Entera Bio Ltd. (NASDAQ: ENTX) has secured positive feedback from the U.S. Food and Drug Administration (FDA) for its Phase 3 registrational protocol for EB613 (oral PTH(1-34), teriparatide), the first oral anabolic tablet in development for the treatment of osteoporosis. The agency accepted the company's plan to conduct a single, randomized, double-blind, placebo-controlled trial in approximately 750 postmenopausal women with osteoporosis. This regulatory alignment follows a Clinical Amendment submitted by Entera to its Investigational New Drug (IND) application in March 2026 and positions the company to advance what could become the first oral anabolic treatment for osteoporosis.

The primary endpoint of the study is the percent change from baseline in total hip bone mineral density (BMD) at Month 12. This data is intended to support a potential New Drug Application (NDA) submission for EB613 for the treatment of women with post-menopausal osteoporosis. The proposed NDA package will include a scientific bridge analysis with Forteo (teriparatide SC injection, Eli Lilly) under the 505(b)(2) pathway and a transiliac crest bone biopsy sub-study in a subset of patients. The FDA's decision builds on its December 2025 qualification of total hip BMD as a validated surrogate endpoint for osteoporosis drug development.

Study Design and Timeline

The FDA agreed to Entera's proposal to follow randomized patients for 24 months in an open-label extension study under a separate protocol. Entera plans to submit data through up to 18 months as part of a 120-day safety update to its NDA. The complete 2-year data will be submitted upon completion of the extension study to characterize the durability of the treatment effect, safety, and sequence data for EB613 followed by a standard anti-resorptive therapy.

Clinical Effectiveness and Market Context

The registrational study is powered to demonstrate EB613's clinical effectiveness with projected increases in total hip BMD comparable to reported outcomes for Forteo at 12 months. These changes are associated with a 60% to 80% relative reduction in vertebral fracture risk. Entera previously completed a 6-month Phase 2 study of EB613 in 161 postmenopausal women, which met its primary and secondary endpoints with statistically significant increases in BMD at the lumbar spine, total hip, and femoral neck.

The market opportunity for EB613 is substantial, as osteoporosis affects an estimated 200 million women worldwide and is responsible for more than two million fractures each year in the United States alone. Forteo, the injectable version of teriparatide, achieved peak annual sales of approximately $1.7 billion prior to patent expiration. Entera Bio aims to democratize anabolic treatment by converting this injectable therapy into a simple daily tablet, potentially addressing the low real-world adoption caused by injection requirements.

Pipeline and Platform Potential

While EB613 remains the lead asset, Entera Bio is advancing a broader pipeline of oral peptide programs using its proprietary N-Tab platform. The company is developing EB612, an oral long-acting PTH tablet for hypoparathyroidism, and EB618, an oral GLP-1/glucagon peptide tablet for obesity and metabolic disease, in collaboration with OPKO Health. Recent data presented at ENDO 2026 highlighted the single-tablet version of EB613, showing a pharmacokinetic and pharmacodynamic profile comparable to both injectable Forteo and the multi-tablet version of EB613.

Miranda Toledano, Chief Executive Officer of Entera, stated that the company has a clear and optimized registrational path to get EB613 to women with osteoporosis. She emphasized the goal of democratizing anabolic treatment to enable millions of women and men to protect their bones and potentially prevent fractures.

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.