OPKO Health, Inc. (NASDAQ: OPK) and Entera Bio Ltd. (NASDAQ: ENTX) announced on March 17, 2025, a strategic collaboration and license agreement to develop the first oral dual agonist GLP-1/glucagon peptide as a once-daily tablet for patients with obesity, metabolic and fibrotic disorders.
The program combines OPKO's proprietary long-acting oxyntomodulin analog (OPK-88006) with Entera's N-Tab™ technology, which enables oral delivery of peptides. The companies reported favorable pharmacodynamic, pharmacokinetic, and bioavailability data in vivo in September 2024 and expect to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) later this year.
Partnership Structure and Financial Terms
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 corresponding percentages of the development costs. To support the collaboration, OPKO purchased 3,685,226 ordinary shares of Entera for $2.17 per share, representing an investment of approximately $8 million.
Entera will use these proceeds to fund its 40% share of costs through Phase 1 of the development program. Following the completion of Phase 1, Entera has the option to continue funding its 40% share to maintain its ownership interest or opt-out, in which case it would retain a 15% ownership interest while OPKO would increase to 85% and assume responsibility for ongoing development activities and funding.
Scientific Rationale and Market Potential
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 offers additional cardioprotective and anti-fibrotic benefits. OPK-88006, OPKO's GLP-1/glucagon dual agonist peptide, has been modified to maintain a long-acting profile while increasing its potential potency.
Currently, there are no approved dual GLP-1/glucagon agonists available on the market, positioning this collaboration to potentially address a significant unmet need in the rapidly growing obesity treatment landscape.
"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.
Miranda Toledano, Entera Chief Executive Officer, added, "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."
Oral Delivery Advantage
The development of an oral GLP-1/glucagon dual agonist represents a significant potential advancement in the treatment of obesity and related conditions. Current GLP-1 receptor agonists like semaglutide (Wegovy) and tirzepatide (Zepbound) are administered via injection, which can present barriers to patient acceptance and adherence.
An oral tablet formulation could offer improved convenience and potentially increase treatment adoption among patients with obesity, which affects approximately 42% of adults in the United States according to CDC data.
Broader Pipeline Context
This collaboration builds on both companies' expertise in their respective fields. Entera Bio is developing several oral peptide therapies, including EB613, an oral PTH(1-34) tablet for postmenopausal women with osteoporosis that is preparing to enter Phase 3 trials. The company is also developing EB612 for hypoparathyroidism and an oral GLP-2 peptide tablet for rare malabsorption conditions in collaboration with OPKO.
OPKO Health, a multinational biopharmaceutical and diagnostics company, continues to expand its portfolio in metabolic disorders and other therapeutic areas through internal development and strategic partnerships.
Development Timeline
With favorable preclinical data already reported, the companies are preparing to advance the oral GLP-1/glucagon dual agonist into clinical development. The anticipated IND filing later this year would mark a significant milestone in bringing this potential first-in-class therapy closer to patients.
The obesity treatment market has seen substantial growth in recent years, with GLP-1 receptor agonists becoming blockbuster therapies. The addition of a dual-mechanism oral option could further expand treatment options for the millions of patients struggling with obesity and related metabolic conditions worldwide.
