OPKO Health And Entera Bio Expand Collaboration To Develop First Once-Daily Oral LA-PTH Tablet For Hypoparathyroidism, Targeting FDA IND Filing In Late 2026

OPKO Health, Inc., through its wholly owned subsidiary OPKO Biologics, and Entera Bio Ltd., a company specializing in oral peptide and protein replacement therapies, announced the expansion of their 2025 Collaboration and License Agreement to advance the development of the first oral long-acting PTH analog (LA-PTH) as a once-daily tablet for patients with hypoparathyroidism.

The expanded program combines OPKO’s proprietary long-acting PTH variants with Entera’s oral delivery platform, N-Tab®. Following encouraging pharmacodynamic and pharmacokinetic data reported in December 2025, the two companies have decided to accelerate development and plan to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) in late 2026.

Under the revised collaboration terms, OPKO and Entera will each hold a 50% ownership interest in the LA-PTH hypoparathyroidism program and share development costs equally. The previously established 60%/40% ownership and cost-sharing structure between OPKO and Entera for the oral oxyntomodulin (OXM) program for metabolic and fibrotic disorders remains unchanged.

In addition, OPKO announced that Steve Rubin, Executive Vice President of Administration and director at OPKO, has joined the board of directors of Entera, replacing Gerry Ostrov. Mr. Rubin brings three decades of experience in corporate governance and strategic oversight of drug development across multiple public biotechnology companies.

Miranda Toledano, Chief Executive Officer of Entera, stated, “Our partnership with OPKO since late 2023 has been highly synergistic. Oral OXM and oral GLP-2 have both shown strong pharmacokinetic profiles and bioavailability. The preclinical data for oral LA-PTH suggest that this program has the potential to significantly transform treatment for patients with hypoparathyroidism. I would also like to thank Gerry Ostrov for his service to Entera and warmly welcome Steve Rubin to our board of directors.”

Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO Health, added, “We are pleased to expand our successful collaboration with Entera to advance this promising long-acting PTH program. This program leverages OPKO’s expertise in long-acting peptides and Entera’s innovative oral peptide technology. Our aim is to provide patients with hypoparathyroidism a convenient, once-daily treatment that eliminates the need for frequent injections while maintaining therapeutic effectiveness.”

Hypoparathyroidism is a rare endocrine disorder that results in low calcium and high phosphorus levels in the blood, requiring ongoing PTH replacement therapy. Currently, the only approved PTH therapy, YORVIPATH® by Ascendis Pharma, requires daily injections, and investigational alternatives may require weekly injections.

Entera previously demonstrated proof-of-concept clinical data for its EB612 program using an unmodified oral PTH(1-34) analog in a 16-week Phase 2 study, which showed a significant reduction in calcium supplement use and stable serum calcium levels above the lower limit for hypoparathyroidism. However, this regimen required four daily doses with total daily doses up to 9 mg. Preclinical data from OPKO’s long-acting PTH variant indicate that a single, once-daily oral tablet could achieve effective PTH replacement at a much lower daily dose.

As part of the collaboration, OPKO and Entera are also developing the first oral dual agonist GLP-1/glucagon peptide for patients with obesity, metabolic disorders, and fibrotic disorders. Since March 2025, the companies have completed in vivo pharmacokinetic and pharmacodynamic validation for both subcutaneous injection and oral tablet formulations of oxyntomodulin.

OPKO plans to initiate Phase 1 single ascending dose and multiple ascending dose studies with the subcutaneous formulation, with data expected by the end of 2026, followed by IND filing for the oral OXM tablet formulation. Oxyntomodulin is a naturally occurring dual agonist peptide that suppresses appetite, induces weight loss, and provides additional cardioprotective and anti-fibrotic effects. Currently, there are no approved dual GLP-1/glucagon agonist therapies.