10-K: Entera Bio Ltd. Files 10-K Report, Outlines Progress in Oral Peptide Therapies

Entera Bio Ltd. released its annual 10-K filing, detailing advancements in its oral peptide programs for osteoporosis and hypoparathyroidism, and a new collaboration with OPKO Biologics.

Summary

• Entera Bio Ltd., a clinical-stage company, is focused on developing oral tablet forms of peptide and protein replacement therapies.
• The company's lead candidate, EB613, is an oral PTH (1-34) tablet for post-menopausal women with osteoporosis, and is preparing for a Phase 3 trial.
• EB612 is being developed as an oral PTH (1-34) tablet for hypoparathyroidism, with ongoing testing of new formulations.
• Entera has a research collaboration with OPKO Biologics to develop oral GLP-2 and Oxyntomodulin tablets.
• The company reported a net loss of $8.9 million in 2023 and has an accumulated deficit of $104.4 million.
• As of March 1, 2024, Entera had approximately $9.8 million in cash and cash equivalents, which is expected to fund operations through the second quarter of 2025.
• The company's independent auditor has raised substantial doubt about its ability to continue as a going concern.
• Entera is seeking additional funding to support its Phase 3 trial for EB613 and other development programs.

Sentiment

Score: 4

Explanation: The document presents a mixed picture. While there is progress in clinical trials and collaborations, the company's financial situation and going concern status raise significant concerns. The sentiment is cautiously optimistic but with a strong dose of realism about the challenges ahead.

Positives

• The FDA has agreed that a single Phase 3 placebo-controlled study with a BMD endpoint could support an NDA submission of EB613.
• The company's N-Tab technology has shown promise in delivering peptides orally.
• The company has a diverse pipeline of oral peptide programs.
• The company has a collaboration with OPKO Biologics to develop oral GLP-2 and Oxyntomodulin tablets.
• The company has received orphan drug designation for EB612 for the treatment of hypoparathyroidism from both the FDA and EMA.

Negatives

• The company has incurred significant losses since its inception and anticipates that it will continue to incur substantial losses for the next several years.
• The company's independent registered public accounting firm has raised substantial doubt as to its ability to continue as a going concern.
• The company has a limited operating history and no history of late stage clinical studies and commercializing pharmaceutical products.
• The company is highly dependent upon its ability to raise additional capital or enter into agreements with collaborators to develop, commercialize and market its products.
• The company may fail to establish, maintain, defend and enforce intellectual property rights with respect to its technology.

Risks

• Clinical development involves a lengthy and expensive process with uncertain outcomes.
• The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time-consuming and inherently unpredictable.
• Preclinical development is uncertain and may not advance to clinical trials.
• Positive results from preclinical studies and early-stage clinical trials may not be predictive of future results.
• The company's ability to continue as a going concern is dependent on access to sources of liquidity.
• The company's ability to raise additional funds or consummate strategic partnerships may not be available on acceptable terms or at all.
• The company's product candidates may fail to achieve market acceptance by physicians, patients, third-party payors and others in the medical community.
• The company relies on third parties to conduct clinical trials and supply or produce product candidates.
• The company's competitive position with respect to other products on the market or in development may be challenged.
• The duration and intensity of the ongoing Israel-Hamas War and its impact on the company's operations and workforce, including research and development and clinical trials, is a risk.

Future Outlook

The company anticipates that its existing cash and cash equivalents will be sufficient to fund its operations through the second quarter of 2025, but additional funding will be required for the Phase 3 trial of EB613 and other development programs. The company is exploring various financing alternatives.

Management Comments

• Management has performed an analysis of our ability to continue as a going concern and our independent registered public accounting firm has raised substantial doubt as to our ability to continue as a going concern.
• Our expectations are based on managements 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.

Industry Context

The document highlights the competitive landscape in the pharmaceutical industry, particularly in the osteoporosis and hypoparathyroidism markets, where Entera faces competition from established products and companies with greater resources. The company is also competing with other non-invasive medical drug delivery technologies.

Comparison to Industry Standards

• The document mentions that Forteo (teriparatide) achieved peak annual sales of $1.7 billion prior to patent expiration, providing a benchmark for the potential market size of EB613.
• The document notes that increases in proximal femoral BMD (TH and FN) and cortical bone after six months of EB613 daily tablet treatment were greater than those previously reported with Forteo at six months (0.1% and 0.3%), suggesting a potential advantage over the injectable treatment.
• The document mentions that less than 10% of currently treated osteoporosis patients agree to injectable osteoanabolic treatment despite guideline recommendations, highlighting the unmet need for oral alternatives.
• The document notes that Natpara, an injectable form of full length human PTH (1-84), was recalled in 2019 due to a plastic particulate and will be permanently phased out globally by the end of 2024, creating an opportunity for EB612.
• The document mentions that there are two injectable PTH candidates for hypoparathyroidism undergoing late-stage clinical development: TransCon PTH, developed by Ascendis Pharma and Eneboparatide, developed by Amolyt Pharma, which are potential competitors to EB612.

Management Changes

Corporate Governance

Related Party Transactions

• The Chairman of the Board and the Chief Executive Officer participated in the 2023 PIPE on the same terms and subject to the same conditions as all other Investors.

Stakeholder Impact

• Shareholders face the risk of dilution from future equity offerings and potential loss of investment due to the company's financial challenges.
• Employees may be affected by potential restructuring or layoffs if the company fails to secure additional funding.
• Customers and patients may benefit from the development of new oral peptide therapies, but the timeline for commercialization is uncertain.
• Suppliers and creditors may face increased risk due to the company's financial instability.

Next Steps

• The company is preparing to initiate a Phase 3 registrational study for EB613 pursuant to the FDAs qualification of a quantitative BMD endpoint which is expected to occur in 2024.
• The company expects in vivo PK/PD data from both the oral GLP-2 tablet program and the oral OXM tablet program in 2024.
• The company expects to collaborate with an investigator sponsored study in the area of stress fractures in athletes and expects to initiate a phase 2 trial for this indication in the second half of 2024.

Key Dates

Keywords

oral peptide, osteoporosis, hypoparathyroidism, PTH, EB613, EB612, N-Tab technology, GLP-2, Oxyntomodulin, OPKO Biologics, clinical trials, bone mineral density, FDA, biopharmaceutical