10q10k10q10k.net

What changed in Entera Bio Ltd.'s 10-K — 2024 vs 2025

vs

Paragraph-level year-over-year comparison of Entera Bio Ltd.'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.

+501 added−462 removedSource: 10-K (2026-03-27) vs 10-K (2025-03-28)

Top changes in Entera Bio Ltd.'s 2025 10-K

501 paragraphs added · 462 removed · 343 edited across 4 sections

Item 1. Business

Business — how the company describes what it does

127 edited+76 added−54 removed178 unchanged
Biggest changeThese sanctions may include, but are not limited to, the FDA’s refusal to allow an applicant to proceed with clinical testing, refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, warning letters, adverse publicity, customer notifications, product recalls, product seizures, refusal to grant export or import approval, total or partial suspension of production or distribution, consent decrees, injunctions, fines, and civil or criminal investigations and penalties brought by the FDA, Department of Justice, or other governmental entities. 23 The process required by the FDA before a new drug or biologic may be marketed in the United States generally involves satisfactorily completing each of the following steps: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the FDA’s Good Laboratory Practice regulations, or GLP; • submission to the FDA of an initial new drug, or IND, application for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent review board, or IRB, representing each clinical site before each clinical trial may be initiated; • performance of adequate and well-controlled clinical trials to establish the safety and efficacy of the product candidate for each proposed indication for use and conducted in accordance with Good Clinical Practice, or GCP, requirements; • submission of data supporting safety and efficacy as well as detailed information on the manufacture and composition of the product in clinical development and proposed labeling; • preparation and submission to the FDA of a New Drug Application, or an NDA, or Biologics License Application, or BLA; • review of the product by an FDA advisory committee, where appropriate or if applicable; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with current Good Manufacturing Practice, or cGMP, standards and to assure that the facilities, methods, and controls are adequate to preserve the product’s identity, strength, quality and purity; • satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with GCP requirements and the integrity of clinical data in support of the NDA or BLA; • payment of user fees and securing FDA approval of the NDA or BLA for the proposed indication; and • compliance with any post-approval requirements, including risk evaluation and mitigation strategies, or REMS, and any post-approval studies required by the FDA.
Biggest changeThe process required by the FDA before a new drug or biologic may be marketed in the United States generally involves satisfactorily completing each of the following steps: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the FDA’s Good Laboratory Practice regulations, or GLP; • submission to the FDA of an initial new drug, or IND, application for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent review board, or IRB, representing each clinical site before each clinical trial may be initiated; • performance of adequate and well-controlled clinical trials to establish the safety and efficacy of the product candidate for each proposed indication for use and conducted in accordance with Good Clinical Practice, or GCP, requirements; • submission of data supporting safety and efficacy as well as detailed information on the manufacture and composition of the product in clinical development and proposed labeling; • preparation and submission to the FDA of a New Drug Application, or an NDA, or Biologics License Application, or BLA; • review of the product by an FDA advisory committee, where appropriate or if applicable; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with current Good Manufacturing Practice, or cGMP, standards and to assure that the facilities, methods, and controls are adequate to preserve the product’s identity, strength, quality and purity; • satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with GCP requirements and the integrity of clinical data in support of the NDA or BLA; • payment of user fees and securing FDA approval of the NDA or BLA for the proposed indication; and • compliance with any post-approval requirements, including risk evaluation and mitigation strategies, or REMS, and any post-approval studies required by the FDA. 24 Preclinical Studies and Investigational New Drug Application Preclinical tests include laboratory evaluations of product chemistry, formulation, and stability, as well as animal studies to evaluate the potential for efficacy and toxicity.
All such reported information is publicly available; • analogous state and non-U.S. laws and regulations, such as state anti-kickback and false claims laws which may apply to items or services reimbursed by any payer, including commercial insurers; state laws that require pharmaceutical companies to comply with the industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require pharmaceutical manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and • regulation by the Centers for Medicare and Medicaid Services and enforcement by the U.S.
All such reported information is publicly available; 33 • analogous state and non-U.S. laws and regulations, such as state anti-kickback and false claims laws which may apply to items or services reimbursed by any payer, including commercial insurers; state laws that require pharmaceutical companies to comply with the industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require pharmaceutical manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and • regulation by the Centers for Medicare and Medicaid Services and enforcement by the U.S.
In the United States, such restrictions under applicable federal and state healthcare laws and regulations, include the following: 32 • the federal Anti-Kickback Statute prohibits, among other things, the knowing and willful offer, payment, solicitation or receipt of any form of remuneration in return for, or to induce, (i) the referral of a person, (ii) the furnishing or arranging for the furnishing of items or services reimbursable under the Medicare, Medicaid or other governmental programs, or (iii) the purchase, lease or order or arranging or recommending purchasing, leasing or ordering of any item or service reimbursable under the Medicare, Medicaid or other governmental programs.
In the United States, such restrictions under applicable federal and state healthcare laws and regulations, include the following: • the federal Anti-Kickback Statute prohibits, among other things, the knowing and willful offer, payment, solicitation or receipt of any form of remuneration in return for, or to induce, (i) the referral of a person, (ii) the furnishing or arranging for the furnishing of items or services reimbursable under the Medicare, Medicaid or other governmental programs, or (iii) the purchase, lease or order or arranging or recommending purchasing, leasing or ordering of any item or service reimbursable under the Medicare, Medicaid or other governmental programs.
For some products for severe or life-threatening diseases, especially if the product may be too toxic to administer to healthy humans, the initial clinical trials may be conducted in individuals having a specific disease for which use the tested product is indicated. • Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications and determine dose tolerance and optimal dosage.
For some products for severe or life-threatening diseases, especially if the product may be too toxic to administer to healthy humans, the initial clinical trials may be conducted in individuals having a specific disease for which use the tested product is indicated 25 • Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications and determine dose tolerance and optimal dosage.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation; • the federal false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for health care benefits, items or services; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information that is stored or transmitted electronically; • the Physician Payments Sunshine Act, created under the Affordable Care Act, and its implementing regulations, which require specified manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to payments or other “transfers of value” made to physicians.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation; • the federal false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for health care benefits, items or services; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information that is stored or transmitted electronically; • the Physician Payments Sunshine Act, created under the Patient Protection Affordable Care Act (the Affordable Care Act), and its implementing regulations, which require specified manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to payments or other “transfers of value” made to physicians.
These laws may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on customers for our drugs, if approved, and, accordingly, our financial operations. Moreover, recently there has been heightened governmental scrutiny over the way manufacturers set prices for their commercial products. There have been several recent U.S.
These laws may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on customers for our drugs, if approved, and, accordingly, our financial operations. 35 Moreover, recently there has been heightened governmental scrutiny over the way manufacturers set prices for their commercial products. There have been several recent U.S.
Certain medicinal products, including products developed by means of biotechnological processes must undergo the centralized authorization procedure for marketing authorization, which, if granted by the European Commission, based on the opinion of the EMA, is automatically valid in all EU member states. Sponsors may elect to file an MAA through the centralized procedures for other classes of products.
Certain medicinal products, including products developed by means of biotechnological processes must undergo the centralized authorization procedure for marketing authorization, which, if granted by the European Commission, based on the opinion of the EMA, is automatically valid in all EU member states. Sponsors may elect to file an MAA through the centralize procedures for other classes of products.
Failure to exhibit due diligence with regard to conducting Phase 4 clinical trials could result in withdrawal of approval for products. 25 Compliance with Current Good Manufacturing Practice Requirements Before approving an NDA or a BLA, the FDA typically will inspect the facility or facilities where the product is manufactured.
Failure to exhibit due diligence with regard to conducting Phase 4 clinical trials could result in withdrawal of approval for products. Compliance with Current Good Manufacturing Practice Requirements Before approving an NDA or a BLA, the FDA typically will inspect the facility or facilities where the product is manufactured.
The last drug approval for osteoporosis occurred in 2019. In the United States, the Foundation for the National Institute of Health-American Society for Bone and Mineral Research-Study to Advance BMD as a Regulatory Endpoint (FNIH-ASBMR-SABRE, previously known as the FNIH-Bone Quality Project [FNIH-BQP], hereinafter SABRE) was launched in 2013.
The last drug approval for osteoporosis occurred in 2019. In the United States, the Foundation for the National Institute of Health-American Society for Bone and Mineral Research-Study to Advance BMD as a Regulatory Endpoint (FNIH-ASBMR-SABRE, previously known as the FNIH-Bone Quality Project [FNIH-BQP], hereinafter “SABRE”) was launched in 2013.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. 26 If the FDA approves a new product, it may limit the approved indications for use of the product. It may also require that contraindications, warnings or precautions be included in the product labeling.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. If the FDA approves a new product, it may limit the approved indications for use of the product. It may also require that contraindications, warnings or precautions be included in the product labeling.
Adoption of such controls and measures, and tightening of restrictive policies in jurisdictions with existing controls and measures, could limit payments for pharmaceuticals such as the product candidates that we are developing and could adversely affect our net revenue and results. 34 Pricing and reimbursement schemes vary widely from country to country.
Adoption of such controls and measures, and tightening of restrictive policies in jurisdictions with existing controls and measures, could limit payments for pharmaceuticals such as the product candidates that we are developing and could adversely affect our net revenue and results. Pricing and reimbursement schemes vary widely from country to country.
Pharmacologic therapy is strongly recommended for patients with a BMD T-score of -2.5 or lower in the spine, femoral neck, total hip, or 1/3 radius. Current osteoporosis drugs may be divided into two categories: antiresorptive and anabolic.
Pharmacologic therapy is strongly recommended for patients with a BMD T-score of -2.5 or lower in the spine, femoral neck, total hip, or 1/3 radius. 13 Current osteoporosis drugs may be divided into two categories: antiresorptive and anabolic.
See “Item 1A.—Risk Factors—Risks Related to Commercialization of Our Product Candidates.” The Israeli Innovation Authority (IIA) Grants We have received grants of approximately $0.5 million from the IIA to partially fund our PTH research and development for Osteoporosis.
See “Item 1A.—Risk Factors—Risks Related to Commercialization of Our Product Candidates.” 21 The Israeli Innovation Authority (IIA) Grants We have received grants of approximately $0.5 million from the IIA to partially fund our PTH research and development for Osteoporosis.
Marketing Authorization Authorization to market a product in the member states of the EU proceeds under one of four procedures: a centralized procedure, a mutual recognition procedure, a decentralized procedure or a national procedure. 29 Centralized Procedure The centralized procedure enables applicants to obtain a marketing authorization that is valid in all EU member states based on a single application.
Marketing Authorization Authorization to market a product in the member states of the EU proceeds under one of four procedures: a centralized procedure, a mutual recognition procedure, a decentralized procedure or a national procedure. Centralized Procedure The centralized procedure enables applicants to obtain a marketing authorization that is valid in all EU member states based on a single application.
We view this potential outcome as testament to the treatment gap and unmet need for a viable alternative to treat the millions of osteoporosis patients who, despite current guidelines and availability of highly efficacious injectable anabolic agents, remain undertreated.
We view this potential outcome as a testament to the treatment gap and unmet need for a viable alternative for the millions of osteoporosis patients who, despite current guidelines and availability of highly efficacious injectable anabolic agents, remain undertreated.
ITEM 1. BUSINESS Overview Entera is a clinical stage company focused on developing first-in-class oral tablet formats of peptides or protein replacement therapies. We focus on underserved, chronic medical conditions for which oral administration of a protein therapy has the potential to significantly shift a treatment paradigm.
ITEM 1. BUSINESS Overview Entera is a clinical stage company focused on developing first-in-class oral tablet formats of peptides or protein replacement therapies. We concentrate on underserved, chronic medical conditions for which oral administration of a protein therapy has the potential to significantly shift a treatment paradigm.
This initiative was established as a public-private partnership with the Federal Drug Administration (FDA) to study whether change in BMD at the lumbar spine, total hip or femoral neck in a placebo-controlled trial of an osteoporosis drug was predictive of vertebral, nonvertebral, hip and all clinical fracture risk reduction.
This initiative was established as a public-private partnership with the FDA to study whether change in BMD at the lumbar spine, total hip or femoral neck in a placebo-controlled trial of an osteoporosis drug was predictive of vertebral, nonvertebral, hip and all clinical fracture risk reduction.
The bone remodeling cycle can be separated into two distinct processes: (i) bone resorption, where cells called osteoclasts function in the resorption of mineralized tissue; and (ii) bone formation, where cells called osteoblasts are responsible for bone matrix synthesis and subsequent mineralization of the bone. In healthy individuals, bone resorption is matched by new bone formation.
The bone remodeling cycle can be separated into two distinct processes: (i) bone resorption, where cells called osteoclasts function in the resorption of mineralized tissue; and (ii) bone formation, where cells called osteoblasts are responsible for bone matrix synthesis and subsequent mineralization of the bone. In healthy individuals, bone resorptions matched by new bone formation.
The pharmacokinetic analysis of the data obtained following the IV injections of the GLP-2 peptide showed the plasma half-life in rats to be about six times longer than the half-life reported for teduglutide in the same animal model.
The pharmacokinetic analysis of the data obtained following the IV injections of the GLP-2 peptide showed the plasma half-life in rats to be approximately six times longer than the half-life reported for teduglutide in the same animal model.
In March 2024, the ASBMR announced that the FDA had communicated to the SABRE project team that a ruling to qualify the treatment-related change in bone mineral density (BMD) as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs would be provided within 10 months.
In March 2024, the ASBMR announced that the FDA had communicated to the SABRE project team that a ruling to qualify the treatment-related change in BMD as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs would be provided within 10 months.
The nominal patent term does not include potential patent extension and/or patent term addition when applicable. The term of individual patents depends upon the legal term for patents in the countries in which they are granted.
The nominal patent term does not include potential patent term extension and/or patent term adjustment when applicable. The term of individual patents depends upon the legal term for patents in the countries in which they are granted.
Bone Mineral Density Dose-related changes in BMD were also observed at the total hip (TH), femoral neck (FN) and lumbar spine (LS) locations with a linear regression showing a statistically significant dose response at all sites; TH (p=0.008), FN (p=0.001), and LS (p Increases in TH (2.07%) and FN (2.92%) BMD in the 2.5 mg EB613 daily tablet titrated group were greater than those previously reported with Forteo® at six months (0.1% and 0.3%) (Leder, 2015).
Statistically significant increases were observed in P1NP (key anabolic marker) at Month 1 (p Bone Mineral Density Dose-related changes in BMD were also observed at the total hip (TH), femoral neck (FN) and lumbar spine (LS) locations with a linear regression showing a statistically significant dose response at all sites; TH (p=0.008), FN (p=0.001), and LS (p Increases in TH (2.07%) and FN (2.92%) BMD in the 2.5 mg EB613 daily tablet titrated group were greater than those previously reported with Forteo® at six months (0.1% and 0.3%) (Leder, 2015).
All clinical trials must first be approved by the Institutional Review Board / Independent Ethics Committee which may request additional prior approval from the Israeli Ministry of Health ("IMOH"), as required under the Guidelines for Clinical Trials in Human Subjects implemented pursuant to the Israeli Public Health Regulations (Clinical Trials in Human Subjects), 5740-1980, as amended from time to time (referred to as "The Israeli Public Health Regulations").
All clinical trials must first be approved by the Institutional Review Board / Independent Ethics Committee which may request additional prior approval from the Israeli Ministry of Health (“IMOH”), as required under the Guidelines for Clinical Trials in Human Subjects implemented pursuant to the Israeli Public Health Regulations (Clinical Trials in Human Subjects), 5740-1980, as amended from time to time (referred to as “The Israeli Public Health Regulations”).
We believe that our success will depend in part on our ability to obtain patent protection for our intellectual property. We also intend to rely on trade secret protection, know-how and the exploitation of in-licensing opportunities to develop our proprietary position. Patent Rights As of March 2025, our global patent portfolio included issued patents and patent applications.
We believe that our success will depend in part on our ability to obtain patent protection for our intellectual property. We also intend to rely on trade secret protection, know-how and the exploitation of in-licensing opportunities to develop our proprietary position. 19 Patent Rights As of March 23, 2026, our global patent portfolio included issued patents and patent applications.
The distribution of our full-time employees according to main areas of activity is set forth in the following table: Employees Area of Activity: Research and Development 16 General and Administrative 2 Total 18 Israeli labor laws govern the length of the workday and workweek, minimum wages for employees, procedures for hiring and dismissing employees, determination of severance pay, annual leave, sick days, advance notice of termination, payments to the National Insurance Institute, and other conditions of employment and include equal opportunity and anti-discrimination laws.
The distribution of our full-time employees according to main areas of activity is set forth in the following table: Employees Area of Activity: Research and Development 17 General and Administrative 3 Total 20 Israeli labor laws govern the length of the workday and workweek, minimum wages for employees, procedures for hiring and dismissing employees, determination of severance pay, annual leave, sick days, advance notice of termination, payments to the National Insurance Institute, and other conditions of employment and include equal opportunity and anti-discrimination laws.
It is responsible for the scientific evaluation of applications for EU marketing authorizations, as well as the development of technical guidance and the provision of scientific advice to sponsors. 28 The process regarding approval of medicinal products in the EU follows roughly the same lines as in the United States and likewise generally involves satisfactorily completing each of the following: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the applicable EU Good Laboratory Practice regulations; • submission to the relevant regulatory agencies in EU member states, or national authorities, of a clinical trial application, or CTA, for each clinical trial, which must be approved before human clinical trials may begin; • performance of adequate and well-controlled clinical trials to establish the safety and efficacy of the product for each proposed indication; • submission to the relevant national authorities of a Marketing Authorisation Application, or MAA, which includes the data supporting safety and efficacy as well as detailed information on the manufacture and composition of the product in clinical development and proposed labeling; • satisfactory completion of an inspection by the relevant national authorities of the manufacturing facility or facilities, including those of third parties, at which the product is produced to assess compliance with cGMP; • potential audits of the non-clinical and clinical trial sites that generated the data in support of the MAA; and • review and approval by the relevant national authority of the MAA before any commercial marketing, sale or shipment of the product.
The process regarding approval of medicinal products in the EU follows roughly the same lines as in the United States and likewise generally involves satisfactorily completing each of the following: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the applicable EU Good Laboratory Practice regulations; • submission to the relevant regulatory agencies in EU member states, or national authorities, of a clinical trial application, or CTA, for each clinical trial, which must be approved before human clinical trials may begin; • performance of adequate and well-controlled clinical trials to establish the safety and efficacy of the product for each proposed indication; • submission to the relevant national authorities of a Marketing Authorisation Application, or MAA, which includes the data supporting safety and efficacy as well as detailed information on the manufacture and composition of the product in clinical development and proposed labeling; • satisfactory completion of an inspection by the relevant national authorities of the manufacturing facility or facilities, including those of third parties, at which the product is produced to assess compliance with cGMP; • potential audits of the non-clinical and clinical trial sites that generated the data in support of the MAA; and • review and approval by the relevant national authority of the MAA before any commercial marketing, sale or shipment of the product.
Our pipeline includes five differentiated, first-in-class oral peptide programs targeting PTH(1-34), GLP-1 and GLP-2: Currently, most protein therapies are administered via frequent intravenous, subcutaneous or intramuscular injections. In chronic diseases where patients require persistent management, these cumbersome, often painful and high-priced injections can create a major treatment gap.
Our pipeline includes differentiated, first-in-class oral peptides targeting PTH(1-34), GLP-1/Glucagon and GLP-2: Currently, most protein therapies are administered via frequent intravenous, subcutaneous or intramuscular injections. In chronic diseases where patients require persistent management, these cumbersome, often painful and high-priced injections can create a major treatment gap.
The program is focused on developing the first oral dual agonist GLP-1/Glucagon peptide as a potential once-daily tablet treatment for patients with obesity and metabolic disorders using the N-Tab™ platform. Currently, there are no approved dual GLP-1/Glucagon agonists available.
The program focuses on developing the first oral dual agonist GLP-1/Glucagon peptide as a potential once-daily tablet treatment for patients with obesity, metabolic and fibrotic disorders using the N-Tab ® platform. Currently, there are no approved dual GLP-1/Glucagon agonists available.
Oral GLP-2 and Oral GLP-1/Glucagon Programs in Collaboration with OPKO Health Oral GLP-2 In May 2023, the results from our oral glucagon-like-peptide 2 (GLP-2) program were published in the International Journal of Peptide Research and Therapeutics, “Oral Delivery Technology Enabling Gastro-Mucosal Absorption of Glucagon-Like-Peptide-2 Analog (Teduglutide, Gattex®) - A Novel Approach for Injection-Free Treatment of Short Bowel Syndrome.” We believe GLP-2 represents a strong candidate for our N-Tab™ technology and warrants further development as an injection-free alternative to patients suffering from short bowel syndrome and other gastrointestinal disorders where GLP-2 plays a role.
In May 2023, the results from our oral GLP-2 program were published in the International Journal of Peptide Research and Therapeutics, “Oral Delivery Technology Enabling Gastro-Mucosal Absorption of Glucagon-Like-Peptide-2 Analog (Teduglutide, Gattex®) - A Novel Approach for Injection-Free Treatment of Short Bowel Syndrome.” We believe GLP-2 represents a strong candidate for our N-Tab® platform and warrants further development as an injection-free alternative to patients suffering from SBS and other gastrointestinal disorders where GLP-2 plays a role.
Following the completion of the Phase 1 stage, we have the option to continue to fund our 40% share to maintain our pro-rata ownership interest in the program. Should we opt-out, we will retain a 15% ownership interest in the Oral OXM program, while OPKO will retain 85% and be responsible for ongoing development activities and funding of the program.
Following the completion of the Phase 1 stage, we have the option to continue to fund our 50% share to maintain our pro-rata ownership interest in the program. Should we opt-out, we will retain a 15% ownership interest in the program, while OPKO will retain 85% and be responsible for all ongoing development activities and funding of the program.
In relation to Oral GLP-1/Glucagon , under the terms of the 2025 Collaboration Agreement, OPKO and Entera hold 60% and 40% pro-rata ownership interests, respectively, in the program and be responsible for 60% and 40% of the program’s development costs, respectively.
In relation to EB618 (Oral GLP-1/Glucagon), under the terms of the A&R Collaboration Agreement, OPKO and Entera hold 60% and 40% pro-rata ownership interests, respectively, in the program and be responsible for 60% and 40% of the program’s development costs, respectively.
Following Type C and Type D meetings with the FDA in March 2023, we announced the FDA’s concurrence that a 2-year, placebo-controlled phase 3 (registrational) study with Total Hip BMD as primary endpoint could support a new drug application (“NDA”) for EB613; however the SABRE BMD endpoint remained unqualified as a surrogate endpoint by FDA at that time.
Following Type C and Type D meetings with the FDA in March 2023, we announced the FDA’s concurrence that a 2-year, placebo-controlled phase 3 (registrational) study with total hip BMD as primary endpoint could support an NDA for EB613; however the SABRE BMD endpoint remained unqualified as a surrogate endpoint by FDA at that time.
For example, in collaboration with OPKO, we are focusing on the development of the first oral OXM, a dual targeted GLP1/glucagon peptide, in tablet form for the treatment of metabolic disorders and the first oral GLP-2 peptide tablet as an injection-free alternative for patients suffering from rare malabsorption conditions, such as short bowel syndrome.
In collaboration with OPKO, we are currently focusing on the development of the first oral OXM, a dual targeted GLP1/glucagon peptide, in tablet form, for the treatment of metabolic disorders and have completed a proof of concept for an oral GLP-2 peptide tablet as an injection-free alternative for patients suffering from rare malabsorption conditions, such as short bowel syndrome.
There were no treatment emergent hypercalcemia adverse events, and serial serum chemistry evaluations found no increase in mean calcium or changes in calcium exceeding predefined limits in patients treated with EB613 2.5 mg daily tablets. 14 There were no reported drug-related SAEs. All adverse events were mild or moderate in intensity.
There were no treatment emergent hypercalcemia adverse events, and serial serum chemistry evaluations found no increase in mean calcium or changes in calcium exceeding predefined limits in patients treated with EB613 2.5 mg daily tablets. There were no reported drug-related SAEs.
