, USA, Israel, Mexico, Europe, Republic of Korea, China N/A 2041 Methods of treating diseases associated with elevated uric acid USA N/A N/A (1) Patent granted in Australia expires in 2029.
Global Pending Jurisdictions Granted Jurisdictions Nominal Expiry Production of High Mannose Proteins in Plant Culture/PCT/ Il2004 000181 N/A Russian Federation, Australia 2029(1) (3) Large Scale Disposable Bioreactor/PCT/Il2008/000614 N/A Australia, Canada, China, Europe, Hong Kong, India, Israel, Republic of Korea, Russian Federation, Singapore, South Africa, USA, Brazil 2028 Stabilized Alpha-galactosidase and uses thereof/PCT/Il2011/ 000209 Brazil Canada, South Africa, Russian Federation, Singapore, Israel, India, New Zealand, Republic of Korea, Australia, China, Japan, USA, Europe, Hong Kong, India, Brazil 2031(3) Nucleic Acid Construct for Expression of Alpha-galactosidase in Plants and Plant Cells/PCT/ Il2011/000719 N/A India, China, Republic of Korea, Japan, Israel, Europe, Hong Kong, USA, Brazil 2031(2) Therapeutic Regimen For The Treatment of Fabry Using Stabilized Alpha-galactosidase/ PCT/Il2018/050018 Europe, Brazil, Japan, Canada, Israel, Republic of Korea, China, Hong Kong South Africa, New Zealand, Russian Federation, USA, Chile, Mexico, Australia 2038 Dry Powder Formulations of DNase 1/PCT/Il2013/050094 N/A Israel, USA 2033 DNase I Polypeptides, Polynucleotides Encoding Same, Methods of Producing DNase I and uses thereof in Therapy/PCT/ Il2013/050097 N/A Europe, Israel, Brazil 2033 ​ 15 Table of Contents Inhalable Liquid Formulations of DNase I/PCT/Il2013/050096 N/A Israel, USA 2033 Removal of Constructs from Transformed Cells/PCT/IL2019/ 051266 USA, Israel, New Zealand, Australia Japan, USA 2040 Long-Acting DNase/PCT/IL2021/051207 Canada, Israel, USA, Japan, Europe, Hong Kong, Republic of Korea, China N/A 2041 Dicer-Like Knock-Out Plant Cells/ PCT/IL2021/051194 Israel, USA, Japan, Europe, Hong Kong, Republic of Korea, China N/A 2041 Modified Uricase and Uses Thereof/PCT/IL2021/051305 Japan, Canada, Brazil, USA, Israel, Mexico, Europe, Republic of Korea, China N/A 2041 Methods of treating diseases associated with elevated uric acid USA N/A N/A (1) Patent granted in Australia expires in 2029.
Phase II clinical trials involve investigations in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and the optimal dosage and schedule. ● Phase III.
Phase 2 clinical trials involve investigations in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and the optimal dosage and schedule. ● Phase 3.
This recombinant enzyme, expressed via our ProCellEx system, is designed to lower urate levels and improve clinical manifestation of the disease while having low immunogenicity and increased half-life of the drug in the blood.
PRX-115, our recombinant uricase enzyme, expressed via our ProCellEx system, is designed to lower urate levels and improve clinical manifestation of the disease while having low immunogenicity and increased half-life of the drug in the blood.
The Letter Agreement changed the obligations of both us and Chiesi under the Chiesi Agreements with respect to, among other things, the evaluation, selection and establishment of an initial alternate source of commercial fill/finish services for PRX-102.
The Letter Agreement changed the obligations of both us and Chiesi under the Chiesi Agreements with respect to, among other things, the evaluation, selection and establishment of an initial alternate source of commercial fill/finish services for pegunigalsidase alfa.
The FDA or the trial sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the study subjects or patients are being exposed to an unacceptable health risk.
The FDA or the trial sponsor 19 Table of Contents may suspend or terminate a clinical trial at any time on various grounds, including a finding that the study subjects or patients are being exposed to an unacceptable health risk.
The ultimate consequences of Gb 3 deposition range from episodes of pain and impaired peripheral sensation to end-organ failure, particularly of the kidneys, but also of the heart and the cerebrovascular system. Fabry disease occurs in one person per 40,000 to 60,000 males. The standard of care for Fabry disease is ERT.
The ultimate consequences of Gb 3 deposition range from episodes of pain and impaired peripheral sensation to end-organ failure, particularly of the kidneys, but also of the heart and the cerebrovascular system. Fabry disease occurs in one person per 40,000 to 60,000 males.
To date, we have successfully developed two commercial products, both of which are enzyme replacement therapies (ERTs): Elfabrio ® (pegunigalsidase alfa) for the treatment of adult patients with a confirmed diagnosis of Fabry disease and Elelyso ® (taliglucerase alfa) for the treatment of adult patients with Gaucher disease.
To date, we have successfully developed two commercial products, both of which are enzyme replacement therapies (ERTs): Elelyso ® (taliglucerase alfa) for the treatment of adult patients and children four years of age and older with Gaucher disease and Elfabrio ® (pegunigalsidase alfa) for the treatment of adult patients with a confirmed diagnosis of Fabry disease.
Subsequently, in November 2024, we amended the agreement to provide that a different Chiesi facility may act as a secondary supplier of such services and that the F/F Agreement shall have an initial term of 10 years, unless terminated earlier in accordance with the terms of the F/F Agreement.
Subsequently, in November 2024, we agreed that a different Chiesi facility may act as a secondary supplier of such services and that the F/F Agreement shall have an initial term of 10 years, unless terminated earlier in accordance with the terms thereof.
To be lawfully marketed in 22 Table of Contents interstate commerce, a biologic product must be the subject of a BLA issued by the FDA on the basis of a demonstration that the product is safe, pure and potent, and that the facility in which the product is manufactured meets standards to assure that the product continues to be safe, pure and potent.
To be lawfully marketed in interstate commerce, a recombinant protein biologic product must be the subject of a BLA issued by the FDA on the basis of a demonstration that the product is safe, pure and potent, and that the facility in which the product is manufactured meets standards to assure that the product continues to be safe, pure and potent.
Pediatric FLY Study Chiesi is sponsoring, with our collaborative efforts, a clinical trial entitled “Multi-Centre, Open-label Trial to Assess the Safety, Pharmacodynamics, Efficacy and Pharmacokinetics of pegunigalsidase alfa in Patients From 2 Years to Less Than 18 Years of Age With Confirmed Fabry Disease” (NCT06328608). Recruitment has commenced.
Pediatric FLY Study Chiesi is sponsoring a clinical trial entitled “Multi-Centre, Open-label Trial to Assess the Safety, Pharmacodynamics, Efficacy and Pharmacokinetics of pegunigalsidase alfa in Patients From 2 Years to Less Than 18 Years of Age With Confirmed Fabry Disease” (NCT06328608). Recruitment is ongoing.
Failure to conduct required post-approval studies, or confirm a clinical benefit during post- 26 Table of Contents marketing studies, would allow the FDA to withdraw the drug from the market on an expedited basis.
Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, would allow the FDA to withdraw the drug from the market on an expedited basis.
Gaucher patients in Brazil are entitled to receive ERT paid for by the Brazilian MoH. The Brazilian MoH clinical treatment guidelines (PCDT) state that BioManguinhos alfataliglicerase is the therapy of choice for newly diagnosed patients. BioManguinhos alfataliglicerase is currently estimated to be used by approximately 25% of Gaucher patients in Brazil.
The Brazilian MoH clinical treatment guidelines (PCDT) state that BioManguinhos alfataliglicerase is the therapy of choice for newly diagnosed patients. BioManguinhos alfataliglicerase is currently estimated to be used by approximately 25% of Gaucher patients in Brazil.
Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and safety reports must be submitted to the FDA and the investigators for serious and unexpected side effects. Phase I, Phase II and Phase III testing may not be completed successfully within any specified period, if at all.
Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and safety reports must be submitted to the FDA and the investigators for serious and unexpected side effects. Phase 1, Phase 2 and Phase 3 testing may not be completed successfully within any specified period, if at all.
Overall, 126 patients who participated in our PRX-102 clinical program initially opted, with the advice of the treating physician, to enroll in one of the extension studies: 97 patients in the 1 mg/kg every two weeks extension study (PB-102-F60, NCT03566017) (10 patients who completed an extension study from the phase I/II study, 18 patients who completed the BRIDGE study; 69 patients who completed the BALANCE study), and 29 patients who completed the BRIGHT study in the 2 mg/kg every four weeks extension study (PB-102-F51, NCT03614234).
Overall, 126 patients who participated in our PRX-102 clinical program initially opted, with the advice of the treating physician, to enroll in one of the extension studies: 97 patients in the 1 mg/kg E2W extension study (PB-102-F60, NCT03566017) (10 patients who completed an extension study from the Phase 1/2 study, 18 patients who completed the BRIDGE study; 69 patients who completed the BALANCE study), and 29 patients who completed the BRIGHT study in the 2 mg/kg E4W extension study (PB-102-F51, NCT03614234).
The current standard of care for Gaucher disease is ERT, which is a medical treatment where recombinant enzymes are injected into patients to replace the lacking or dysfunctional enzyme. In Gaucher disease, recombinant GCD is infused to replace the mutated or deficient natural GCD enzyme. Elelyso is the only alternative ERT treatment of Gaucher disease to Cerezyme and Vpriv.
The current standard of care for Gaucher disease is ERT, which is a medical treatment where recombinant enzymes are injected into patients to replace the lacking or dysfunctional enzyme. In Gaucher disease, recombinant GCD is infused to replace the mutated or deficient natural GCD enzyme.
During the year ended December 31, 2024, we received the following: ● New patents in each of USA, Australia, Chile and Mexico for the patent family named “Therapeutic Regimen For the Treatment of Fabry Using Stabilized Alpha-galactosidase, adding to the single previously granted patent in such family. ● A new patent in Japan for the patent family named “Removal of Constructs from Transformed Cells.” Our competitive position and future success depend, in part, on our ability, and that of our licensees, to obtain and leverage the intellectual property rights covering our product candidates, know-how, methods, processes and other technologies, to protect our trade secrets, to prevent others from using our intellectual property and to operate without infringing on the intellectual property rights of third parties.
Additionally, we have approximately 45 pending patent applications. 14 Table of Contents During the year ended December 31, 2025, we received the following: ● New patents in each of USA, and Australia for the patent family named “Therapeutic Regimen For the Treatment of Fabry Using Stabilized Alpha-galactosidase, adding to the single previously granted patent in such family. ● A new patent in USA for the patent family named “Removal of Constructs from Transformed Cells.” Our competitive position and future success depend, in part, on our ability, and that of our licensees, to obtain and leverage the intellectual property rights covering our product candidates, know-how, methods, processes and other technologies, to protect our trade secrets, to prevent others from using our intellectual property and to operate without infringing on the intellectual property rights of third parties.
Extension Studies Two long-term open-label extension studies were available for patients who completed the BALANCE , BRIDGE and BRIGHT studies, and the extension of the phase I/II study.
Extension Studies Two long-term open-label extension studies were available for patients who completed the BALANCE, BRIDGE, and BRIGHT studies, and the extension of the Phase 1/2 study.
In March 2023, we initiated our phase I clinical trial of PRX-115 for the potential treatment of uncontrolled gout entitled “A Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Properties of PRX-115 in Adult Volunteers With Elevated Uric Acid Levels” (NCT05745727), or the FIH study.
We completed a Phase 1 clinical trial of PRX-115 for the potential treatment of uncontrolled gout entitled “A Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Properties of PRX-115 in Adult Volunteers With Elevated Uric Acid Levels” (NCT05745727), or the FIH study.
The study was conducted at New Zealand Clinical Research (NZCR) under the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) and the Health and Disability Ethics Committee (HDEC) guidelines. The study was initially designed to include seven sequential dosing cohorts, each composed of eight subjects (six active and two placebo), a 3:1 ratio.
The FIH study was conducted at New Zealand Clinical Research (NZCR) under the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) and the Health and Disability Ethics Committee (HDEC) guidelines. The completed study included eight sequential dosing cohorts, each composed of eight subjects (six active and two placebo), a 3:1 ratio.
Chiesi agreed to make tiered payments of 15% to 40% of its net sales under the Chiesi US Agreement to Protalix Ltd., depending on the amount of annual sales, subject to certain terms and conditions, as consideration for product supply.
Chiesi is required to make payments to Protalix Ltd. ranging from 15% to 40% of its net sales under the Chiesi US Agreement to Protalix Ltd., depending on the amount of annual sales, subject to certain terms and conditions, as consideration for product supply.
Product Development Pipeline Our corporate strategy includes development of treatments for rare and orphan diseases. To execute on the strategy, we are turning our focus to new, early-stage product candidates that treat indications for which there are high unmet needs in terms of efficacy and safety, including renal diseases. Treatments of interest will address both genetic and non-genetic diseases.
To execute on our strategy, we are turning our focus to new, early-stage product candidates that treat indications for which there are high unmet needs in terms of efficacy and safety, including renal diseases. We believe our treatments of interest will address both genetic and non-genetic diseases.
While we cannot predict whether any proposed cost-containment measures will be adopted or otherwise implemented in the future, the announcement or adoption of these proposals could have a material adverse effect on our ability to obtain adequate prices for our product candidates and operate profitably. Different pricing and reimbursement schemes exist in other countries.
While we cannot predict whether any proposed cost-containment measures will be adopted or otherwise implemented in the future, the announcement or adoption of these proposals could have a material adverse effect on our ability, or the ability of our commercialization partners, to obtain adequate prices for our product candidates and operate profitably.
In the phase III clinical program overall, two potential dosing regimens for PRX-102 were analyzed; 1 mg/kg every two weeks, with the potential for improved efficacy and safety offering a potential alternative to existing enzyme replacement therapies, and 2 mg/kg every four weeks.
In the Phase 3 clinical program overall, two potential dosing regimens for PRX-102 were analyzed; 1 mg/kg E2W, with the potential for improved efficacy and safety offering a potential alternative to existing enzyme replacement therapies, and 2 mg/kg E4W.
Both have a black box warning for anaphylaxis and other major side-effects. The FDA label of Krystexxa was amended in 2022 to include co-treatment of methotrexate to prolong efficacy and increases tolerability in patients with refractory gout. Krystexxa is no longer marketed in the European Union.
