What changed in Entera Bio Ltd.'s 10-K — 2023 vs 2024
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Paragraph-level year-over-year comparison of Entera Bio Ltd.'s 2023 and 2024 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 2024 report.
+147 added−914 removedSource: 10-K (2025-03-28) vs 10-K (2024-03-08)
Top changes in Entera Bio Ltd.'s 2024 10-K
147 paragraphs added · 914 removed · 104 edited across 1 sections
- Item 1. Business+147 / −914 · 104 edited
Item 1. Business
Business — how the company describes what it does
104 edited+43 added−810 removed212 unchanged
Item 1. Business
Business — how the company describes what it does
104 edited+43 added−810 removed212 unchanged
2023 filing
2024 filing
Biggest changeAlthough a number of these, and other proposed measures may require authorization through additional legislation to become effective, Congress has indicated that it will continue to seek new legislative measures to control drug costs. 33 Additionally, CMS issued a final rule, effective on July 9, 2019, that requires direct-to-consumer advertisements of prescription drugs and biological products, for which payment is available through or under Medicare or Medicaid, to include in the advertisement the Wholesale Acquisition Cost, or list price, of that drug or biological product if it is equal to or greater than $35 for a monthly supply or usual course of treatment.
Biggest changeAlthough a number of these, and other proposed measures may require authorization through additional legislation to become effective, Congress has indicated that it will continue to seek new legislative measures to control drug costs.
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.
The main characteristics of the regulation include: • A streamlined application procedure via a single entry point, known as the Clinical Trials Information System; • A single set of documents to be prepared and submitted for the application as well as simplified reporting procedures which will spare sponsors from submitting broadly identical information separately to various and different national authorities; 27 • A harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts; • Strictly defined deadlines for the assessment of clinical trial application; and • The involvement of the ethics committees in the assessment procedure in accordance with the national law of the member state concerned but within the overall timelines defined by the Regulation (EU) No 536/2014.
The main characteristics of the regulation include: • A streamlined application procedure via a single-entry point, known as the Clinical Trials Information System; • A single set of documents to be prepared and submitted for the application as well as simplified reporting procedures which will spare sponsors from submitting broadly identical information separately to various and different national authorities; • A harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts; • Strictly defined deadlines for the assessment of clinical trial application; and • The involvement of the ethics committees in the assessment procedure in accordance with the national law of the member state concerned but within the overall timelines defined by the Regulation (EU) No 536/2014.
These 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 or Department of Justice, or other governmental entities. 21 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; • 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.
These 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.
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.
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.
CMS issued a final rule, effective on July 9, 2019, that requires direct-to-consumer advertisements of prescription drugs and biological products, for which payment is available through or under Medicare or Medicaid, to include in the advertisement the Wholesale Acquisition Cost, or list price, of that drug or biological product if it is equal to or greater than $35 for a monthly supply or usual course of treatment.
Additionally, CMS issued a final rule, effective on July 9, 2019, that requires direct-to-consumer advertisements of prescription drugs and biological products, for which payment is available through or under Medicare or Medicaid, to include in the advertisement the Wholesale Acquisition Cost, or list price, of that drug or biological product if it is equal to or greater than $35 for a monthly supply or usual course of treatment.
Statistically significant increases were observed in P1NP (key anabolic marker) at Month 1 (p The decrease in bone resorption (CTX) resulting from EB613 daily tablets was unanticipated based on historical results from subcutaneously daily injectable PTH, Forteo®; and indicates a potential dual mechanism of action for the EB613 PTH (1-34) tablets which seems to induce bone formation and decrease bone resorption, with a lower rate of bone turnover.
Statistically significant increases were observed in P1NP (key anabolic marker) at Month 1 (p The decrease in bone resorption (CTX) resulting from EB613 daily tablets was unanticipated based on historical results from subcutaneously daily injectable PTH, Forteo®; and indicates a potential dual mechanism of action for EB613 which seems to induce bone formation and decrease bone resorption, with a lower rate of bone turnover.
We are developing our product candidates to potentially become the first oral, daily tablet peptide or peptide 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, 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.
