Corbus CRB-913 Delivers 5% Weight Loss in Phase 1b Obesity Study

Key Points

• CRB-913 produced a 5% placebo-adjusted weight loss at the highest 60-milligram daily dose after 12 weeks, with statistically significant weight loss reported across all three tested doses.
• The peripherally restricted CB1 inverse agonist showed no suicidality or serious treatment-related adverse events; psychiatric and gastrointestinal side effects were generally mild or moderate.
• Corbus plans to present additional data at ObesityWeek and advance CRB-913 into the proposed Phase 2 CANYON-2 trial, while longer and larger studies are needed to confirm durability, safety and efficacy.

Corbus Pharmaceuticals NASDAQ: CRBP reported top-line results from CANYON-1, a Phase 1b trial evaluating CRB-913, an oral, peripherally restricted CB1 inverse agonist for obesity. The 12-week, placebo-controlled study enrolled 254 patients across 15 U.S. sites, with participants having an average body mass index of approximately 37 and 71% of participants being female.

Chief Executive Officer Yuval Cohen said the trial was designed to assess whether a CB1 inverse agonist could produce weight loss while limiting the psychiatric safety concerns associated with earlier, brain-penetrant drugs in the class. According to Cohen, CRB-913 was engineered to minimize brain exposure, with approximately 2% of the brain penetration of rimonabant and 15 times less brain penetration than Novo Nordisk's discontinued CB1 inverse agonist monlunabant.

Weight-Loss Results

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At the highest tested dose of 60 milligrams once daily, CRB-913 achieved an average 5% placebo-adjusted weight loss at 12 weeks, according to the company. Cohen said all participants who completed treatment in the 60-milligram cohort lost weight, and the study showed no evidence of a weight-loss plateau over the 12-week period.

The trial evaluated three dose levels and placebo. Cohen said all three active doses achieved statistically significant weight loss compared with placebo, with separation between dose groups becoming more apparent as participants were titrated to higher doses. The highest individual weight loss reported in the 60-milligram group was slightly more than 13%, although Cohen characterized that result as an outlier.

Corbus compared its early results with published data for oral GLP-1 therapies, while cautioning that such cross-trial comparisons have limitations. Cohen said CRB-913's 12-week weight-loss profile appeared to be in line with oral GLP-1 therapies, while emphasizing that CRB-913 works through a distinct mechanism and is not an incretin-based drug.

Safety and Tolerability

The company highlighted psychiatric and gastrointestinal tolerability as central considerations for the program. Earlier CB1 inverse agonists, including rimonabant, faced concerns involving depression and suicidality. Cohen said CANYON-1 recorded no suicidality and no serious treatment-related adverse events across dose cohorts.

All reported psychiatric adverse events were mild or moderate, transient and resolved, according to the company. The 60-milligram group had one moderate case of depressive symptoms. Anxiety and insomnia rates were described as low and not notably different from placebo, while irritability occurred only in active-treatment participants and was mild.

Cohen said the company used a more stringent PHQ-9 psychiatric screening threshold than is typical in obesity studies. In response to an analyst question about the applicability of the data to a broader population, he said roughly 4% of screened patients failed the PHQ-9 criterion, suggesting the enrolled study population was not materially different in that regard from a general U.S. obesity population.

On gastrointestinal events, Cohen said the company observed less vomiting and constipation, as well as a lower nausea rate, than reported in published studies of oral semaglutide and orforglipron. Diarrhea appeared to be at similar or slightly higher levels, he said. All gastrointestinal adverse events in CANYON-1 were mild or moderate, with no severe or serious gastrointestinal events reported.

Treatment discontinuations for any reason averaged about 20%, a rate Cohen said was broadly typical for obesity studies and similar to placebo. He also noted that participants in the blinded early-stage study could not reduce their dose after titration, an option that may help reduce discontinuations in later studies.

Experts Urge Longer-Term Evaluation

Harold Bays, medical director of the Louisville Metabolic and Atherosclerosis Research Center and an investigator in the study, said the results support the hypothesis that peripheral CB1 activity may provide clinically meaningful weight loss without the psychiatric effects associated with older brain-penetrant therapies.

However, Bays stressed that larger and longer clinical trials will be necessary to establish the treatment's safety and efficacy profile. He said he would be cautious about moving to higher doses before understanding the effects of longer exposure at 60 milligrams, noting that participants at the top dose had only been on that dose for part of the 12-week study.

Bays said CRB-913 could potentially serve patients who cannot tolerate GLP-1 receptor agonists and could eventually be evaluated in combination with oral GLP-1 drugs or other obesity therapies. He cautioned that the gastrointestinal tolerability of such combinations remains unknown and would need to be evaluated in clinical studies.

Next Steps

Corbus said it will present additional CANYON-1 data at ObesityWeek in Washington, D.C., where the program was selected for a late-breaking presentation. The company plans to engage with the Food and Drug Administration regarding CANYON-2, a proposed Phase 2 monotherapy trial that Cohen said the company intends to begin as quickly as possible next year.

The company also plans to evaluate CRB-913 in potential combinations with therapies from other pathways, including oral GLP-1 treatments. Cohen said preclinical work involving CB1 inverse agonism and GLP-1 agonists suggested additive weight-loss effects, though combination safety and efficacy have not yet been established clinically.

About Corbus Pharmaceuticals (NASDAQ:CRBP)

Corbus Pharmaceuticals Holdings, Inc is a clinical-stage biopharmaceutical company dedicated to the development and commercialization of therapeutic candidates for rare, life-threatening inflammatory and fibrotic diseases. The company's lead investigational therapy, lenabasum, is a synthetic, oral cannabinoid receptor type 2 (CB2) agonist designed to resolve chronic inflammation by harnessing the body's innate resolution pathways. Corbus operates by advancing small-molecule compounds through preclinical and clinical studies to address unmet medical needs in autoimmune and inflammatory disorders.

Lenabasum is currently under evaluation in a Phase 3 clinical trial for diffuse cutaneous systemic sclerosis (dcSSc) and in a Phase 2 study for cystic fibrosis–related inflammation.

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