Both have a black box warning for anaphylaxis and other major side-effects. The FDA label of Krystexxa was amended in 2022 to include co-treatment of methotrexate to prolong efficacy and increase tolerability in patients with refractory gout. Krystexxa is marketed only in the US.
Foreign Regulation We are subject to regulations and product registration requirements in many foreign countries in which we may sell our products, including in the areas of product standards, packaging requirements, labeling requirements, import and export restrictions and tariff regulations, duties and tax requirements.
Foreign Regulation Pharmaceutical products are subject to regulations and product registration requirements in many foreign countries, including in the areas of product standards, packaging requirements, labeling requirements, import and export restrictions and tariff regulations, duties and tax requirements.
The design of the study is based on the Initial Pediatric Study Plan (iPSP) agreed to with the FDA and the paediatric investigation plan (PIP) for Elfabrio, which has been accepted, as amended, by the Paediatric Committee (PDCO) of the EMA.
The design of the study is based on the Initial Pediatric Study Plan (iPSP) agreed to with the FDA and the paediatric investigation plan (PIP) for Elfabrio, which has been accepted, as amended, by the Paediatric Committee (PDCO) of the EMA. The study involves the 1 mg/kg E2W dosage regimen.
Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety 23 Table of Contents concerns or non-compliance with FDA requirements, in which case clinical trials may not begin or continue until the FDA notifies the sponsor that the hold has been lifted.
Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns or non-compliance with FDA requirements, in which case clinical trials may not begin or continue until the FDA notifies the sponsor that the hold has been lifted. FDA may also place a trial on a partial clinical hold.
Elelyso is the first plant cell derived recombinant protein to be approved by the FDA for the treatment of Gaucher disease and is now approved in 23 markets including the United States, Brazil, Israel and others.
Elelyso is the first plant cell derived recombinant protein to be approved by the FDA for the treatment of Gaucher disease and is now approved in more than 40 markets including the United States, Brazil, Israel, and others. It is not approved in the EU.
Our Marketed Products Elelyso for the Treatment of Gaucher Disease Elelyso (taliglucerase alfa), our first commercial product, was approved by the FDA in 2012 for injection as an ERT for the long-term treatment of adult patients with a confirmed diagnosis of type 1 Gaucher disease. In August 2014, the FDA approved Elelyso for injection for pediatric patients.
Elelyso for the Treatment of Gaucher Disease Elelyso (taliglucerase alfa), our first commercial product, was approved by the FDA in 2012 for injection as an ERT for the long-term treatment of adult patients with a confirmed diagnosis of type 1 Gaucher disease. In August 2014, the FDA approved Elelyso for injection for children four years of age and greater.
We maintain an approximately 3,400 sq/ft pilot plant for protein development and to manufacture supplies for clinical trials (phase I and phase II). Elelyso, Elfabrio and our drug product candidates must be manufactured in a clean environment and in compliance with cGMPs set by the FDA and other relevant foreign regulatory authorities.
We maintain an approximately 316 sq/m pilot plant for protein development and to manufacture supplies for clinical trials (Phase 1 and Phase 2). Elelyso, Elfabrio, PRX-115 and our other drug product candidates must be manufactured in a clean environment and in compliance with cGMPs set by the FDA and other relevant foreign regulatory authorities.
No assurance can be made that approval to any such transfer, if requested, will be granted. 32 Table of Contents Under the Research Law and the regulations promulgated thereunder, the NATI Council may allow the transfer outside of Israel of know-how derived from an approved program and the related manufacturing rights in limited circumstances which are currently as follows: ● in the event of a sale of know-how itself to a non-affiliated third party, provided that upon such sale the owner of the know-how pays to NATI an amount, in cash, as set forth in the Research Law (and the regulations promulgated thereunder).
Under the Research Law and the regulations promulgated thereunder, the NATI Council may allow the transfer outside of Israel of know-how derived from an approved program and the related manufacturing rights in limited circumstances which are currently as follows: ● in the event of a sale of know-how itself to a non-affiliated third party, provided that upon such sale the owner of the know-how pays to NATI an amount, in cash, as set forth in the Research Law (and the regulations promulgated thereunder).
The global market for Fabry disease, that includes agalsidase beta, Sanofi’s Fabrazyme ® , agalsidase alfa, Shire’s Replagal ® and Amicus Therapeutics’ Galafold ® , among others, is forecasted to be approximately $2.3 billion in 2025 and is forecasted to grow at a CAGR of 6.6% from 2024-2030 reaching approximately $3.1 billion in annual sales in 2030.
The global market for therapies for Fabry disease, that includes agalsidase alfa, agalsidase beta, and Amicus Therapeutics’ Galafold ® , among others, is forecasted to be approximately $2.3 billion in 2026 and is forecasted to grow at a CAGR of 6.3% from 2025-2031 reaching approximately $3.2 billion in annual sales in 2031.
We work to continually enhance, strengthen, and protect our intellectual property and now hold a broad portfolio of approximately 75 patents globally, including in Europe, the United States, Israel and additional countries worldwide. Our patents are designed to protect our proprietary technology, proprietary products and product candidates, and their methods of use. Additionally, we have approximately 50 pending patent applications.
We work to continually enhance, strengthen, and protect our intellectual property and now hold a broad portfolio of approximately 70 patents globally, including in Europe, the US, Israel and additional countries worldwide. Our patents are designed to protect our proprietary technology, proprietary products and product candidates, and their methods of use.
In addition, we continuously work on the further development and enhancement of our ProCellEx technology. Accordingly, we are turning our focus to new, early-stage product candidates that treat indications for which there are high unmet needs in terms of efficacy and safety, including renal diseases. Treatments of interest will address both genetic and non-genetic diseases.
Accordingly, we are turning our focus to new, early-stage product candidates that treat indications for which there are high unmet needs in terms of efficacy and safety, including renal diseases. We believe that our treatments of interest will address both genetic and non-genetic diseases.
A number of companies have developed or are developing alternative expression technologies. Examples include Crucell N.V.’s (acquired by Johnson & Johnson) expression system based on human-cell technology, Dyadic International Inc.’s expression system based on a fungus, Pfenex Inc.’s (acquired by Ligand Pharmaceuticals Incorporated) bacteria-based expression system, and others. Companies developing alternate plant-based technologies include iBio, Inc., Medicago, Inc., and eleva.
Examples include Crucell N.V.’s (acquired by Johnson & Johnson) expression system based on human-cell technology, Dyadic International Inc.’s expression system based on a fungus, Pfenex Inc.’s (acquired by Ligand Pharmaceuticals Incorporated) bacteria-based expression system, and others. Companies developing alternate plant-based technologies include iBio, Inc., Medicago, Inc., and Eleva Biologics. Unlike ProCellEx, these alternate technologies are not cell-based.
In preclinical studies, PRX-102 showed significantly longer half-life due to higher enzyme stability, enhanced activity in Fabry disease affected organs leading to reduction of the accumulated substrate and reduced immunogenicity, which together can potentially lead to improved efficacy through increased substrate clearance and significantly lower formation of anti-drug antibodies, or ADAs.
In preclinical studies, PRX-102 showed significantly longer half-life due to higher enzyme stability, enhanced activity in Fabry disease affected organs leading to reduction of the accumulated substrate and reduced immunogenicity, which together can potentially lead to improved efficacy through increased substrate clearance and significantly lower formation of anti-drug antibodies, or ADAs. 8 Table of Contents The Phase 3 clinical program included three individual studies; the BALANCE study, the BRIDGE study and the BRIGHT study.
Other Healthcare Laws and Compliance Requirements In the United States, our activities are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including the Centers for Medicare and Medicaid Services, other divisions of the U.S. Department of Health and Human Services (e.g., the Office of Inspector General), the U.S.
Other Healthcare Laws and Compliance Requirements In the United States, our activities and those of our commercialization partners are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including the Centers for Medicare and Medicaid Services, other divisions of the U.S.
The global market for Gaucher disease, that includes Sanofi’s Cerezyme ® , Shire’s (acquired by Takeda Pharmaceutical Company Limited) Vpriv ® and Sanofi’s Cerdelga ® , among others, was $1.7 billion in 2024, is forecasted to be approximately $1.7 billion in 2025 and is forecasted to grow at a compound annual growth rate (CAGR) of approximately -0.46% from 2024-2030.
The global market for therapies for Gaucher disease, including Sanofi’s Cerezyme ® , Shire’s (acquired by Takeda Pharmaceutical Company Limited) Vpriv ® and Sanofi’s Cerdelga ® , among others, was $1.65 billion in 2025, is forecasted to be approximately $1.6 billion in 2026 and is forecasted to grow at a compound annual growth rate (CAGR) of approximately 0.5% from 2025-2031.
The FDA has developed, and is continuously updating, the requirements with respect to cell and gene therapy products and has issued documents concerning the regulation of cellular and tissue-based products.
The FDA has developed, and is continuously updating, the requirements and has issued documents concerning the regulation of cellular and tissue-based products.
Elfabrio (pegunigalsidase alfa\PRX-102) – Chiesi Farmaceutici We have entered into two exclusive global licensing and supply agreements for PRX-102 for the treatment of Fabry disease with Chiesi; the Exclusive License and Supply Agreement dated as of October 17, 2017, made by and between Protalix Ltd. and Chiesi, or the Chiesi Ex-US Agreement, and the Exclusive License and Supply Agreement dated as of July 23, 2018 , made by and between Protalix Ltd. and Chiesi, or the Chiesi US Agreement.
We have partnered with Chiesi for the development and commercialization of Elfabrio for the treatment of Fabry disease through two exclusive global licensing and supply agreements; the Exclusive License and Supply Agreement dated as of October 17, 2017, by and between Protalix Ltd. and Chiesi, or the Chiesi Ex-US Agreement, and the Exclusive License and Supply Agreement dated as of July 23, 2018, by and between Protalix Ltd. and Chiesi, or the Chiesi US Agreement.
Product Pipeline ​ ​ ProCellEx: Our Proprietary Protein Expression System ProCellEx is our proprietary platform used to produce and manufacture recombinant proteins through plant cell-based expression in suspension.
We are also exploring novel platform technologies to expand our pipeline. ​ ProCellEx: Our Proprietary Protein Expression System ProCellEx is our proprietary platform used to produce and manufacture recombinant proteins through plant cell-based expression in suspension.
A company that qualifies as a foreign investors’ company and has an Approved Enterprise program is eligible for tax benefits for a 10-year benefit period and may enjoy a reduced corporate tax rate of 10% to 23%, depending on the amount of the company’s shares held by non-Israeli shareholders. 30 Table of Contents If a company that has an Approved Enterprise program is a wholly-owned subsidiary of another company, the percentage of foreign investments is determined based on the percentage of foreign investment in the parent company.
A company that qualifies as a foreign investors’ company and has an Approved Enterprise program is eligible for tax benefits for a 10-year benefit period and may enjoy a reduced corporate tax rate of 10% to 23%, depending on the amount of the company’s shares held by non-Israeli shareholders.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeOur Bylaws provide that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States of America shall be the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act or the Exchange Act against any person in connection with any offering of the corporation’s securities.
Biggest changeOur Bylaws provide that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States of America shall be the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act or the Exchange Act against any person in connection with any offering of the corporation’s securities. 56 Table of Contents The choice of forum provisions above may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers or other employees or could result in increased costs for a stockholder to bring a claim, both of which may discourage such lawsuits against us and our directors, officers and other employees.
Risks Relating to our Operations in Israel ● Our results may be adversely affected by political, economic and military conditions in Israel. ● The Israeli government grants we have received for certain research and development expenditures restrict our ability to manufacture products and transfer technologies outside of Israel and require us to satisfy specified conditions.
Risks Relating to our Operations in Israel ● Our results may be adversely affected by military, political and economic conditions in Israel. ● The Israeli government grants we have received for certain research and development expenditures restrict our ability to manufacture products and transfer technologies outside of Israel and require us to satisfy specified conditions.
PRX-115 and PRX-119 are still in clinical development and their risk of failure is high. Failure or delay can occur at any time during the preclinical or clinical trial process.
PRX-115 and PRX-119 are still in clinical and preclinical development and their risk of failure is high. Failure or delay can occur at any time during the preclinical or clinical trial process.
The revenues we generate from royalties and commercial milestone payments and other sources may not be sufficient to fund our planned operations and capital expenditures. Accordingly, we may need to finance our future cash needs through corporate collaboration, licensing or similar arrangements, public or private equity offerings or debt financings.
The revenues we generate from royalties and commercial milestone payments and other sources may not be sufficient to fund our planned operations and capital expenditures. Accordingly, we may need to finance future cash needs through corporate collaboration, licensing, or similar arrangements, public or private equity offerings or debt financings.
As an example, the EMA has required that Chiesi submit pharmacovigilance documents intended to provide post-authorization evaluation of Elfabrio’s risk-benefit balance at defined time points after authorization, beginning within six months of authorization, and that an educational program about home administration be agreed upon with the National Competent Authority prior to the use of Elfabrio in the home setting.
As an example, the EMA has required that Chiesi submit pharmacovigilance documents intended to provide post-authorization evaluation of Elfabrio’s risk-benefit balance at defined time points after authorization, beginning within six months of authorization, and that an educational program about home administration be agreed upon with the National Competent Authority (as defined by the EMA) prior to the use of Elfabrio in the home setting.
Risks Related to Clinical Trials and Regulatory Matters ● We may not obtain the necessary U.S., EMA or other worldwide regulatory approvals to commercialize our drug candidates in a timely manner, if at all. 35 Table of Contents ● We may experience delays in obtaining regulatory approvals with respect to any drug candidate. ● Preclinical and clinical trials are very expensive, time-consuming and difficult to design and implement and may result in unforeseen costs. ● If the results of our clinical trials do not support our claims relating to a drug candidate, or if serious side effects are identified, the completion of development of such drug candidate may be significantly delayed or we may be forced to abandon development altogether. ● We may find it difficult to enroll patients in our clinical trials or patients may discontinue their participation in our clinical trials. ● Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of our product candidates in other jurisdictions. ● Dependence upon third-party service providers in connection with our clinical trials expose us to risks.
