OPKO Health and Entera Bio Enter into Collaboration Agreement to Advance Oral GLP-1/Glucagon Tablet Candidate into the Clinic to Treat Obesity and Metabolic Disorders

Rhea-AI Summary

OPKO Health (NASDAQ: OPK) and Entera Bio have formed a collaboration agreement to develop the first oral dual agonist GLP-1/glucagon peptide tablet for treating obesity and metabolic disorders. The program combines OPKO's long-acting oxyntomodulin analog (OPK-88006) with Entera's N-Tab™ technology.

The partnership structure gives OPKO a 60% ownership stake and Entera 40%, with corresponding cost-sharing responsibilities. OPKO has purchased 3,685,226 Entera shares at $2.17 per share, with proceeds funding Entera's Phase 1 development costs. After Phase 1, Entera can maintain its 40% stake by continuing funding, or opt-out to retain 15% ownership while OPKO increases to 85%.

The companies reported favorable pharmacodynamic, pharmacokinetic, and bioavailability data in September 2024 and plan to file an FDA Investigational New Drug application later in 2025. The treatment aims to suppress appetite, induce weight loss, and provide cardioprotective and anti-fibrotic benefits through its novel dual-action mechanism.

Positive

• First-in-class oral GLP-1/glucagon dual agonist tablet development
• Favorable preliminary data reported in September 2024
• Strategic partnership reducing development costs through 60/40 split
• Advancing toward IND filing in 2025

Negative

• Significant ongoing development costs and funding requirements
• No approved dual GLP-1/glucagon agonists in market yet - regulatory uncertainty
• Risk of Entera reducing stake to 15% if unable to fund development costs

Insights

Pharmaceutical Analyst

This collaboration between OPKO Health and Entera Bio marks a significant development in the highly competitive obesity treatment market. The companies are joining forces to develop what could be the first oral dual agonist GLP-1/glucagon peptide tablet, combining OPKO's oxyntomodulin analog with Entera's proprietary N-Tab™ delivery technology.

Several aspects make this partnership noteworthy. First, the oral delivery format would address a key limitation of current GLP-1 therapies which require injection. Second, the dual agonist mechanism targeting both GLP-1 and glucagon pathways could potentially offer superior efficacy compared to single-target GLP-1s like semaglutide. Oxyntomodulin's natural ability to suppress appetite while offering cardioprotective and anti-fibrotic benefits suggests a potentially differentiated therapeutic profile.

The deal structure reveals strategic thinking by both companies. OPKO's $8 million investment in Entera (3.68M shares at $2.17) effectively finances Entera's Phase 1 obligations while securing OPKO the controlling interest (60%). The flexible structure allowing Entera to reduce its stake post-Phase 1 mitigates risk for the smaller partner while maintaining significant upside potential.

With an IND filing expected later this year and preliminary data already reported, the program appears to be progressing steadily, though clinical success remains to be demonstrated. The companies are entering a market with enormous potential, but also intense competition from established players developing their own oral GLP-1 formulations.

Financial Analyst

This collaboration agreement presents a strategic alignment of complementary technologies in the explosively growing GLP-1 obesity treatment sector. OPKO contributes its peptide expertise and long-acting oxyntomodulin analog, while Entera provides the critical oral delivery technology that could overcome the injection barrier of current market leaders.

The financial structure reveals thoughtful risk allocation. OPKO's $8 million investment in Entera (purchasing shares at $2.17) effectively provides Entera with capital to fund its development obligations through Phase 1 while giving OPKO majority control (60%) of the program. For context, this investment represents a significant portion of Entera's $1.19B market cap, underscoring OPKO's commitment.

The tiered ownership structure with Entera's option to maintain 40% or drop to 15% post-Phase 1 creates valuable flexibility. This approach allows the smaller partner to reassess its commitment based on early clinical results while preserving meaningful economics regardless of their choice. The arrangement minimizes near-term dilution for Entera shareholders while providing sufficient program funding.

