Entera Bio Ltd. reported preclinical data at ENDO 2026 for its EB612 and EB618 pipeline programs, which are being co-developed with OPKO Health Inc. The data highlighted robust bioavailability and sustained pharmacological effects for both candidates, supporting their continued clinical development. EB612, a first-in-class long-acting PTH(1-34) oral peptide for hypoparathyroidism, produced sustained increases in serum calcium across three preclinical models. EB618, a first-in-class dual GLP-1/glucagon oral receptor agonist for obesity, demonstrated dose-proportional pharmacokinetics and a robust effect on blood glucose in non-human primates.

EB612 Preclinical Results

EB612 is formulated with Entera's N-Tab® oral peptide platform and aims to provide an oral alternative to injectable therapies. In a thyroparathyroidectomized rat model, daily dosing for 7 days restored serum calcium and reduced phosphate to levels comparable to sham control animals. In a minipig model, a single oral dose reached maximal plasma levels 2 to 3 hours post-dose, with drug detectable for more than three days, accompanied by a rapid and long-lasting increase in serum Ca. In a non-human primate model, a single oral dose produced a robust and sustained increase in serum calcium for approximately three days, with correlating suppression of endogenous PTH levels. EB612 was well tolerated with no safety concerns identified.

EB618 Preclinical Results

EB618 is a proprietary long-acting oxyntomodulin analog formulated with the N-Tab® platform. In a pharmacokinetic-pharmacodynamic study in non-human primates, EB618 exhibited robust bioavailability with dose-proportional systemic exposure across three tested tablet strengths and low variability. A dose-proportional pharmacologic effect on postprandial blood glucose levels was observed. EB618 was well tolerated at doses exceeding the anticipated clinical dose range by more than tenfold, with no safety concerns identified.

Development Timeline

Entera and OPKO expanded their collaboration in February 2026 to advance EB612 on a 50/50 basis, with an intention to file an investigational new drug application in late 2026. The data support the continued clinical development of EB618 as a potential first-in-class oral once-daily GLP-1/glucagon receptor agonist for obesity and metabolic disorders.

Entera Bio Ltd. presented comparative Phase 1 data at ENDO 2026 demonstrating that its single tablet EB613 achieved pharmacokinetic (PK) and pharmacodynamic (PD) profiles comparable to both multi-tablet EB613 and the standard injectable Forteo® (teriparatide SC injection, Eli Lilly). The findings support advancing the single tablet regimen as the final candidate for a planned Phase 3 study in postmenopausal women with osteoporosis, potentially simplifying treatment protocols for patients who currently rely on daily or monthly injections.

The oral presentation, titled "Transforming Anabolic Treatments for Osteoporosis: New Clinical Data Supports a Single EB613 Tablet [Oral PTH(1-34)] as the Final Candidate for a Phase 3 Study," was delivered by Clinical Pharmacologist Helen S. Pentikis, PhD. It was featured as a Late-Breaking Oral Presentation at ENDO 2026, the annual meeting of the Endocrine Society, held in Chicago, Illinois.

Key Clinical Findings

The Phase 1 study (NCT05965167) evaluated 15 healthy participants who received single-tablet EB613, multi-tablet oral EB613, and subcutaneous Forteo® at doses ranging from 1 mg to 3 mg. The data indicated that single tablet EB613 showed a PK profile comparable to multi-tablet EB613, with similar Cmax, Tmax, and total systemic exposure (AUC). The AUC of both oral formulations was comparable with Forteo®, exhibiting a slightly shorter duration of exposure consistent with prior Phase 1 studies.

Comparable calcemic effects (serum calcium) and consistent suppression of endogenous PTH(1-84) were observed for both oral EB613 treatments and Forteo®. The safety profile of EB613 was consistent with Forteo®, with no drug-related serious adverse events; all other adverse events were mild and resolved with no action taken.

Patient Preference and Strategic Impact

Based on an administration experience quality-of-life questionnaire, 14 of 15 participants preferred the single tablet to multi-tablet EB613, and all participants preferred a daily oral EB613 over the daily injection. Miranda Toledano, Chief Executive Officer of Entera, stated that simplifying the dosing regimen to a single daily tablet could make anabolic treatment far more acceptable to patients and healthcare providers, potentially reducing the treatment gap in osteoporosis.

Entera Bio focuses on the development of oral peptides, and the EB613 program represents a core component of its pipeline. The company is developing EB613 as the first oral, once-daily anabolic tablet treatment for osteoporosis, aiming to provide an alternative to injectable therapies like Forteo®, Tymlos®, and Evenity®.