Risks Related to Clinical Trials and Regulatory Matters ● We may not obtain the necessary U.S., EMA, or other worldwide regulatory approvals to commercialize our drug candidates in a timely manner, if at all. 31 Table of Contents ● We may experience delays in obtaining regulatory approvals with respect to any drug candidate. ● Preclinical and clinical trials are very expensive, time-consuming and difficult to design and implement and may result in unforeseen costs. ● If the results of our clinical trials do not support our claims relating to a drug candidate, or if serious side effects are identified, the completion of development of such drug candidate may be significantly delayed or we may be forced to abandon development altogether. ● We may find it difficult to enroll patients in our clinical trials or patients may discontinue their participation in our clinical trials. ● Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of our product candidates in other jurisdictions. ● Dependence upon third-party service providers in connection with our clinical trials expose us to risks.
If we fail to comply with the regulatory requirements in international markets and/or receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of our product candidates will be harmed, which may have a material adverse effect on our prospects, business, results of operations and financial condition.
If we or our partners fail to comply with the regulatory requirements in international markets and/or receive applicable marketing approvals, the target market will be reduced and our ability to realize the full market potential of our product candidates will be harmed, which may have a material adverse effect on our prospects, business, results of operations, and financial condition.
Future acceptance and use of any of our products will depend upon a number of factors including: ● perceptions by physicians, patients, third party payors and others in the medical community about the safety and effectiveness of Elfabrio or Elelyso, or any future product, if any; ● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; ● the prevalence and severity of any side effects, including any limitations or warnings contained in our products’ approved labeling, including the boxed warning associated with Elfabrio in the United States; 38 Table of Contents ● pharmacological benefits of Elfabrio or Elelyso, or any future product, if any relative to competing products and products under development; ● the efficacy and potential advantages relative to competing products and products under development; ● relative convenience and ease of administration; ● effectiveness of education, marketing and distribution efforts by Chiesi, Pfizer and any other relevant licensees and distributors; ● publicity concerning Elfabrio or Elelyso, or any future product, if any, or concerning competing products and treatments; and ● the price for our products and competing products.
Future acceptance and use of any of our products will depend upon a number of factors including: ● perceptions by physicians, patients, third party payors and others in the medical community about the safety and effectiveness of Elfabrio or Elelyso, or any future product, if any; ● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; 34 Table of Contents ● the prevalence and severity of any side effects, including any limitations or warnings contained in our products’ approved labeling, including the boxed warning associated with Elfabrio in the United States; ● pharmacological benefits of Elfabrio or Elelyso, or any future product, if any relative to competing products and products under development; ● the efficacy and potential advantages relative to competing products and products under development; ● relative convenience and ease of administration; ● effectiveness of education, marketing and distribution efforts by Chiesi, Pfizer and any other relevant licensees and distributors; ● publicity concerning Elfabrio or Elelyso, or any future product, if any, or concerning competing products and treatments; and ● the price for our products and competing products.
Our policy is to enter agreements relating to the non-disclosure of confidential information with third parties, including our contractors, consultants, advisors and research collaborators, as well as agreements that purport to require the disclosure and assignment to us of the rights to the ideas, developments, discoveries and inventions of our employees and consultants while we employ them.
Our policy is to enter into agreements relating to the non-disclosure of confidential information with third parties, including our contractors, consultants, advisors and research collaborators, as well as agreements that purport to require the disclosure and assignment to us of the rights to the ideas, developments, discoveries and inventions of our employees and consultants while we employ them.
Risks Related to Investing in our Common Stock ● The market price of our common stock may fluctuate significantly; future sales of our common stock could reduce our stock price. ● Compliance with changing regulation of corporate governance and public disclosure may result in additional expenses or divert management’s attention. ● Delaware law and our organizational documents contain certain anti-takeover provisions. ● Our Amended and Restated Bylaws provide for limits on our stockholders ’ ability to obtain a favorable judicial forum. * * * 36 Table of Contents Risks Related to the Commercialization and Continued Approval of our Products We currently depend heavily on the generation of revenues from the sales of Elfabrio and Elelyso.
Risks Related to Investing in our Common Stock ● The market price of our common stock may fluctuate significantly; future sales of our common stock could reduce our stock price. ● Compliance with changing regulation of corporate governance and public disclosure may result in additional expenses or divert management’s attention. ● Delaware law and our organizational documents contain certain anti-takeover provisions. ● Our Amended and Restated Bylaws provide for limits on our stockholders ’ ability to obtain a favorable judicial forum. * * * 32 Table of Contents Risks Related to the Commercialization and Continued Approval of our Products We currently depend heavily on the generation of revenues from the sales of Elfabrio and Elelyso.
Furthermore, any additional source of financing will likely involve the issuance of our equity securities, which will have a dilutive effect on our stockholders. 53 Table of Contents Risks Related to Intellectual Property Matters If we fail to adequately protect or enforce our intellectual property rights or secure rights to third party patents, the value of our intellectual property rights would diminish and our business, competitive position and results of operations would suffer.
Furthermore, any additional source of financing will likely involve the issuance of equity securities, which will have a dilutive effect on our stockholders. 49 Table of Contents Risks Related to Intellectual Property Matters If we fail to adequately protect or enforce our intellectual property rights or secure rights to third party patents, the value of our intellectual property rights would diminish and our business, competitive position and results of operations would suffer .
If a dispute arises, a court may determine that the right belongs to a third party, and enforcement of our rights can be costly and unpredictable. In addition, we rely on trade secrets and proprietary know-how that we seek 54 Table of Contents to protect in part by confidentiality agreements with our employees, contractors, consultants, advisors and others.
If a dispute arises, a court may determine that the right belongs to a third party, and enforcement of our rights can be costly and unpredictable. In addition, we rely on trade secrets and proprietary know-how that we seek 50 Table of Contents to protect in part by confidentiality agreements with our employees, contractors, consultants, advisors and others.
Our Amended and Restated Bylaws, or our Bylaws, provide that, unless we consent to the selection of an alternative forum, the Court of Chancery of the State of Delaware (or, if the Court of Chancery does not have jurisdiction, another State court in Delaware or the federal district court for the District of Delaware) is the sole and exclusive forum for (i) any derivative action or proceeding brought on our behalf, (ii) any action asserting a claim of breach of fiduciary duty owed by any of our directors, stockholders, officers or other employees to us or to our stockholders, (iii) any action 60 Table of Contents asserting a claim arising pursuant to the DGCL or our Certificate of Incorporation, as amended, or our Bylaws, or (iv) any action asserting a claim governed by the internal affairs doctrine.
Our Amended and Restated Bylaws, or our Bylaws, provide that, unless we consent to the selection of an alternative forum, the Court of Chancery of the State of Delaware (or, if the Court of Chancery does not have jurisdiction, another State court in Delaware or the federal district court for the District of Delaware) is the sole and exclusive forum for (i) any derivative action or proceeding brought on our behalf, (ii) any action asserting a claim of breach of fiduciary duty owed by any of our directors, stockholders, officers or other employees to us or to our stockholders, (iii) any action asserting a claim arising pursuant to the DGCL or our Certificate of Incorporation, as amended, or our Bylaws, or (iv) any action asserting a claim governed by the internal affairs doctrine.
If we fail to satisfy these conditions, we may be required to refund grants previously received together with interest and penalties which could have a material adverse effect on our business and results of operations. In the past, our research and development efforts have been financed, in part, through grants that we have received from NATI.
If we fail to satisfy these conditions, we may be required to refund grants previously received together with interest and penalties which could have a material adverse effect on our business and results of operations. In the past, our research and development efforts were financed, in part, through grants that we received from NATI.
If we or any of our current or future partners breach or terminate the agreements that make up such arrangements, our partners otherwise fail to conduct their obligations under such arrangements in a timely manner, there is a dispute about their obligations or if either party terminates the applicable agreement or elects not to continue the arrangement, we may not enjoy the benefits of the agreements or receive a sufficient amount of royalty or 41 Table of Contents milestone payments from them, if any, which may have a material adverse effect on our business, results of operations and financial condition.
If we or any of our current or future partners breach or terminate the agreements that make up such arrangements, our partners otherwise fail to conduct their obligations under such arrangements in a timely manner, there is a dispute about their obligations or if either party terminates the applicable agreement or elects not to continue the arrangement, we may not enjoy the benefits of the agreements or receive a sufficient amount of royalty or milestone payments from them, if any, which may have a material adverse effect on our business, results of operations, and financial condition.
If we or any of our collaborators are found to be in violation of any of the laws described above and other applicable state and federal fraud and abuse laws, we may be subject to penalties, including civil and criminal penalties, damages, fines, exclusion from government healthcare reimbursement programs and the curtailment or restructuring or our operations, any of which could have a material adverse effect on our business, results of operations and financial condition.
If we or any of our 36 Table of Contents collaborators are found to be in violation of any of the laws described above and other applicable state and federal fraud and abuse laws, we may be subject to penalties, including civil and criminal penalties, damages, fines, exclusion from government healthcare reimbursement programs and the curtailment or restructuring or our operations, any of which could have a material adverse effect on our business, results of operations, and financial condition.
In-licensing additional drug candidates may significantly increase our capital requirements, and place a strain on the time of our existing personnel, which may delay or otherwise adversely affect the development of our existing drug candidates or cause us to re-prioritize our drug pipeline if we do not have the necessary capital 43 Table of Contents resources to develop all of our drug candidates, which may have a material adverse effect on our business, results of operations and financial condition.
In-licensing additional drug candidates may significantly increase our capital requirements, and place a strain on the time of our existing personnel, which may delay or otherwise adversely affect the development of our existing drug candidates or cause us to re-prioritize our drug pipeline if we do not have the necessary capital resources to develop all of our drug candidates, which may have a material adverse effect on our business, results of operations, and financial condition.
Furthermore, the approval of pharmaceutical products generally includes requirements related to the preparation of a Risk Evaluation and Mitigation Strategy, or REMS, or a risk management plan as required by the EMA, which could include a medication guide outlining the risks of such side effects for distribution to patients, a communication plan for healthcare providers and/or other elements to assure safe use.
Furthermore, the approval of pharmaceutical products generally includes requirements related to the preparation of a Risk Evaluation and Mitigation Strategy, or REMS, or a risk management plan as required by the EMA, which could include a medication guide outlining the risks of such side 33 Table of Contents effects for distribution to patients, a communication plan for healthcare providers and/or other elements to assure safe use.
Our failure to adhere to or successfully implement processes in response to changing regulatory requirements in this area could result in legal liability or impairment to our reputation in the marketplace, which could have a material adverse effect on our business, financial condition and results of operations. 45 Table of Contents We could be subject to securities class action litigation.
Our failure to adhere to or successfully implement processes in response to changing regulatory requirements in this area could result in legal liability or impairment to our reputation in the marketplace, which could have a material adverse effect on our business, results of operations, and financial condition. We could be subject to securities class action litigation.
Our product candidates may fail to show the required safety and effectiveness through clinical trials despite positive results in preclinical studies or having successfully advanced through initial clinical trials. Any failure or delay in commencement or completion of any clinical trials of our product candidates will have a material adverse effect on our business, results of operations and financial condition.
Our product candidates may fail to show the required safety and effectiveness through clinical trials despite positive results in preclinical studies or having successfully advanced through initial clinical trials. 46 Table of Contents Any failure or delay in commencement or completion of any clinical trials of our product candidates will have a material adverse effect on our business, results of operations, and financial condition.
The results of our clinical trials with respect to any drug candidate might not support our claims of safety or efficacy, the results of our clinical trials may fail to conclusively show superiority over other commercially available treatments for the same or similar indications, the effects of our drug candidates may not be the desired effects or may include 50 Table of Contents undesirable side effects or the drug candidates may have other unexpected characteristics.
The results of our clinical trials with respect to any drug candidate might not support our claims of safety or efficacy, the results of our clinical trials may fail to conclusively show superiority over other commercially available treatments for the same or similar indications, the effects of our drug candidates may not be the desired effects or may include undesirable side effects, or the drug candidates may have other unexpected characteristics.
Thus, any patents we own or license from or to third parties may not provide any protection against our competitors and those who infringe upon our patents. Furthermore, the life of our patents is limited.
Thus, any patents we own or license from or to third parties may not provide any protection against our competitors and those who infringe upon our patents. Furthermore, the term of our patents is limited.
The successful worldwide commercialization of Elfabrio and Elelyso depends on several factors, including the following: ● Chiesi’s efforts under the Chiesi Agreements and the effectiveness of Chiesi’s commercial strategy and its execution of that strategy, including its pricing strategy, its development and maintenance of successful sales and marketing organizations and the effectiveness of its efforts to obtain adequate third-party reimbursements and, to a lesser extent, Pfizer’s and Fiocruz’s efforts; ● expanding the scope of the countries in which our products are approved for marketing; ● maintaining the cGMP compliance of our manufacturing facility or establishing manufacturing arrangements with third parties; ● the willingness of patients with Fabry disease and Gaucher disease to switch from other treatments to Elfabrio or Elelyso, as the case may be; ● competition from other approved treatments of Fabry disease and Gaucher disease; ● the continued acceptable safety and efficacy profile of Elfabrio and Elelyso; and ● other risks described in these Risk Factors.
The successful worldwide commercialization of Elfabrio and Elelyso depends on several factors, including the following: ● the effectiveness of Chiesi’s commercial strategy and its execution of that strategy, including its pricing strategy, its development and maintenance of successful sales and marketing organizations, and the effectiveness of its efforts to obtain adequate third-party reimbursements and, to a lesser extent, Pfizer’s and Fiocruz’s commercial efforts; ● expansion by Chiesi and Pfizer of the scope of the countries in which our products are approved for marketing; ● maintaining the cGMP compliance of our manufacturing facility or establishing manufacturing arrangements with third parties; ● the willingness of patients with Fabry disease and Gaucher disease to switch from other treatments to Elfabrio or Elelyso, as the case may be; ● competition from other approved treatments of Fabry disease and Gaucher disease; ● the continued acceptable safety and efficacy profile of Elfabrio and Elelyso; and ● other risks described in these Risk Factors.
Service of process upon us or our non-U.S. resident directors and officers and enforcement of judgments obtained in the United States against us or our non-U.S. resident directors and executive officers may be difficult to obtain within the United States.
Service of process upon us or our non-U.S. resident directors and officers and enforcement of judgments against us or our non-U.S. resident directors and executive officers may be difficult to obtain within the United States.