The physiological pulses help encourage bone turnover through activation of both osteoblasts and osteoclasts, the two main types of cells responsible for bone remodeling. In the absence of adequate parathyroid function producing these pulses, it is difficult for the body to regulate homeostatic processes, and osteoporosis may ensue.
The effects of PTH on bone depends on the duration of exposure. The physiological pulses help encourage bone turnover through activation of both osteoblasts and osteoclasts, the two main types of cells responsible for bone remodeling. In the absence of adequate parathyroid function producing these pulses, it is difficult for the body to regulate homeostatic processes, and osteoporosis may ensue.
On the same day, we announced that we plan to continue our dialogue with the FDA and await the final qualification of the SABRE criteria and their guidance on the statistical evaluation of our BMD endpoint before initiating a Phase 3 study for EB613.
On the same day, we announced that we planned to continue our dialogue with the FDA and await the final qualification of the SABRE qualification and FDA’s guidance on the statistical evaluation of our BMD endpoint before initiating a Phase 3 study for EB613.
We believe that the key competitive factors that will affect the development and commercial success of our product candidates for osteoporosis, hypoparathyroidism and any other product candidates that we develop, are the efficacy, safety and tolerability profile, convenience in dosing, product labeling, price and availability of reimbursement from the government and other third-parties.
We believe that the key competitive factors that will affect the development and commercial success of our product candidates are their efficacy, safety and tolerability profile, convenience in dosing, product labeling, price and availability of reimbursement from the government and other third-parties.
Such a non-Israeli interested party is required to sign an undertaking towards the IIA in which it undertakes to comply with the Research Law. Notice or undertaking to the IIA may not be required in respect of purchase of Ordinary Shares in standard acquisition or trading in the stock exchange following to an IPO that was approved by the IIA.
Such a non-Israeli interested party is required to sign an undertaking towards the IIA in which it undertakes to comply with the Research Law. Notice or undertaking to the IIA may not be required with respect to the purchase of Ordinary Shares in standard acquisition or market purchases following an initial public offering (IPO) that was approved by the IIA.
Regulatory Requirements After a Marketing Authorization Has Been Obtained If we obtain authorization for a medicinal product in the EU, we will be required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products: Pharmacovigilance and Other Requirements We will, for example, have to comply with the EU’s stringent pharmacovigilance or safety reporting rules, pursuant to which post-authorization studies and additional monitoring obligations can be imposed. 31 Other requirements relate to, for example, the manufacturing of products and active pharmaceutical ingredients (“APIs”) in accordance with good manufacturing practice standards.
Regulatory Requirements After a Marketing Authorization Has Been Obtained If we obtain authorization for a medicinal product in the EU, we will be required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products: Pharmacovigilance and Other Requirements We will, for example, have to comply with the EU’s stringent pharmacovigilance or safety reporting rules, pursuant to which post-authorization studies and additional monitoring obligations can be imposed.
From a technical standpoint, oral delivery of therapeutic proteins is challenging due to the enzymatic degradation within the gastrointestinal tract and poor absorption into the blood stream due to the protein’s polarity and molecular weight.
From a technical standpoint, oral delivery of peptides and therapeutic proteins is challenging due to the enzymatic degradation within the gastrointestinal tract and poor absorption into the blood stream.
EB613: First Daily Osteoanabolic Tablet Treatment for the Treatment of Osteoporosis EB613 is the first once daily PTH (1-34, teriparatide) tablet treatment, and has the same amino acid sequence as Forteo ® (teriparatide daily subcutaneous injection), a leading anabolic agent which has been marketed for 23 years, and achieved peak annual sales of $1.7 billion prior to patent expiration in 2018.
EB613: Potentially the First Oral PTH(1-34) Anabolic Tablet Treatment for Post-Menopausal Women with Osteoporosis EB613 is the first once daily PTH(1-34, teriparatide) tablet treatment and has the same amino acid sequence as Forteo ® (teriparatide daily subcutaneous injection), a leading anabolic agent which has been marketed for 24 years and achieved peak annual sales of $1.7 billion prior to patent expiration in 2018.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters or holds on post-approval clinical trials; • refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties. 27 The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters or holds on post-approval clinical trials; • refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
Based on the outcomes of our FDA meetings, we believe that EB613 may be the first osteoporosis program to be permitted by FDA to pursue a placebo controlled, BMD endpoint registrational Phase 3 study to support an NDA.
We believe that EB613 may be the first osteoporosis program to be permitted by FDA to pursue a placebo controlled, BMD endpoint registrational Phase 3 study in support of an NDA.
If the MAA of a medicinal product designated as an orphan drug includes the results of all studies conducted in compliance with an agreed PIP, and a corresponding statement is subsequently included in the marketing authorization granted, the ten-year period of market exclusivity will be extended to twelve years.
If the MAA of a medicinal product designated as an orphan drug includes the results of all studies conducted in compliance with an agreed PIP, and a corresponding statement is subsequently included in the marketing authorization granted, the ten-year period of market exclusivity will be extended to twelve years. 31 Regulatory Data Protection EU legislation also provides for a system of regulatory data and market exclusivity.
Eneboparatide, once-daily injectable long-acting parathyroid hormone 1 (PTH1) receptor agonist, developed by Amolyt Pharma (acquired by AstraZeneca 2024) reported topline data that the primary endpoint for its Phase 3 study was met in March 2025.
Eneboparatide, once-daily injectable long-acting parathyroid hormone 1 (PTH1) receptor agonist, developed by Amolyt Pharma (acquired by AstraZeneca 2024) reported topline data that the primary endpoint for its Phase 3 study was met in March 2025. A long acting once weekly injectable PTH peptide prodrug (MBX2109) developed by MBX Biosciences, Inc. reported positive Phase 2 topline data in 2025.
As of December 31, 2024, the total royalty amount that would be payable by the Company to the IIA, before interest and payments as described above, is approximately $460 thousand.
As of December 31, 2025, the total royalty amount that would be payable by the Company to the IIA, before interest and payments as described above, is approximately $460 thousand. As of December 31, 2025, we had paid royalties to the IIA in the amount of $96 thousand.
These provisions primarily concern pension fund benefits for all employees, insurance for work-related accidents, recuperation pay and travel expenses. We generally provide our employees with benefits and working conditions beyond the required minimums. We have never experienced any employment-related work stoppages and believe our relationships with our employees are good.
These provisions primarily concern pension fund benefits for all employees, insurance for work-related accidents, recuperation pay and travel expenses. We generally provide our employees with benefits and working conditions beyond the required minimums.
As of December 31, 2024, we had paid royalties to the IIA in the amount of $96 thousand. 22 In addition to paying any royalties due, we must abide by other restrictions associated with receiving such grants under the Research Law that continue to apply even following repayment to the IIA.
In addition to paying any royalties due, we must abide by other restrictions associated with receiving such grants under the Research Law that continue to apply even following repayment to the IIA.
EB613 Phase 2 Study in Post-Menopausal Women with Low Bone Mass and Osteoporosis The Phase 2 clinical trial of EB613 was a dose-ranging, placebo-controlled, double-blind study in 161 postmenopausal women with osteoporosis or low BMD conducted at four leading medical centers in Israel.
As a result, no drug accumulation is expected with once daily tablet dosing. 14 EB613 Phase 2 Study in Post-Menopausal Women with Low Bone Mass and Osteoporosis This Phase 2 clinical trial of EB613 was a dose-ranging, placebo-controlled, double-blind study in 161 postmenopausal women with osteoporosis or low BMD conducted at four leading medical centers in Israel.
This could cause significant delays or difficulties in completing planned clinical trials in a timely manner. 24 Clinical Trials Clinical trials involve the administration of the investigational product candidate to healthy volunteers or patients with the disease to be treated under the supervision of a qualified principal investigator in accordance with GCP requirements.
Clinical Trials Clinical trials involve the administration of the investigational product candidate to healthy volunteers or patients with the disease to be treated under the supervision of a qualified principal investigator in accordance with GCP requirements.
We intend to explore opportunities to diversify and shorten the preclinical and clinical development of these candidates in a capital-efficient manner, including selectively pursuing research and clinical development partnerships with biopharmaceutical companies with specific domain expertise as well as with biopharmaceutical companies with proven commercial footprints to de-risk our late-stage programs.
We intend to explore opportunities to diversify and shorten the preclinical and clinical development of these candidates in a capital-efficient manner, including selectively pursuing research and clinical development partnerships with biopharmaceutical companies with specific domain expertise as well as with biopharmaceutical companies with proven commercial footprints to de-risk our late-stage programs. 12 PTH Parathyroid hormone (PTH) is an 84-amino acid hormone that regulates calcium and phosphate homeostasis and bone metabolism in the body.
We expect that additional state and federal healthcare reform measures, as well as legal changes by foreign governments, will be adopted in the future, any of which could limit the amounts that governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures. 35 Employees As of December 31, 2024, we had a total of 20 employees, of whom 18 are full-time employees all based in Israel.
We expect that additional state and federal healthcare reform measures, as well as legal changes by foreign governments, will be adopted in the future, any of which could limit the amounts that governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.
Bone Biomarkers (PD Effect) The primary bone biomarker endpoint of the Phase 2 clinical study—change in P1NP at Month 3—was met.
All adverse events were mild or moderate in intensity. 15 Bone Biomarkers (PD Effect) The primary bone biomarker endpoint of the Phase 2 clinical study—change in P1NP at Month 3—was met.
This order issued by the FDA would delay a proposed clinical trial until all outstanding concerns have been adequately addressed and the FDA has notified the company that investigations may proceed.
This order issued by the FDA would delay a proposed clinical trial until all outstanding concerns have been adequately addressed and the FDA has notified the company that investigations may proceed. This could cause significant delays or difficulties in completing planned clinical trials in a timely manner.
The results of the preclinical tests, together with manufacturing information and analytical data, are submitted to the FDA as part of an IND application. Some preclinical tests may continue even after submission of the IND application.
The conduct of the preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements, including GLP. The results of the preclinical tests, together with manufacturing information and analytical data, are submitted to the FDA as part of an IND application. Some preclinical tests may continue even after submission of the IND application.
We are developing our product candidates to potentially become the first oral, daily tablet peptide or protein replacement therapies designed for patients to live injection-free as they actively manage their chronic diseases. We aspire to continue to validate our platform across a variety of additional high value therapeutic proteins.
We are developing our product candidates to potentially become the first oral, single daily tablet peptide or protein replacement therapies designed to expand access for patients and healthcare practitioners. We aspire to continue to validate our platform across a variety of additional high value therapeutic proteins.
If we fail to comply with the Research Law, we may be forced to return the grants and/or be subject to other payments to the IIA, monetary fines and/or criminal charges. Oramed Patent Transfer Agreement In 2011, we entered into a patent transfer agreement with Oramed Ltd.
If we fail to comply with the Research Law, we may be forced to return the grants and/or be subject to other payments to the IIA, monetary fines and/or criminal charges. OPKO Collaboration and License Agreements 2023 Collaboration Agreement In September 2023, we entered into the 2023 Collaboration Agreement with OPKO Biologics.
We plan to file an Investigational New Drug application with the FDA later this year. Our Strategy Our goal is to develop first-in-class oral peptides and protein replacement therapies for underserved, chronic medical conditions for which a tablet treatment has the potential to significantly shift a treatment paradigm.
Our Strategy Our goal is to develop first-in-class oral peptides and protein replacement therapies for ignored, underserved, chronic medical conditions for which a tablet treatment has the potential to significantly shift a treatment paradigm.
If any of the physicians or other providers or entities with whom we expect to do business are found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded health care programs. 33 Environmental, Health and Safety We are further subject to various foreign, national, federal, state and local laws and regulations relating to environmental, health and safety matters, in a number of jurisdictions, governing, inter alia, (i) the use, storage, registration, handling, emission and disposal of chemicals, waste materials and sewage; and (ii) chemical, air, water and ground contamination, air emissions and the cleanup of contaminated sites, including any contamination that results from spills due to our failure to properly dispose of chemicals, waste materials and sewage.
Environmental, Health and Safety We are further subject to various foreign, national, federal, state and local laws and regulations relating to environmental, health and safety matters, in a number of jurisdictions, governing, inter alia, (i) the use, storage, registration, handling, emission and disposal of chemicals, waste materials and sewage; and (ii) chemical, air, water and ground contamination, air emissions and the cleanup of contaminated sites, including any contamination that results from spills due to our failure to properly dispose of chemicals, waste materials and sewage.
Government Regulation and Product Approval Government authorities in the United States, at the federal, state and local level, and in other countries and jurisdictions, including the EU, extensively regulate, among other things, the research, development, testing, manufacture, pricing, quality control, approval, packaging, storage, recordkeeping, labelling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of pharmaceutical products.
However, it is our intention to complete such contracts in anticipation of commercial manufacturing activities, so that if approved, we will have such contracts in place. 23 Government Regulation and Product Approval Government authorities in the United States, at the federal, state and local level, and in other countries and jurisdictions, including the EU, extensively regulate, among other things, the research, development, testing, manufacture, pricing, quality control, approval, packaging, storage, recordkeeping, labelling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of pharmaceutical products.
The study achieved its primary and secondary endpoints, including a reduction in calcium supplements, reductions in serum phosphate and 24-hour urine calcium excretion, maintenance of ACa within the reference range, and an improvement in quality of life. Specific results of this trial included: Phase 2 PK/PD Clinical Trial We initiated a two-part Phase 2 PK/PD trial in 2014.
The study achieved its primary and secondary endpoints, including a reduction in calcium supplements, reductions in serum phosphate and 24-hour urine calcium excretion, maintenance of ACa within the reference range, and an improvement in quality of life.
The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional marketing authorization. 30 Period of Authorization and Renewals A marketing authorization will be valid for five years in principle, and the marketing authorization may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by a national authority.
Period of Authorization and Renewals A marketing authorization will be valid for five years in principle, and the marketing authorization may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by a national authority.
We leverage our N-Tab™ platform, which is designed to simultaneously stabilize the peptide in the gastrointestinal tract and promote its absorption into the bloodstream. 7 EB613 Program Our most advanced product candidate, EB613, oral PTH(1-34), is being developed as the first oral, osteoanabolic (bone building) once-daily tablet treatment for post-menopausal women with low bone mineral density (“BMD”) and high-risk osteoporosis.
We leverage our N-Tab ® platform, which is designed to simultaneously stabilize large (4kD+) hydrophilic peptides in the gastrointestinal tract and promote their absorption into the bloodstream. 7 EB613 Program Our most advanced product candidate, EB613 (oral teriparatide, or oral PTH[1-34]), is being developed as the first oral, osteoanabolic (bone building) tablet treatment for osteoporosis.
We believe that the granted patents as well as certain of the pending claims contained in our patent applications, if issued in substantially the same form, would cover our proprietary technology platform (N-Tab™) and the candidates used in various pipeline programs as indicated in the following table: Subject Mater # Pending Applications # Issued Patents Geographical Scope Nominal Patent Term EB613 80 49 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2029 - 2044 EB612 73 44 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2029 - 2044 GLP1/Glucagon 58 8 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2036 - 2044 GLP2 57 8 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2036 - 2044 Platform (N-Tab™) 116 56 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2029 - 2044 20 Issued patents and any patent that may issue from the pending patent applications are currently expected to expire by the Nominal Patent Term as noted in the above table, assuming national phase filings are timely effected.
Subject Mater # Pending Applications # Issued Patents Geographical Scope Nominal Patent Term EB613 79 51 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2029 - 2044 EB612 73 44 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2029 - 2044 GLP-1/Glucagon 58 8 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2036 - 2044 GLP-2 57 8 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2036 - 2044 Platform (N-Tab ® ) 131 56 United States, Europe, Japan, China, Canada, Singapore, United Arab Emirates, Israel, Brazil, Mexico, South Africa, India, Australia, New Zealand, Russia, South Korea and Hong Kong 2029 - 2044 Issued patents and any patent that may issue from the pending patent applications are currently expected to expire by the Nominal Patent Term as noted in the above table, assuming national phase filings are timely effected.
For this and a more comprehensive discussion of risks related to our intellectual property, see “Item 1A.—Risk Factors-Risks Related to Our Intellectual Property.” 21 Commercialization Strategy We hold global rights to our internally developed product candidates (including EB613 and EB612), and intend to maximize the value of these candidates commercially with strong partners that have the requisite commercial infrastructure within a specific therapeutic indication, target or geography.
For this and a more comprehensive discussion of risks related to our intellectual property, see “Item 1A.—Risk Factors-Risks Related to Our Intellectual Property.” Commercialization Strategy We hold global rights to our internally developed product candidate EB613 and intend to maximize the value of EB613 with strong partners that have the requisite commercial infrastructure to successfully launch a candidate that we believe has the potential for significant sales.
To permit the FDA to end another manufacturer’s orphan exclusivity period, the FDA must determine that the manufacturer has demonstrated clinical superiority by showing the later drug is safer, more effective, or otherwise makes a major contribution to patient care.
To permit the FDA to end another manufacturer’s orphan exclusivity period, the FDA must determine that the manufacturer has demonstrated clinical superiority by showing the later drug is safer, more effective, or otherwise makes a major contribution to patient care. 28 The period of exclusivity begins on the date that the marketing application is approved by the FDA and applies only to the indication for which the product has been designated.
Hypocalcemia can cause weakness, muscle cramps, excessive nervousness, headaches and uncontrollable twitching and tetany. Hyperphosphatemia can result in soft tissue calcium deposition, which may lead to severe issues, including damage to the circulatory and central nervous systems. In contrast to osteoporosis, longer persistence of PTH in plasma is a desirable property for the treatment of hypoparathyroidism.
Individuals with a deficiency of parathyroid hormone may exhibit hypocalcemia and hyperphosphatemia. Hypocalcemia can cause weakness, muscle cramps, excessive nervousness, headaches and uncontrollable twitching and tetany. Hyperphosphatemia can result in soft tissue calcium deposition, which may lead to severe issues, including damage to the circulatory and central nervous systems.
Conditional marketing authorizations are valid for one year, and may be renewed annually, if the risk-benefit balance remains positive, and after an assessment of the need for additional or modified conditions and/or specific obligations.
Conditional marketing authorizations are valid for one year, and may be renewed annually, if the risk-benefit balance remains positive, and after an assessment of the need for additional or modified conditions and/or specific obligations. The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional marketing authorization.
In September 2019, we presented the results of Part 2 at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting. 19 Planned Additional Clinical Development and Regulatory Pathway We have since developed a new generation of EB612 based on new intellectual property of our N-Tab™ Technology, which we have designed to optimize its PK profile and the potential for reduced daily dosing.
Planned Additional Clinical Development and Regulatory Pathway We have since developed a new generation of EB612 based on new intellectual property of our N-Tab ® platform, which we have designed to optimize its PK profile and the potential for reduced daily dosing.
EB613 is positioned to potentially be the first, once daily osteoanabolic tablet treatment for women with high-risk post-menopausal osteoporosis. 12 Phase 1 Safety, PK and PD Data for Oral PTH(1-34) Tablet Programs Our Oral PTH(1-34) tablet candidates, including EB613 and EB612, have been administered collectively to a total of 102 healthy subjects in three Phase 1 studies.
EB613 is positioned to potentially be the first, once daily osteoanabolic tablet treatment for women with high-risk post-menopausal osteoporosis. Phase 1 Safety, PK and PD Data for Oral PTH(1-34) Tablet Programs We have completed a comprehensive nonclinical and clinical package for EB613, including three Phase 1 studies and three Phase 2 clinical studies.
However, it was recalled in 2019 due to a plastic particulate and was permanently phased out globally at the end of 2024. TransCon PTH, once-daily injectable, long-acting prodrug of parathyroid hormone (PTH(1-34)) developed by Ascendis Pharma A/S was FDA Approved in August 2023 and EU Approved in November 2023.
TransCon PTH, once-daily injectable, long-acting prodrug of parathyroid hormone (PTH(1-34)) developed by Ascendis Pharma A/S was FDA Approved in August 2023 and EU Approved in November 2023.
We are preparing to initiate a Phase 3 registrational study for EB613 pursuant to the FDA’s qualification of a quantitative BMD endpoint, which we currently expect to occur in 2025. 10 • Advancing the First Daily PTH(1-34) Peptide Replacement Tablet Therapy for the Treatment of Hypoparathyroidism: In 2015, we successfully completed a Phase 2a four-month trial in 19 patients with hypoparathyroidism which demonstrated clinical benefit, including a statistically significant reduction in calcium supplementation, maintenance of calcium levels above the lower target level for Hypoparathyroidism patients (>7.5 mg/dL) throughout the study and statistically significant rapid decline in median serum phosphate levels two hours following the first dose, which was maintained for the duration of the study.
Entera currently retains global rights to EB613. • Advancing Potentially the First Oral LA-PTH Analog as a Once-Daily Tablet for Patients with Hypoparathyroidism as part of our Collaboration with OPKO: In 2015, we successfully completed a Phase 2a four-month trial in 19 patients with hypoparathyroidism, which demonstrated clinical benefit, including a statistically significant reduction in calcium supplementation, maintenance of calcium levels above the lower target level for Hypoparathyroidism patients (>7.5 mg/dL) throughout the study and statistically significant rapid decline in median serum phosphate levels two hours following the first dose, which was maintained for the duration of the study.
Prevalence It is estimated that hypoparathyroidism affects approximately 200,000 people across the United States, the European Union and Japan, with approximately 43% of cases characterized as mild, 39% characterized as moderate, and 18% characterized as severe. 17 Limitations of current treatments for hypoparathyroidism Historically, the treatments for hypoparathyroidism have been calcium supplements, vitamin D supplements and phosphate binders.
Here, hormone replacement therapy is warranted. 17 Prevalence It is estimated that hypoparathyroidism affects approximately 200,000 people across the United States, the European Union and Japan, with approximately 43% of cases characterized as mild, 39% characterized as moderate, and 18% characterized as severe.
In September 2023, we entered into a research collaboration agreement (the “2023 Collaboration Agreement”) with OPKO Biologics, Inc., a subsidiary of OPKO Health, Inc. (“OPKO”). Under the terms of this agreement, OPKO has agreed to supply its proprietary long-acting GLP-2 peptide and certain Oxyntomodulin (OXM) analogs for the development of oral tablet candidates using our proprietary N-Tab™ technology.
Under the terms of this agreement, OPKO has agreed to supply its proprietary long-acting GLP-2 peptide and certain Oxyntomodulin (OXM) analogs for the development of oral tablet candidates using our proprietary N-Tab ® platform.
Conditional Approval In specific circumstances, EU legislation (Article 14(7) Regulation (EC) No 726/2004 and Regulation (EC) No 507/2006 on Conditional Marketing Authorisations for Medicinal Products for Human Use) enables applicants to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.
After a drug has been authorized and launched, it is a condition of maintaining the marketing authorization that all aspects relating to its quality, safety and efficacy must be kept under review. 30 Conditional Approval In specific circumstances, EU legislation (Article 14(7) Regulation (EC) No 726/2004 and Regulation (EC) No 507/2006 on Conditional Marketing Authorisations for Medicinal Products for Human Use) enables applicants to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.
Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process.
The FDA may approve a second application for the same product for a different use or a subsequent application for a different drug for the same indication. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process.
Pharmaceutical Pricing and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any drug products for which we plan to seek regulatory approval.
These regulations establish new and potentially significant fees for discharging forbidden or irregular sewage into the sewage system. 34 Pharmaceutical Pricing and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any drug products for which we plan to seek regulatory approval.
For instance, Israeli regulations were promulgated in 2011 relating to the discharge of industrial sewage into the sewer system. These regulations establish new and potentially significant fees for discharging forbidden or irregular sewage into the sewage system.
For instance, Israeli regulations were promulgated in 2011 relating to the discharge of industrial sewage into the sewer system.
Similarly, failure to comply with the EU’s requirements regarding the protection of individual personal data can also lead to significant penalties and sanctions. Individual EU member states may also impose various sanctions and penalties in case we do not comply with locally applicable requirements.
Individual EU member states may also impose various sanctions and penalties in case we do not comply with locally applicable requirements.
Regulatory Data Protection EU legislation also provides for a system of regulatory data and market exclusivity. Upon receiving marketing authorization, new chemical entities approved on the basis of complete independent data package benefit from eight years of data exclusivity and an additional two years of market exclusivity.
Upon receiving marketing authorization, new chemical entities approved on the basis of complete independent data package benefit from eight years of data exclusivity and an additional two years of market exclusivity. Data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar (abbreviated) application.

