Entera Bio (NASDAQ:ENTX) plans to begin a Phase 3 study of its oral osteoporosis candidate EB613 after reaching agreement with the U.S. Food and Drug Administration on a 12-month, placebo-controlled registrational trial, Chief Executive Officer Miranda Toledano said during a discussion hosted by Canaccord Genuity.
The company’s lead candidate is an oral formulation of teriparatide, a 34-amino-acid functional region of parathyroid hormone that is currently used in injectable osteoporosis treatments. Toledano said Entera expects to enroll approximately 750 postmenopausal women with osteoporosis who are at risk of fracture.
Oral Peptide Technology
Toledano said Entera’s N-Tab, or Entera Tablets, platform is designed to enable oral delivery of native peptides, which can be difficult to administer in tablet form because they are susceptible to degradation in the gastrointestinal tract and may not readily enter the bloodstream.
According to Toledano, the platform uses excipients intended to locally deactivate digestive enzymes around the tablet, helping stabilize the peptide. It also uses SNAC, a transcellular permeation enhancer intended to increase epithelial-cell permeability and support systemic absorption.
“Every candidate in the Entera pipeline is a pure peptide,” Toledano said, noting that the company focuses on amino-acid sequences rather than a medicinal-chemistry approach. She said certain other pipeline programs may use acylation to extend a peptide’s half-life, but EB613 is based on unmodified teriparatide.
Teriparatide’s short blood half-life of approximately five to six minutes is suited to producing the short, pulsatile pharmacokinetic profile associated with bone formation, Toledano said.
FDA Pathway and Phase 3 Design
Entera received minutes from its end-of-Phase 2 meeting with the FDA in February 2022. At that time, the company had considered a conventional bioequivalence approach using FORTEO, an injectable teriparatide product, as an active control.
However, Toledano said FDA determined that EB613 was not bioidentical to FORTEO because changes in the route of administration produced differences in pharmacokinetics. While EB613 has a similar time to peak concentration, Toledano said it has a shorter exposure duration and elimination phase, along with a slightly higher peak concentration.
The FDA ultimately qualified total hip BMD as a surrogate efficacy endpoint for fracture in December 2025, according to Toledano. Entera subsequently submitted a clinical amendment in the first quarter of 2026 and announced agreement with the agency on June 22, 2026, to use a 12-month double-blind study rather than a previously discussed 24-month placebo-controlled registrational trial.
“It is the ideal way to get 613 expeditiously now through this program,” Toledano said.
In addition to BMD and safety results, Entera expects to provide the FDA with a scientific bridge analysis against FORTEO, supported by a population pharmacokinetic substudy. The company also plans a small transiliac crest biopsy substudy and will measure bone-turnover markers including P1NP and CTX.
Phase 2 Results and Market Positioning
Toledano said Entera’s six-month, dose-escalating, placebo-controlled Phase 2 study showed total hip BMD increases of between 1.34% and 1.57% at the 2.5-milligram dose, including titrated and non-titrated treatment approaches.
For comparison, she said FORTEO produced total hip BMD increases of approximately 1.7% to 2% at 12 months in prior studies. Entera has designed its Phase 3 program around achieving a result in that range, she said.
Toledano characterized osteoporosis as a widely diagnosed but undertreated chronic disease. She estimated that 10 million to 12 million people in the U.S. have been diagnosed with osteoporosis, while approximately 54 million Americans have low bone mass. She said the condition disproportionately affects postmenopausal women.
- Entera estimates that fewer than 40% of diagnosed U.S. osteoporosis patients receive or are willing to take available treatments.
- Toledano said antiresorptive drugs account for an estimated 80% of prescriptions, including oral bisphosphonates and denosumab products.
- She estimated that injectable anabolic treatments, including FORTEO, Tymlos and EVENITY, are used by less than 10% to 15% of patients.
Entera believes EB613 could address what Toledano described as a gap between widely used antiresorptive therapies and less commonly used injectable anabolic medicines. She said the company aims to offer an anabolic, bone-forming treatment in a tablet format that could be used more broadly across primary care, gynecology, endocrinology, rheumatology and orthopedic settings.
On reimbursement, Toledano said Entera believes EB613’s cost-of-goods profile could support pricing in line with existing anabolic therapies and their generic equivalents. She also cited an economic rationale for treatments that may help reduce fracture risk, noting that she estimates there are roughly 2 million fractures in the U.S. annually that cost about $54 billion.
About Entera Bio (NASDAQ:ENTX)
Entera Bio, Inc is a clinical‐stage biopharmaceutical company pioneering the development of orally delivered peptide therapeutics. Utilizing its proprietary oral delivery platform, Entera Bio seeks to overcome the challenges of gastrointestinal absorption for large peptide molecules. The technology is designed to facilitate transit across the intestinal epithelium while preserving peptide structure and bioactivity, offering the potential for daily oral dosing in lieu of injectable formulations.
The company’s lead candidate, EB613, is an oral parathyroid hormone (PTH) analog under investigation for the treatment of osteoporosis.
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