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.
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").
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. 31 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.
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.
Our ability to deliver our oral PTH(1-34) peptide in a simple mini tablet format with reproduceable, dose dependent pharmacokinetics and rapid biological responses across gender, age, and health status was highlighted as part of two poster sessions at the ASBMR 2023 Annual Meeting.
Our ability to deliver our oral PTH(1-34) peptide in a simple tablet format with reproduceable, dose dependent pharmacokinetics and rapid biological responses across gender, age, and health status was highlighted as part of two poster sessions at the ASBMR 2023 Annual Meeting.
These restrictions may impair our ability to outsource manufacturing, engage in change of control transactions or otherwise transfer our “know-how” (in its meaning under the Research Law) in or outside of Israel, and may require us to obtain the approval of the IIA for certain actions and transactions and pay additional royalties and other amounts to the IIA.
These restrictions may impair our ability to outsource manufacturing, engage in change of control transactions or otherwise transfer our IIA-related “know-how” (in its meaning under the Research Law) in or outside of Israel, and may require us to obtain the approval of the IIA for certain actions and transactions and pay additional royalties and other amounts to the IIA.
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.
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.
A well-controlled, statistically robust Phase 3 trial may be designed to deliver the data that regulatory authorities will use to decide whether or not to approve, and, if approved, how to appropriately label a drug: such Phase 3 studies are referred to as “pivotal.” In some cases, the FDA may approve an NDA or a BLA for a product candidate but require the sponsor to conduct additional clinical trials to further assess the drug’s safety and effectiveness after NDA or BLA approval.
A well-controlled, statistically robust Phase 3 trial may be designed to deliver the data that regulatory authorities will use to decide whether or not to approve, and, if approved, how to appropriately label a drug: such Phase 3 studies are referred to as “pivotal.” In some cases, the FDA may approve an NDA or a BLA for a product candidate but require the sponsor to conduct additional clinical trials to further assess the product candidate’s safety and effectiveness after NDA or BLA approval.
If a clinical trial outside the United States is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of a NDA so long as the clinical trial is conducted in consistent with GCP and in compliance with an international guideline for the ethical conduct of clinical research known as the Declaration of Helsinki and/or the laws and regulations of the country or countries in which the clinical trial is performed, whichever provides the greater protection to the participants in the clinical trial.
If a clinical trial outside the United States is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of a NDA so long as the clinical trial is conducted in accordance with GCP and in compliance with an international guideline for the ethical conduct of clinical research known as the Declaration of Helsinki and/or the laws and regulations of the country or countries in which the clinical trial is performed, whichever provides the greater protection to the participants in the clinical trial.
The increases in proximal femoral BMD (TH and FN) and cortical bone after six months of EB613 daily tablet treatment were unanticipated given that the reported subcutaneous Forteo® injection increases are typically small and not significant at six months. 13 The results of the Phase 2 study supported the selection of the 2.5 mg dose with a titration regimen to be used in the proposed pivotal Phase 3 study of EB613.
The increases in proximal femoral BMD (TH and FN) and cortical bone after six months of EB613 daily tablet treatment were unanticipated given that the reported subcutaneous Forteo® injection increases are typically small and not significant at six months. 15 The results of the Phase 2 study supported the selection of the 2.5 mg dose with a titration regimen to be used in the proposed pivotal Phase 3 study of EB613.
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 manner in which 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. 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.
FDA Type D Meeting In February 2023, we announced that a Type D meeting protocol review had been accepted by the FDA to provide responses by March 30th, 2023. The pivotal, Phase 3 study protocol is entitled “A 24-Month Phase 3, Randomized, Double-Blind, Global Multicenter Study Comparing the Effects of Oral hPTH(1-34) (EBP05[EB613]) Daily Tablets vs.
FDA Type D Meeting In February 2023, we announced that a Type D meeting protocol review had been accepted by the FDA to provide responses by March 30th, 2023. The pivotal, Phase 3 study protocol is entitled “A 24-Month Phase 3, Randomized, Double-Blind, Global Multicenter Study Comparing the Effects of Oral PTH(1-34) (EBP05[EB613]) Daily Tablets vs.