… 177 more changes not shown on this page.

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

148 edited+34 added−30 removed426 unchanged
Biggest changeIn addition, the government may assert that a claim including items or services resulting from a violation of the Stark Law constitutes a false or fraudulent claim for purposes of the False Claims Act; • the federal False Claims Act imposes civil penalties, and provides for civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; • HIPAA imposes criminal and civil liability for executing a scheme to defraud any health care benefit program or making false statements relating to health care matters.
Biggest changeIn addition, the government may assert that a claim including items or services resulting from a violation of the Stark Law constitutes a false or fraudulent claim for purposes of the False Claims Act; • the federal False Claims Act imposes civil penalties, and provides for civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; • the Civil Monetary Penalty Act of 1981 imposes penalties against any person or entity that, among other things, is determined to have presented or caused to be presented a claim to a federal health care program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent, or offering or transferring remuneration to a federal health care beneficiary that a person knows or should know is likely to influence the beneficiary’s decision to order or receive items or services reimbursable by the government from a particular provider or supplier.
Any collaboration we enter into may pose a number of risks, including the following: • Collaborators may have significant discretion in determining the efforts and resources that they will apply to these collaborations; • Collaborators may not perform their obligations as expected; • Collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; • Collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • Collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • Product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; • A collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; • Disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or termination of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive; • Collaborators may not properly obtain, maintain, defend or enforce our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation or other intellectual property-related proceedings, including proceedings challenging the scope, ownership, validity and enforceability of our intellectual property. • Collaborators may own or co-own intellectual property covering our product candidates or research programs that results from our collaboration with them, and in such cases, we may not have the exclusive right to commercialize such intellectual property or such product candidates or research programs; 59 • Collaborators may infringe, misappropriate or otherwise violate the intellectual property rights of third parties, which may expose us to litigation and potential liability; • Collaborators may fail to comply with applicable laws, rules or regulations when performing services for us, which may expose us to legal proceedings and potential liability; and • Collaborations may be terminated for convenience by the collaborator and, if terminated, we may suffer from negative publicity and we may find it more difficult to attract new collaborators. • The Israel-Hamas War may cause us to fail to meet contractually obligated deadlines with our collaboration partners or otherwise strain our relationships with current collaborators or other business partners.
Any collaboration we enter into may pose a number of risks, including the following: • Collaborators may have significant discretion in determining the efforts and resources that they will apply to these collaborations; • Collaborators may not perform their obligations as expected; • Collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; • Collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; 60 • Collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • Product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; • A collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; Disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or termination of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive; • Collaborators may not properly obtain, maintain, defend or enforce our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation or other intellectual property-related proceedings, including proceedings challenging the scope, ownership, validity and enforceability of our intellectual property. • Collaborators may own or co-own intellectual property covering our product candidates or research programs that results from our collaboration with them, and in such cases, we may not have the exclusive right to commercialize such intellectual property or such product candidates or research programs; • Collaborators may infringe, misappropriate or otherwise violate the intellectual property rights of third parties, which may expose us to litigation and potential liability; • Collaborators may fail to comply with applicable laws, rules or regulations when performing services for us, which may expose us to legal proceedings and potential liability; and • Collaborations may be terminated for convenience by the collaborator and, if terminated, we may suffer from negative publicity and we may find it more difficult to attract new collaborators. • The Israel-Hamas War may cause us to fail to meet contractually obligated deadlines with our collaboration partners or otherwise strain our relationships with current collaborators or other business partners.
All such reported information is publicly available; 53 • analogous state and non-U.S. laws and regulations, such as certain state anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and • regulation by the CMS and enforcement by the HHS Office of Inspector General or the U.S.
All such reported information is publicly available; • analogous state and non-U.S. laws and regulations, such as certain state anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and • regulation by the CMS and enforcement by the HHS Office of Inspector General or the U.S.
The degree of market acceptance of our product candidates will depend on a number of factors, including: • limitations or warnings contained in the approved labeling for a product candidate; • changes in the standard of care for the targeted indications for any of our product candidates; • limitations in the approved clinical indications for our product candidates; • demonstrated clinical safety and efficacy compared to other products; • lack of significant adverse side effects; • sales, marketing and distribution support; • availability and extent of coverage and reimbursement from managed care plans and other third-party payors; • timing of market introduction and perceived effectiveness of competitive products; • the degree of cost-effectiveness of our product candidates; • availability of alternative therapies at similar or lower cost, including generic and over-the-counter products; • the extent to which the product candidate is approved for inclusion on formularies of hospitals and third-party payors, including managed care organizations; • whether the product is designated under physician treatment guidelines as a first-line therapy or as a second- or third-line therapy for particular diseases; • adverse publicity about our product candidates or favorable publicity about competitive products; • convenience and ease of administration of our products; and • potential product liability claims.
The degree of market acceptance of our product candidates will depend on a number of factors, including: • limitations or warnings contained in the approved labeling for a product candidate; • changes in the standard of care for the targeted indications for any of our product candidates; • limitations in the approved clinical indications for our product candidates; • demonstrated clinical safety and efficacy compared to other products; • lack of significant adverse side effects; • sales, marketing and distribution support; 57 • availability and extent of coverage and reimbursement from managed care plans and other third-party payors; • timing of market introduction and perceived effectiveness of competitive products; • the degree of cost-effectiveness of our product candidates; • availability of alternative therapies at similar or lower cost, including generic and over-the-counter products; • the extent to which the product candidate is approved for inclusion on formularies of hospitals and third-party payors, including managed care organizations; • whether the product is designated under physician treatment guidelines as a first-line therapy or as a second- or third-line therapy for particular diseases; • adverse publicity about our product candidates or favorable publicity about competitive products; • convenience and ease of administration of our products; and • potential product liability claims.
If microbial, viral or other contaminations are discovered in our product candidates or in the manufacturing facilities in which our product candidates are made, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination. • The manufacturing facilities in which our product candidates are made could be adversely affected by equipment failures, labor shortages, natural disasters, power failures, outbreaks of an infectious disease such as the duration and intensity of the ongoing war in Israel, other geopolitical tensions such as the ongoing conflict between Russia and Ukraine, and numerous other factors. • We and our contract manufacturing organizations, or CMOs, must comply with applicable cGMP regulations and guidelines.
If microbial, viral or other contaminations are discovered in our product candidates or in the manufacturing facilities in which our product candidates are made, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination. • The manufacturing facilities in which our product candidates are made could be adversely affected by equipment failures, labor shortages, natural disasters, power failures, outbreaks of an infectious disease such as the duration and intensity of the ongoing war in Israel, other geopolitical tensions such as the ongoing conflict between Russia and Ukraine, and numerous other factors. 56 • We and our contract manufacturing organizations, or CMOs, must comply with applicable cGMP regulations and guidelines.
Despite the time and expense invested in clinical development of product candidates, regulatory approval is never guaranteed. 46 The FDA or comparable foreign regulatory authorities can delay, limit or deny approval of a product candidate for many reasons, including: • such authorities may disagree with the number, design, size, conduct or implementation of our clinical trials or any of our collaborators’ clinical trials; • we or any of our development partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a product candidate is safe and effective for any indication; • the results of clinical trials may not meet the level of statistical significance or clinical significance required by the FDA, EMA or other regulatory agencies for approval; • such authorities may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that authority’s jurisdiction; • the data collected from non-clinical studies and clinical trials of our product candidates may not be sufficient to support the submission of an application for regulatory approval; • the results of clinical trials may not demonstrate the safety or efficacy required by such authorities for approval; • we or any of our future development partners may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • such authorities may disagree with our interpretation of data from preclinical studies or clinical trials or the use of results from studies that served as precursors to our current or future product candidates; • such authorities may find deficiencies in our manufacturing processes or facilities or those of third-party manufacturers with which we or any of our future development partners contract for clinical and commercial supplies; • the FDA may require development of a REMS as a condition of approval; and • the approval policies or regulations of such authorities may significantly change in a manner rendering our or any of our future development partners’ clinical data insufficient for approval.
Despite the time and expense invested in clinical development of product candidates, regulatory approval is never guaranteed. 47 The FDA or comparable foreign regulatory authorities can delay, limit or deny approval of a product candidate for many reasons, including: • such authorities may disagree with the number, design, size, conduct or implementation of our clinical trials or any of our collaborators’ clinical trials; • we or any of our development partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a product candidate is safe and effective for any indication; • the results of clinical trials may not meet the level of statistical significance or clinical significance required by the FDA, EMA or other regulatory agencies for approval; • such authorities may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that authority’s jurisdiction; • the data collected from non-clinical studies and clinical trials of our product candidates may not be sufficient to support the submission of an application for regulatory approval; • the results of clinical trials may not demonstrate the safety or efficacy required by such authorities for approval; • we or any of our future development partners may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • such authorities may disagree with our interpretation of data from preclinical studies or clinical trials or the use of results from studies that served as precursors to our current or future product candidates; • such authorities may find deficiencies in our manufacturing processes or facilities or those of third-party manufacturers with which we or any of our future development partners contract for clinical and commercial supplies; • the FDA may require development of a REMS as a condition of approval; and • the approval policies or regulations of such authorities may significantly change in a manner rendering our or any of our future development partners’ clinical data insufficient for approval.
Our clinical trials may be suspended or terminated at any time by the FDA (for trials in the United States), other regulatory authorities (for trials conducted outside the United States), the IRB /ethics committee overseeing any given clinical trial, any of our clinical trial sites with respect to that site, or us, due to a number of factors, including: • failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols; • failing to establish clinical endpoints acceptable to the FDA and other regulatory authorities; • findings of an inspection of the clinical trial operations or trial sites by the FDA or other regulatory authorities; • unforeseen issues, including serious adverse events associated with a product candidate, or lack of effectiveness or any determination that a clinical trial presents unacceptable health risks; • lack of adequate funding to continue the clinical trial due to unforeseen costs or other business decisions; and • upon a breach or pursuant to the terms of any agreement with, or for any other reason by, current or future collaborators that have responsibility for the clinical development of any of our product candidates. 49 Moreover, principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and receive compensation in connection with such services.
Our clinical trials may be suspended or terminated at any time by the FDA (for trials in the United States), other regulatory authorities (for trials conducted outside the United States), the IRB /ethics committee overseeing any given clinical trial, any of our clinical trial sites with respect to that site, or us, due to a number of factors, including: • failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols; • failing to establish clinical endpoints acceptable to the FDA and other regulatory authorities; • findings of an inspection of the clinical trial operations or trial sites by the FDA or other regulatory authorities; • unforeseen issues, including serious adverse events associated with a product candidate, or lack of effectiveness or any determination that a clinical trial presents unacceptable health risks; • lack of adequate funding to continue the clinical trial due to unforeseen costs or other business decisions; and • upon a breach or pursuant to the terms of any agreement with, or for any other reason by, current or future collaborators that have responsibility for the clinical development of any of our product candidates. 50 Moreover, principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and receive compensation in connection with such services.
Any of the foregoing could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects. 64 Our commercial success depends significantly on our ability to operate without infringing the patents and other proprietary rights of third parties. We may face claims that we are violating the intellectual property rights of others.
Any of the foregoing could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects. Our commercial success depends significantly on our ability to operate without infringing the patents and other proprietary rights of third parties. We may face claims that we are violating the intellectual property rights of others.
The royalty rate may increase to 5%, with respect to approved applications filed following any year in which we achieve sales of over $70 million. 72 Under the Research Law, we are prohibited from manufacturing products for commercial use developed using these grants outside of the State of Israel without special approvals.
The royalty rate may increase to 5%, with respect to approved applications filed following any year in which we achieve sales of over $70 million. Under the Research Law, we are prohibited from manufacturing products for commercial use developed using these grants outside of the State of Israel without special approvals.
This lowered credit rating, as well as the ongoing war and conflicts described above, could make it more difficult for us to raise capital, if needed, and negatively influence the market price of our Ordinary Shares. We could experience disruptions if acts associated with such conflicts result in any serious damage to our facilities.
This credit rating, as well as the ongoing war and conflicts described above, could make it more difficult for us to raise capital, if needed, and negatively influence the market price of our Ordinary Shares. We could experience disruptions if acts associated with such conflicts result in any serious damage to our facilities.
Should any of the events described above occur, this could have a material adverse effect on our business, financial condition and results of operations. 58 Risks Related to Our Dependence on Third Parties We are highly dependent upon our ability to enter into agreements with collaborators to develop, commercialize and market our products.
Should any of the events described above occur, this could have a material adverse effect on our business, financial condition and results of operations. Risks Related to Our Dependence on Third Parties We are highly dependent upon our ability to enter into agreements with collaborators to develop, commercialize and market our products.
We do not know whether any Phase 2, Phase 3 or other clinical trials we or any of our collaborators may conduct will demonstrate consistent or adequate efficacy and safety to obtain regulatory approval to market our product candidates. Even if regulatory approvals are obtained for our product candidates, we will be subject to ongoing government regulation.
We do not know whether any Phase 2, Phase 3 or other clinical trials we or any of our collaborators may conduct will demonstrate consistent or adequate efficacy and safety to obtain regulatory approval to market our product candidates. 51 Even if regulatory approvals are obtained for our product candidates, we will be subject to ongoing government regulation.
An inactive market may also impair our ability to raise capital by selling Ordinary Shares and may impair our ability to acquire other companies by using our Ordinary Shares as consideration . 69 Our stock price may continue to be volatile, and securities class action litigation has often been instituted against companies following periods of volatility of their stock price.
An inactive market may also impair our ability to raise capital by selling Ordinary Shares and may impair our ability to acquire other companies by using our Ordinary Shares as consideration . Our stock price may continue to be volatile, and securities class action litigation has often been instituted against companies following periods of volatility of their stock price.
If another company develops an alternative technology for oral delivery of such molecules in small tablet form that is equal to or better than our technology, we may be unable to compete. 54 The osteoporosis market is already served by a variety of competing products.
If another company develops an alternative technology for oral delivery of such molecules in small tablet form that is equal to or better than our technology, we may be unable to compete. The osteoporosis market is already served by a variety of competing products.
If trademarks and trade names related to our product candidates are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected. We are currently in the process of registering the trademark N-Tab™ for our oral platform technology, globally.
If trademarks and trade names related to our product candidates are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected. We are currently in the process of registering the trademark N-Tab ® for our oral platform, globally.
However, for as long as we are a non-accelerated filer, our independent registered public accounting firm will not be required to attest to the effectiveness of our internal controls over financial reporting pursuant to Section 404. An independent assessment of the effectiveness of our internal controls could detect problems that our management’s assessment might not.
However, as long as we are a non-accelerated filer, our independent registered public accounting firm will not be required to attest to the effectiveness of our internal controls over financial reporting pursuant to Section 404. An independent assessment of the effectiveness of our internal controls could detect problems that our management’s assessment might not.
Furthermore, we have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by biotech companies in rapidly evolving fields. 40 To become and remain profitable, we must succeed in developing and commercializing products that generate significant revenues.
Furthermore, we have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by biotech companies in rapidly evolving fields. To become and remain profitable, we must succeed in developing and commercializing products that generate significant revenues.
In addition, some of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates. We may not be successful in our efforts to use and expand our N-Tab™ platform, to other product candidates.
In addition, some of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates. 42 We may not be successful in our efforts to use and expand our N -Tab® platform, to other product candidates.
If the defective product candidates cannot be replaced in a timely fashion, we may incur significant delays in our development programs that could adversely affect the value of such product candidates. 55 We currently have no sales, marketing or distribution infrastructure.
If the defective product candidates cannot be replaced in a timely fashion, we may incur significant delays in our development programs that could adversely affect the value of such product candidates. We currently have no sales, marketing or distribution infrastructure.
If we are unable to obtain adequate levels of coverage and reimbursement for our product candidates, their marketability will be negatively and materially impacted. Reimbursement may impact the demand for, or the price of, any product for which we obtain marketing approval.
If we are unable to obtain adequate levels of coverage and reimbursement for our product candidates, their marketability will be negatively and materially impacted. 58 Reimbursement may impact the demand for, or the price of, any product for which we obtain marketing approval.
Furthermore, we may not be able to secure and maintain suitable research institutions to conduct our clinical trials. Independent clinical investigators and CROs that we engage to conduct our clinical trials may not devote sufficient time or attention to our clinical trials or be able to repeat their past success.
Furthermore, we may not be able to secure and maintain suitable research institutions to conduct our clinical trials. 61 Independent clinical investigators and CROs that we engage to conduct our clinical trials may not devote sufficient time or attention to our clinical trials or be able to repeat their past success.
The addition of such employees and managers may have an impact on the decisions that we make over time. 43 In conjunction with the addition of these employees and senior members of management, we intend to grow our company.
The addition of such employees and managers may have an impact on the decisions that we make over time. In conjunction with the addition of these employees and senior members of management, we intend to grow our company.
The amount and timing of our funding requirements will depend on many factors, including but not limited to: • the scope, progress, timing, cost and results of research, preclinical development, and clinical trials; • the costs, timing and outcome of seeking and obtaining approvals from the FDA, EMA or other regulatory agencies in relation to registrational strategies and potential NDA or BLA approvals for our product candidates; • the costs associated with manufacturing our product candidates and potentially establishing sales, marketing, and distribution capabilities in the absence of commercial partnerships; • the costs associated with obtaining, maintaining, expanding, defending and enforcing the scope of our intellectual property portfolio, including the amount and timing of any payments we may be required to make in connection with the licensing, filing, defense and enforcement of any patents or other intellectual property rights; 38 • the extent to which we acquire or in-license other products or technologies; • the economic and other terms, timing of and success of any collaboration, licensing, or other arrangements into which we entered or may enter in the future, including the timing of achievement of milestones and receipt of any milestone or royalty payments under these agreements; • our need and ability to hire additional management, scientific, and medical personnel; • the effect of competing products that may limit market penetration of our product candidates; • the amount and timing of revenues, if any, we receive from commercial sales of any product candidates for which we receive marketing approval in the future; and • our need to implement additional internal systems and infrastructure, including financial and reporting systems to support our current operations as a public company.