Any failure to comply with the supply commitments to Pfizer and/or Chiesi may have a material adverse effect on our business, results of operations and financial condition. Our strategy, in certain cases, is to enter into collaboration agreements with third parties to leverage our ProCellEx system to develop product candidates.
Any failure to comply with the supply commitments to Pfizer and/or Chiesi may have a material adverse effect on our business, results of operations, and financial condition. Our strategy, in certain cases, is to enter into collaboration agreements with third parties to develop product candidates.
Failure to enter into such agreements, or non-compliance by us or our collaborators with such agreements, may have a material adverse effect on our business, results of operations and financial condition. Our strategy, in certain cases, is to enter into arrangements with pharmaceutical companies to leverage our ProCellEx system to develop additional product candidates.
Failure to enter into such agreements, or non-compliance by us or our collaborators with such agreements, may have a material adverse effect on our business, results of operations, and financial condition. Our strategy, in certain cases, is to enter into arrangements with pharmaceutical companies to develop additional product candidates.
Therefore, subjects that participate in ongoing clinical trials for products that are competitive with our drug candidates are not available for our clinical trials. An inability to enroll a sufficient number of patients for any of our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether.
Therefore, subjects that participate in ongoing clinical trials for products that are competitive with our drug candidates are not available for 47 Table of Contents our clinical trials. An inability to enroll a sufficient number of patients for any of our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether.
Members of our Board of Directors and our executive officers, could face an increased risk of personal liability in 59 Table of Contents connection with the performance of their duties. As a result, we may have difficulty attracting and retaining qualified directors and executive officers, which could have a material adverse effect on our business.
Members of our Board of Directors and our executive officers, could face an increased risk of personal liability in connection with the performance of their duties. As a result, we may have difficulty attracting and retaining qualified directors and executive officers, which could have a material adverse effect on our business.
Our competitive position and future revenues will depend in part on our ability and the ability of our licensors and collaborators to obtain and maintain patent protection for our products, methods, processes and other technologies, to preserve our trade secrets, to prevent third parties from infringing on our proprietary rights and to operate without infringing the proprietary rights of third parties.
Our competitive position and future revenues depends in part on our ability and the ability of our licensors and collaborators to obtain and maintain patent protection for our products, methods, processes, and other technologies, to preserve our trade secrets, to prevent third parties from infringing on our proprietary rights, and to operate without infringing the proprietary rights of third parties.
For example, Chiesi must follow a risk management plan agreed upon with the EMA with respect to Elfabrio, which 37 Table of Contents includes risk minimization measures in connection with risks associated with hypersensitivity reactions and possible medication errors in the home infusion setting. Our product candidates, if approved, may also be subject to certain post-authorization reporting requirements.
For example, Chiesi must follow a risk management plan agreed upon with the EMA with respect to Elfabrio, which includes risk minimization measures in connection with risks associated with hypersensitivity reactions and possible medication errors in the home infusion setting. Our product candidates, if approved, may also be subject to certain post-authorization reporting requirements.
Preclinical tests and phase I and phase II clinical trials are primarily designed to test safety, to study pharmacokinetics and pharmacodynamics and to understand the side effects of product candidates at various doses and regimens. Success in preclinical studies and early clinical trials does not ensure that later large-scale efficacy trials will be successful nor does it predict final results.
Preclinical tests and Phase 1 and Phase 2 clinical trials are primarily designed to test safety, to study pharmacokinetics and pharmacodynamics, and to understand the side effects of product candidates at various doses and regimens. Success in preclinical studies and early clinical trials does not ensure that later large-scale efficacy trials will be successful nor does it predict final results.
Any failure by the Brazilian MoH to purchase BioManguinhos alfataliglicerase, by us to supply BioManguinhos alfataliglicerase for purchase or by Fiocruz to distribute BioManguinhos alfataliglicerase in Brazil, or the experience of significant delays in any of the foregoing, may have a material adverse effect on our business, results of operations and financial condition.
Any failure by the Brazilian MoH to purchase BioManguinhos alfataliglicerase or by Fiocruz to distribute BioManguinhos alfataliglicerase in Brazil, or the experience of significant delays in any of the foregoing, may have a material adverse effect on our business, results of operations, and financial condition.
Protalix Ltd. may not receive the required approvals for any proposed transfer and, if received, Protalix Ltd. may be required to pay NATI a portion of the consideration that it 57 Table of Contents receives upon any sale of such technology by a non-Israeli entity.
Protalix Ltd. may not receive the required approvals for any proposed transfer and, if received, Protalix Ltd. may be required to pay NATI a portion of the consideration that it receives upon any sale of such technology by a non-Israeli entity.
Investors may have difficulties enforcing a U.S. judgment, including judgments based upon the civil liability provisions of the U.S. federal securities laws against us, our executive officers and most of our directors or asserting U.S. securities laws claims in Israel.
Investors may have difficulties enforcing a U.S. judgment, including judgments based upon the civil liability provisions of the U.S. federal securities laws, against us, our executive officers and most of our directors or asserting U.S. securities laws claims outside the U.S.
In addition, we and contract manufacturers are subject to the rules and regulations of the FDA and comparable foreign regulatory authorities and face the risk that any of those authorities may find that they are not in compliance with applicable regulations.
In addition, we and contract manufacturers are subject to the rules and regulations of the FDA and comparable 38 Table of Contents foreign regulatory authorities and face the risk that any of those authorities may find that they are not in compliance with applicable regulations.
Any failure or perceived failure by us to comply with local or foreign laws or regulation, our internal policies and procedures or our contracts governing our processing of personal information could result in negative publicity, government investigations and enforcement actions, claims by third parties and damage to our reputation, any of which could have a material adverse effect on our business, results of operation and financial condition.
Any failure or perceived failure by us to comply with local or foreign laws or regulation, our internal policies and procedures or our contracts governing our processing of personal information could result in negative publicity, government investigations 41 Table of Contents and enforcement actions, claims by third parties and damage to our reputation, any of which could have a material adverse effect on our business, results of operations, and financial condition.
In addition, full reimbursement may not be available for high priced products. Moreover, eligibility for coverage does not imply that any approved product will be reimbursed in all cases or at a rate that allows us to make a profit or even cover our costs.
In addition, full reimbursement may not be available for high priced products. Moreover, eligibility for coverage does not imply that any approved product will be reimbursed in all cases or at a rate 35 Table of Contents that allows us to make a profit or even cover our costs.
In addition, we, the FDA or other regulatory authorities may suspend any clinical trial at any time if it appears that we are exposing participants in the trial to unacceptable safety or health risks or if the FDA or such other regulatory authorities, as applicable, find deficiencies in our IND submissions or the conduct of the trial.
In addition, we, the FDA or other regulatory authorities may suspend a clinical trial at any time if it appears that participants in the trial are being exposed to unacceptable safety or health risks or if the FDA or such other regulatory authorities, as applicable, find deficiencies in our IND submissions or the conduct of the trial.
As of December 31, 2024, we held, or had license rights to, approximately 75 patents. If patent rights covering our products or technologies are not sufficiently broad, they may not provide us with sufficient proprietary protection or competitive advantages against competitors with similar products and technologies.
As of December 31, 2025, we held, or had license rights to, approximately 70 patents. If patent rights covering our products or technologies are not sufficiently broad, they may not provide us with sufficient proprietary protection or competitive advantages against competitors with similar products and technologies.
If we face such litigation, it could result in substantial costs and divert management’s attention and resources, which could have a material adverse effect on our business, results of operation and financial condition. If product liability claims are brought against us, it may result in reduced demand for our products and product candidates or damages that exceed our insurance coverage.
Any such litigation, could result in substantial costs and divert management’s attention and resources, which could have a material adverse effect on our business, results of operations, and financial condition. If product liability claims are brought against us, it may result in reduced demand for our products and product candidates or damages that exceed our insurance coverage.
Our collaborators may also have relationships with other commercial entities, some of whom may compete with us. If our collaborators also assist our competitors, our competitive position could be harmed. We have only limited experience in regulatory affairs, and some of our drug candidates may be based on new technologies.
Our collaborators may also have relationships with other commercial entities, some of whom may compete with us. If our collaborators also assist our competitors, our competitive position could be harmed. We have limited experience in regulatory affairs compared to our larger competitors, and some of our drug candidates may be based on new technologies.
Ongoing and revived hostilities or other Israeli political or economic factors, could prevent or delay shipments of our products, harm our operations and product development and cause any future sales to decrease.
Ongoing and revived hostilities or other Israeli political or economic factors, could prevent or delay shipments of our products, harm our operations and product development, interrupt or delay our clinical activities, and cause any future sales to decrease.
In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we intend to charge for our drugs is also subject to approval.
In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we or our partners intend to charge for our products is also subject to approval.
HIPAA created several new federal crimes, including health care fraud, and false statements relating to health care matters. The health care fraud statute prohibits knowingly and willfully executing a scheme to defraud any health care 40 Table of Contents benefit program, including private third-party payers.
HIPAA created several new federal crimes, including health care fraud, and false statements relating to health care matters. The health care fraud statute prohibits knowingly and willfully executing a scheme to defraud any health care benefit program, including private third-party payers.
We anticipate that the market price of our common stock is likely to continue to fluctuate significantly in response to numerous factors, some of which are beyond our control, such as: ● sales of Elfabrio by Chiesi; ● purchases of BioManguinhos alfataliglicerase in Brazil; ● the progress and results of the studies of our product candidates under development; ● the announcement of new products or product enhancements by us or our competitors; 58 Table of Contents ● developments concerning intellectual property rights and regulatory approvals; ● variations in our and our competitors’ results of operations; ● changes in earnings estimates or recommendations by securities analysts; ● developments in the biotechnology industry; and ● general market conditions and other factors, including factors unrelated to our operating performance, such as the Israel-Hamas war.
We anticipate that the market price of our common stock is likely to continue to fluctuate significantly in response to numerous factors, some of which are beyond our control, such as: ● Chiesi’s sales of Elfabrio; ● purchases of BioManguinhos alfataliglicerase in Brazil; ● the progress and results of the studies of our product candidates under development; ● the announcement of new products or product enhancements by us or our competitors; ● developments concerning intellectual property rights and regulatory approvals; ● variations in our and our competitors’ results of operations; ● changes in earnings estimates or recommendations by securities analysts; ● developments in the biotechnology industry; and 54 Table of Contents ● general market conditions and other factors, including factors unrelated to our operating performance, such as the local military conflict.
We expect to continue to incur significant operating expenditures, and we anticipate that our expenses will increase in the foreseeable future as we seek to in-license additional technologies, continue to undertake preclinical development and clinical trials for our current and new drug candidates and seek regulatory approvals for our drug candidates.
We expect to continue to incur significant operating expenditures as we progress with the clinical development of PRX-115, and we anticipate that our expenses will increase in the foreseeable future as we seek to in-license additional technologies, continue to undertake preclinical development and clinical trials for our current and new drug candidates and seek regulatory approvals for our drug candidates.
We have filed U.S. and international patent applications for process patents, as well as composition of matter patents, for Elfabrio, Elelyso and our product candidates.
We have filed U.S. and international patent applications for process patents, as well as composition of matter patents, for our products and product candidates.
Approvals of BLAs, NDAs, MAAs and comparable marketing authorization applications worldwide requires that we demonstrate that the subject drug candidate is safe and effective for its intended use which requires significant research, animal or preclinical trials and human or clinical tests trials.
Approvals of marketing authorization applications worldwide generally requires that we demonstrate that the subject drug candidate is safe and effective for its intended use which requires significant research, animal or preclinical trials and human or clinical tests trials.
While our assessment of our internal control over financial reporting resulted in our 44 Table of Contents conclusion that as of December 31, 2024, our internal control over financial reporting was effective, we cannot predict the outcome of our testing or any subsequent testing by our auditor in future periods.
While our assessment of our internal control over financial reporting resulted in our conclusion that as of December 31, 2025, our internal control over financial reporting was effective, we cannot predict the outcome of our testing or any subsequent testing by our auditor in future periods.
As of December 31, 2024, we had approximately 50 pending patent applications. However, the filing of a patent application does not mean that we will be issued a patent, or that any patent eventually issued will be as broad as requested in the patent application or sufficient to protect our technology.
As of December 31, 2025, we had approximately 45 pending patent applications. However, the filing of a patent application does not mean that there will be a resulting patent, or that any patent eventually issued will be as broad as requested in the patent application or sufficient to protect our technology.
If we are unable to enhance our portfolio of product candidates, our business may be adversely affected. A key element of our business strategy is to establish a portfolio of product candidates as targets for development and eventual commercialization. We seek to do so through our internal research programs and strategic collaborations.
If we are unable to enhance our portfolio of product candidates, our business may be adversely affected. A key element of our business strategy is to establish a portfolio of product candidates, particularly in the rare and orphan disease spaces, as targets for development and eventual commercialization. We seek to do so through our internal research programs and strategic collaborations.
In addition, we may sell additional shares of our common stock in the future to raise capital. At December 31, 2024, there were outstanding options to purchase common stock issued covering approximately 7.4 million shares of our common stock with a weighted average exercise price of $1.98 per share.
In addition, we may sell additional shares of our common stock in the future to raise capital. At December 31, 2025, there were outstanding options to purchase common stock issued covering approximately 8.3 million shares of our common stock with a weighted average exercise price of $1.76 per share.
These measures, however, may not adequately protect us from material adverse effects. The tax benefits available to us require that we meet several conditions and may be terminated or reduced in the future, which would increase our taxes. We are able to take advantage of tax exemptions and reductions resulting from the “Approved Enterprise” status of our facilities in Israel.
The tax benefits available to us require that we meet several conditions and may be terminated or reduced in the future, which would increase our taxes. We are able to take advantage of tax exemptions and reductions resulting from the “Approved Enterprise” status of our facilities in Israel.
Any failure or delay in the establishment of a portfolio of product candidates as targets for development and eventual commercialization may have a material adverse effect on our business, results of operations and financial condition.
Any failure or delay in the establishment of a portfolio of product candidates may have a material adverse effect on our business, results of operations, and financial condition.
A failure to maintain or regain compliance with applicable listing standards could adversely affect the liquidity of our common stock and could result in an event of default under the 2024 Indenture, which would have a material adverse effect on our business, results of operations and financial condition.
