OPKO Health and Entera Bio have expanded their existing collaboration to advance the development of a first-in-class oral long-acting parathyroid hormone (LA-PTH) tablet for the treatment of hypoparathyroidism, marking a potential shift away from injectable hormone replacement therapies for the rare endocrine disorder.
The expanded program combines OPKO’s proprietary long-acting PTH variants with Entera Bio’s N-Tab oral peptide delivery platform. Following favorable pharmacokinetic and pharmacodynamic data reported in December 2025, the companies have accelerated development and plan to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration in late 2026. The oral LA-PTH tablet is being developed as a once-daily therapy.
Under the revised agreement, OPKO and Entera will hold equal 50 percent ownership of the LA-PTH hypoparathyroidism program and will share development costs equally. The companies will continue with their previously established 60/40 ownership and cost-sharing structure for the oral oxyntomodulin (OXM) program targeting metabolic and fibrotic disorders.
The collaboration now includes three active development programs that combine Entera’s oral peptide technology with OPKO’s protein engineering capabilities. In parallel, the partners are advancing injectable and oral formulations of oxyntomodulin, a dual GLP-1/glucagon agonist. Initial Phase 1 data from the injectable formulation are expected in late 2026, with the oral tablet formulation planned to enter clinical development thereafter.
As part of the expanded partnership, OPKO executive vice president Steve Rubin has joined Entera Bio’s board of directors, succeeding Gerry Ostrov. Rubin brings more than three decades of experience in corporate governance and strategic oversight across publicly listed biotechnology companies.
Hypoparathyroidism is a rare and chronic endocrine disorder characterized by low calcium and elevated phosphorus levels due to insufficient parathyroid hormone production. Current treatment options rely primarily on daily injectable PTH replacement therapies, while some investigational approaches require weekly injections. The oral LA-PTH program aims to address the treatment burden by offering a once-daily tablet at a significantly lower dose than earlier oral PTH approaches.
Entera previously demonstrated clinical proof of concept for oral PTH therapy in a Phase 2 study using an unmodified PTH(1-34) analog, which showed reduced dependence on calcium supplements and stable serum calcium levels, but required multiple daily doses. Preclinical data from the new long-acting PTH variant support the feasibility of a simplified once-daily oral regimen.
In addition to the hypoparathyroidism program, OPKO and Entera are progressing development of oral and injectable oxyntomodulin for obesity, metabolic disorders, and fibrotic diseases. The peptide hormone acts as a dual GLP-1 and glucagon receptor agonist, with effects on appetite suppression, weight loss, and potential cardioprotective and anti-fibrotic benefits. There are currently no approved dual GLP-1/glucagon agonist therapies on the market.