The amount and timing of our funding requirements will depend on many factors, including but not limited to: • the scope, progress, timing, cost and results of research, preclinical development, and clinical trials; • the costs, timing and outcome of seeking and obtaining approvals from the FDA, EMA or other regulatory agencies in relation to registrational strategies and potential NDA or BLA approvals for our product candidates; • the costs associated with manufacturing our product candidates and potentially establishing sales, marketing, and distribution capabilities in the absence of commercial partnerships; • the costs associated with obtaining, maintaining, expanding, defending and enforcing the scope of our intellectual property portfolio, including the amount and timing of any payments we may be required to make in connection with the licensing, filing, defense and enforcement of any patents or other intellectual property rights • the extent to which we acquire or in-license other products or technologies; • the economic and other terms, timing of and success of any collaboration, licensing, or other arrangements into which we entered or may enter in the future, including the timing of achievement of milestones and receipt of any milestone or royalty payments under these agreements; • our need and ability to hire additional management, scientific, and medical personnel; • the effect of competing products that may limit market penetration of our product candidates; • the amount and timing of revenues, if any, we receive from commercial sales of any product candidates for which we receive marketing approval in the future; and • our need to implement additional internal systems and infrastructure, including financial and reporting systems to support our current operations as a public company. 39 Many of these factors are outside of our control.
Third parties who are otherwise willing to pay a premium over prevailing market prices to gain control of us may be unable or unwilling to do so because of these provisions of Israeli law and our Articles. 75 Your rights and responsibilities as a shareholder are governed by Israeli law, which may differ in some respects from the rights and responsibilities of shareholders of U.S. companies.
Third parties who are otherwise willing to pay a premium over prevailing market prices to gain control of us may be unable or unwilling to do so because of these provisions of Israeli law and our Articles. 76 Your rights and responsibilities as a shareholder are governed by Israeli law, which may differ in some respects from the rights and responsibilities of shareholders of U.S. companies.
In addition, a proxy contest for the election of directors at our annual meeting would require us to incur significant legal fees and proxy solicitation expenses and require significant time and attention by management and our Board. The perceived uncertainties as to our future direction also could affect the market price and volatility of our securities.
In addition, a proxy contest for the election of directors at our annual meeting would require us to incur significant legal fees and proxy solicitation expenses and require significant time and attention by management and our Board. The perceived uncertainties as to our future direction also could affect the market price and volatility of our securities. ITEM 1B.
Our product candidates utilize our proprietary N-Tab™ technology and know-how relating to the development of oral peptides and oral protein replacement therapies in tablet form. We seek to protect our proprietary position by filing patent applications in the United States and certain foreign jurisdictions relating to our product candidates and technologies that are important to our business.
Our product candidates utilize our proprietary N-Tab ® platform and know-how relating to the development of oral peptides and oral protein replacement therapies in tablet form. We seek to protect our proprietary position by filing patent applications in the United States and certain foreign jurisdictions relating to our product candidates and technologies that are important to our business.
We expect that additional state and federal healthcare reform measures will be adopted in the future. 52 The delivery of healthcare in the EU, including the establishment and operation of health services and the pricing and reimbursement of medicines, is almost exclusively a matter for national, rather than EU, law and policy.
We expect that additional state and federal healthcare reform measures will be adopted in the future. 53 The delivery of healthcare in the EU, including the establishment and operation of health services and the pricing and reimbursement of medicines, is almost exclusively a matter for national, rather than EU, law and policy.
Any such development could have a material adverse effect on our business, prospects, financial condition and results of operations. 63 We may become involved in proceedings to protect or enforce our proprietary rights, which could be expensive and time consuming, and may ultimately be unsuccessful.
Any such development could have a material adverse effect on our business, prospects, financial condition and results of operations. 64 We may become involved in proceedings to protect or enforce our proprietary rights, which could be expensive and time consuming, and may ultimately be unsuccessful.
Even if we are successful in expanding our drug delivery technology to other peptides for other indications as we have to GLP-2 and GLP-1/Glucagon , the potential product candidates that we identify may not be suitable for clinical development, to the extent they are shown to have harmful side effects or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance.
Even if we are successful in expanding our technology platform to other peptides for other indications as we have to GLP-1/Glucagon and GLP-2, the potential product candidates that we identify may not be suitable for clinical development, to the extent they are shown to have harmful side effects or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance.
The FDA also agreed that Total BMD could serve as the primary endpoint of the registrational study in post-menopausal osteoporosis patients. In February 2023, we announced that a Type D meeting protocol review had been accepted by the FDA.
The FDA also agreed that Total BMD could serve as the primary endpoint of the registrational study in post-menopausal osteoporosis patients. In February 2023, we announced that a Type D meeting had been accepted by the FDA.
Our Oral GLP-1/Glucagon program may compete with approved GLP-1 injectables, Rybelsus and experimental incretin targeted injectables and oral small molecules and potential oral peptide candidates in the metabolic indications we pursue.. These factors may make it difficult for us to enroll enough subjects to complete our clinical trials in a timely and cost-effective manner.
Our Oral GLP-1/Glucagon program may compete with approved GLP-1 injectables, Wegovy pill, and experimental incretin targeted injectables and oral small molecules and potential oral peptide candidates in the metabolic indications we pursue. These factors may make it difficult for us to enroll enough subjects to complete our clinical trials in a timely and cost-effective manner.
It is not clear what, if any, impact such legislation will have on the operation of our business. Additionally, the United States Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations.
It is not clear what, if any, impact such past or potential future legislation will have on the operation of our business. Additionally, the United States Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations.
Our Oral GLP-1/Glucagon program may compete with approved GLP-1 injectables, Rybelsus and many experimental incretin targeted injectables, oral peptide candidates and oral small molecules developed for metabolic indications. We are subject to manufacturing risks that could substantially increase our costs and limit supply of our products.
Our Oral GLP-1/Glucagon program may compete with approved GLP-1 injectables, Wegovy pill and many experimental incretin targeted injectables, oral peptide candidates and oral small molecules developed for metabolic indications. We are subject to manufacturing risks that could substantially increase our costs and limit supply of our products.
In October 2024, Israel initiated both air and ground operations against Hezbollah in Lebanon, culminating in a ceasefire agreement between Israel and Lebanon on November 27, 2024, the results of which are uncertain.
In October 2024, Israel initiated both air and ground operations against Hezbollah in Lebanon, culminating in a ceasefire agreement between Israel and Lebanon on November 27, 2024, the results of which remain uncertain.
We qualify as a “smaller reporting company,” and we expect to take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not smaller reporting companies, including reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.
We qualify as a “smaller reporting company,” and we are taking advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not smaller reporting companies, including reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.
Our ability to generate future revenue and value from product sales depends heavily on our success in many areas, including but not limited to: • the completion of future development efforts for EB613, EB612 or other product candidates; • securing additional funding as may be needed to continue the development of EB613 or any other product candidates; • obtaining required regulatory and marketing approvals for the clinical development, manufacturing and commercialization of EB613, EB612 and any other product candidates we may develop; • obtaining adequate reimbursement from third-party payors for any product that may be commercialized, if approved; • managing our spending as costs and expenses increase due to the preparation of regulatory filings, potential regulatory approvals, manufacturing scale-up and potential commercialization; • continuing to build and maintain our intellectual property portfolio; • recruiting and retaining qualified executive management and other personnel; • building and maintaining appropriate research and development, clinical, regulatory, sales, manufacturing, financial reporting, distribution, and marketing capabilities on our own or through third parties; • gaining market acceptance for our product candidates; • developing and maintaining successful strategic relationships and collaborations; • developing a sustainable and scalable manufacturing process for any approved product candidates and maintaining supply and manufacturing relationships with third parties that can support clinical development and market demand for our product candidates, if approved; • establishing sales, marketing, and distribution capabilities in the United States and the EU independently or in collaboration with strategic partners; • obtaining market acceptance for any of our product candidates that receive marketing approval, if any, as viable treatment options; • addressing any competing technological and market developments; • negotiating favorable terms in any collaboration, licensing, or other arrangements into which we may enter; and • attracting, hiring and retaining qualified personnel.
Our ability to generate future revenue and value from product sales depends heavily on our success in many areas, including but not limited to: • the completion of future development efforts for EB613 for osteoporosis and EB612 for hypoparathyroidism, other oral peptides for obesity, metabolic disorders and gastrointestinal rare diseases, or any other product candidates; • securing additional funding as may be needed to continue the development of EB613 or any other product candidates; • obtaining required regulatory and marketing approvals for the clinical development, manufacturing and commercialization of EB613, EB612 and any other product candidates we may develop; • obtaining adequate reimbursement from third-party payors for any product that may be commercialized, if approved; • managing our spending as costs and expenses increase due to the preparation of regulatory filings, potential regulatory approvals, manufacturing scale-up and potential commercialization; 41 • continuing to build and maintain our intellectual property portfolio; • recruiting and retaining qualified executive management and other personnel; • building and maintaining appropriate research and development, clinical, regulatory, sales, manufacturing, financial reporting, distribution, and marketing capabilities on our own or through third parties; • gaining market acceptance for our product candidates; • developing and maintaining successful strategic relationships and collaborations; • developing a sustainable and scalable manufacturing process for any approved product candidates and maintaining supply and manufacturing relationships with third parties that can support clinical development and market demand for our product candidates, if approved; • establishing sales, marketing, and distribution capabilities in the United States and the EU independently or in collaboration with strategic partners; • obtaining market acceptance for any of our product candidates that receive marketing approval, if any, as viable treatment options; • addressing any competing technological and market developments; • negotiating favorable terms in any collaboration, licensing, or other arrangements into which we may enter; and • attracting, hiring and retaining qualified personnel.
Our most advanced programs, EB613 may compete with marketed drugs, such as Prolia®, bisphosphonates, Forteo®, Tymlos®, Evenity®, and osteoanabolic drugs in clinical development for osteoporosis; the EB612 program may compete with marketed drugs of hypoparathyroidism such as TransCon™ PTH and those in clinical development such as Eneboparatide and MBX2109.
Our most advanced program, EB613 may compete with marketed drugs, such as Prolia®, bisphosphonates, Forteo®, Tymlos®, Evenity®, and osteoanabolic drugs in clinical development for osteoporosis such as Angitia’s AGA2118; the EB612 program may compete with marketed drugs of hypoparathyroidism such as TransCon™ PTH and those in clinical development such as Eneboparatide and MBX2109.
The market price of our Ordinary Shares on Nasdaq may fluctuate as a result of a number of factors, some of which are beyond our control, including, but not limited to: • our clinical trial results and the timing of the release of such results; • the amount of our cash resources and our ability to obtain additional funding; • the announcement of research activities, business developments, technological innovations or new products, or acquisitions or expansion plans by us or our competitors; • the success or failure of our research and development projects or those of our competitors; • our entering into or terminating strategic relationships; 68 • changes in laws or government regulation; • actual or anticipated fluctuations in our and our competitors’ results of operations and financial condition; • regulatory developments and the decisions of regulatory authorities as to the approval or rejection of new or modified products and plans for clinical development; • the departure of our key personnel; • disputes related to intellectual property and proprietary rights, including patents, litigation matters and our ability to obtain intellectual property protection for our technologies; • our sale, or the sale by our significant shareholders, of Ordinary Shares or other securities in the future; • public concern regarding the safety, efficacy or other aspects of the products or methodologies we are developing; • market conditions in our industry and changes in estimates of the future size and growth rate of our markets; • market acceptance of our products; • the mix of products that we sell and related services that we provide; • the success or failure of our licensees to develop, obtain approval for and commercialize our licensed products, for which we are entitled to contingent payments and royalties; • the publication of the results of preclinical or clinical trials for EB613, EB612 or any other oral peptide product candidates we may develop, including the oral GLP-2 and OXM programs we are developing with OPKO; • the failure by us to achieve a publicly announced milestone; • delays between our expenditures to develop and market new or enhanced products and the generation of sales from those products; • changes in the amounts that we spend to develop, acquire or license new products, technologies or businesses; • changes in our expenditures to promote our products; • variances in our financial performance from the expectations of market analysts; • the limited trading volume of our Ordinary Shares; and • general economic and market conditions, including factors unrelated to our industry or operating performance, such as the duration and intensity of the ongoing Israel-Hamas War, and other geopolitical tensions.
The market price of our Ordinary Shares on Nasdaq may fluctuate as a result of a number of factors, some of which are beyond our control, including, but not limited to: • our clinical trial results and the timing of the release of such results; • the amount of our cash resources and our ability to obtain additional funding; • the announcement of research activities, business developments, technological innovations or new products, or acquisitions or expansion plans by us or our competitors; • the success or failure of our research and development projects or those of our competitors; • our entering into or terminating strategic relationships; • changes in laws or government regulation; • actual or anticipated fluctuations in our and our competitors’ results of operations and financial condition; • regulatory developments and the decisions of regulatory authorities as to the approval or rejection of new or modified products and plans for clinical development; • the departure of our key personnel; • disputes related to intellectual property and proprietary rights, including patents, litigation matters and our ability to obtain intellectual property protection for our technologies; • our sale, or the sale by our significant shareholders, of Ordinary Shares or other securities in the future; • public concern regarding the safety, efficacy or other aspects of the products or methodologies we are developing; • market conditions in our industry and changes in estimates of the future size and growth rate of our markets; • market acceptance of our products; • the mix of products that we sell and related services that we provide; • the success or failure of our licensees to develop, obtain approval for and commercialize our licensed products, for which we are entitled to contingent payments and royalties; • the publication of the results of preclinical or clinical trials for EB613, EB612 or any other oral peptide product candidates we may develop, including the programs we are developing with OPKO; • the failure by us to achieve a publicly announced milestone; • delays between our expenditures to develop and market new or enhanced products and the generation of sales from those products; • changes in the amounts that we spend to develop, acquire or license new products, technologies or businesses; 69 • changes in our expenditures to promote our products; • variances in our financial performance from the expectations of market analysts; • the limited trading volume of our Ordinary Shares; and • general economic and market conditions, including factors unrelated to our industry or operating performance, such as political and economic instability in the Middle East.
We believe that the key competitive factors that will affect the development and commercial success of our oral PTH product candidates, and any other product candidates that we develop, are efficacy, safety and tolerability profile, convenience in dosing, product labeling, price and availability of reimbursement from the government and other third-parties.
We believe that the key competitive factors that will affect the development and commercial success of our product candidates, are efficacy, safety and tolerability profile, convenience in dosing, product labeling, price and availability of reimbursement from the government and other third-parties.
Notice or undertaking to the IIA may not be required in respect of purchase of Ordinary Shares in standard acquisition or trading in the stock exchange following to an IPO that was approved by the IIA. These restrictions will continue to apply even after we have repaid the full amount of the grants and the interest.
Notice or undertaking to the IIA may not be required in respect of purchase of Ordinary Shares in standard acquisition or market purchases following an IPO that was approved by the IIA. These restrictions will continue to apply even after we have repaid the full amount of the grants and the interest.
Given our current plans, we anticipate that our existing cash and cash equivalents will be sufficient to fund our operations into the third quarter of 2026, excluding the initiation of the Phase 3 study for EB613 in osteoporosis.
Given our current plans, we anticipate that our existing cash and cash equivalents will be sufficient to fund our ongoing operations through the middle of the third quarter of 2026, excluding the initiation of the Phase 3 study for EB613 in osteoporosis.
Given our current plans, we anticipate that our existing cash and cash equivalents will be sufficient to fund our operations into the third quarter of 2026, excluding the initiation of the Phase 3 study for EB613 in osteoporosis.
Given our current plans, we anticipate that our existing cash and cash equivalents will be sufficient to fund our ongoing operations through the middle of the third quarter of 2026, excluding the initiation of the Phase 3 study for EB613 in osteoporosis.
We are also collaborating on an undisclosed peptide for this indication using our N-Tab™ Technology. 48 Drug development is a long, expensive and uncertain process, and delay or failure can occur at any stage of any of our clinical trials for a number of reasons including: • difficulties obtaining regulatory approval to commence a clinical trial or complying with conditions imposed by a regulatory authority regarding the scope or term of a clinical trial; • delays in reaching or failing to reach agreement on acceptable terms with prospective contract research organizations, or CROs, contract manufacturing organizations, and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly; • failure of our third-party contractors, such as CROs and contract manufacturing organizations, or our investigators to comply with regulatory requirements or otherwise meet their contractual obligations in a timely manner; • insufficient or inadequate supply or quality of a product candidate or other materials necessary to conduct our clinical trials; • difficulties obtaining institutional review board or ethics committee approval to conduct a clinical trial at a prospective site; • the FDA, EMA or other regulatory authority may require changes to any of our trial designs, our pre-clinical strategy or our manufacturing plans; • various challenges recruiting and enrolling subjects to participate in clinical trials, including size and nature of subject population, proximity of subjects to clinical sites, eligibility criteria for the trial, budgetary limitations, nature of trial protocol, the patient referral practices of physicians, changes in the readiness of subjects to volunteer for a trial, the availability of approved effective treatments for the relevant disease and competition from other clinical trial programs for similar indications; • difficulties in maintaining contact with subjects who withdraw from the trial, resulting in incomplete data; • governmental or regulatory delays and changes in regulatory requirements, policy and guidelines; • the FDA or other regulatory authorities may impose a clinical hold, or we or our investigators, IRBs, or ethics committees may elect to suspend or terminate clinical research or trials; • varying interpretations of data by the FDA and foreign regulatory agencies; and • inaccurate interpretations by us of the FDA’s guidance for the clinical and regulatory path for our product candidates.
We intend to accelerate development and currently expect to submit an IND application to the FDA in late 2026. 49 Drug development is a long, expensive and uncertain process, and delay or failure can occur at any stage of any of our clinical trials for a number of reasons including: • difficulties obtaining regulatory approval to commence a clinical trial or complying with conditions imposed by a regulatory authority regarding the scope or term of a clinical trial; • delays in reaching or failing to reach agreement on acceptable terms with prospective contract research organizations, or CROs, contract manufacturing organizations, and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly; • failure of our third-party contractors, such as CROs and contract manufacturing organizations, or our investigators to comply with regulatory requirements or otherwise meet their contractual obligations in a timely manner; • insufficient or inadequate supply or quality of a product candidate or other materials necessary to conduct our clinical trials; • difficulties obtaining institutional review board or ethics committee approval to conduct a clinical trial at a prospective site; • the FDA, EMA or other regulatory authority may require changes to any of our trial designs, our pre-clinical strategy or our manufacturing plans; • various challenges recruiting and enrolling subjects to participate in clinical trials, including size and nature of subject population, proximity of subjects to clinical sites, eligibility criteria for the trial, budgetary limitations, nature of trial protocol, the patient referral practices of physicians, changes in the readiness of subjects to volunteer for a trial, the availability of approved effective treatments for the relevant disease and competition from other clinical trial programs for similar indications; • difficulties in maintaining contact with subjects who withdraw from the trial, resulting in incomplete data; • governmental or regulatory delays and changes in regulatory requirements, policy and guidelines; • the FDA or other regulatory authorities may impose a clinical hold, or we or our investigators, IRBs, or ethics committees may elect to suspend or terminate clinical research or trials; • varying interpretations of data by the FDA and foreign regulatory agencies; and • inaccurate interpretations by us of the FDA’s guidance for the clinical and regulatory path for our product candidates.
In response to the foregoing developments, certain leading international financial institutions, including investment banks, investors and key economists, have indicated several causes for concern, including that such proposed changes, if adopted, may cause a downgrade to Israel’s sovereign credit rating and Israel’s international standing, which would adversely affect the macroeconomic condition in which we operate, and also potentially deter foreign investment into Israel or Israeli companies, which may hinder our ability to raise additional funds, if deemed necessary by our management and the Board.
In response to the foregoing developments, certain leading international financial institutions, including investment banks, investors and key economists, have indicated several causes for concern, including that such proposed changes, if adopted, may cause a downgrade to Israel’s sovereign credit rating and Israel’s international standing, which would adversely affect the macroeconomic condition in which we operate, and also potentially deter foreign investment into Israel or Israeli companies, which may hinder our ability to raise additional funds, if deemed necessary by our management and the Board. 73 Security, political and economic instability in the Middle East may harm our business.