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, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of pharmaceutical products.
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 timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional marketing authorization. 28 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.
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.
Failure to exhibit due diligence with regard to conducting Phase 4 clinical trials could result in withdrawal of approval for products. 23 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. 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.
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. 15 Limitations of current treatments for hypoparathyroidism Historically, the treatments for hypoparathyroidism have been calcium supplements, vitamin D supplements and phosphate binders.
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.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. 24 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. 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.
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. 32 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. 34 Pricing and reimbursement schemes vary widely from country to country.
We believe that the key competitive factors that will affect the development and commercial success of our oral PTH 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 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.
This could cause significant delays or difficulties in completing planned clinical trials in a timely manner. 22 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.
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.
Pursuant to the Israeli Public Health Regulations, such authorization generally cannot be granted unless, among other things, the relevant institutions ethics committee has provided its prior approval of the testing and that the trial complies with the standards set forth by the Declaration of Helsinki.
Pursuant to the Israeli Public Health Regulations, such authorization generally cannot be granted unless, among other things, the relevant institutions' ethics committee has provided its prior approval of the testing and that the trial complies with the standards set forth by the Declaration of Helsinki.
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. The conduct of the preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements.
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. The conduct of the preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements, including GLP.
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 15 General and Administrative 2 Total 17 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 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 concentration of PTH (1-34) in blood after administration of Oral PTH (1-34) in the trial was sufficient to produce the observed pharmacodynamic effects and did not induce hypercalcemia. No serious adverse events were reported.
The concentration of PTH(1-34) in blood after administration of EB612 in the trial was sufficient to produce the observed pharmacodynamic effects and did not induce hypercalcemia. No serious adverse events were reported.
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 obesity 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.
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.
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.
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.
We believe that EB612 may have inherent advantages compared to injectable forms because this is a protein replacement therapy requiring long term use, and we believe that patients have a preference for oral medication, and our tablets may enable more flexibility for titration and more individualized treatment. 16 Phase 2a Clinical Trial In 2015, we successfully completed a multicenter Phase 2a clinical trial of EB612 in hypoparathyroidism patients.
We believe that EB612 may have inherent advantages compared to injectable forms because this is a protein replacement therapy requiring long term use, and we believe that patients have a preference for oral medication, and our tablets may enable more flexibility for titration and more individualized treatment in this heterogeneous disease. 18 Phase 2a Clinical Trial In 2015, we successfully completed a multicenter Phase 2a clinical trial of EB612 in hypoparathyroidism patients.
For patients undergoing treatment, stable or increasing BMD at the spine and hip indicates a satisfactory response. The three currently approved osteoanabolic drugs that stimulate bone formation all require daily or monthly subcutaneous injections: teriparatide (hPTH[1-34]); abaloparatide (a PTH-related protein analog); and romosozumab (an antibody that inhibits sclerostin and also inhibits bone resorption).
For patients undergoing treatment, stable or increasing BMD at the spine and hip indicates a satisfactory response. The three currently approved osteoanabolic drugs that stimulate bone formation all require daily or monthly subcutaneous injections: teriparatide (PTH(1-34) ), Forteo®); abaloparatide (a PTH-related protein analog, Tymlos®)); and romosozumab (an antibody that inhibits sclerostin and also inhibits bone resorption, Evenity®).
On the same day, we announced that we plan to continue our dialogue with the FDA and await the final qualification of the ASBMR-FNIH SABRE BQP 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 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.
We are preparing to initiate a Phase 3 registrational study for EB613 pursuant to the FDA’s qualification of a quantitative BMD endpoint which is expected to occur in 2024. • 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.
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.
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 research and development.
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.
Worldwide, osteoporosis affects an estimated 200 million women, according to the International Osteoporosis Foundation, or IOF, and causes more than 8.9 million fractures annually, which is equivalent to an osteoporotic fracture occurring approximately every three seconds.
