Entera Bio and OPKO Health Update on Oral Oxyntomodulin Tablet for Obesity and Metabolic Disorders

Entera Bio Ltd., listed on the NASDAQ under the ticker ENTX, and OPKO Health, Inc., listed on NASDAQ as OPK, have announced promising results from their collaborative research. This partnership aims to develop the first oral dual agonist GLP-1/glucagon peptide, utilizing OPKO's proprietary long-acting oxyntomodulin (OXM) analog and Entera’s N-Tab™ technology. The goal is to create a once-daily oral treatment for obesity, metabolic, and fibrotic disorders.

OXM is a peptide hormone found naturally in the small intestine, known for its appetite-suppressing and weight-loss-inducing properties. The collaborative team has successfully completed in vivo proof-of-concept pharmacokinetic/pharmacodynamic (PK/PD) studies using rodent and pig models. The studies demonstrated significant systemic exposure and favorable pharmacokinetic profiles for oral OXM following a single dose.

In the pig model, the results showed high plasma concentrations and prolonged systemic exposure of oral OXM, paralleling the half-life of semaglutide, the only approved oral GLP-1 analog. Additionally, a glucose tolerance test in rats revealed that oral OXM significantly reduced plasma glucose levels post-administration, compared to placebo. These findings will be presented at an upcoming clinical conference.

Miranda Toledano, the Chief Executive Officer of Entera, expressed satisfaction with the progress, noting that the data supports the move towards IND-enabling efforts for the program.

Previously, OPKO's phase 2B study involving weekly injections of pegylated OXM showed significant weight loss and reduction in HbA1c, triglycerides, and cholesterol levels in 113 obese and diabetic patients. The OXM agonist peptide has been modified to enhance its potency while retaining its long-acting profile. As of now, there are no approved OXM agonists on the market, with existing developments being either small molecules or requiring subcutaneous injections.

Entera Bio is a clinical-stage company dedicated to developing oral peptide or protein replacement therapies for unmet medical needs, leveraging its N-Tab™ technology platform. Entera's pipeline includes five oral peptide programs, expected to enter clinical phases by 2025. The company's leading candidate, EB613, is being developed as the first oral, osteoanabolic once-daily tablet treatment for post-menopausal women with low bone mineral density (BMD) and high-risk osteoporosis. A phase 2 study has met its primary and secondary endpoints, and Entera is preparing for a phase 3 study, expected to begin by January 2025. Additionally, Entera is developing EB612, an oral PTH (1-34) tablet for hypoparathyroidism.

In collaboration with OPKO, Entera is also working on developing the first oral oxyntomodulin, a dual-targeted GLP-1/glucagon peptide for obesity treatment, and the first oral GLP-2 peptide tablet for rare malabsorption conditions like short bowel syndrome.

OPKO Health is a global biopharmaceutical and diagnostics company aiming to lead in large, rapidly growing markets through its expertise in discovery, development, and commercialization, coupled with its proprietary technologies.

By developing oral treatments for significant health conditions, Entera and OPKO are poised to transform standards of care, offering new hope for patients with obesity, metabolic disorders, and other medical needs.