Security, political and economic instability in the Middle East may harm our business . Our principal research facilities are located in Israel. In addition, most of our key employees, officers and directors are residents of Israel. Accordingly, political, economic and military conditions in the Middle East may affect our business directly.
Our principal research facilities are located in Israel. In addition, most of our key employees, officers and two directors are residents of Israel. Accordingly, political, economic and military conditions in the Middle East may affect our business directly.
Our global patent portfolio includes issued patents and patent applications. We believe that the granted patents as well as certain of the pending claims contained in our patent applications, if issued in substantially the same form, would cover our proprietary technology platform (N-Tab™) and the formulations used in various pipeline programs through 2044 not including patent term extensions.
We believe that the granted patents as well as certain of the pending claims contained in our patent applications, if issued in substantially the same form, would cover our proprietary technology platform (N-Tab ® ) and the formulations used in various pipeline programs through 2046 not including patent term extensions and patent term adjustments.
In addition, our remediation efforts may not be successful. Moreover, there could be public announcements regarding any cybersecurity incidents and any steps we take to respond to or remediate such incidents, and if securities analysts or investors perceive these announcements to be negative, it could, among other things, have a substantial adverse effect on the price of our Ordinary Shares.
Moreover, there could be public announcements regarding any cybersecurity incidents and any steps we take to respond to or remediate such incidents, and if securities analysts or investors perceive these announcements to be negative, it could, among other things, have a substantial adverse effect on the price of our Ordinary Shares.
The objective of the Type D meeting review was to confirm that the protocol fully meets FDA’s expectations, including the analysis of the primary endpoint and the population PK evaluations, ahead of potential initiation of the Phase 3 study.
The objective of the Type D meeting review was to confirm that the protocol fully meets FDA’s expectations, including the analysis of the primary endpoint and the population PK evaluations to serve as the Scientific Bridge to Forteo, ahead of potential initiation of the Phase 3 study.
Israel has conducted multiple targeted strikes against these terror organizations. 73 In addition, since April 2024, Israel has experienced direct attacks from Iran, involving hundreds of drones and ballistic missiles launched towards mostly densely populated civilian towns across Israel and some military bases, threatening continued aggression while also exerting considerable influence over regional militia groups encouraging them to launch attacks against Israel.
In addition, since April 2024, Israel has experienced direct attacks from Iran, involving hundreds of drones and ballistic missiles launched towards mostly densely populated civilian towns across Israel and some military bases, threatening continued aggression while also exerting considerable influence over regional militia groups encouraging them to launch attacks against Israel.
If third parties have prepared and filed patent applications in the United States that also claim technology to which we have rights, we may have to participate in interference proceedings in the USPTO, to determine priority of invention for patent applications filed before March 16, 2013, or in derivation proceedings to determine inventorship for patent applications filed after such date.
If third parties have prepared and filed patent applications in the United States that also claim technology to which we have rights, we may have to participate in interference proceedings in the USPTO, to determine priority of invention for patent applications filed with an effective filing date, or claiming priority to an application with a filing date, before March 16, 2013, or in derivation proceedings to determine inventorship for patent applications claiming priority to an application with a filing date after such date.
The Bipartisan Budget Act of 2018, or the BBA, among other things, amended the ACA, effective January 1, 2019, to close the coverage gap in most Medicare drug plans.
The Bipartisan Budget Act of 2018, or the BBA, among other things, amended the ACA to close the coverage gap in most Medicare drug plans.
Failure of clinical investigators or CROs to meet their obligations to us or comply with GCP procedures could adversely affect the clinical development of our product candidates and harm our business. 60 If the third parties or consultants that assist us in conducting our clinical trials do not perform their contractual duties or obligations, experience work stoppages, do not meet expected deadlines, terminate their agreements with us or need to be replaced, or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical trial protocols or GCPs, or for any other reason, we may need to conduct additional clinical trials or enter into new arrangements with alternative third parties, which could be difficult, costly or impossible, and our clinical trials may be extended, delayed or terminated or may need to be repeated.
If the third parties or consultants that assist us in conducting our clinical trials do not perform their contractual duties or obligations, experience work stoppages, do not meet expected deadlines, terminate their agreements with us or need to be replaced, or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical trial protocols or GCPs, or for any other reason, we may need to conduct additional clinical trials or enter into new arrangements with alternative third parties, which could be difficult, costly or impossible, and our clinical trials may be extended, delayed or terminated or may need to be repeated.
These provisions prohibit such employees and key consultants, if they cease working for us, from competing directly with us or working for our competitors or clients for a limited period of time.
Our agreements with our employees and key consultants generally include non-competition provisions. These provisions prohibit such employees and key consultants, if they cease working for us, from competing directly with us or working for our competitors or clients for a limited period of time.
In addition, the United States has recently enacted wide-ranging patent reform legislation, which includes provisions that affect the way patent applications are prosecuted, redefine prior art, may affect patent litigation, and switch the U.S. patent system from a “first to invent” system to a “first inventor to file” system.
In addition, in 2013, the United States enacted wide-ranging patent reform legislation, which includes provisions that affect the way patent applications are prosecuted, redefine prior art, may affect patent litigation, and switch the U.S. patent system from a “first to invent” system to a “first inventor to file” system. The United States may enact other patent reforms in the future.
Since the onset of these events, hostilities have persisted across Israel, along Israel's northern border with Lebanon, primarily involving the Hezbollah terror organization, as well as other extremist groups in the region, including the Houthis in Yemen and various militia groups in Syria and Iraq.
Since the onset of these events, hostilities have persisted across Israel, along Israel’s northern border with Lebanon, primarily involving the Hezbollah terror organization, as well as other extremist groups in the region, including the Houthis in Yemen and various militia groups in Syria and Iraq. Israel has conducted multiple targeted strikes against these terror organizations.
As of March 15, 2025 N-Tab™ is registered in Israel and pending in the United States, Europe, Japan, Great Britain, Canada, Brazil, Norway, China, Australia, and Switzerland. In the future, our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.
As of March 23, 2026, N-Tab ® is registered in Israel and pending in the United States, Europe, Great Britain, Norway, China and Australia. In the future, our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.
If we do not adequately obtain, maintain, protect and enforce our proprietary rights in our technologies, competitors may be able to use our technologies and erode or negate any competitive advantage we may have, which could have a material adverse effect on our business and our ability to achieve profitability. 62 We have limited patent protection with respect to our product candidates and technologies.
If we do not adequately obtain, maintain, protect and enforce our proprietary rights in our technologies, competitors may be able to use our technologies and erode or negate any competitive advantage we may have, which could have a material adverse effect on our business and our ability to achieve profitability.
For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to certain third parties. Furthermore, many countries limit the enforceability of patents against third parties, including government agencies or government contractors.
For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to certain third parties. Furthermore, many countries limit the enforceability of patents against third parties, including government agencies or government contractors. In these countries, patents may provide limited or no benefit.
In addition to rising inflation, the global economy has also been impacted by fluctuating foreign exchange rates and geopolitical tensions, such as the ongoing conflict between Russia and Ukraine and the Israel-Hamas War, which may contribute to rising energy costs and disruptions to the global supply chain.
In addition to rising inflation, the global economy has also been impacted by fluctuating foreign exchange rates and geopolitical tensions, such as the ongoing conflict between Russia and Ukraine and the regional conflicts throughout the Middle East, which may contribute to rising energy costs and disruptions to the global supply chain.
Our operations may be disrupted by the obligations of personnel to perform military service. Our employees in Israel, including executive officers, generally, may be called upon to perform military reserve duty until they generally reach the age of 45 (or older in some cases).
Our operations may be disrupted by the obligations of personnel to perform military service. Our employees in Israel, including executive officers, generally, may be called upon to perform military reserve duty until they generally reach the age of 40 or 45 (or older in some cases, depending on rank, the nature of the service, and other factors).
In addition, manufacturers of drug products and their facilities are subject to continual review and periodic inspections by the FDA and other regulatory authorities for compliance with cGMP, requirements and other regulations. 50 If we, our drug products or the manufacturing facilities for our drug products, fail to comply with applicable regulatory requirements, a regulatory agency may: • issue warning letters or untitled letters or take similar enforcement actions; • seek an injunction or impose civil or criminal penalties or monetary fines; • suspend or withdraw marketing approval; • suspend any ongoing clinical trials; • refuse to approve pending applications or supplements to applications; • suspend or impose restrictions on operations, including costly new manufacturing requirements; • seize or detain products, refuse to permit the import or export of products, exclude products from federal healthcare programs, or request that we initiate a product recall; or • refuse to allow us to enter into supply contracts, including government contracts.
If we, our drug products or the manufacturing facilities for our drug products, fail to comply with applicable regulatory requirements, a regulatory agency may: • issue warning letters or untitled letters or take similar enforcement actions; • seek an injunction or impose civil or criminal penalties or monetary fines; • suspend or withdraw marketing approval; • suspend any ongoing clinical trials; • refuse to approve pending applications or supplements to applications; • suspend or impose restrictions on operations, including costly new manufacturing requirements; • seize or detain products, refuse to permit the import or export of products, exclude products from federal healthcare programs, or request that we initiate a product recall; or • refuse to allow us to enter into supply contracts, including government contracts.
While we have not experienced any such system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could cause damage or destroy assets, compromise business systems, or otherwise result in a material disruption of our programs and business operations.
Our key business partners face similar risks, and a security breach of their systems could adversely affect our security posture. 44 While we have not experienced any such system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could cause damage or destroy assets, compromise business systems, or otherwise result in a material disruption of our programs and business operations.
Service of process upon us, our directors and officers and the Israeli experts, if any, a significant number of whom reside outside the United States, may be difficult to obtain within the United States.
We are incorporated under the laws of the State of Israel. Service of process upon us, our directors and officers and the Israeli experts, if any, a significant number of whom reside outside the United States, may be difficult to obtain within the United States.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained. Depending on decisions by the U.S.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained.
The Company is engaged in research and development activities, and it has not derived significant income from its activities and has incurred an accumulated deficit and negative cash flows from operating activities since inception. These factors raise substantial doubt as to the Company's ability to continue as a going concern.
The Company is engaged in research and development activities, and it has not derived significant income from its activities and has incurred an accumulated deficit in the amount of $125.4 million as of December 31, 2025 and negative cash flows from operating activities. These factors raise substantial doubt as to the Company’s ability to continue as a going concern.
Each of our oral peptide candidates, including EB613 and EB612, are still in clinical development and face a variety of risks and uncertainties, including the following: • future clinical trial results may show that our oral PTH is not effective, including if our platform is not effective, our product candidates are not effective, our clinical trial designs are flawed, or clinical trial investigators or subjects do not comply with trial protocols; • our product candidates may not be well tolerated or may cause negative side effects; • our ability to complete the development and commercialization of our oral PTH for our intended uses may be significantly dependent upon our ability to obtain and maintain experienced and committed collaborators to assist us with obtaining clinical and regulatory approvals for, and the manufacturing, marketing and distribution of, our oral PTH; • even if our oral PTH is shown to be safe and effective for its intended purposes, we may face significant or unforeseen difficulties in obtaining or manufacturing sufficient quantities at reasonable prices, or at all; 47 • even if our oral PTH is successfully developed, commercially produced and receives all necessary regulatory approvals, there is no guarantee that there will be market acceptance; • even if our oral PTH is successfully developed, commercially produced and receives all necessary regulatory approvals for the treatment of Osteoporosis, there is no guarantee that we will successfully develop and commercialize it for other indications, including hypoparathyroidism and delayed union fractures; and • our competitors may develop therapeutics or other treatments that are superior to or less costly than our own with the result that our products, even if they are successfully developed, manufactured and approved, may not generate significant revenues.
Each of our oral peptide candidates, including EB613 and EB612 for hypoparathyroidism or other oral peptides for obesity, metabolic disorders and gastrointestinal rare diseases, are still in clinical development and face a variety of risks and uncertainties, including the following: • future clinical trial results may show that our oral PTH is not effective, including if our platform is not effective, our product candidates are not effective, our clinical trial designs are flawed, or clinical trial investigators or subjects do not comply with trial protocols; • our product candidates may not be well tolerated or may cause negative side effects; • our ability to complete the development and commercialization of our oral PTH for our intended uses may be significantly dependent upon our ability to obtain and maintain experienced and committed collaborators to assist us with obtaining clinical and regulatory approvals for, and the manufacturing, marketing and distribution of, our oral PTH; • even if our oral PTH is shown to be safe and effective for its intended purposes, we may face significant or unforeseen difficulties in obtaining or manufacturing sufficient quantities at reasonable prices, or at all; • even if our oral PTH is successfully developed, commercially produced and receives all necessary regulatory approvals, there is no guarantee that there will be market acceptance; • even if our oral PTH is successfully developed, commercially produced and receives all necessary regulatory approvals for the treatment of Osteoporosis, there is no guarantee that we will successfully develop and commercialize it for other indications, including hypoparathyroidism and delayed union fractures; and • our competitors may develop therapeutics or other treatments that are superior to or less costly than our own with the result that our products, even if they are successfully developed, manufactured and approved, may not generate significant revenues. 48 If we are unsuccessful in dealing with any of these risks, or if we or a potential partner are unable to successfully commercialize our oral PTH, LA-PTH, GLP-1/Glucagon , GLP-2 or any other product candidate we may develop in the future, it would likely have a material adverse effect on our business, prospects, financial condition and results of operations.
Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for any of our product candidates or products we develop; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial participants or cancellation of clinical trials; • costs to defend the related litigation, which may be only partially recoverable even in the event of successful defense; • a diversion of management’s time and our resources; • substantial monetary awards to trial participants or patients; • regulatory investigations, product recalls, withdrawals or labeling, marketing or promotional restrictions; • loss of revenue; and • the inability to commercialize any products we develop.
Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for any of our product candidates or products we develop; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial participants or cancellation of clinical trials; • costs to defend the related litigation, which may be only partially recoverable even in the event of successful defense; • a diversion of management’s time and our resources; • substantial monetary awards to trial participants or patients; • regulatory investigations, product recalls, withdrawals or labeling, marketing or promotional restrictions; • loss of revenue; and • the inability to commercialize any products we develop. 59 Although the clinical trial process is designed to identify and assess potential side effects, it is always possible that a drug, even after regulatory approval, may exhibit unforeseen side effects.
For example, in 2024, the value of the NIS increased against the U.S dollar by 0.55%, which was potentially computed by inflation in Israel of 3.5%. In 2023, the value of the NIS depreciated against the U.S. dollar by 3.1%, which was potentially computed by inflation in Israel of 3%.
For example, in 2025, the value of the NIS increased against the U.S dollar by 14%, which was potentially computed by inflation in Israel of 2.6%. In 2024, the value of the NIS increased against the U.S. dollar by 0.55%, which was potentially computed by inflation in Israel of 3.5%.
As of March 20, 2025, we had cash and cash equivalents of approximately $21 million, of which $8 million is designated solely to fund our development cost obligations under the collaboration agreement with OPKO.
As of March 23, 2026, we had cash and cash equivalents of approximately $12.6 million, of which $7.8 million is designated solely to fund our development cost obligations under the collaboration agreement with OPKO.
On the same day, we announced that we plan to continue our dialogue with the FDA and await the final qualification of the SABRE qualification and FDA’s guidance on the statistical evaluation of our BMD endpoint before initiating a Phase 3 study for EB613.
On the same day, we announced that we planned to continue our dialogue with the FDA and await the final qualification of the SABRE qualification and FDA’s guidance on the statistical evaluation of our BMD endpoint before initiating a Phase 3 study for EB613 which has since been obtained in December 2025.
Our Oral GLP-2 Program will compete with Gattex™, the only approved GLP-2 treatment for short bowel syndrome and experimental GLP-2 injectables such as Zealand’s glepaglutide (FDA CRL 12/24) and Vectiv/ Ironwood’s apraglutide (Submitted 01/025).
Our Oral GLP-2 Program will compete with Gattex™, the only approved GLP-2 treatment for short bowel syndrome and experimental GLP-2 injectables such as Zealand’s glepaglutide (FDA CRL 12/24) and Vectiv/ Ironwood’s apraglutide (FDA demanded another phase 3 trial 04/25).
In light of the intensity of the ongoing Israel-Hamas War, the escalation of Hezbollah's and Iran’s attack of Israeli civilian and military sites, in September 2024, the international rating agency Moody's downgraded Israel's credit rating from A2 to Baa1, reflecting heightened geopolitical risks.
In light of the intensity of the ongoing Israel-Hamas War, the escalation of Hezbollah’s and Iran’s attack of Israeli civilian and military sites, in September 2024, the international rating agency Moody’s downgraded Israel’s credit rating from ‘A2’ to ‘Baa1’, reflecting heightened geopolitical risks. In July 2025, this downgrade was affirmed by Moody's.
We expect to continue to incur substantial losses for the next several years, and we expect these losses to increase as we continue our development of and potentially seek regulatory approval for, EB613 and EB612 and our collaboration with OPKO related to GLP-2 and OXM.
As of December 31, 2025, we had an accumulated deficit of $125.4 million. We expect to continue to incur substantial losses for the next several years, and we expect these losses to increase as we continue our development of and potentially seek regulatory approval for EB613 and EB612, as well as our collaboration with OPKO related to OXM and GLP-2.
The amount of our future net losses will depend, in part, on the amount and timing of our expenses, our ability to enter into strategic partnerships or less dilutive funding agreements or our ability to raise additional capital. These net losses have had, and will continue to have, an adverse effect on our stockholders’ equity and working capital.
The amount of our future net losses will depend, in part, on the amount and timing of our expenses, our ability to enter into strategic partnerships or less dilutive funding agreements or our ability to raise additional capital.
Additionally, the facilities to manufacture our product candidates must be the subject of a satisfactory inspection before the FDA, the EMA or other regulatory authorities approve an NDA or grant a marketing authorization for the product candidate manufactured at that facility.
We entered into long-term supply agreements with several manufacturers for commercial supplies. Additionally, the facilities to manufacture our product candidates must be the subject of a satisfactory inspection before the FDA, the EMA or other regulatory authorities approve an NDA or grant a marketing authorization for the product candidate manufactured at that facility.
We are currently planning and preparing to initiate a phase 3 study for our most advanced product candidate, EB613, pending FDA’s qualification of the SABRE BMD endpoint. Developing therapeutics, including conducting preclinical studies and clinical trials, is expensive.
We are currently planning and preparing to initiate a phase 3 study for our most advanced product candidate, EB613, following the FDA’s feedback on our phase 3 protocol submission. Developing therapeutics, including conducting preclinical studies and clinical trials, is expensive.
Our Oral GLP-2 Program will compete with Gattex™, the only approved GLP-2 treatment for short bowel syndrome and experimental GLP-2 injectables such as Zealand’s glepaglutide (FDA CRL 12/24) and Vectiv/ Ironwood’s apraglutide (Submitted 01/025).
Our Oral GLP-2 program will compete with Gattex™, the only approved GLP-2 treatment for short bowel syndrome and experimental GLP-2 injectables such as Zealand’s glepaglutide (FDA CRL 12/24) and Vectiv/ Ironwood’s apraglutide (FDA has required another phase 3 trial 04/25)).
In the United States, in March 2010, the Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively, the ACA, intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for health care and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
These limitations could in turn reduce the revenue that we will be able to generate in the future from sales of our products and licenses of our technology. 52 In the United States, in March 2010, the Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively, the ACA, intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for health care and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
Further, the ACA imposed a significant annual fee on companies that manufacture or import branded prescription drug products. Substantial new provisions affecting compliance were enacted, which may affect our business practices with health care practitioners.
Further, the ACA imposed a significant annual fee on companies that manufacture or import branded prescription drug products. Substantial new provisions affecting compliance were enacted, which may affect our business practices with health care practitioners. The ACA appears likely to continue the pressure on pharmaceutical pricing and may also increase our regulatory burdens and operating costs.
Moreover, exchange rate fluctuations in currency exchange rates in countries other than Israel where we operate, perform our clinical trials or conduct business may also negatively affect our earnings and results of operations.
In addition, if the value of the U.S. dollar decreases against the NIS, our earnings may be negatively impacted. Moreover, exchange rate fluctuations in currency exchange rates in countries other than Israel where we operate, perform our clinical trials or conduct business may also negatively affect our earnings and results of operations.