A failure to maintain or regain compliance with applicable listing standards could adversely affect the liquidity of our common stock which would have a material adverse effect on our business, results of operations, and financial condition.
Any failure to commercialize Elfabrio or Elelyso globally or the experience of significant delays in doing so will have a material adverse effect on our business, results of operations and financial condition.
Any failure to continue or expand the commercialization of either Elfabrio or Elelyso globally or the experience of significant delays in doing so may have a material adverse effect on our business, results of operations, and financial condition.
To date, we have not suffered any disruptions to our operations from the 56 Table of Contents absence of employees in connection with the current military action.
To date, we have not suffered any disruptions to our operations from the absence of employees in connection with the current military actions.
Our NOL carryforwards as of December 31, 2024, are equal to approximately $227.2 million, of which approximately $22.2 million may be restricted under Section 382 of the Internal Revenue Code, or the IRC. IRC Section 382 applies whenever a corporation with NOLs experiences an ownership change.
Our NOL carryforwards as of December 31, 2025, are equal to approximately $219.8 million, of which approximately $20.0 million may be restricted under Section 382 of the Internal Revenue Code, or the IRC. IRC Section 382 applies whenever a corporation with NOLs experiences an ownership change.
Also at December 31, 2024, there were 4,139,412 shares of common stock available for future for issuance in connection with future grants of incentives under our Amended and Restated Protalix BioTherapeutics, Inc. 2006 Stock Incentive Plan, as amended .
Also at December 31, 2025, there were 2,092,933 shares of common stock available for future for issuance in connection with future grants of incentives under our Amended and Restated Protalix BioTherapeutics, Inc. 2006 Stock Incentive Plan, as amended.
If coverage and reimbursement are not available or are 39 Table of Contents available only to limited levels, the sales of Elfabrio, Elelyso or other future products, if any, may be diminished or we may not be able to sell such products profitably.
Limited reimbursement amounts may reduce the demand for, or the price of, Elfabrio, Elelyso or any other future products. If coverage and reimbursement are not available or are available only to limited levels, the sales of Elfabrio, Elelyso or other future products, if any, may be diminished or we may not be able to sell such products profitably.
In addition, the FDA and other regulatory authorities, as applicable, must approve any manufacturer and/or replacement manufacturer, including us. 42 Table of Contents Any failure to identify and maintain fill and finish service providers could delay our preclinical and clinical trials, the approval, if any, of our potential drug candidates by the FDA and other regulatory authorities, or the commercialization of our drug candidates, or could result in higher product costs or otherwise deprive us of potential product revenues.
Any failure to identify and maintain fill and finish service providers could delay our preclinical and clinical trials, the approval, if any, of our potential drug candidates by the FDA, and other regulatory authorities, or the commercialization of our drug candidates, or could result in higher product costs or otherwise deprive us of potential product revenues.
In that event, the U.S. dollar cost of our operations in Israel will increase and our U.S. dollar-measured results of operations will be adversely affected. To the extent that the value of the NIS increases against the U.S. dollar, our expenses on a dollar cost basis increase.
In that event, the U.S. dollar cost of our operations in Israel, and other such jurisdictions, will increase, and our U.S. dollar-measured results of operations will be adversely affected. To the extent that the value of any such foreign currency, including the NIS or the Euro, increases against the U.S. dollar, our expenses on a dollar cost basis increase.
Accordingly, our ability to conduct our operations, service any current or future debt and pay dividends, if any, is dependent upon the earnings from the business conducted by Protalix Ltd.
We are a holding company with no operations of our own. Accordingly, our ability to conduct our operations, service any current or future debt and pay dividends, if any, is dependent upon the earnings from the business conducted by Protalix Ltd.
Failure to comply with applicable requirements of the FDA or comparable foreign regulatory authorities could result in, among other things, any of the following actions: ● warning letters; ● fines and other monetary penalties; ● unanticipated expenditures; ● delays in the FDA’s or other foreign regulatory authorities’ approving, or the refusal of any regulatory authority to approve, any drug candidate; ● product recall or seizure; ● interruption of manufacturing or clinical trials; ● operating restrictions; ● injunctions; and ● criminal prosecutions. 48 Table of Contents In addition to the approval requirements, other numerous and pervasive regulatory requirements apply, both before and after approval, to us, our drug candidates, our suppliers, contract manufacturers, and contract testing laboratories.
Failure to comply with applicable requirements of the FDA or comparable foreign regulatory authorities could result in, among other things, any of the following actions: ● warning letters; 44 Table of Contents ● fines and other monetary penalties; ● unanticipated expenditures; ● delays in the FDA’s or other foreign regulatory authorities’ approving, or the refusal of any regulatory authority to approve, any drug candidate; ● product recall or seizure; ● interruption of manufacturing or clinical trials; ● operating restrictions; ● injunctions; and ● criminal prosecutions.
These factors may affect our ability or the time we require to obtain necessary regulatory approvals. We have only limited experience in filing and prosecuting the applications necessary to gain regulatory approvals for medical devices and drug candidates.
These factors may affect our ability or the time we require to obtain necessary regulatory approvals. We have limited experience in filing and prosecuting the applications necessary to gain regulatory approvals for medical devices and drug candidates compared to certain large, multinational pharmaceutical companies with whom we compete.
A majority of our directors and all of our executive officers are residents of Israel, and accordingly, most of their assets and our assets are located outside the United States.
A majority of our directors and all of our executive officers are residents of either Israel or other non-U.S. countries, and accordingly, most of their assets and our assets are located outside the United States.
We have agreed to sell drug substance to Pfizer and Chiesi for the production of Elelyso and Elfabrio, respectively. With respect to Elelyso, our drug substance supply commitment is for a 15-year period after the execution of the Amended Pfizer Agreement, subject to certain terms and conditions.
We have agreed to sell drug substance to Pfizer and Chiesi for the production of Elelyso and Elfabrio, respectively. With respect to Elelyso, our drug substance supply commitment is until 2030, subject to certain terms and conditions.
Any such disruption may have a material adverse effect on our business, results of operations and financial condition. A certain portion of our expenses is incurred in New Israeli Shekels and, accordingly, our results of operations may be seriously harmed by currency fluctuations and inflation. We report our financial statements in U.S. dollars, our functional currency.
Any such disruption may have a material adverse effect on our business, results of operations, and financial condition. 52 Table of Contents A certain portion of our expenses is incurred in non-U.S. Dollar currencies, including New Israeli Shekels and the Euro, and, accordingly, our results of operations may be seriously harmed by currency fluctuations and inflation.
These inefficiencies may require us to use more of our NOLs than we otherwise might and may result in a tax liability without a corresponding distribution from our subsidiaries which could have a material adverse effect on our business, results of operations and financial condition. In addition, on December 22, 2017, the U.S.
These inefficiencies may require us to use more of our NOLs than we otherwise might and may result in a tax liability without a corresponding distribution from our subsidiaries which could have a material adverse effect on our business, results of operations, and financial condition. 42 Table of Contents We are a holding company with no operations of our own.
Currently, our sources of potential revenues are royalties and commercial milestone payments generated from Pfizer, Fiocruz and Chiesi. We have also generated revenues from research and development services and milestone and other payments we received in connection with our agreements with our commercialization partners, and generated capital from equity and debt offerings and other sources.
In the past, we have also generated revenues from research and development services and milestone and other payments we received in connection with our agreements with our commercialization partners, and generated capital from equity and debt offerings and other sources.
Protalix Ltd. is our wholly-owned subsidiary and thus a controlled foreign corporation of our company for U.S. federal income tax purposes. This organizational structure may create inefficiencies, as certain types of income and investments of Protalix Ltd. that otherwise would not be currently taxable under general U.S. federal income tax principles may become taxable.
This organizational structure may create inefficiencies, as certain types of income and investments of Protalix Ltd. that otherwise would not be currently taxable under general U.S. federal income tax principles may become taxable.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, while a failure or delay in obtaining 51 Table of Contents regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee regulatory approval for such product candidate will be obtained or maintained in any other jurisdiction, while a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others.
We have limited experience in selling, marketing or distributing products and limited internal capability to do so. We currently have very limited sales, marketing or distribution capabilities and no experience in building a sales force and distribution capabilities.
We have limited experience in selling, marketing or distributing products and limited internal capability to do so. We currently have very limited sales, marketing or distribution capabilities and no experience in building a sales force and distribution capabilities. Currently, the distribution of our commercial products are performed by Pfizer, Chiesi, and Fiocruz (in Brazil).
Although most of our expenses are incurred in U.S. dollars, we pay a portion of our expenses in New Israeli Shekels, or NIS, and as a result, we are exposed to risk to the extent that the inflation rate in Israel exceeds the rate of devaluation of the NIS in relation to the U.S. dollar or if the timing of these devaluations lags behind inflation in Israel.
Although most of our expenses are incurred in U.S. dollars, we pay a portion of our expenses in foreign currencies, including New Israeli Shekel and the Euro, and as a result, we are exposed to risk to the extent that the inflation rates in the jurisdictions in which we operate exceed the rate of devaluation of the applicable local currencies in relation to the U.S. dollar, or if the timing of these devaluations lags behind inflation in such jurisdictions.
We do not control and may not be able to effectively influence Fiocruz’s ability to distribute BioManguinhos alfataliglicerase in Brazil. Fiocruz has not complied with the purchase requirements of the Brazil Agreement in the past, and we expect Fiocruz will continue to not comply and may otherwise materially breach the agreement.
Fiocruz has not complied with the purchase requirements of the Brazil Agreement in the past, and we expect Fiocruz will continue to not comply and may otherwise materially breach the agreement.
Risks Related to our Financial Condition and Capital Requirements ● We may need to raise additional capital to operate our business, which may not be available on favorable terms, or at all. Risks Related to Intellectual Property Matters ● We may fail to adequately protect or enforce our intellectual property rights or secure rights to third party patents.
Risks Related to our Financial Condition and Capital Requirements ● We may need to raise additional capital to operate our business, which may not be available on favorable terms, or at all.
The approval process for any drug candidate may also be delayed by changes in government regulation, future legislation or administrative action or changes in policy of the FDA and comparable foreign authorities that occur prior to or during their respective regulatory reviews of such drug candidate.
The approval process for any drug candidate may also be delayed by changes in government regulation, future legislation or administrative action, or changes in policy of the FDA and comparable foreign authorities that occur prior to or during their respective regulatory reviews of such drug candidate. 45 Table of Contents Delays in obtaining regulatory approvals with respect to any drug candidate may materially and adversely affect our prospects, business, results of operations and financial condition.
Continued non-compliance may have a material adverse effect on our business, results of operations and financial condition. We face the risk of lower than anticipated purchases of BioManguinhos alfataliglicerase by the Brazilian MoH. In addition, we may fail to supply the intended amounts on time, if at all.
Continued non- 37 Table of Contents compliance may result in our decision to terminate the agreement, and may have a material adverse effect on our business, results of operations, and financial condition. We face the risk of lower than anticipated purchases of BioManguinhos alfataliglicerase by the Brazilian MoH.
Effective internal control over financial reporting is necessary for us to provide reliable financial reports. Any failure to implement required new or improved controls, or difficulties encountered in their implementation could cause us to fail to meet our reporting obligations.
Any failure to implement required new or improved controls, or difficulties encountered in their implementation could cause us to fail to meet our reporting obligations.
If we cannot enforce our employees’ non-compete agreements, we may be unable to prevent our competitors from benefiting from the expertise of our former employees, which may have a material adverse effect on our business, results of operations and financial condition.
If we cannot enforce our employees’ non-compete agreements, we may be unable to prevent our competitors from benefiting from the expertise of our former employees, which may have a material adverse effect on our business, results of operations, and financial condition. 40 Table of Contents If we fail to maintain an effective system of internal control over financial reporting, we may not be able to accurately report our financial results or prevent fraud.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeWe work with third-party service providers from time to time that assist us to identify, assess and manage cybersecurity risks, including professional SEIM SOC and other services firms, threat intelligence service providers, cybersecurity consultants, cybersecurity software providers, managed cybersecurity service providers, and penetration testing.
Biggest changeWe work with third-party service providers that monitor our systems on a continuous, round-the-clock basis, and assist us to identify, assess and manage cybersecurity risks, including professional SEIM SOC and other services firms, threat intelligence service providers, cybersecurity consultants, cybersecurity software providers, managed cybersecurity service providers, and penetration testing.
We conduct a thorough risk assessment by identifying critical assets, recognizing potential threats and vulnerabilities, and implement strategies to mitigate these risks and their possible impacts. We establish incident response plans and provide cybersecurity training to our employees and monitor their activity to ensure adherence to our security protocols.
We conduct a thorough risk assessment by identifying critical assets, recognizing potential threats and vulnerabilities, and implement strategies to mitigate these risks and their possible impacts. We establish incident response plans and provide cybersecurity and phishing training to our employees and monitor their activity to ensure adherence to our security protocols.
In addition, the company’s incident response processes include reporting to our Board of Directors for certain cybersecurity incidents. Management is involved with our efforts to prevent, detect, and mitigate cybersecurity incidents by overseeing preparation of cybersecurity policies and procedures, testing incident response plans and engaging vendors to conduct penetration tests.
In addition, our incident response processes include reporting to our Board of Directors for certain cybersecurity incidents. Management is involved with our efforts to prevent, detect, and mitigate cybersecurity incidents by overseeing preparation of cybersecurity policies and procedures, testing incident response plans and engaging vendors to conduct penetration tests.
No risks from cybersecurity threats have occurred that have materially affected or are reasonably likely to materially affect our business, results of operations or financial condition. 61 Table of Contents Governance Our cybersecurity risk assessment and management processes are implemented and maintained by certain members of our management, including our Senior Director, Information Technology, who reports to our Sr.
No risks from cybersecurity threats have occurred that have materially affected or are reasonably likely to materially affect our business, results of operations or financial condition. Governance Our cybersecurity risk assessment and management processes are implemented and maintained by certain members of our management, including our Senior Director, Information Technology, who reports to our Sr. Vice President, Operations.
Vice President, Operations. Management is also responsible for hiring appropriate personnel, integrating cybersecurity considerations into our overall risk management strategy, and for communicating key priorities to employees, as well as for approving budgets, helping prepare for cybersecurity incidents, approving cybersecurity processes, and reviewing security assessments and other security-related reports.
