Regor Therapeutics announced positive topline results from its Phase 2a clinical trial of RGT-075, an oral, once-daily small molecule GLP-1 receptor agonist, for the treatment of obesity. The trial demonstrated a statistically significant 5% placebo-adjusted weight loss in patients with obesity, with a favorable safety profile. These findings support the initiation of the Phase 2b COMO-1 trial to further evaluate RGT-075's efficacy and safety.
The Phase 2a trial, conducted across ten clinical centers in the US, involved 73 patients with obesity who received 125 mg of RGT-075 once daily. The primary outcome was weight loss at 12 weeks, with six weeks on the target dose. Results showed a statistically significant 5% placebo-adjusted weight loss with no plateau observed. There were no treatment-related severe adverse events, and the discontinuation rate due to adverse events was 4%, identical to the placebo group. Only one patient (2%) required a dose reduction to 60 mg once daily and successfully completed the study.
Favorable Tolerability Profile
In the RGT-075 treatment arm, mild-to-moderate nausea and vomiting were reported in 40% and 24% of patients, respectively. Michael Grimm, M.D., Ph.D., Head of Metabolic Diseases at Regor, commented, "Even with only six weeks of titration, our tolerability results are already comparable to those observed for semaglutide in longer studies." He also noted the drug's efficacy in improving HbA1c and blood pressure.
RGT-075 has demonstrated a promising pharmacokinetic profile, with a peak-to-trough ratio (PTR) of under 5. Developers hypothesize that delivering target 24-hour plasma concentration with a relatively low PTR correlates with improved tolerability to GI-related symptoms.
COMO-1 Phase 2b Trial
Regor has initiated the COMO-1 Phase 2b dose-finding trial for RGT-075. This multicenter, randomized, double-blind, placebo-controlled study will evaluate multiple doses up to 225 mg of RGT-075 over 36 weeks compared with placebo in adult patients with obesity or overweight with weight-related comorbidities. Approximately 240 adult participants will be enrolled and randomized to RGT-075 or placebo. All participants on RGT-075 will be given RGT-075 once daily (QD) titrated up over 12 weeks. The primary endpoint is percent change in body weight from baseline to week 36. Secondary endpoints include safety and tolerability of the monthly titration scheme, as well as pharmacokinetics of RGT-075. Topline data from the Phase 2b study are expected at the end of 2025.
Management Commentary
Regor CEO Xiayang Qiu, Ph.D., stated, "The existing GLP-1 peptide drugs have demonstrated immense value and unprecedented promise. However, we have heard loud and clear the pleas of physicians and patients for an oral version that can provide sustainable benefits and be accessible for the hundreds of millions of patients living with obesity and weight-related comorbidities." Dr. Qiu added, "We chose to pursue the small molecule route because of its proven suitability for long-term use as once-daily oral medications, along with the inherent advantage of easier manufacturing and supply in desired quantities. We succeed when patients have better options, and we believe RGT-075 has achieved an early proof-of-concept milestone through this phase 2a study."
About RGT-075
RGT-075 is an orally bioavailable, once-daily, small molecule GLP-1R full agonist discovered and developed by Regor for the treatment of metabolic diseases, such as type-2 diabetes mellitus and obesity or overweight with weight-related comorbidities. Regor previously completed Phase 2a studies in patients with obesity, Phase 1 single ascending dose (SAD) in healthy volunteers and multiple ascending dose (MAD) in patients with diabetes. RGT-075 was safe and well-tolerated in clinical trials completed to date, with emerging efficacies comparable to the approved peptide GLP-1 drugs.