… 132 more changes not shown on this page.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

0 edited+10 added−2 removed0 unchanged
Removed
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 78 Item 6. [Reserved] 78 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 79 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 88 Item 8. Financial Statements and Supplementary Data 89 Item 9.
Added
ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES. Market for our Ordinary Shares Our Ordinary Shares are listed on the Nasdaq Capital Market under the symbol “ENTX”. As of March 23, 2026, there were approximately 44 holders of record of our Ordinary Shares.
Removed
Changes in and Disagreements With Accountants on Accounting and Financial Disclosure 117
Added
This number does not include the number of persons whose shares are in nominee or in “street name” accounts through brokers. Dividends The Company has never declared or paid cash dividends on its Ordinary Shares and has no intention to pay any cash dividend for the foreseeable future.
Added
The Company currently plans to retain future earnings, if any, to finance the development of its business and for other corporate purposes. The actual amount, timing, and frequency of future dividends, if any, will be at the sole discretion of the board of directors and will be declared based upon various factors, many of which are beyond our control.
Added
If the Company decides to distribute a cash dividend, Israeli residents who are individuals are generally subject to Israeli income tax at a rate of either 25% or 30%, if the recipient of such dividend is a “substantial shareholder” at the time of distribution or at any time during the preceding 12-month period, unless the cash dividend is paid out of income that has been tax exempt due to an “approved enterprise” status under the Law for the Encouragement of Capital Investments, 5719-1959, in which case the Company will be subject to corporate tax at a rate then in effect under Israeli law on the amount of cash dividend and in addition, an Israeli shareholder, corporation or individual, will be subject to a tax rate of 20% on such cash dividend distribution.
Added
In addition, Israeli resident corporations are generally exempt from Israeli corporate tax for dividends paid on our Ordinary Shares.
Added
Pursuant to the Convention Between the Government of the United States of America and the Government of Israel with Respect to Taxes on Income, as amended (the “U.S.-Israel Tax Treaty”), the maximum tax on dividends paid to a holder of our Ordinary Shares who qualifies as a resident of the United States within the meaning of the U.S.-Israel Tax Treaty is 25% or 15% in case of dividends paid out of the profits of an “approved enterprise”, subject to certain conditions.
Added
Furthermore, dividends not generated by an “approved enterprise” paid to a U.S. corporation holding at least 10% of our issued voting power during the part of the tax year which precedes the date of payment of the dividend and during the whole of its prior tax year (if any), are generally taxed at a rate of 12.5%, subject to certain conditions.
Added
Individuals who are subject to income tax in Israel (whether any such individual is an Israeli resident or non-Israeli resident, and with respect to a non-Israeli resident, subject to tax treaties not otherwise limiting the applicable tax rate to such non-Israeli resident) are also subject to an additional surtax at a rate of 3% on annual income (including, but not limited to, income derived from dividends, interest and capital gains) exceeding a certain threshold (currently, NIS 721,560 for 2025 through 2027, which amount is linked to the annual change in the Israeli consumer price index (the “Threshold Amount”).
Added
According to legislation effective as of January 1, 2025, an additional 2% excess tax will be imposed on “Capital-Sourced Income” (defined as income from any source other than employment income, business income or income from “personal effort”), provided that the Individual’s Capital Sourced Income exceeds the Threshold Amount.
Added
This additional excess tax applies, among other things, to income from capital gains, dividends, interest, rental income, or the sale of real property. ITEM 6. [Reserved]