Market opportunity for oral GLP-1 therapies is substantial, with the obesity treatment market projected to reach tens of billions annually. An effective oral dual-agonist could capture significant market share from injectable products due to patient preference, though regulatory success and differentiated efficacy will be critical determinants of commercial value.

With an IND filing expected later this year, investors should recognize that meaningful revenue remains years away, but this collaboration accelerates both companies' positions in a high-value therapeutic category.

MIAMI and JERUSALEM, March 17, 2025 (GLOBE NEWSWIRE) -- OPKO Health, Inc. (NASDAQ: OPK) and Entera Bio Ltd. (NASDAQ: ENTX), a leader in the development of oral peptides and proteins replacement therapies, entered into a collaboration and license agreement to advance into the clinic the first oral dual agonist GLP-1/glucagon peptide as a once-daily tablet treatment for patients with obesity, metabolic and fibrotic disorders. The program combines OPKO’s proprietary long-acting oxyntomodulin analog (OPK-88006) and Entera’s proprietary N-Tab™ technology. Favorable pharmacodynamic, pharmacokinetic and bioavailability data in vivo were reported in September 2024. The companies expect to file an Investigational New Drug application with the U.S. Food and Drug Administration (FDA) later this year.

Under the terms of the agreement, OPKO and Entera will 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 connection with the execution of the agreement, OPKO purchased 3,685,226 ordinary shares of Entera for a purchase price equal to $2.17 per share. Entera has agreed to utilize the proceeds from the sale of the shares to fund its 40% share of costs through Phase 1 of the development program. Following the completion of the Phase 1 stage, Entera has the option to continue to fund its 40% share to maintain its pro-rata ownership interest of the program. Should Entera opt-out, Entera 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.

“We are pleased to continue working with Entera on this promising program to develop the first oral GLP-1/glucagon dual agonist in addition to our subcutaneous injectable dual agonist GLP-1/glucagon program. Our goal with this franchise is to provide additional options for patients with obesity, metabolic and fibrotic diseases,” said Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO.

“We have enjoyed our synergistic partnership with OPKO. This expanded collaboration on the GLP-1/glucagon program reinforces our shared vision to develop first in class differentiated oral peptide treatments for patients to better manage their health,” said Miranda Toledano, Entera Chief Executive Officer.

Oxyntomodulin is a naturally occurring GLP-1/glucagon dual agonist peptide hormone found in the small intestine that acts to suppress appetite, induce weight loss and has additional cardioprotective and anti-fibrotic attributes. OPK-88006 is a GLP-1/glucagon dual agonist peptide that has been modified to maintain its long-acting profile while increasing its potential potency. Currently, there are no approved dual GLP-1/glucagon agonists available.

About Entera Bio

Entera is a clinical stage company focused on developing oral peptide and protein replacement therapies for significant unmet medical needs where an oral tablet form holds the potential to transform the standard of care. The Company leverages on a disruptive and proprietary technology platform (N-Tab™) and its pipeline includes five differentiated, first-in-class oral peptide programs targeting PTH(1-34), GLP-1 and GLP-2. The Company’s 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 BMD and high-risk osteoporosis. A placebo controlled, dose-ranging Phase 2 study of EB613 tablets (n=161) met primary (PD/bone turnover biomarker) and secondary endpoints (BMD). Entera is preparing to initiate a Phase 3 registrational study for EB613 pursuant to the FDA’s qualification of a quantitative BMD endpoint. The EB612 program is being developed as the first oral PTH(1-34) tablet peptide replacement therapy for hypoparathyroidism. Entera is also developing the first oral oxyntomodulin, a dual targeted GLP-1/glucagon peptide, in tablet form for the treatment of obesity; and 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 Health. For more information on Entera Bio, visit www.enterabio.com or follow us on LinkedIn, Twitter, Facebook, Instagram.