Worldwide, osteoporosis affects an estimated 200 million women, according to the International Osteoporosis Foundation (the “IOF”) and causes more than 8.9 million fractures annually, which is equivalent to an osteoporotic fracture occurring approximately every three seconds.
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.
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.
We initiated a PK study in May 2023, which is testing various potential drug candidates based on our new platform, including several which could be developed for the treatment of hypoparathyroidism.
We initiated a PK study in May 2023, which tested various potential drug candidates based on our new platform, including several which could be developed for the treatment of hypoparathyroidism.
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) - 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.
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.
Early in the first quarter of 2022, Entera received additional EOP2 minutes from the FDA, suggesting that a non-inferiority head-to-head study versus Forteo® Phase 3 design may not be favorable to the success of the study and potential approvability of EB613 oral PTH tablets given EB613’s different PK profile, PD (biomarker) profile and BMD outcomes from the phase 2.
Early in the first quarter of 2022, Entera received additional EOP2 minutes from the FDA, suggesting that a non-inferiority head-to-head study versus Forteo® Phase 3 design may not be favorable to the success of the program and potential approvability of EB613 given EB613’s PK profile, PD (biomarker) profile and BMD outcomes from the phase 2.
Our website address is included in this report only as an inactive textual reference. Information contained on, or available through, our website is not incorporated by reference in, or made a part of, this report. 34 ITEM 1A .
Our website address is included in this report only as an inactive textual reference. Information contained on, or available through, our website is not incorporated by reference in, or made a part of, this report.
Our strategy to achieve these goals includes: • Advancing EB613, Potentially the First Daily Anabolic PTH(1-34) Tablet into Phase 3 for the Treatment of Post-Menopausal Women with Low Bone Mass and Osteoporosis : Our six-month placebo-controlled Phase 2 double-blind, dose-ranging trial of EB613 in 161 patients with low bone mass and osteoporosis met both primary and secondary endpoints and was selected for oral presentation at the American Society of Bone Mineral Research (ASBMR) annual conference in 2021.
Our strategy to achieve these goals includes: • Advancing EB613, Potentially the First Daily Anabolic PTH(1-34) Tablet Treatment into Phase 3 for the Treatment of Post-Menopausal Women with Low Bone Mass and Osteoporosis : Our six-month placebo-controlled Phase 2 double-blind, dose-ranging trial of EB613 in 161 patients with low bone mass and osteoporosis met both primary and secondary endpoints was selected for oral presentation at the ASBMR annual conference in 2021 and published at JBMR in March 2024.
The results of the preclinical tests, together with manufacturing information and analytical data, are submitted to the FDA as part of an Investigational New Drug (“IND”) application. Some preclinical tests may continue even after submission of the IND application.
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 FDA released a final rule on September 24, 2020, effective November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada. Further, on November 20, 2020, the U.S.
The FDA released a final rule on September 24, 2020, effective November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada.
EB613 is positioned to potentially be the first, once daily osteoanabolic mini tablet treatment for women with high-risk post-menopausal osteoporosis and no prior fractures. 10 Phase 1 Safety, PK and PD Data for Oral PTH(1-34) Tablet Programs Our Oral PTH (1-34) formulations, 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. 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.
There were no treatment emergent hypercalcemia adverse events, and serial serum chemistry evaluations found no increase in group 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.
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.
BMD is the first surrogate endpoint undergoing qualification by the FDA under the 21st Century Cures Act which was signed into law on December 13, 2016, to help accelerate medical product development and bring new innovations and advances to patients who need them faster and more efficiently. An update on the qualification of this endpoint is expected in 2024.
BMD is the first surrogate endpoint undergoing qualification by the FDA under the 21st Century Cures Act which was signed into law on December 13, 2016, to help accelerate medical product development and bring new innovations and advances to patients who need them faster and more efficiently.
Our commercial opportunity could be reduced or eliminated if our competitors have products that are better in one or more of these categories. We expect that, if approved, our oral PTH product candidates for osteoporosis, hypoparathyroidism and other product candidates that we develop, would compete with a number of existing products.