Item 7. Management's Discussion & Analysis

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

68 edited+38 added−33 removed33 unchanged
Biggest changeResults of Operations Comparison of Years Ended December 31, 2024 and 2023 Year Ended December 31, Increase (Decrease ) 2024 2023 $ % (In thousands, except for percentage information) Revenues $ 181 $ - $ 181 100 % Cost of revenues $ 172 $ - $ 172 100 % Operating expenses: Research and development expenses $ 4,499 $ 4,510 $ (11 ) (0.2 )% General and administrative expenses $ 5,095 $ 4,430 $ 665 15 % Other income $ - $ (49 ) $ 49 100 % Operating loss $ 9,585 $ 8,891 $ 694 8 % Financial income, net $ (58 ) $ (31 ) $ (27 ) 87 % Income tax expenses $ 14 $ 29 $ (15 ) (52 )% Net loss $ 9,541 $ 8,889 $ 652 7 % Revenue Revenues for the year ended December 31, 2024 were $181 thousand, which were attributable to research services we provided pursuant to the research services agreement.
Biggest changeResults of Operations Comparison of Years Ended December 31, 2025 and 2024 Year Ended December 31, Increase (Decrease ) 2025 2024 $ % (In thousands, except for percentage information) Revenues $ 42 $ 181 $ (139 ) (77 )% Cost of revenues $ 42 $ 172 $ (130 ) (76 )% Operating expenses: Research and development expenses $ 6,004 $ 4,499 $ 1,505 33 % General and administrative expenses $ 5,525 $ 5,095 $ 430 8 % Operating loss $ 11,529 $ 9,585 $ 1,944 20 % Financial income, net $ (90 ) $ (58 ) $ (32 ) 55 % Income tax expenses $ - $ 14 $ (14 ) (100 )% Net loss $ 11,439 $ 9,541 $ 1,898 20 % Revenue Revenues for the year ended December 31, 2025 and 2024 were $42 thousand and $181 thousand, respectively, which were attributable to research services we provided pursuant to a research services agreement with an external party.
Our losses may fluctuate significantly from quarter to quarter and year to year, depending on the timing of our clinical trials, our expenditures on research and development activities, and payments under collaborations agreements. Our recurring losses from operations, negative cash flows and lack of liquidity raise substantial doubt as to the Company’s ability to continue as a going concern.
Our losses may fluctuate significantly from quarter to quarter and year to year, depending on the timing of our clinical trials, our expenditures on research and development activities, and payments under our collaborations agreements. Our recurring losses from operations, negative cash flows and lack of liquidity raise substantial doubt as to the Company’s ability to continue as a going concern.
Under the terms of the Patent Transfer Agreement, we agreed to pay Oramed royalties equal to 3% of our net revenues generated, directly or indirectly, from exploitation of the assigned patent rights, including the sale, lease or transfer of the assigned patent rights or sales of products or services covered by the assigned patent rights.
Under the terms of the Patent Transfer Agreement, we agreed to pay Oramed royalties equal to 3% of our net revenues generated, directly or indirectly, from our exploitation of the assigned patent rights, including the sale, lease or transfer of the assigned patent rights or sales of products or services covered by the assigned patent rights.
Because of the numerous risks and uncertainties associated with the development of our product candidates, and the extent to which we may enter into collaborations with third parties for development of these or other product candidates, we are unable to estimate the amounts of increased capital outlays and operating expenses associated with completing the development of our current and future product candidates.
Because of the numerous risks and uncertainties associated with the development of our product candidates, and the extent to which we may enter into additional collaborations with third parties for development of these or other product candidates, we are unable to estimate the amounts of increased capital outlays and operating expenses associated with completing the development of our current and future product candidates.
The royalty rate may increase to 5%, with respect to approved applications filed following any year in which we achieve sales of over $70 million. The amount that must be repaid may be increased up to six times the amount of the grant received and the interest.
The royalty rate may increase to 5%, with respect to approved applications filed following any year in which we achieve sales of over $70 million. 82 The amount that must be repaid may be increased up to six times the amount of grant received and the interest.
Research and development activities are the primary focus of our business. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials.
Research and development activities are our primary focus. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials.
We focus on underserved, chronic medical conditions for which oral administration of a protein therapy has the potential to significantly shift a treatment paradigm. Our pipeline includes five differentiated, first-in-class oral peptide programs targeting PTH(1-34), GLP-1 and GLP-2.Currently, most protein therapies are administered via frequent intravenous, subcutaneous, or intramuscular injections.
We focus on underserved, chronic medical conditions for which oral administration of a protein therapy has the potential to significantly shift a treatment paradigm. Our pipeline includes differentiated, first-in-class oral peptide programs targeting PTH(1-34), GLP-1/Glucagon and GLP-2. Currently, most protein therapies are administered via frequent intravenous, subcutaneous, or intramuscular injections.
We do not undertake any obligation to update forward-looking statements except as required by applicable law. We intend that all forward-looking statements be subject to the safe harbor provisions of PSLRA. Overview Entera is a clinical stage company focused on developing first-in-class oral tablet formats of peptides or protein replacement therapies.
We do not undertake any obligation to update forward-looking statements except as required by applicable law. We intend that all forward-looking statements be subject to the safe harbor provisions of PSLRA. 79 Business Overview Entera is a clinical stage company focused on developing first-in-class oral tablet formats of peptides or protein replacement therapies.
Severance Obligations We have long-term liabilities for severance pay that are calculated pursuant to Israeli law generally based on the most recent salary of the relevant employees multiplied by the number of years of employment to the extent not covered by our regular deposits with defined contribution plans. As of December 31, 2024, our severance pay liability, net was immaterial.
Severance Obligations We have long-term liabilities for severance pay that are calculated pursuant to Israeli law generally based on the most recent salary of the relevant employees multiplied by the number of years of employment to the extent not covered by our regular deposits with defined contribution plans. As of December 31, 2025, our severance pay liability, net was immaterial.
These potential future commitments include a commitment to pay Oramed royalties equal to 3% of our net revenues pursuant to the terms of the Patent Transfer Agreement between us and Oramed and a commitment to pay royalties to the IIA. 87 Critical Accounting Policies and Estimates We prepare our consolidated financial statements in accordance with U.S. generally accepted accounting principles, or GAAP.
These potential future commitments include a commitment to pay Oramed royalties equal to 3% of our net revenues pursuant to the terms of the Patent Transfer Agreement between us and Oramed and a commitment to pay royalties to the IIA. 89 Critical Accounting Policies and Estimates We prepare our consolidated financial statements in accordance with U.S. generally accepted accounting principles, or GAAP.
We expect that our general and administrative expenses will increase in the future as we increase our headcount and expand our administrative function to support our operations. 83 Financial Income, Net Financial income, net is composed primarily of interest income from bank deposits and exchange rate differences of certain currencies against our functional currency, which is the U.S. Dollar.
We expect that our general and administrative expenses will increase in the future as we increase our headcount and expand our administrative function to support our operations. Financial Income, Net Financial income, net is composed primarily of interest income from bank deposits and exchange rate differences of certain currencies against our functional currency, which is the U.S.
Prior to its termination, we had been required to pay to the IIA 5.38% of each payment made to us under such collaboration agreement with an ultimately liability of up to 600% of the grant received plus interest. As of December 31, 2024, we had paid royalties to the IIA in the amount of $96 thousand.
Prior to its termination, we had been required to pay to the IIA 5.38% of each payment made to us under such collaboration agreement with an ultimately liability of up to 600% of the grant received plus interest. As of December 31, 2025, we had paid royalties to the IIA in the amount of $96 thousand.
We continuously evaluate various financing alternatives in the public or private equity markets or through license of our N-Tab™ technology to additional external parties through partnerships or research collaborations as we will need to finance future research and development activities, general and administrative expenses and working capital through fund raising.
We continuously evaluate various financing alternatives in the public or private equity markets or through license of our N-Tab ® platform to additional external parties through partnerships or research collaborations as we will need to finance future research and development activities, general and administrative expenses and working capital through fund raising.
Our independent registered public accounting firm included an explanatory paragraph in its report on our financial statements as of, and for the year ended, December 31, 2024, expressing the existence of substantial doubt about our ability to continue as a going concern.
Our independent registered public accounting firm included an explanatory paragraph in its report on our financial statements as of, and for the year ended, December 31, 2025, expressing the existence of substantial doubt about our ability to continue as a going concern.
Our independent registered public accounting firm included an explanatory paragraph in its report on our financial statements as of, and for the year ended, December 31, 2024, expressing the existence of substantial doubt about our ability to continue as a going concern.
Our independent registered public accounting firm included an explanatory paragraph in its report on our financial statements as of, and for the year ended, December 31, 2025, expressing the existence of substantial doubt about our ability to continue as a going concern.
Under the terms of this agreement, OPKO has agreed to supply its proprietary long-acting GLP-2 peptide and certain OXM analogs for the development of oral tablet candidates using our proprietary N-Tab™ technology.
Under the terms of this agreement, OPKO has agreed to supply its proprietary long-acting GLP-2 peptide and certain OXM analogs for the development of oral tablet candidates using our proprietary N-Tab ® platform.
Other general and administrative expenses include D&O insurance and other insurance, communication expenses, professional fees for legal and accounting services, costs associated with maintaining and prosecuting our intellectual property portfolio and business development expenses.
Other general and administrative expenses include D&O insurance and other insurance, communication expenses, professional fees for legal, accounting and investor relations services, costs associated with maintaining and prosecuting our intellectual property portfolio and business development expenses.
EB613 is intended to provide an oral anabolic treatment earlier in an osteoporosis patient’s journey to increase skeletal mass, reduce the risk of fracture and consequently limit the progression of the disease, and its associated disability and mortality. A placebo controlled, dose ranging Phase 2 study of EB613 tablets (n= 161) met primary (pharmacodynamic/bone turnover biomarker) and secondary endpoints (BMD).
EB613 is intended to provide an oral anabolic treatment earlier in an osteoporosis patient’s journey to increase skeletal mass, reduce the risk of fracture and limit the disease progression, and decrease disability and mortality. . A placebo controlled, dose ranging Phase 2 study of EB613 tablets (n= 161) met primary (pharmacodynamic/bone turnover biomarker) and secondary endpoints (BMD).
For example, if the FDA or other regulatory authority were to require us to conduct preclinical or clinical studies beyond those that we currently anticipate as necessary for development, if we experience significant delays in enrollment in any clinical trials, or if we encounter difficulties in manufacturing our clinical supplies, then we could be required to expend significant additional financial resources and time on the completion of the clinical development.
For example, if the FDA or other regulatory authority were to require us to conduct preclinical or clinical studies beyond those that we currently anticipate will be required for the completion of clinical development, if we experience significant delays in enrolment in any clinical trials or if we encounter difficulties in manufacturing our clinical supplies, then we could be required to expend significant additional financial resources and time on the completion of the clinical development.
In chronic diseases where patients require persistent management, these cumbersome, often painful and high-priced injections can create a major treatment gap. From a technical standpoint, oral delivery of therapeutic proteins is challenging due to the enzymatic degradation within the gastrointestinal tract and poor absorption into the blood stream due to the proteins’ polarity and molecular weight.
In chronic diseases where patients require persistent management, these cumbersome, often painful and high-priced injections can create a major treatment gap. From a technical standpoint, oral delivery of peptides and therapeutic proteins is challenging due to the enzymatic degradation within the gastrointestinal tract and poor absorption into the blood stream.
Our future capital requirements will depend on many factors, including: • the costs, timing and outcome of clinical trials for, and regulatory review of our oral peptide programs, including EB613 and EB612 and any other product candidates we may develop; • the costs of development activities for any other product candidates we may pursue; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; and • our ability to establish collaborations on favorable terms, if at all.
Our future capital requirements will depend on many factors, including: • the costs, timing and outcome of clinical trials for, and regulatory review of our oral peptide programs, including EB613 for osteoporosis and EB612 for hypoparathyroidism or other oral peptides for obesity, metabolic disorders and gastrointestinal rare diseases and any other product candidates we may develop; • the costs of development activities for any other product candidates we may pursue; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; and • our ability to establish collaborations on favorable terms, if at all.
The sales agent is entitled to a fixed commission of 3% of the aggregate gross proceeds as well as and reimbursement of expenses. As of December 31, 2024, we had sold 2,240,156 shares under the Leerink ATM Program for aggregate proceeds of $3.8 million, net of issuance costs.
The sales agent is entitled to a fixed commission of 3% of the aggregate gross proceeds as well as and reimbursement of expenses. As of December 31, 2025, we had sold 4,940,156 Ordinary Shares under the Leerink ATM Program for aggregate proceeds of $9.8 million, net of issuance costs.
For the years ended December 31, 2024 and 2023, our operating losses were $9.6 million and $8.9 million, respectively, and we expect to continue to incur significant expenses and losses for the foreseeable future. As of December 31, 2024, we had an accumulated deficit of $113.9 million.
For the years ended December 31, 2025 and 2024, our operating losses were $11.5 million and $9.6 million, respectively, and we expect to continue to incur significant expenses and losses for the foreseeable future. As of December 31, 2025, we had an accumulated deficit of $125.4 million.
Under the 2025 Collaboration Agreement, we granted to OPKO an exclusive, sublicensable and non-transferable, worldwide license to certain of our intellectual property and technology solely to develop, manufacture, and commercialize any GLP-1/Glucagon dual agonist as an oral treatment form for the treatment of obesity, metabolic, cardiovascular, and fibrotic disorders in humans, and OPKO has granted to us a non-exclusive, non-sublicensable and non-transferable license to certain of its intellectual property and technology to the extent necessary for us to perform our obligations in relation to the Program, in each case subject to the exceptions contained therein. 81 Under the terms of the 2025 Collaboration Agreement, we and OPKO will retain 40% and 60%, respectively, of all proceeds deriving from the Program, and will be responsible for 40% and 60% of the Program’s development costs, respectively.
Under the 2025 Collaboration Agreement, we granted to OPKO an exclusive, sublicensable and non-transferable, worldwide license to certain of our intellectual property and technology solely to develop, manufacture, and commercialize any GLP-1/Glucagon dual agonist as an oral treatment form for the treatment of obesity, metabolic, cardiovascular, and fibrotic disorders in humans, and OPKO has granted to us a non-exclusive, non-sublicensable and non-transferable license to certain of its intellectual property and technology to the extent necessary for us to perform our obligations in relation to the Program, in each case subject to the exceptions contained therein.
Net Cash Used in Investing Activities Net Cash used in investing activities for the years ended December 31, 2024 and December 31, 2023 primarily consisted purchase of property and equipment Net Cash Provided by Financing Activities Net cash provided by financing activities for year ended December 31, 2024 consisted of the net proceeds of $3.8 million from the issuance of Ordinary Shares under the Leerink ATM Program and $0.8 million from the issuance of Ordinary Shares upon the exercise of outstanding options and warrants.
Net Cash provided by financing activities for the year ended December 31, 2024 consisted of net proceeds of $3.8 million from the issuance of Ordinary Shares under the Leerink ATM Program and $0.8 million from the issuance of Ordinary Shares upon the exercise of outstanding options and warrants.
In September 2024, we jointly announced with OPKO topline pharmacokinetic/pharmacodynamic (PK/PD) results for the OXM program. The program is focused on developing the first oral dual agonist GLP-1/Glucagon peptide as a potential once-daily tablet treatment for patients with obesity and metabolic disorders using the N-Tab™ platform.
The program focuses on developing the first oral dual agonist GLP-1/Glucagon peptide as a potential once-daily tablet treatment for patients with obesity and metabolic disorders using the N-Tab ® platform. Currently, there are no approved dual GLP-1/Glucagon agonists available. In September 2024, we jointly announced with OPKO topline PK/PD results for the OXM program..
A change in the outcome of any of these variables with respect to the development of EB613, EB612 or any other product candidate that we may develop could result in significant changes in the costs and timing associated with the development of our product candidates.
A change in the outcome of any of these variables with respect to the development of EB613, EB612, OXM or any other product candidate that we may develop could significantly change the costs and timing associated with the development of any such product candidate.
Taxes on Income We have not generated taxable income since our inception, and as of December 31, 2024, we had carry-forward tax losses of $83.5 million. We anticipate that we will be able to carry forward these tax losses indefinitely to future tax years.
Dollar. 85 Taxes on Income We have not generated taxable income since our inception. As of December 31, 2025, we had carry-forward tax losses of $91.8 million. We anticipate that we will be able to carry forward these tax losses indefinitely to future tax years.
Oral OXM exhibited significant systemic exposure across two in vivo models, a favorable PK profile and bioavailability. The high plasma concentrations with prolonged systemic exposure were consistent with the reported half-life for semaglutide (Rybelsus®), the only approved oral GLP-1 analog. Oral OXM showed a statistically significant reduction in plasma glucose levels compared with placebo.
The high plasma concentrations with prolonged systemic exposure were consistent with the reported half-life for semaglutide (Rybelsus®), the only approved oral GLP-1 analog. Oral OXM showed a statistically significant reduction in plasma glucose levels compared with placebo.
For the years ended December 31, 2024 and 2023, our research and development expenses were $4.5 million and $4.5 million, respectively. Research and development expenses for the years ended December 31, 2024 and 2023 were primarily for the development of EB613, EB612 and our collaboration with OPKO related to GLP-2 and OXM.
For the years ended December 31, 2025 and 2024, our research and development expenses were $6.0 million and $4.5 million, respectively. Research and development expenses for the year ended December 31, 2025 were primarily for the development of EB613 and next-generation of EB613, EB612 and our collaboration with OPKO related to OXM.
Israeli Innovation Authority Grants We have received grants of approximately $0.5 million from the IIA to partially fund our PTH research and development for Osteoporosis. The grants are subject to certain requirements and restrictions under the Research Law.
All other provisions of the Patent Transfer Agreement remain in full force and effect. Israeli Innovation Authority Grants We have received grants of approximately $0.5 million from the IIA to partially fund our PTH research and development for Osteoporosis. The grants are subject to certain requirements and restrictions under the Research Law.
If we are unable to raise additional funds through equity or debt financings or collaborations, when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts. 86 Cash Flows Year Ended December 31, 2024 Compared to Year Ended December 31, 2023 The following table sets forth the primary sources and uses of cash for each of the years set forth below: Year ended December 31, 2024 2023 (in thousands) Net Cash used in operating activities $ (6,818 ) $ (7,310 ) Net Cash used in investing activities (3 ) (17 ) Net Cash provided by financing activities 4,476 6,036 Net decrease in cash and cash equivalents $ (2,345 ) $ (1,291 ) Net Cash Used in Operating Activities Net Cash used in operating activities for the year ended December 31, 2024 was $6.8 million, consisting primarily of our operating loss of $9.6 million, and a decrease of $0.2 million in our working capital and other expenses which was partially offset by approximately $2.6 million of share-based compensation and depreciation expenses.
If we are unable to raise additional funds through equity or debt financing or collaborations, when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts. 88 Cash Flows Year Ended December 31, 2025 Compared to Year Ended December 31, 2024 The following table sets forth the primary sources and uses of cash: Year ended December 31, 2025 2024 (in thousands) Net Cash used in operating activities $ (7,370 ) $ (6,818 ) Net Cash used in investing activities (107 ) (3 ) Net Cash provided by financing activities 13,710 4,476 Effect of Exchange Rate changes on cash and cash equivalents 36 - Net decrease in cash and cash equivalents $ 6,197 $ (2,345 ) Net Cash Used in Operating Activities Net Cash used in operating activities for the year ended December 31, 2025 was $7.4 million, consisting primarily of our operating loss of $11.5 million, which was partially offset by approximately $2.8 million of share-based compensation and depreciation expenses and a decrease of $1.3 million in changes in operating assets and liabilities and other expenses.
We leverage our N-Tab™ platform which is designed to simultaneously stabilize the peptide in the gastrointestinal tract and promote its absorption into the bloodstream. EB613 Program Our most advanced product candidate, EB613, oral PTH(1-34), is being developed as the first oral, osteoanabolic (bone building) once-daily tablet treatment for post-menopausal women with low bone mineral density (“BMD”) and high-risk osteoporosis.
We leverage our N-Tab ® platform, which is designed to simultaneously stabilize large (4kD+) hydrophilic peptides in the gastrointestinal tract and promote their absorption into the bloodstream. EB613 Program Our most advanced product candidate, EB613, oral PTH(1-34), is being developed as the first oral, osteoanabolic (bone building) once-daily tablet treatment for osteoporosis.
