Entera Bio Ltd. (NASDAQ:ENTX): Oral Peptide Delivery Pioneer Advancing Promising Pipeline

Published on September 24, 2024 | Ticker: ENTX

Entera Bio Ltd. (NASDAQ:ENTX) is a clinical-stage biopharmaceutical company focused on developing first-in-class oral tablet formats of peptides or protein replacement therapies. The company's proprietary N-Tab™ oral delivery technology aims to overcome the challenges of oral administration of therapeutic proteins by simultaneously stabilizing the peptide in the gastrointestinal tract and promoting its absorption into the bloodstream.

Business Overview

Entera's most advanced product candidate, EB613, is an oral formulation of parathyroid hormone (PTH) (1-34) 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 with no prior fracture. The company's EB612 program is being developed as the first oral PTH(1-34) tablet peptide replacement therapy for hypoparathyroidism.

In addition to its oral PTH programs, Entera is collaborating with OPKO Biologics to develop oral formulations of OPKO's proprietary long-acting GLP-2 peptide and Oxyntomodulin (OXM) analogs using Entera's N-Tab™ technology. The GLP-2 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. The OXM program aims to create the first oral tablet version of this naturally occurring peptide hormone with dual GLP-1 and glucagon agonist activity for the potential treatment of obesity.

Financials

Entera has not generated any revenue from product sales to date. For the full year 2023, the company reported an annual net loss of $8.9 million, annual revenue of $0, annual operating cash flow of -$7.3 million, and annual free cash flow of -$7.3 million.

For the first quarter of 2024, Entera reported a net loss of $2.0 million, with research and development expenses of $0.7 million and general and administrative expenses of $1.3 million. The company had $9.2 million in cash and cash equivalents as of March 31, 2024.

Entera's Pipeline and Development Progress

EB613 for Osteoporosis

Entera's lead product candidate, EB613, is an oral formulation of PTH (1-34) being developed as a potential treatment for osteoporosis. In a Phase 2 study, EB613 met its primary and secondary endpoints, demonstrating improvements in bone turnover biomarkers and bone mineral density.

Following discussions with the FDA, Entera announced that the agency concurred that a 2-year, placebo-controlled Phase 3 study with Total Hip BMD as the primary endpoint could support a New Drug Application (NDA) for EB613. This potential pathway is further bolstered by the recent announcement from the American Society for Bone and Mineral Research (ASBMR) 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. Entera believes EB613 stands as the first program to potentially avail itself of this ASBMR-SABRE BMD endpoint qualification.

EB612 for Hypoparathyroidism

Entera's EB612 program is being developed as the first oral PTH(1-34) tablet peptide replacement therapy for hypoparathyroidism. The company is currently testing new generations of its 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.

Oral GLP-2 and Oral GLP-1/Glucagon Programs

In May 2023, Entera published positive results from its oral GLP-2 program in the International Journal of Peptide Research and Therapeutics. The company believes GLP-2 represents a strong candidate for its N-Tab™ technology and warrants further development as an injection-free alternative for patients suffering from short bowel syndrome and other gastrointestinal disorders.

In September 2023, Entera entered into a research collaboration agreement with OPKO Biologics to develop oral tablet formulations of OPKO's proprietary long-acting GLP-2 peptide and Oxyntomodulin (OXM) analogs using Entera's N-Tab™ technology. In March 2024, the companies announced positive in vivo pharmacokinetic (PK) results from their collaborative research on the oral GLP-2 program.

Intellectual Property and Collaborations

Entera's proprietary N-Tab™ oral delivery technology is protected by a portfolio of patents and patent applications. In 2011, the company entered into a patent transfer agreement with Oramed, under which Entera acquired all of Oramed's rights, title, and interest in the patent rights licensed to Entera at its inception, subject to a worldwide, royalty-free, exclusive, irrevocable, perpetual, and sub-licensable license granted to Oramed.

Entera has also received grants totaling approximately $0.5 million from the Israeli Innovation Authority (IIA) to partially fund its research and development activities. The grants are subject to certain requirements and restrictions, including the payment of royalties to the IIA on any revenues derived from the sale of products or services developed using the grant funds.

Risks and Challenges

Entera's business is subject to various risks and uncertainties, including the lengthy and expensive clinical development process, the unpredictable regulatory approval pathway, the need for additional funding to advance its pipeline, and the competitive landscape in the treatment of osteoporosis, hypoparathyroidism, and other target indications.

The ongoing conflict between Israel and Hamas, as well as the potential for escalation of tensions with Iran and its proxies in the Middle East, could also impact the company's operations and workforce, including its research and development and clinical trials, although the company has not experienced any material disruptions to date.

Outlook

Entera's proprietary N-Tab™ oral delivery technology has the potential to significantly shift treatment paradigms for chronic conditions that currently rely on injectable protein therapies. The company's advanced pipeline, including the EB613 osteoporosis and EB612 hypoparathyroidism programs, as well as its collaborative efforts in oral GLP-2 and OXM formulations, position Entera as a pioneer in the field of oral peptide delivery.

Conclusion

With a strong intellectual property portfolio, strategic collaborations, and a seasoned management team, Entera is well-positioned to continue advancing its pipeline and exploring the full potential of its innovative technology. As the company navigates the clinical and regulatory landscape, investors will closely follow its progress in potentially bringing the first oral PTH and other peptide therapies to market, which could have a transformative impact on patient care and quality of life.

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