Management is also responsible for hiring appropriate personnel, integrating cybersecurity considerations into our overall risk management strategy, and for communicating key priorities to employees, as well as for approving budgets, helping prepare for cybersecurity incidents, approving cybersecurity processes, and reviewing security 57 Table of Contents assessments and other security-related reports.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeOur original lease for the facility was in effect until 2016 and we have exercised two of three options to extend the term, each for an additional five-year period. The lease is currently in effect until 2026 and we retain an additional option to extend the term for another five-year period thereafter.
Biggest changeOur original lease for the facility was in effect until 2016 and included three options to extend the leases for additional five-year periods. The leases have been amended to provide that the third option period for all leases will end on December 31, 2031, and will be associated with a uniform rent increase equal to 7.5%.
Item 2. Properties We maintain a U.S. corporate office in Hackensack, New Jersey. Our headquarters, including a manufacturing facility, executive offices and other facilities, are located in Carmiel, Israel.
Item 2. Properties Our headquarters, including a manufacturing facility, executive offices and other facilities, are located in Carmiel, Israel. We also maintain a U.S. corporate office in Hackensack, New Jersey.
In addition, we are entitled to use an additional 14,500 sq/ft in the same facility, which we may utilize in connection with any future expansion of our manufacturing facilities. Our facilities are equipped with the requisite laboratory services required to conduct our business, and we believe that the existing facilities are adequate to meet our needs for the foreseeable future.
In addition, we are entitled to use an additional 1,347 sq/m in the same facility, which we may utilize in connection with any future expansion of our manufacturing facilities. Our facilities are equipped with the requisite laboratory services required to conduct our business, and we believe that the existing facilities are adequate to meet our needs for the foreseeable future.
Our facilities in Israel currently contain approximately 14,700 sq/ft of manufacturing space and 3,400 sq/ft for a pilot plant, 11,700 sq/ft for offsite warehouse space and approximately 43,100 sq/ft of laboratories, front warehouse and office space, and are leased at a rate of approximately $85,000 per month.
Our facilities in Israel currently contain approximately 1,466 sq/m of manufacturing space and 316 sq/m for a pilot plant, 1,057 sq/m for offsite warehouse space and approximately 4,400 sq/m of laboratories, front warehouse and office space, and are leased at a rate of approximately $90,000 per month.
Upon the exercise of each option to extend the term of the lease includes a 10% increase to the then current base rent. Item 3. Legal Proceedings We are not involved in any material legal proceedings. Item 4. Mine Safety Disclosures Not applicable. 62 Table of Contents PART II
Each option to renew a lease in each of the four option periods shall include a rent increase equal to 5% of the rent payable for the applicable previous option period. Item 3. Legal Proceedings We are not involved in any material legal proceedings. Item 4. Mine Safety Disclosures Not applicable. 58 Table of Contents PART II
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Thereafter, each lease will extend automatically, on an individual basis, for up to four additional five-year periods unless we provide the lessor with six months’ advance notice that we do not intend that any individual option extension become effective.

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeItem 4. Mine Safety Disclosures 62 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 63 Item 6. [Reserved] 63 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 64 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 72 Item 8.
Biggest changeItem 4. Mine Safety Disclosures 58 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity Securities 59 Item 6. [Reserved] 59 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 60 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 70 Item 8.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeSecurities Authorized for Issuance under Equity Compensation Plans The following table provides information as of December 31, 2024 with respect to the shares of our common stock that may be issued under our existing equity compensation plan. ​ ​ ​ ​ ​ ​ ​ ​ ​ A B C ​ ​ ​ ​ ​ ​ ​ Number of Securities Remaining ​ ​ Number of Securities ​ ​ ​ ​ Available for Future Issuance ​ ​ to be Issued ​ Weighted Average ​ Under Equity Compensation Plans ​ ​ Upon Exercise of ​ Exercise Price of ​ (Excluding Securities Reflected in Plan Category ​ Outstanding Options ​ Outstanding Options ​ Column A) Equity Compensation Plans Approved by Stockholders 7,402,295 ​ $ 1.98 4,139,412 Equity Compensation Plans Not Approved by Stockholders — ​ — — Total 7,402,295 ​ $ 1.98 4,139,412 ​ Recent Sales of Unregistered Securities None.
Biggest changeSecurities Authorized for Issuance under Equity Compensation Plans The following table provides information as of December 31, 2025 with respect to the shares of our common stock that may be issued under our existing equity compensation plan. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ A ​ ​ ​ B ​ ​ ​ C ​ ​ ​ ​ ​ ​ ​ Number of Securities Remaining ​ ​ Number of Securities ​ ​ ​ ​ Available for Future Issuance ​ ​ to be Issued ​ Weighted Average ​ Under Equity Compensation Plans ​ ​ Upon Exercise of ​ Exercise Price of ​ (Excluding Securities Reflected in Plan Category ​ Outstanding Options ​ Outstanding Options ​ Column A) Equity Compensation Plans Approved by Stockholders 8,274,278 ​ $ 1.76 2,092,933 Equity Compensation Plans Not Approved by Stockholders - ​ - — Total 8,274,278 ​ $ 1.76 2,092,933 ​ Recent Sales of Unregistered Securities None.
Holders As of March 1, 2025, there were approximately 60 holders of record of our common stock. A substantially greater number of holders of our common stock are “street name” or beneficial holders, whose shares are held of record by banks, brokers and other financial institutions.
Holders As of March 1, 2026, there were approximately 96 holders of record of our common stock. A substantially greater number of holders of our common stock are “street name” or beneficial holders, whose shares are held of record by banks, brokers, and other financial institutions.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

55 edited+31 added−36 removed34 unchanged
Biggest changeThe difference resulted primarily from a decrease of approximately $1.4 million in lower interest and related expenses due to the note conversions executed in 2023 and the September 2024 repayment in full of all the outstanding principal and interest payable under the 2024 Notes, as well as an increase in interest income, net of $0.7 million.
Biggest changeFinancial Expenses and Income, Net Financial expenses and income, net were as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ ​ ​ ​ ​ (U.S. dollars in thousands) ​ ​ ​ 2023 ​ ​ ​ 2024 ​ ​ ​ 2025 ​ ​ ​ 2025 vs. 2024 ​ ​ ​ 2024 vs. 2023 Financial expenses (income), net ​ $ 1,894 ​ $ (237) ​ $ 108 ​ $ 345 ​ $ (2,131) ​ The difference from financial expenses, net for the year ended December 31, 2025 compared to financial income, net for the year ended December 31, 2024 resulted primarily from approximately $1.3 million exchange rate costs partially offset by approximately $1.0 million lower notes interest expenses due to the September 2024 repayment in full of all 66 Table of Contents the outstanding principal and interest payable under the 2024 senior secured convertible promissory notes, or the 2024 Notes.
We intend to use our ProCellEx platform and PEGylation capabilities, as well as other modalities such as small molecules and antibodies, to take advantage of highly innovative opportunities. We are also exploring novel platform technologies.
We currently intend to use our ProCellEx platform and PEGylation capabilities, as well as other modalities such as small molecules and antibodies, to take advantage of highly innovative opportunities. We are also exploring novel platform technologies.
See “ Risk Factors—Significant parts of our operations are located in Israel and, therefore, our results may be adversely affected by political, economic and military conditions in Israel. ” We believe that our cash and cash equivalents and short-term bank deposits as of December 31, 2024 are sufficient to satisfy our capital needs for at least 12 months from the date that these financial statements are issued.
See “ Risk Factors—Significant parts of our operations are located in Israel and, therefore, our results may be adversely affected by political, economic, and military conditions in Israel .” We believe that our cash and cash equivalents and short-term bank deposits as of December 31, 2025 are sufficient to satisfy our capital needs for at least 12 months from the date that these financial statements are issued.
Fiocruz’s purchases of BioManguinhos alfataliglicerase to date have been significantly below certain agreed-upon purchase milestones and, accordingly, we have the right to terminate the Brazil Agreement. Notwithstanding the termination right, we are, at this time, continuing to supply BioManguinhos alfataliglicerase to Fiocruz and patients continue to be treated with BioManguinhos alfataliglicerase in Brazil.
Fiocruz’s purchases of BioManguinhos alfataliglicerase to date under such agreement have been significantly below certain agreed-upon purchase milestones and, accordingly, we have the right to terminate the Brazil Agreement. Notwithstanding the termination right, we are, at this time, continuing to supply BioManguinhos alfataliglicerase to Fiocruz and patients continue to be treated with BioManguinhos alfataliglicerase in Brazil.
We base our estimates on historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the 66 Table of Contents carrying value of assets and liabilities that are not readily apparent from other sources.
We base our estimates on historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the 62 Table of Contents carrying value of assets and liabilities that are not readily apparent from other sources.
Since its approval by the FDA, Elelyso has been marketed by Pfizer in accordance with the Pfizer Agreement. In October 2015, Protalix Ltd. and Pfizer entered into the Amended Pfizer Agreement, pursuant to which we sold to Pfizer our share in the collaboration created under the Pfizer Agreement for the commercialization of Elelyso.
Since its approval by the FDA, Elelyso has been marketed by Pfizer. In October 2015, Protalix Ltd. and Pfizer entered into the Amended Pfizer Agreement, pursuant to which we sold to Pfizer our share in the collaboration created under our original agreement with Pfizer for the commercialization of Elelyso.
The consideration for Protalix Ltd. is based on the drug product supplied to Chiesi and the average selling price of the drug product in the relevant territory multiplied by tiered payments as described in the relevant agreement.
The consideration for Protalix Ltd. is based on the drug product supplied to Chiesi and the average selling price of the drug product in each relevant territory multiplied by payments as described in the relevant agreement.
See “ Risk Factors—We may not obtain the necessary U.S., EMA or other worldwide regulatory approvals to commercialize our drug candidates in a timely manner, if at all, which would have a material adverse effect on our business, results of operations and financial condition. ” We expect our research and development expenses to continue to be our primary expense in the future as we continue the advancement of our clinical trials and preclinical product development programs for our product candidates.
See “ Risk Factors—We may not obtain the necessary U.S., EMA, or other worldwide regulatory approvals to commercialize our drug candidates in a timely manner, if at all, which would have a material adverse effect on our business, results of operations and financial condition .” We expect our research and development expenses to continue to be our primary expense in the future as we continue the advancement of our clinical trials and preclinical product development programs for our product candidates, in particular with respect to the RELEASE study.
The tax valuation allowance totaled approximately $50.7 million at December 31, 2024 (see Note 12 to our consolidated financial statements for additional information). Should our actual future taxable income by tax jurisdiction vary from estimates, additional allowances or reversals thereof may be necessary. Significant judgment is required in evaluating our uncertain tax positions.
The tax valuation allowance totaled approximately $50.4 million at December 31, 2025 (see Note 12 to our consolidated financial statements for additional information). Should our actual future taxable income by tax jurisdiction vary from estimates, additional allowances or reversals thereof may be necessary. Significant judgment is required in evaluating our uncertain tax positions.
Uncertain tax position totaled approximately $0.8 million at December 31, 2024 (see Note 12 to our consolidated financial statements for additional information). Research and Development Expense We expect our research and development expense to remain our primary expense in the near future as we continue to develop our product candidates.
Uncertain tax position totaled approximately $ 0.8 million at December 31, 2025 (see Note 12 to our consolidated financial statements for additional information). Research and Development Expense We expect our research and development expense to remain our primary expense in the near future as we continue to develop PRX-115 and our product candidates.
For a discussion of our accounting treatment for revenue recognition, see Note 1(k) to our consolidated financial statements .
For a discussion of our accounting treatment for revenue recognition, see Note 1(t) to our consolidated financial statements .
If all of the contingencies with respect to milestone payments under our research and license agreements are met, as of December 31, 2024, the aggregate milestone payments payable would be approximately $8.4 million, and would be payable, if at all, as our projects progress over the course of a number of years.
If all of the contingencies with respect to milestone payments under our research and license agreements are met, as of December 31, 2025, the aggregate milestone 69 Table of Contents payments payable would be approximately $8.4 million, and would be payable, if at all, as our projects progress over the course of a number of years.
Obtaining marketing approval with respect to any product candidate in any country is dependent on our ability to implement the necessary regulatory steps required to obtain such approvals, and demonstrate the safety and efficacy of its product candidates. We cannot reasonably predict the outcome of these activities. In March 2023, we initiated a phase I First-in-Human clinical trial of PRX-115.
Obtaining marketing approval with respect to any product candidate in any country is dependent on our ability to implement the necessary regulatory steps required to obtain such approvals, and demonstrate the safety and efficacy of its product candidates. We cannot reasonably predict the outcome of these activities. We have completed a Phase 1 First-in-Human clinical trial of PRX-115.
As part of the sale, we agreed to transfer our rights to Elelyso in Israel to Pfizer while gaining full rights to it in Brazil.
As part of the sale, we agreed to transfer our rights 61 Table of Contents to Elelyso in Israel to Pfizer while gaining full rights to it in Brazil.
We believe that the funds currently available to us are sufficient to satisfy our capital needs for at least 12 months from the date that these financial statements are issued . As discussed above, we may be required to raise additional capital to develop our product candidates and continue research and development activities.
We believe that the funds currently available to us are sufficient to satisfy our capital needs for at least 12 months from the date this report is issued. As discussed above, we may be required to raise additional capital to develop our product candidates and continue research and development activities.
Accordingly, we are turning our focus to new, early-stage product candidates that treat indications for which there are high unmet needs in terms of efficacy and safety, including renal diseases. Treatments of interest will address both genetic and non-genetic diseases.
To execute on the strategy, we are turning our focus to new, early-stage product candidates that treat indications for which there are high unmet needs in terms of efficacy and safety, including renal diseases. We believe our treatments of interest will address both genetic and non-genetic diseases.
The leases relate primarily to office, laboratory and manufacturing space and vehicles used by our employees. Our aggregate future minimum commitments under these facility and vehicles leases over the next five fiscal years is approximately $2.8 million as of December 31, 2024.
The leases relate primarily to office, laboratory and manufacturing space and vehicles used by our employees. Our aggregate future minimum commitments under these facility and vehicles leases over the next five fiscal years is approximately $1.7 million as of December 31, 2025.