Our commercial opportunity could be reduced or eliminated if our competitors have products that are better in one or more of these categories. We expect that, if approved, our oral PTH product candidates for osteoporosis, hypoparathyroidism and other product candidates that we are developing for metabolic disorders and short bowel syndrome, would compete with a number of existing products.
In April 2023, we reported that the FDA would not be opposed to Entera initiating the Phase 3 study under the proposed FNIH BQP pathway and that the Company’s proposed PK sampling scheme seemed reasonable.
In April 2023, we reported that the FDA would not be opposed to Entera initiating the Phase 3 study under the proposed SABRE endpoint and that the Company’s proposed PK sampling scheme seemed reasonable.
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.
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.
In an ongoing phase 1 study evaluating the current EB613 formulation, Forteo and new formulations for EB613 and EB612, 30 healthy subjects have been administered various doses (PTH (1-34) 1.5 mg – 2.5 mg) tablets and regimens (QD or BID) of oral PTH in the first two cohorts completed in 2023.
In the first two cohorts of a 2023 phase 1 study evaluating the current EB613 formulation, Forteo and new formulations for EB613 and EB612, 30 healthy subjects were administered various doses (PTH(1-34) 1.5 mg – 2.5 mg) and regimens (QD or BID) of oral PTH.
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. Currently, most protein therapies are administered via frequent intravenous, subcutaneous or intramuscular injections.
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.
In September 2023, we entered into a research collaboration agreement with OPKO. Under the terms of this agreement, OPKO has agreed to supply its proprietary long-acting GLP-2 peptide and certain Oxyntomodulin analogs for the development of oral tablet formulations using our proprietary N-Tab™ technology.
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.
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.
This trial was designed to provide a bridge from our completed Phase 2a trials, which was conducted prior to the marketing approval of Natpara, and our planned future clinical trials, and to also allow us to better understand the relative strength and dose of our product as compared to the then marketed product, Natpara.
This trial was designed to provide a bridge from our completed Phase 2 study, which was conducted prior to the marketing approval of Natpara, and to allow us to better understand the relative strength and dose of EB612 as compared to the then marketed product, Natpara.
EB613: First Daily Osteoanabolic Mini Tablets for the Treatment of Osteoporosis EB613 is the first once daily tablet formulation of hPTH (1-34), (teriparatide) and has the same amino acid sequence as Forteo ® (teriparatide daily subcutaneous injection), a leading anabolic agent which achieved peak annual sales of $1.7 billion prior to patent expiration.
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.
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.
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.
Both TransCon™ PTH and eneboparatide require a daily subcutaneous injection. EB612 Our product candidate for hypoparathyroidism, EB612, is the first oral formulation of PTH (1-34, teriparatide) hormone replacement treatment developed in a tablet form. The FDA and the EMA have granted EB612 orphan drug designation for the treatment of hypoparathyroidism.
EB612 Our product candidate for hypoparathyroidism, EB612, is the first oral PTH (1-34) hormone replacement treatment developed in a tablet form. The FDA and the EMA have granted EB612 orphan drug designation for the treatment of hypoparathyroidism.
Orphan drug designation provides a number of benefits, including fee reductions, regulatory assistance, and the possibility to apply for a centralized EU marketing authorization (see “Government Regulation and Product Approval-Regulation Outside the United States-Centralized Authorization Procedure”), as well as 10 years of market exclusivity following a marketing authorization.
Orphan drug designation provides a number of benefits, including fee reductions, regulatory assistance, and the possibility to apply for a centralized EU marketing authorization, as well as 10 years of market exclusivity following a marketing authorization.
As a result, no drug accumulation is expected with once daily tablet dosing. 11 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.
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.
In November 2023, we reported that the American Society for Bone and Mineral Research (ASBMR) announced that the SABRE (Strategy to Advance BMD as a Regulatory Endpoint) 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.
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.
Based on the outcome of our October 2022 Type C meeting with the FDA, 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 a NDA.
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.
Both these peptides have well characterized pre-clinical PK/PD and toxicology. 8 PTH Parathyroid hormone (PTH) is an 84-amino acid hormone that regulates calcium and phosphate homeostasis and bone metabolism in the body. In healthy individuals, PTH is generally produced at very low basal levels, at a blood concentration of 15 - 25 pg/mL.
