A Pill to End the Needle: OPKO & Entera Target New Oral PTH Therapy

MIAMI and TEL AVIV – February 04, 2026 – In a move that could transform the lives of thousands of patients reliant on daily injections, OPKO Health and Entera Bio announced today an expanded partnership to accelerate the development of a first-in-class, once-daily oral tablet for hypoparathyroidism. The companies are fast-tracking the program, aiming to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) by late 2026.

This collaboration deepens the alliance between OPKO's advanced protein chemistry and Entera's proprietary oral peptide delivery platform, N-Tab®. The new agreement signals strong confidence in their combined approach, which has already yielded promising results in preclinical studies and two other joint programs. For patients and physicians grappling with the challenges of a rare endocrine disorder, this development represents a significant step toward a more convenient and potentially more stable treatment paradigm.

Addressing a Major Unmet Need

Hypoparathyroidism is a rare and debilitating condition where the body produces insufficient parathyroid hormone (PTH), leading to dangerously low calcium and high phosphorus levels in the blood. The global market for its treatment was valued at approximately $1.3 billion in 2023 and is projected to surpass $2.8 billion by 2032, driven by a growing patient population and a demand for better therapies.

Globally, an estimated 6 to 37 out of every 100,000 people suffer from the chronic disorder, with the majority of cases arising after thyroid or neck surgery. The current standard of care involves a complex regimen of calcium and active vitamin D supplements, which often fails to mimic the body's natural hormone function and can lead to significant fluctuations in calcium levels, kidney damage, and a diminished quality of life.

For patients requiring hormone replacement, the options have been limited and burdensome. The only approved long-acting PTH replacement therapy available in Europe requires daily injections. In the U.S., a previous injectable, Natpara, was recalled and is being discontinued, leaving a significant treatment gap. This reliance on injections creates a daily burden for patients, impacting everything from lifestyle flexibility to treatment adherence. The prospect of a once-daily oral tablet could fundamentally change this landscape, offering a non-invasive, simpler, and more discreet way to manage the chronic condition.

"Our goal is to provide patients with hypoparathyroidism a more convenient treatment option that eliminates the burden of daily injections while maintaining therapeutic efficacy," stated Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO Health.

The Science Behind the Synergy

The long-standing challenge in pharmaceutical science has been the oral delivery of large-molecule drugs like peptides and proteins, which are typically destroyed by the digestive system before they can be absorbed into the bloodstream. The OPKO-Entera partnership tackles this problem by combining two proprietary technologies.

Entera Bio brings its N-Tab® platform, an innovative technology designed to protect peptides from enzymatic degradation in the gut and enhance their absorption into circulation. The company has already demonstrated clinical proof-of-concept with an earlier oral PTH formulation in a Phase 2 study.

OPKO Health contributes its expertise in protein engineering with a proprietary long-acting PTH (LA-PTH) variant. This modified hormone is designed to have a much longer half-life in the body. The synergy is clear: Entera's technology gets OPKO's engineered hormone into the body, and OPKO's hormone is designed to work effectively over a 24-hour period.

The decision to accelerate the program was fueled by highly favorable preclinical data from December 2025. In a key study involving minipigs, a single oral dose of the LA-PTH formulation maintained elevated calcium levels for over three days, providing strong evidence for its potential as a once-daily therapy at a significantly lower dose than previously tested oral PTH analogs.

A Deepening Strategic Alliance

The expanded collaboration is not just a scientific venture but a significant strategic alignment. Under the new terms, OPKO and Entera will share ownership and development costs for the LA-PTH program on a 50/50 basis. This balanced structure reflects a deep commitment from both sides and a shared belief in the program's potential for success. It contrasts with their existing arrangement for another drug candidate, oral oxyntomodulin, which operates on a 60/40 (OPKO/Entera) split.

Further cementing the alliance, Steve Rubin, a seasoned executive from OPKO, has been appointed to Entera Bio's board of directors. Rubin, who serves as Executive Vice President of Administration at OPKO and sits on the boards of several other public biotech companies, brings over three decades of experience in corporate governance and strategic oversight of drug development. His appointment is seen as a move to harmonize the strategic vision of both companies and provide high-level guidance as their joint programs advance toward commercialization.

"The partnership that our team has forged with OPKO since late 2023 has been very synergistic," said Miranda Toledano, Chief Executive Officer of Entera. "I would also like to... extend a warm welcome to Steve Rubin to our board of directors."

A Platform for Broader Innovation

The success with LA-PTH is the third program to validate the powerful combination of Entera's N-Tab® platform and OPKO's protein chemistry. The partnership is also making significant strides on another high-potential candidate: an oral oxyntomodulin (OXM) for obesity and other metabolic and fibrotic disorders. Oxyntomodulin is a dual GLP-1/glucagon agonist, a class of drugs that has shown immense promise for weight loss and metabolic health.

Currently, there are no approved dual GLP-1/glucagon agonists on the market, oral or injectable. The collaboration has already completed key preclinical validation for both an injectable and an oral tablet formulation of OXM. OPKO is now planning to initiate a Phase 1 clinical trial of the injectable version, with initial data anticipated by the end of 2026. Following that, the partners intend to file an IND for the oral tablet, which could position them as a leader in the next generation of metabolic therapies.

This multi-program success demonstrates that the collaboration is more than a single-shot effort; it's a functioning platform for innovation. By successfully formulating multiple complex peptides for oral delivery, OPKO and Entera are not only advancing specific treatments but are also building a blueprint for how to convert a wide range of injectable-only medicines into patient-friendly oral tablets.