As of December 31, 2024, we had cash and cash equivalents of $8.7 million. Our primary uses of cash have been to fund research and development, general and administrative and working capital requirements, and we expect these will continue to be our primary uses of cash.
Our primary uses of cash have been to fund research and development, general and administrative and working capital requirements, and we expect these will continue to be our primary uses of cash.
Currently, such activities in Israel remain largely unaffected. During the years ended December 31, 2024 and December 31, 2023, the impact of this war on the Company’s results of operations and financial condition was immaterial. See Item 1.A.
During the years ended December 31, 2025 and December 31, 2024, the impact of this war on the Company’s results of operations and financial condition was immaterial. See Item 1.A.
As of March 20, 2025 we had cash and cash equivalents of $21 million, of which $8 million has been designated to fund the collaboration activity with OPKO under the 2025 Collaboration Agreement.
As of March 23, 2026 we had cash and cash equivalents of $12.6 million, of which $7.8 million has been designated to fund the collaboration activity with OPKO under the A&R Collaboration Agreement.
Any delay or our inability to secure such funding will delay or prevent the commencement of these studies. Our expectations are based on management’s current assumptions, clinical development plans and regulatory submission timelines, which may prove to be wrong, and we could spend our available financial resources much faster than we currently expect.
Our expectations are based on management’s current assumptions, clinical development plans and regulatory submission timelines, which may prove to be wrong, and we could spend our available financial resources much faster than we currently expect.
The decrease of $0.5 million in cash used in operating activities for the year ended December 31, 2024 compared to the same period in 2023 was mainly attributed to an increase of $0.7 million in our operating loss and a decrease of $0.4 million in working capital and others primarily due to payments to suppliers and services providers, which was partially offset by a decrease of $0.8 million in share-based compensation and depreciation expenses.
The increase of $0.6 million in cash used in operating activities for the year ended December 31, 2025 compared to 2024 was mainly attributed to an increase of $1.9 million in our operating loss, a decrease of $1.1 million in changes in operating assets and liabilities and other expenses primarily due to payments to suppliers and services providers, which was partially offset by an increase of $0.2 million in share-based compensation and depreciation expenses.
Recent Developments Potentially Affecting Our Business Collaboration and License Agreement with OPKO On March 16, 2025, we entered into the 2025 Collaboration Agreement with OPKO and its wholly owned subsidiary, OPKO Biologics Ltd., to collaborate with respect to the preclinical and clinical development and decision making related to the Oral OXM program for the treatment of obesity, metabolic and fibrotic disorders in humans (the “Program”).
In March 2025, we entered into the 2025 Collaboration Agreement with OPKO and OPKO Biologics to collaborate with respect to the preclinical and clinical development and decision making related to the Oral OXM program for the treatment of obesity, metabolic and fibrotic disorders in humans.
Net Cash used in operating activities for the year ended December 31, 2023 was $7.3 million, consisting primarily of our operating loss of $8.9 million and an increase of $0.2 million in our working capital, which was partially offset by approximately $1.8 million of share-based compensation and depreciation expenses.
Net Cash used in operating activities for the year ended December 31, 2024, was $6.8 million, consisting primarily of our operating loss of $9.6 million, which was partially offset by approximately $2.6 million of share-based compensation and depreciation expenses and a decrease of $0.2 million in changes in operating assets and liabilities and other expenses.
Equity Offerings On September 2, 2022, we entered into a Sales Agreement with Leerink Partners LLC (f/k/a SVB Securities LLC), as sales agent, to implement an ATM program (the “Leerink ATM Program”) under which we were originally able to sell up to 5,000,000 Ordinary Shares under our currently effective Registration Statement on Form S-3 and a related prospectus supplement forming a part thereof.
Equity Offerings On September 2, 2022, we entered into a Sales Agreement with Leerink Partners LLC (f/k/a SVB Securities LLC), as sales agent, to implement an ATM program (the “Leerink ATM Program”) under which we were originally able to sell up to 5,000,000 Ordinary Shares in an at-the-market offering registered under the Securities Act.
Financial Overview We are primarily engaged in research and development activities, and we have not derived significant income from our activities. Since our inception, we have raised a total of $111.1 million from a combination of public and private equity offerings, IIA grants and the exercise of options and warrants. Since inception, we have incurred significant losses.
Since our inception, we have raised a total of $111.6 million from a combination of public and private equity offerings, IIA grants and the exercise of options and warrants. Since inception, we have incurred significant losses.
Financial Income, Net Financial income, net for the year ended December 31, 2024 was $58,000, compared to $31,000 for the year ended December 31, 2023. Our financial income is composed mainly of interest income from bank deposits and exchange rate differences of certain currencies against our functional currency, which is the U.S. Dollar.
Our financial income is composed mainly of interest income from bank deposits and exchange rate differences of certain currencies against our functional currency, which is the U.S. Dollar. Financial income, net increased predominantly due to increased interest income from our bank deposits.
Additional financing may not be available when we need it or may not be available on terms that are favorable to us. 80 Patent Transfer, Licensing Agreements and Grant Funding Oramed Patent Transfer Agreement In 2011, we entered into the Patent Transfer Agreement with Oramed, pursuant to which Oramed assigned to us all of its rights, title and interest in the patent rights that Oramed licensed to us when we were originally organized, subject to a worldwide, royalty-free, exclusive, irrevocable, perpetual and sub-licensable license granted to Oramed under the assigned patent rights to develop, manufacture and commercialize products or otherwise exploit such patent rights in the fields of diabetes and influenza.
(“Oramed”), which we refer to as the Patent Transfer Agreement, pursuant to which Oramed assigned to us all of its rights, title and interest in the patent rights Oramed licensed to us when we were originally organized, subject to a worldwide, royalty-free, exclusive, irrevocable, perpetual and sub-licensable license granted to Oramed under the assigned patent rights to develop, manufacture and commercialize products or otherwise exploit such patent rights in the fields of diabetes and influenza.
Funding Requirements Given our current plans, we believe that our existing cash resources will be sufficient to meet our projected operating requirements into the third quarter of 2026.
Given our current cash position and plans, we believe that our existing cash resources will be sufficient to meet our projected operating requirements through the middle of the third quarter of 2026, excluding the Phase 3 study of EB613 in osteoporosis.
As of December 31, 2024, Entera Bio Inc. had tax loss carry-forwards of $172 thousand.
As of December 31, 2025, Entera Bio Inc. had tax loss carry-forwards of $0.2 million.
The proceeds received are not reflected in our cash balance as of December 31, 2024. We have agreed to use the proceeds from the issuance of such Ordinary Shares solely to fund our development cost obligations under the 2025 Collaboration Agreement.
We have agreed to use the proceeds from the issuance of such Ordinary Shares solely to fund our development cost obligations under the A&R Collaboration Agreement.
See “Item 1A—Risk Factors-Risks Related to Our Financial Position and Need for Additional Capital.” As of December 31, 2024, we had cash and cash equivalents of $8.7 million.
See “Item 1A—Risk Factors-Risks Related to Our Financial Position and Need for Additional Capital.” 83 As of December 31, 2025, we had cash and cash equivalents of $14.9 million, of which $7.8 million has been designated to fund the collaboration activity with OPKO under the A&R Collaboration Agreement.
EB612 Program Our product candidate, EB612, is being developed as the first oral PTH(1-34) tablet peptide replacement therapy for patients with hypoparathyroidism.
Subject to regulatory feedback, we are planning to initiate the Phase 3 study in the second half of 2026. EB612 Program Our product candidate, EB612, is being developed as the first oral PTH(1-34) tablet peptide replacement therapy for patients with hypoparathyroidism.
The decrease was partially offset by an increase of $0.8 million in materials and other consulting, including regulatory required in connection with the optimization processes related to the preparation of the EB613 phase 3 study. 84 General and Administrative Expenses General and administrative expenses for the year ended December 31, 2024 were $5.1 million, compared to $4.4 million for the year ended December 31, 2023.
The increase was partially offset by a decrease of $0.2 million in materials and production costs related to the preparation of the EB613 phase 3 program. 86 General and Administrative Expenses General and administrative expenses for the year December 31, 2025 were $5.5 million as compared to $5.1 million for year ended December 31, 2024.
We expect that our research and development expenses will increase significantly in future periods as we advance our clinical candidates into later stages of clinical development and invest in additional preclinical candidates.
We expect that our research and development expenses will increase significantly in future periods as we advance our clinical candidates into later stages of clinical development and invest in additional preclinical candidates. 84 Our research and development expenses may vary substantially from period to period based on the timing of our research and development activities, including due to the timing of initiation of clinical trials and the enrolment of patients in clinical trials.
“Risk Factors—Risks Relating to Our Incorporation and Location in Israel — Security, political and economic instability in the Middle East may harm our business.” Financial Overview Revenue To date, we have not generated any revenue from sales of our products, and we do not expect to receive any revenue from any product candidates that we develop unless and until we obtain regulatory approval and successfully commercialize our products.
Revenue To date, we have not generated any revenue from sales of our products, and we do not expect to receive any revenue from any product candidates that we develop unless and until we obtain regulatory approval and successfully commercialize our products.
In addition to paying any royalties due, we must abide by other restrictions associated with receiving such grants under the Research Law that continue to apply following repayment to the IIA.
In addition to paying any royalties due, we must abide by other restrictions associated with receiving such grants under the Research Law that continue to apply following repayment to the IIA. Recent Developments Potentially Affecting Our Business Israel-Hamas War and Regional Conflicts In October 2023, Israel was attacked by Hamas, a terrorist organization and entered a state of war.
None of the warrants contain any “ratchet”, “reset” or other adjustments related to financial antidilution. 85 If all Ordinary Share Warrants were exercised for cash, then the Company would receive additional proceeds of approximately $7.9 million. There can be no assurance that the holders of the Ordinary Share Warrants exercise their respective warrants for cash, or at all.
None of the warrants contain any “ratchet”, “reset” or other adjustments related to financial antidilution. 87 As of December 31, 2025, we have received approximately $0.6 million of net proceeds from the exercise of outstanding Ordinary Share Warrants. If all Ordinary Share Warrants were exercised for cash, then the Company would receive additional proceeds of approximately $7.8 million.
For the years ended December 31, 2024 and 2023, our operating losses were $9.6 million and $8.9 million, respectively. We expect to continue to incur significant expenses and losses for the next several years as we advance our products through development and provide administrative support for our operations.
We expect to continue to incur significant expenses and losses for the next several years as we advance our products through development and provide administrative support for our operations. These factors raise substantial doubt about our ability to continue as a going concern.
Our ability to commence the Phase 3 study of EB613 in osteoporosis will depend on finalizing discussions with the FDA in connection with its anticipated qualification of the SABRE total hip BMD endpoint and will require additional funding, which may not be available on reasonable terms, or at all.
Our ability to commence the Phase 3 program of EB613 in osteoporosis will require additional funding, which may not be available on reasonable terms, or at all. Any delay or our inability to secure such funding will delay or prevent the commencement of these studies.
Since our inception, we have raised a total of $111.1 million, including $36.3 million through at-the-market-offering (“ATM”) programs, an aggregate of $28.9 million in private placements since our IPO, $11.2 million in our IPO in 2018 and $34.7 million in aggregate funding from a combination of IIA grants, exercise of options and warrants and private placements of Ordinary Shares, preferred shares and debt prior to our IPO.
Since our inception and through December 31, 2025, we have raised a total of $111.6 million from a combination of public and private equity offerings, IIA grants and the exercise of options and warrants, including $36.4 million through at-the-market-offering (“ATM”) programs.
We did not recognize any revenue for the year ended December 31, 2023. Cost of Revenues Cost of revenues for the year ended December 31, 2024 was $172 thousand, which was attributable to research services we provided pursuant to the research services agreement. We did not recognize any cost of revenues for the year ended December 31, 2023.
The Company completed the first stage of its obligations under the research services agreement in the first quarter of 2025. Cost of Revenues Cost of revenues for the year ended December 31, 2025 and 2024 was $42 thousand and $172 thousand, respectively, which was attributable to research services we provided pursuant to a research services agreement with an external party.
In connection with the execution of the 2025 Collaboration Agreement, we issued and sold to OPKO an aggregate of 3,685,226 Ordinary Shares for a purchase price of $8.0 million, representing a purchase price per share equal to approximately $2.17, which was the volume weighted average price per share for the 30 trading days immediately preceding the date of such agreement.
In connection with the execution of the 2025 Collaboration Agreement, we issued and sold to OPKO an aggregate of 3,685,226 Ordinary Shares for a purchase price of $8.0 million, the proceeds of which we have agreed to use solely to fund our development cost obligations under the 2025 Collaboration Agreement, subject to the expiration or termination of the agreement.
Our ability to commence the Phase 3 study of EB613 in osteoporosis will depend on finalizing discussions with the FDA in connection with their anticipated qualification of the SABRE total hip BMD endpoint and will require additional funding, which may not be available on reasonable terms, or at all.
Our ability to commence the Phase 3 study of EB613 in osteoporosis will require additional funding, which may not be available on reasonable terms, or at all. Any delay or our inability to secure such funding will delay or prevent the commencement of this study. In order to fund further operations, we will need to raise additional capital.
Since the commencement of these events, there have been continuous rocket strikes across Israel, including with Hezbollah in Lebanon, the Houthi movement which controls parts of Yemen, and with Iran. As of the date of this Annual Report, the war is ongoing and continues to evolve. The Company's headquarters and its R&D operations are located in Israel.
Since the commencement of these events, there have been additional active hostilities, including with Hezbollah in Lebanon, the Houthi movement which controls parts of Yemen, and with Iran.
Subsequent to such sales, in January 2025, we filed a supplement to the prospectus supplement relating to the Leerink ATM Program, which provides us the ability, but not the obligation, to sell up to an additional 30,000,000 Ordinary Shares under the Leerink ATM Program.
We currently have the ability, but not the obligation, to sell up to an additional 30,000,000 Ordinary Shares under the Leerink ATM Program under our currently effective Registration Statement on Form S-3.
Any delay or our inability to secure such funding will delay or prevent the commencement of this study. In order to fund further operations, we will need to raise additional capital. We may raise these funds through a variety of means, including private or public equity offerings, debt financings, strategic collaborations and licensing arrangements.
We may raise these funds through a variety of means, including private or public equity offerings, debt financing, strategic collaborations and licensing arrangements. Additional financing may not be available when we need it or may not be available on terms that are favorable to us.
Net Cash provided by financing activities for the year ended December 31, 2023 primarily reflects net proceeds of $6 million from issuance of the Units in the December 2023 Private Placement.
Net Cash Provided by Financing Activities Net cash provided by financing activities for year ended December 31, 2025 consisted of the net proceeds of $6.1 million from the issuance of Ordinary Shares under the Leerink ATM Program, $0.5 million from the issuance of Ordinary Shares upon the exercise of warrants and $7.1 million from issuance of Ordinary Shares in connection with the entry into the 2025 Collaboration Agreement.
Under this agreement, we and OPKO have each agreed to be responsible for specific phases of development of the two oral peptides to the point of demonstrated in vivo feasibility. In March 2024, we announced positive in vivo pharmacokinetic (PK) results from our collaborative research, combining a proprietary long acting GLP-2 agonist developed by OPKO with Entera’s proprietary N-Tab™ technology.
Under this agreement, we and OPKO have each agreed to be responsible for specific phases of development of the two oral peptides to the point of demonstrated in vivo feasibility. 81 2025 Collaboration Agreement In March 2025, we entered into the 2025 Collaboration Agreement with OPKO and OPKO Biologics to collaborate with respect to the preclinical and clinical development and decision making related to the Oral OXM program for the treatment of obesity, metabolic and fibrotic disorders in humans (the “Program”).
The following table summarizes the allocation of our share-based compensation expense: Year ended December 31, 2024 2023 (in thousands ) Cost of revenues $ 7 $ - Research and development 839 424 General and administrative 1,710 1,265 Total $ 2,556 $ 1,689 Recently Issued Accounting Pronouncements Certain recently issued accounting pronouncements are discussed in Note 2 to the consolidated financial statements included elsewhere in this Annual Report.
Recently Issued Accounting Pronouncements Certain recently issued accounting pronouncements are discussed in Note 2 to the consolidated financial statements included elsewhere in this Annual Report.
Research and Development Expenses Research and development expenses for the years ended December 31, 2024 and December 31, 2023 were each $4.5 million. There was a decrease of $0.8 million in clinical expenses for our Phase 1 PK study related to our new formulations for EB612, which occurred in 2023.
Research and Development Expenses Research and development expenses for the year ended December 31, 2025 were $6.0 million as compared to $4.5 million for year ended December 31, 2024.
The program is focused on developing the first and only GLP-2 peptide tablet alternative for patients suffering from short bowel syndrome and additional disorders involving mucosal inflammation and nutrient malabsorption. OXM is a naturally occurring peptide hormone found in the colon, with glucagon-like-peptide 1 (GLP-1) and glucagon dual agonist activity that suppresses appetite and induces weight loss.
Management’s Discussion and Analysis of Financial Condition and Results of Operations—Patent Transfer, Licensing Agreements and Grant Funding—OPKO Collaboration and License Agreements, contained in this Annual Report. Oral GLP-2 This program focuses on developing the first GLP-2 peptide tablet alternative for patients suffering from short bowel syndrome and additional disorders involving mucosal inflammation and nutrient malabsorption.
Removed
Following Type C and Type D meetings with the FDA, we announced in 2023 the FDA’s concurrence that a 2-year, placebo-controlled phase 3 (registrational) study with Total Hip BMD as primary endpoint could support a new drug application (“NDA”) for EB613, however the SABRE BMD endpoint remained unqualified as a surrogate endpoint by FDA.
Added
In July 2025, we announced that in a written response to a Type A meeting request, the FDA agreed that the NDA filing for EB613 could be supported by a phase 3 study in women with postmenopausal osteoporosis, where change in total hip BMD is evaluated as the primary endpoint, and incidence of new or worsening vertebral fractures is evaluated as the key secondary endpoint at 24 months.
Removed
In November 2023, the ASBMR announced that the SABRE project team had submitted its full qualification plan to the FDA for the use of BMD as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs.
Added
In December 2025, the FDA released the Determination for Qualification of BMD qualifying total hip BMD as a surrogate efficacy endpoint for fracture that could be used in future studies of new anti-osteoporosis therapies.
Removed
In March 2024, the ASBMR announced that the FDA had communicated to the SABRE project team that a ruling to qualify the treatment-related change in bone mineral density (BMD) as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs would be provided within 10 months.
Added
FDA’s suggested a context of use (COU): “The percentage change from baseline at 24 months in total hip bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) can be used as a validated surrogate endpoint for the assessment of investigational therapies for postmenopausal women with osteoporosis at risk for fracture.” In February 2026, we submitted to the FDA a clinical amendment which included the EB613 Phase 3 protocol, statistical analysis plan and open-label extension synopsis.
Removed
The EB613 osteoporosis clinical program has been developed under the auspices of this new approach to osteoporosis drug development. We believe EB613 stands as the first program to potentially avail itself of the ASBMR-SABRE BMD endpoint. SABRE is expected to provide an update on its FDA interactions and the qualification of the BMD endpoint in 2025.
Added
In December 2025, we announced new in vivo PK/PD data supporting the development of a proprietary long-acting PTH (LA-PTH) analog utilizing our N-Tab ® platform.
Removed
With respect to our EB612 program, we are currently testing new generations of our N-Tab™ Technology with the naked PTH(1-34) peptide to assess the effectiveness of once or twice a day dosing regimens, as well as collaborating with a third party on another peptide in this field.
Added
Preclinical findings demonstrated a markedly prolonged plasma half-life and sustained elevation of serum calcium levels for more than three days following administration of a single oral tablet, in contrast to unmodified PTH(1-34) controls, which showed no calcium response. These data support the development of a once-daily oral PTH tablet for patients with hypoparathyroidism.
Removed
In June 2024, Phase 1 clinical data for EB612 was presented at the Endocrine Society ENDO 2024 Annual Meeting.
Added
In February 2026, we announced the expansion of our collaboration with OPKO Biologics and OPKO to jointly advance this LA-PTH program. Under the expanded collaboration, Entera and OPKO each hold a 50% pro-rata ownership interest in the LA-PTH hypoparathyroidism program, and each is responsible for 50% of development costs.

… 59 more changes not shown on this page.

Other ENTX 10-K year-over-year comparisons