PTH Parathyroid hormone (PTH) is an 84-amino acid hormone that regulates calcium and phosphate homeostasis and bone metabolism in the body. In healthy individuals, PTH is generally produced at very low basal levels, at a blood concentration of 15 - 25 pg/mL.
As of December 31, 2023, we owed $13,000 to the IIA, which was paid in February 2024. 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.
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.
We view this 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 anabolic agents, are unwilling to take daily or monthly injections.
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.
Such SPCs extend the rights under the basic patent for the drug. 29 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.
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.
No drug-related severe adverse events (SAEs) were reported, and four subjects reported four mild adverse events (AEs) of nausea (N=1), palpitation (N=1), and headache (N=2). These AEs are consistent with those reported with injectable PTH analogs.
No drug-related severe adverse events (SAEs) were reported, and four subjects reported four mild adverse events (AEs) of nausea (N=1), palpitation (N=1), and headache (N=2).
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.
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.
All adverse events were mild or moderate in intensity. 12 Bone Biomarkers (PD Effect) The primary bone biomarker endpoint of the Phase 2 clinical study—change in P1NP at Month 3—was met.
Bone Biomarkers (PD Effect) The primary bone biomarker endpoint of the Phase 2 clinical study—change in P1NP at Month 3—was met.
In general, until the grants are repaid with interest, royalties are payable to the Israeli government in the amount of 3% on revenues derived from sales of products or services developed in whole or in part using the IIA grants, including EB613, EB612 and any other oral PTH product candidates we may develop.
In general, until the grants are repaid with interest, royalties are payable to the Israeli government in the amount of 3% on revenues derived from sales of products or services developed in whole or in part using the IIA grants.
The IOF has estimated that 1.6 million hip fractures occur worldwide each year, and by 2050 this number could reach between 4 to 6 million.
The IOF has estimated that 1.6 million hip fractures occur worldwide each year, and by 2050 this number could reach between 4 to 6 million. The IOF estimates that, in Europe alone, the annual cost of osteoporotic fractures could surpass €76 billion by 2050.
Additionally, we agreed not to engage, directly or indirectly, in any activities in the fields of diabetes and influenza.
Additionally, we agreed not to engage, directly or indirectly, in any activities in the fields of diabetes and influenza that involve the use of, or utilize, the patents underlying the Patent Transfer Agreement.
The IOF estimates that, in Europe alone, the annual cost of osteoporotic fractures could surpass €76 billion by 2050. 9 Current Osteoporosis Treatment Paradigm The goal of pharmacological treatment of osteoporosis is to maintain or increase bone mass and strength and to prevent fractures throughout a patient’s life. It is critical to identify patients who have significant bone loss.
Current Osteoporosis Treatment Paradigm The goal of pharmacological treatment of osteoporosis is to maintain or increase bone mass and strength and to prevent fractures throughout a patient’s life. It is critical to identify patients who have significant bone loss.
Following the completion of a Type C and a Type D meeting with the U.S. Food and Drug Administration’s (FDA), 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.
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.
Additionally, we are also collaborating with a third party to combine our N-Tab™ Technology with another peptide for hypoparathyroidism. 17 Intellectual Property Our success depends in part on our ability to protect the proprietary nature of our product candidates, technology, and know-how; operate without infringing on the proprietary rights of others and preventing others from infringing on our proprietary rights.
Intellectual Property Our success depends in part on our ability to protect the proprietary nature of our product candidates, technology, and know-how; operate without infringing on the proprietary rights of others and preventing others from infringing on our proprietary rights.
Individual EU member states may also impose various sanctions and penalties in case we do not comply with locally applicable requirements.
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.
Planned Additional Clinical Development and Regulatory Pathway We have since developed an improved formulation 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.
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.
The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability. 25 Orphan Drug Designation Orphan drug designation in the United States is designed to encourage sponsors to develop drugs intended for rare diseases or conditions.
Drugs and biologics may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.
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