About OPKO Health

OPKO Health is a multinational biopharmaceutical and diagnostics company that seeks to establish industry-leading positions in large, rapidly growing markets by leveraging its discovery, development and commercialization expertise, and its novel and proprietary technologies. For more information, visit www.opko.com.

Cautionary Statement Regarding Forward Looking Statements
Various statements in this press release are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements (other than statements of historical facts) in this press release, including those regarding our prospects, plans, financial position, business strategy and expected financial and operational results, may constitute forward-looking statements. Words such as, but not limited to, “anticipate,” “believe,” “can,” “could,” “expect,” “estimate,” “design,” “goal,” “intend,” “may,” “might,” “objective,” “plan,” “predict,” “project,” “target,” “likely,” “should,” “will” and “would,” or the negative of these terms and similar expressions or words, identify forward-looking statements. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Forward-looking statements should not be read as a guarantee of future performance or results and may not be accurate indications of when such performance or results will be achieved.

Important factors that could cause actual results to differ materially from those reflected in Entera’s and OPKO’s forward-looking statements include, among others: changes in the interpretation of clinical data; results of our clinical trials; the FDA’s interpretation and review of our results from and analysis of our clinical trials; unexpected changes in our ongoing and planned preclinical development and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates; the potential disruption and delay of manufacturing supply chains; loss of available workforce resources, whether by Entera, OPKO or their respective collaboration and laboratory partners; impacts to research and development or clinical activities that Entera or OPKO may be contractually obligated to provide; overall regulatory timelines; the size and growth of the potential markets for our product candidates; the scope, progress and costs of developing our product candidates; the parties’ reliance on third parties to conduct clinical trials; Entera’s and OPKO’s expectations regarding licensing, business transactions, including OPKO’s development efforts should Entera opt-out, and strategic collaborations; Entera’s operation as a development stage company with limited operating history; Entera’s ability to continue as a going concern absent access to sources of liquidity; Entera’s ability to comply with Nasdaq’s minimum listing standards and other matters related to compliance with the requirements of being a public company in the United States; Entera’s and OPKO’s intellectual property positions and their ability to protect their respective intellectual property; and other factors that are described in the “Cautionary Statements Regarding Forward-Looking Statements,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of each of Entera’s and OPKO’s most recent Annual Reports on Form 10-K filed with the SEC, as well as the companies’ respective subsequently filed Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. There can be no assurance that the actual results or developments anticipated by Entera and OPKO will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Entera or OPKO, as applicable. Therefore, no assurance can be given that the outcomes stated or implied in such forward-looking statements and estimates will be achieved. Entera and OPKO caution investors not to rely on the forward-looking statements made in this press release. The information in this press release is provided only as of the date of this press release, and neither Entera nor OPKO undertakes any obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law.

Contacts:

Entera Bio
Miranda Toledano
Chief Executive Officer
miranda@enterabio.com

OPKO Health
Alliance Advisors IR
Yvonne Briggs, 310-691-7100
ybriggs@allianceadvisors.com

or

Bruce Voss, 310-691-7100
bvoss@allianceadvisors.com

FAQ

What is the ownership structure of the OPKO-Entera GLP-1/glucagon collaboration?

OPKO holds 60% ownership while Entera holds 40%, with matching development cost responsibilities. After Phase 1, Entera can maintain 40% by continuing funding or reduce to 15% ownership.

How much did OPKO invest in Entera Bio shares for the OPK-88006 development?

OPKO purchased 3,685,226 Entera ordinary shares at $2.17 per share to fund Entera's 40% share of Phase 1 development costs.

When will OPKO and Entera file the IND application for their oral GLP-1/glucagon tablet?

The companies plan to file an Investigational New Drug application with the FDA later in 2025.

What are the therapeutic benefits of OPKO's OPK-88006 dual agonist?

OPK-88006 is designed to suppress appetite, induce weight loss, and provide cardioprotective and anti-fibrotic benefits through its GLP-1/glucagon dual-action mechanism.