In addition, since December 31, 2024, we issued 908,000 shares of our common stock in connection with the exercise of warrants issued in 2020 generating proceeds equal to approximately $2.1 million. The warrants expired on March 11, 2025. Accordingly, no warrants remain outstanding.
In addition, during the first quarter of the year ended December 31, 2025, we issued 908,000 shares of our common stock in connection with the exercise of warrants issued in 2020 generating proceeds equal to approximately $2.1 million. The warrants expired on March 11, 2025. Accordingly, no warrants remain outstanding.
Our first product, Elelyso, an ERT for the treatment of patients with Gaucher disease, was first approved by the FDA in May 2012 and is now approved for marketing in 23 markets including Brazil, Israel and others.
Our first product, Elelyso, an ERT for the treatment of patients with Gaucher disease, was first approved by the FDA in May 2012 and is now approved for marketing in more than 40 markets including Brazil, Israel and others. It is not approved for marketing in the EU.
As of December 31, 2024, we have a contractual obligation of approximately $0.6 million for employee rights upon retirement. We are also party to certain research and license agreements.
As of December 31, 2025, we had a contractual obligation of approximately $0.7 million for employee rights upon retirement. We are also party to certain research and license agreements.
Our product pipeline currently includes, among other candidates: (1) PRX-115, our plant cell-expressed recombinant PEGylated uricase (urate oxidase) – a chemically modified enzyme to treat uncontrolled gout; and 64 Table of Contents (2) PRX-119, our plant cell-expressed PEGylated recombinant human DNase I product candidate which we have designed for long and customized systemic circulation in the bloodstream for NETs-related diseases.
Except with respect to Elfabrio and Elelyso, we hold the worldwide commercialization rights to our other proprietary development candidates. 60 Table of Contents Our product pipeline currently includes, among other candidates: (1) PRX-115, our plant cell-expressed recombinant PEGylated uricase (urate oxidase) – a chemically modified enzyme to treat uncontrolled gout; and (2) PRX-119, our plant cell-expressed PEGylated recombinant human DNase I product candidate which we have designed for long and customized systemic circulation in the bloodstream for NETs-related diseases.
Research and development expense consists of: ● internal costs associated with research and development activities; ● payments made to third party contract research organizations, investigative/clinical sites and consultants; ● manufacturing development costs; ● personnel-related expenses, including salaries, benefits, travel and related costs for the personnel involved in research and development; ● activities relating to the advancement of product candidates through preclinical studies and clinical trials; and ● facilities and other allocated expenses, which include direct and allocated expenses for rent and maintenance of facilities, as well as laboratory and other supplies. 67 Table of Contents The following table identifies our current major research and development projects: Project Status Expected Near Term Milestones PRX-115 – PEGylated Uricase Phase I (completed) Phase II clinical trial expected to launch in the second half of 2025. ​ PRX-119 – Long Acting DNase I Preclinical ​ ​ We anticipate incurring increasing costs in connection with the continued development of PRX-115 and PRX-119 and in the expansion of our pipeline.
Research and development expense consists of: ● internal costs associated with research and development activities, in particular with respect to the RELEASE study; ● payments made to third-party contract research organizations, investigative/clinical sites, and consultants; ● manufacturing development costs; ● personnel-related expenses, including salaries, benefits, travel, and related costs for the personnel involved in research and development; ● activities relating to the advancement of product candidates through preclinical studies and clinical trials; and ● facilities and other allocated expenses, which include direct and allocated expenses for rent and maintenance of facilities, as well as laboratory and other supplies. 63 Table of Contents The following table identifies our current major research and development projects: Project ​ ​ ​ Status ​ ​ ​ Expected Near Term Milestones PRX-115 – PEGylated Uricase Phase I (completed) Completion of enrollment in the RELEASE study ​ PRX-119 – Long Acting DNase I Preclinical IND-enabling studies ​ ​ ​ ​ ​ Secarna - novel ASO therapies ​ Discovery ​ Lead identification ​ We anticipate incurring increasing costs in connection with the continued development of PRX-115 and PRX-119 and in the expansion of our pipeline.
Liquidity and Capital Resources Our sources of liquidity include our cash balances and bank deposits. At December 31, 2024, we had $34.8 million in cash and cash equivalents and short term bank deposits.
Liquidity and Capital Resources Our sources of liquidity include our cash balances and bank deposits. At December 31, 2025, we had $30.3 million in cash and cash equivalents and short-term bank deposits.
To date, we have successfully developed two commercial products, both of which are ERTs; Elfabrio (pegunigalsidase alfa) for the treatment of adult patients with a confirmed diagnosis of Fabry disease and Elelyso (taliglucerase alfa) for the treatment of adult patients with Gaucher disease.
To date, we have successfully developed two commercial ERTs: Elelyso ® (taliglucerase alfa) for the treatment of adult patients and children four years of age and older with Gaucher disease and Elfabrio ® (pegunigalsidase alfa) for the treatment of adult patients with a confirmed diagnosis of Fabry disease.
Elfabrio, our second commercial product, an ERT for the treatment of Fabry disease, was approved by the EC for marketing in the EU and by the FDA for marketing in the United States in May 2023 for adult patients. Both approvals cover the 1 mg/kg every two weeks dosage.
Elfabrio, our second commercial product, an ERT for the treatment of Fabry disease, was approved by the EC for marketing in the EU and by the FDA for marketing in the United States in May 2023 for adult patients. Both approvals cover the 1 mg/kg E2W dosage. Subsequently, it has been approved in more than 10 additional markets.
This study included 64 adult male and female subjects in a dose escalation design with eight sequential dosing cohorts, each composed of eight subjects (six active and two placebo) which is now complete.
This study included 64 adult male and female subjects in a dose escalation design with eight sequential dosing cohorts, each composed of eight subjects (six active and two placebo) which is now complete. The results are summarized in Item 1 of this annual report on Form 10-K.
Future Funding Requirements Since our inception, we have incurred significant research and development expenditures which have not been offset by revenues. We have not generated significant revenues from sales of Elelyso, and commercial sales of Elfabrio only 70 Table of Contents commenced in the middle of 2023.
Future Funding Requirements Since our inception, we have incurred significant research and development expenditures which have not been offset by revenues. We have not generated significant revenues from sales of Elelyso or Elfabrio.
In 2024, we generated $12.6 million from sales of Elelyso to Pfizer and $11.0 million from sales of BioManguinhos alfataliglicerase to the Brazilian MoH.
In 2025, we generated $18.2 million from sales of Elelyso to Pfizer and $11.1 million from sales of BioManguinhos alfataliglicerase to the Brazilian MoH.
Our material cash needs for the next 24 months will include, among other expenses, (i) costs of preclinical and clinical trials, (ii) employee salaries, (iii) payments for rent and operation of our manufacturing facilities, (iv) fees to our consultants and legal advisors, patent advisors and fees for service providers in connection with our research and development efforts and (v) tax payments.
Currently, our material cash needs include, among other expenses, (i) costs of preclinical and clinical trials, in particular 68 Table of Contents those of our RELEASE study, (ii) employee salaries, (iii) payments for rent and operation of our manufacturing facilities, (iv) fees to our consultants and legal advisors, patent advisors, and fees for service providers in connection with our research and development efforts, (v) expansion of addition manufacturing space within our current facility, and (vi) tax payments.
To the extent we need to obtain additional financing in excess of such anticipated revenues, it may be difficult for us to do so given the volatility of the price of our common stock.
Although we expect the revenues generated from the sales of Elfabrio and Elelyso will increase, such revenues may not be sufficient to fund the expenditures. To the extent we need to obtain additional financing in excess of such anticipated revenues, it may be difficult for us to do so given the volatility of the price of our Common Stock.
As of December 31, 2024, we are subject to open purchase orders issued to certain suppliers and other vendors mainly in connection with our research and development and manufacturing activities that were outstanding as of December 31, 2024 for approximately $9.2 million over the next five fiscal years. 71 Table of Contents We have a contractual obligation of approximately $1.5 million as of December 31, 2024 payable over the fiscal year ending December 31, 2025 in connection with contractual arrangements we enter into in the normal course of business with CROs, CMOs and other clinical providers and consultants for clinical trials, preclinical and other research studies and manufacturing services in connection with our primary product development process.
We have a contractual obligation of approximately $17.7 million as of December 31, 2025 payable over the fiscal year ending December 31, 2025 in connection with contractual arrangements we enter into in the normal course of business with CROs, CMOs and other clinical providers and consultants for clinical trials, preclinical and other research studies and manufacturing services in connection with our primary product development process.
We expect to continue to incur significant, increasing research and development expenses as we enter into a more advanced stage of preclinical and clinical trials for certain of our product candidates.
The increase in research and development expenses resulted primarily from preparations for the RELEASE study. We expect to continue to incur significant, increasing research and development expenses as we progress with the RELEASE study and commence more advanced stages of preclinical and clinical trials for certain of our other product candidates.
Under each of the Chiesi Agreements, Chiesi made an upfront payment to Protalix Ltd. of $25.0 million in connection with the execution of each agreement.
Under each of the Chiesi Agreements, Chiesi made an upfront payment to Protalix Ltd. of $25.0 million in connection with the execution of each agreement and Protalix Ltd. received additional payments of $25.0 million under the Chiesi Ex-US Agreement, and $20.0 million under the Chiesi US Agreement, to cover pegunigalsidase alfa development costs, all of which have been received in full.
W e have generated operating losses from our continuing operations since our inception although the revenues generated in the years ended December 31, 2023 and 2024 exceeded our expenditures for the same period.
We have generated operating losses from our continuing operations since our inception although the revenues generated in the years ended December 31, 2023 and 2024 exceeded our expenditures for the same periods. As the 2024 Notes were paid in full during the year ended December 31, 2024, we are no longer subject to the financial limitations related to such notes.
The net income for the year ended December 31, 2023 of $8.3 million was decreased by a $13.2 million decrease in contracts liability, a $3.1 million increase in deferred tax assets, a $2.2 million increase in inventories, a $0.4 million increase in accounts receivable-trade and other assets and a $0.4 million financial income-net.
The net loss for the year ended December 31, 202 5 of $6.6 million was increased by a $5.9 million increase in accounts receivable-trade and other assets and a $4.5 million increase in inventories, and was offset by $2.3 million in share-based compensation and $1.5 million in depreciation.
Contractual obligations Our contractual obligations include operating lease obligations, purchase obligations, certain clinical contracts and the liability for employee rights upon retirement. We lease certain assets under operating leases, which expire through 2026, with an option to extend the lease on our main facility to 2031.
Contractual obligations Our contractual obligations include operating lease obligations, purchase obligations, certain clinical contracts, and the liability for employee rights upon retirement. We lease certain assets under operating leases which are currently in effect until December 31, 2031 with up to four five-year automatic extensions at our discretion.
Recently Issued Accounting Pronouncements Certain recently issued and recently adopted accounting pronouncements are discussed in Note 1(r) of the financial statements included in Item 8 of this Annual Report on Form 10-K.
We do not believe currency fluctuations have had a material effect on our results of operations during the years ended December 31, 2023 or 2024 Recently Issued Accounting Pronouncements Certain recently issued and recently adopted accounting pronouncements are discussed in Note 1(t) of the financial statements included in Item 8 of this Annual Report on Form 10-K.
In addition, under the Chiesi Ex-US Agreement, Protalix Ltd. was entitled to additional payments of up to $25.0 million in pegunigalsidase alfa development costs, and to receive additional payments of up to $320.0 million, in the aggregate, in regulatory and commercial milestone payments.
Protalix Ltd. currently remains eligible to receive additional payments of up to a maximum of $270.0 million, in the aggregate and including the $25.0 million currently payable, subject to the satisfaction of certain regulatory and commercial milestones under the Chiesi Ex-US Agreement.
The net income was increased by a $5.3 million increase in accounts payable and accruals, $3.4 million in share-based compensation and $1.2 million in depreciation. Net cash used in investing activities for the year ended December 31, 2023 was $16.7 million and consisted primarily of net investment in bank deposits.
Net cash used in investing activities for the year ended December 31, 202 5, was $2.4 million and consisted of $1.6 million purchase of property and equipment, $0.7 million increase in restricted deposit and $5.0 million investment in bank deposit offset by $5.0 million deposit withdrawal.
We have elected to store manufactured drug substance in multiple locations, both within and outside of Israel, to mitigate the risk of loss due to the military operations. It is currently not possible to predict the duration or severity of the ongoing conflict or its effects on our business, operations and financial conditions.
We have elected to store manufactured drug substance in multiple locations, both within and outside of Israel, to mitigate the risk of loss. As of the issuance of these financial statements, the impact of the military action has not had an adverse effect on our operations.
Revenues from license and R&D services are comprised primarily of revenues we recognized in connection with the Chiesi Agreements. The revenues from license and R&D services for the year ended December 31, 2023 included the $20.0 million regulatory milestone payment from Chiesi in connection with the FDA approval of Elfabrio granted during that period.
Revenues from license and R&D services are comprised primarily of revenues we recognized in connection with the Chiesi Agreements.
During the year ended December 31, 2024, we raised gross proceeds equal to approximately $3.8 million from the sale, in the aggregate, of 2,216,692 shares of our common stock under our ATM program. All such sales were completed during the quarter ended December 31, 2024.
During the year ended December 31, 2025, we sold, in the aggregate, 2,775,215 shares of common stock under the 2023 Sales Agreement. We generated gross proceeds equal to approximately $7.0 million in connection with such sales. All such sales were effected during the first half of 2025.
Under the Chiesi US Agreement, Protalix Ltd. was entitled to payments of up to a maximum of $20.0 million to cover development costs for pegunigalsidase alfa, and is entitled to receive additional payments of up to a maximum of $760.0 million, in the aggregate, in regulatory and commercial milestone payments.
Under the Chiesi US Agreement, Protalix Ltd. currently remains eligible to receive additional payments of up to a maximum of $740.0 million, in the aggregate, subject to the satisfaction of certain regulatory and commercial milestones. Following the approval of Elfabrio by the FDA, we received a milestone payment equal to $20.0 million.
As the 2024 Notes were paid in full during the year ended December 31, 2024, we are no longer subject to the financial limitations related to such notes. As we increase our research and developments efforts with respect to our current and future product candidates, we expect to continue to incur significant expenditures.
