Entera Bio Ltd. and OPKO Health, Inc. have announced promising topline pharmacokinetic/pharmacodynamic (PK/PD) results from their collaborative research on an oral oxyntomodulin (OXM) analog. This program aims to develop a once-daily oral dual agonist GLP-1/glucagon peptide for treating obesity, metabolic, and fibrotic disorders.
The collaboration leverages OPKO's long-acting OXM analog and Entera’s N-Tab™ technology to create an oral tablet formulation. OXM, a naturally occurring peptide hormone, suppresses appetite and induces weight loss.
Preclinical Study Highlights
In vivo proof-of-concept PK/PD studies were conducted in rodent and pig models. The studies met their objectives, demonstrating significant systemic exposure of oral OXM after a single dose in both models. The oral OXM exhibited a favorable PK profile and bioavailability. In the pig model, high plasma concentrations and prolonged systemic exposure of oral OXM were observed, comparable to semaglutide (Rybelsus®), the only approved oral GLP-1 analog.
Glucose Tolerance Test Results
To evaluate the pharmacologic effect of oral OXM, a glucose tolerance test was performed in rats. The results showed a statistically significant reduction in plasma glucose levels post-glucose administration compared to placebo, suggesting potential in glucose control.
Future Plans
Entera and OPKO are preparing to present these data at an upcoming clinical conference. The positive results support the advancement of the program toward Investigational New Drug (IND)-enabling efforts, marking a significant step toward clinical development.
Prior Clinical Data
OPKO previously reported that weekly injections of pegylated OXM led to significant weight loss and reductions in HbA1c, triglyceride, and cholesterol levels in a Phase 2B study involving 113 obese and diabetic patients. The OXM agonist peptide has been modified to enhance its potency while maintaining its long-acting profile. Currently, there are no approved OXM agonists available, and other candidates in development are either small molecules or require subcutaneous injections.