As we increase our research and developments efforts with respect to our current and future product candidates, we expect to continue to incur significant expenditures. We cannot anticipate the costs or the timing of the occurrence of such costs.
As of December 31, 2024, shares of common stock for total gross proceeds of approximately $2.5 million were available to be sold under the 2023 Sales Agreement. Since December 31, 2024, we sold the remaining shares of common stock available for sale under the 2023 Sales Agreement thereby completing the ATM program thereunder.
As of December 31, 2025, approximately $15.7 million in shares of common stock remain available to be sold under the 2023 Sales Agreement.
Financial Expenses and Income, Net Financial income, net was $0.2 million for the year ended December 31, 2024, compared to financial expenses, net of $1.9 million for the year ended December 31, 2023.
For the year ended December 31, 2025, the currency fluctuations were expenses of $1.2 million.
During the year ended December 31, 2023, we raised gross proceeds equal to approximately $24.9 million from the sale of 12,560,150 shares of our common stock under our ATM program. Cash Flows Net cash provided by operations was $8.7 million for the year ended December 31, 2024 .
Net cash provided by financing activities for the year ended December 31, 202 5, was $9.3 million and consisted of $6.8 million proceeds from issuance of Common Stock under the Sales Agreement, net and $2.5 million from the exercise of warrants and options. Net cash provided by operations was $8.7 million for the year ended December 31, 2024 .
Effective in 2022, Section 174 of the TCJA requires all U.S. companies, for tax purposes, to capitalize and subsequently amortize R&D expenses that fall within the scope of Section 174 over five years for research activities conducted in the United States and over 15 years for research activities conducted outside of the United States rather than deducting such costs in the current year. 69 Table of Contents Year ended December 31, 2023 Compared to the Year Ended December 31, 2022 For a discussion of the year ended December 31, 2023 compared to the year ended December 31, 2022, see Management’s Discussion and Analysis of Financial Condition and Results of Operations included in our Annual Report on Form 10-K for the year ended December 31, 2023.
Year ended December 31, 2024 Compared to the Year Ended December 31, 2023 For a discussion of the year ended December 31, 2024 compared to the year ended December 31, 2023, see Management’s Discussion and Analysis of Financial Condition and Results of Operations included in our Annual Report on Form 10-K for the year ended December 31, 2024.
Revenues from License and R&D services We recorded revenues from license and R&D services of $0.4 million for the year ended December 31, 2024, a decrease of $24.7 million, or 98%, compared to revenues of $25.1 million for the year ended December 31, 2023.
Revenues from License and R&D services Revenues from license and R&D services were as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ ​ ​ ​ ​ (U.S. dollars in thousands) ​ ​ ​ 2023 ​ ​ ​ 2024 ​ ​ ​ 2025 ​ ​ ​ 2025 vs. 2024 ​ ​ ​ 2024 vs. 2023 Revenues from license and R&D services ​ $ 25,076 ​ $ 418 ​ $ 942 ​ $ 524 ​ $ (24,658) ​ Revenues from license and R&D services for the year ended December 31, 2025 represent a 125% increase compared to revenues for the year ended December 31, 2024.
Pursuant to the terms of the 2021 Sales Agreement, we were able to sell from time to time through the Agent shares of our common stock having an aggregate offering price of up to $20.0 million, or the ATM Shares.
Wainwright & Co., LLC, as our sales agent, or the Agent, for the sale of up to $20.0 million of our common stock from time to time .
Because our operations are conducted in the State of Israel, the business and operations may be directly affected by economic, political, geopolitical and military conditions in Israel. In October 2023, Hamas terrorists infiltrated Israel’s southern border from the Gaza Strip and conducted a series of attacks on civilian and military targets.
There may be periods during which no orders are placed by either Pfizer or Fiocruz, whether as a result of inventory de-stocking or other factors. Because our operations are conducted in the State of Israel, the business and operations may be directly affected by economic, political, geopolitical and military conditions in Israel.
The increase resulted primarily from an increase of $11.8 million in sales to Chiesi, an increase of $0.6 million in sales to Brazil and an increase of $0.1 million in sales to Pfizer.
The increase in cost of goods sold was primarily the result of an increase in sales to Pfizer and Fiocruz (Brazil) partially offset by a decrease in sales to Chiesi.
The income taxes resulted primarily from the provision for current taxes on income mainly derived from GILTI income mainly in respect of Section 174 of the TCJA.
The tax expenses resulted primarily from taxes on income mainly derived from global intangible low-taxed income resulting primarily from limitations under IRC Section 174.
On February 27, 2023, we entered into an At The Market Offering Agreement, or the 2023 Sales Agreement, with the Agent. Pursuant to the terms of the 2023 Sales Agreement, we may sell, from time to time through the Agent, ATM Shares having an aggregate offering price of up to $20.0 million.
Subsequently, on March 17, 2025, we entered into an amendment to the 2023 Sales Agreement pursuant to which the aggregate gross sales price of shares of common stock available for sale under the 2023 Sales Agreement was increased by $20.0 million.
Selling, General and Administrative Expenses Selling, general and administrative expenses were $12.2 million for the year ended December 31, 2024, a decrease of $2.8 million, or 19%, from $15.0 million for the year ended December 31, 2023. The decrease resulted primarily from a decrease of $1.8 million in professional fees and of $1.0 million in salaries and related expenses .
Selling, General, and Administrative Expenses Selling, general, and administrative expenses were as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ ​ ​ ​ ​ (U.S. dollars in thousands) ​ ​ ​ 2023 ​ ​ ​ 2024 ​ ​ ​ 2025 ​ ​ ​ 2025 vs. 2024 ​ ​ ​ 2024 vs. 2023 SG&A expenses ​ $ 14,959 ​ $ 12,193 ​ $ 11,682 ​ $ (511) ​ $ (2,766) ​ Selling, general, and administrative expenses for the year ended December 31, 2025 represent a 4% decrease compared to selling, general, and administrative expenses for the year ended December 31, 2024.
Removed
Overview We are a biopharmaceutical company focused on the development and commercialization of recombinant therapeutic proteins primarily based on our proprietary ProCellEx protein expression system.
Added
Overview We are a commercial stage biopharmaceutical company focused on the discovery, development, production and commercialization of innovative therapeutics for rare diseases with significant unmet needs. We are the first and only company to gain FDA approval of a protein produced through plant cell-based expression in suspension.
Removed
Elfabrio, which we referred to as PRX-102 during its development stage, has been approved for marketing in the United States, the European Union, Great Britain, Switzerland, Peru, Israel, Russia and Singapore. Chiesi is our commercialization partner for Elfabrio.
Added
ProCellEx ® , our unique, proprietary plant cell-based protein expression system represents a new method for developing recombinant proteins in an industrial-scale manner. Our corporate strategy includes development of treatments for rare and orphan diseases.
Removed
We are committed to leveraging our track record of success as we progress with the development of treatments for rare and orphan diseases. In addition, we continuously work on the further development and enhancement of our ProCellEx technology.
Added
Consistent with this strategy. we are developing PEGylated uricase, or PRX-115, for the treatment of uncontrolled gout, Long Acting (LA) DNase I, or PRX-119, for the treatment of NETs-related diseases, and a number of other technologies and preclinical assets. We have completed a Phase 1 First-in-Human clinical trial of PRX-115.
Removed
In June 2012, the CHMP issued a positive opinion regarding the benefit of Elelyso but did not immediately grant marketing authorization because of the ten-year market exclusivity granted to Vpriv in August 2010 for the same condition, which was extended for an additional two years, and expired in August 2022.
Added
Currently, we are actively recruiting for, and the first patients have been randomized in the RELEASE study, a Phase 2 clinical trial of PRX-115 for the treatment of uncontrolled gout.
Removed
We have entered into two exclusive global licensing and supply agreements for Elfabrio with Chiesi. In October 2017 and July 2018, Protalix Ltd., our wholly-owned subsidiary, entered into the Chiesi Agreements pursuant to which Chiesi was granted an exclusive license for all markets, both within and outside of the United States to commercialize Elfabrio.
Added
Commercialization of Elfabrio is governed by the Chiesi Agreements. In 2025, we generated $22.5 million from sales of Elfabrio to Chiesi. On March 5, 2026, the EC ratified the CHMP positive opinion issued in January 2026.
Removed
In 2024, we generated $29.3 million from sales of Elfabrio to Chiesi. We continuously evaluate potential strategic marketing partnerships as well as collaboration programs with biotechnology and pharmaceutical companies and academic research institutions. Except with respect to Elfabrio and Elelyso, we hold the worldwide commercialization rights to our other proprietary development candidates.
Added
The EC decision approves, in the EU, the 2 mg/kg E4W dosing regimen for Elfabrio in Fabry disease adult patients stable with an ERT treatment. We continuously evaluate potential strategic marketing partnerships as well as collaboration programs with biotechnology and pharmaceutical companies and academic research institutions.
Removed
The results were announced in a poster presentation at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19, 2024 and are summarized in Item 1 of this annual report on Form 10-K. We are currently preparing for a phase II clinical trial of PRX-115 which we expect will commence in the second half of 2025.
Added
Currently, we are actively recruiting patients for, and the first patients have been randomized in, the RELEASE study. On February 27, 2023, we entered into that certain At The Market Offering Agreement, as may be amended from time to time, or the 2023 Sales Agreement, with H.C.
Removed
On July 2, 2021, we entered into an At The Market Offering Agreement, or the 2021 Sales Agreement, with H.C. Wainwright & Co., LLC, as our sales agent, or the Agent, which was amended on May 2, 2022.
Added
Under the terms of the Chiesi Agreements, Chiesi is solely responsible for the global commercialization and medical programs of Elfabrio, including patient acquisition and retention, and distribution of Elfabrio to patients. We manufacture Elfabrio drug substance and, after the fill\finish process is complete, we sell the resulting drug product to Chiesi.
Removed
During the term of the 2021 Sales Agreement which ended during the quarter ended March 31, 2023, we sold a total of 13,980,060 ATM Shares for total gross proceeds of approximately $20.0 million, thereby completing the ATM program under said agreement.
Added
Operationally, Chiesi conducts its own internal commercial forecasting to guide inventory needs. To date, Chiesi has placed bulk orders for Elfabrio. As a result, the orders we receive from Chiesi may not be timed precisely to Chiesi’s pace of patient acquisition and retention.
Removed
To date, Protalix Ltd. has received the complete amount of development costs to which it is entitled under the Chiesi Agreements. In addition, following the approval of Elfabrio by the FDA, we received a milestone payment equal to $20.0 million.
Added
Accordingly, our sales of Elfabrio to Chiesi may not reflect patient demand for Elfabrio as we sell the fulfilled orders to Chiesi’s inventory.
Removed
On May 13, 2021, we signed a binding term sheet with Chiesi pursuant to which we and Chiesi amended the Chiesi Agreements in order to provide us with near-term capital.
Added
In addition, on a period-to-period basis, there may be variations in the orders placed by Chiesi resulting in variability in our period-to-period results as we, in turn, recognize revenues from sales of Elfabrio upon delivery of the drug product to Chiesi.
Removed
Chiesi agreed to make a $10.0 million payment to us before the end of the second quarter of 2021 in exchange for a $25.0 million reduction in a longer term regulatory milestone payment provided in the Chiesi Ex-US Agreement. All other regulatory and commercial milestone payments remain unchanged. We received the payment in June 2021.
Added
There may be periods during which no orders are placed by Chiesi, whether as a result of inventory de-stocking or other factors. We do not anticipate that these Chiesi ordering patterns will change until the demand characteristics for Elfabrio stabilize, the launch of Elfabrio matures and Elfabrio’s share of the market for Fabry disease treatment increases globally.
Removed
We also agreed to negotiate certain manufacturing related matters. Under the terms of both of the Chiesi Agreements, Protalix Ltd. is required to manufacture all of the Elfabrio drug substance needed under the agreements, subject to certain exceptions, and Chiesi will purchase Elfabrio drug product from Protalix, subject to certain terms and conditions.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeIn the future, we may enter into currency hedging transactions to decrease the risk of financial exposure from fluctuations in the exchange rate of the U.S. dollar against the NIS.
Biggest changeIn 2026, we entered into certain currency hedging transactions, and we expect to continue to enter into currency hedging transactions, to decrease the risk of financial exposure from fluctuations in the exchange rate of the U.S. dollar against the NIS. These measures, however, may not adequately protect us from material adverse effects due to the impact of inflation in Israel.
Foreign currency translation gains or losses are recognized in the statement of operations. Approximately 37% of our costs, including salaries, expenses and office expenses, are incurred in NIS. Inflation in Israel may have the effect of increasing the U.S. dollar cost of our operations in Israel.
Foreign currency translation gains or losses are recognized in the statement of operations. Approximately 41% of our costs, including salaries, expenses and office expenses, are incurred in NIS. Inflation in Israel may have the effect of increasing the U.S. dollar cost of our operations in Israel.
We do not use derivative financial instruments to limit exposure to interest rate risk. Our interest gains may decline in the future as a result of changes in the financial markets.
We do not use derivative financial instruments to limit exposure to interest rate risk. Our interest gains may decline in the future as a result of changes in the financial markets. 70 Table of Contents
The exchange rate of the U.S. dollar to the NIS, based on exchange rates published by the Bank of Israel, was as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ ​ 2022 ​ 2023 ​ 2024 ​ Average rate for period 3.360 ​ 3.687 ​ 3.700 ​ Rate at period-end 3.519 ​ 3.627 ​ 3.647 ​ ​ To date, we have not engaged in hedging transactions.
The exchange rate of the U.S. dollar to the NIS, based on exchange rates published by the Bank of Israel, was as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ ​ ​ 2023 ​ 2024 ​ 2025 ​ Average rate for period ​ 3.687 ​ 3.700 ​ 3.452 ​ Rate at period-end ​ 3.627 ​ 3.647 ​ 3.190 ​ As of December 31, 2025, we have not engaged in hedging transactions.
These measures, however, may not adequately protect us from material adverse effects due to the impact of inflation in Israel. 72 Table of Contents Interest Rate Risk Our exposure to market risk is confined to our cash and cash equivalents.
Interest Rate Risk Our exposure to market risk is confined to our cash and cash equivalents.

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