Corbus Pharmaceuticals' CRB-913 Shows Promising Weight Loss Results in Phase 1a Obesity Trial
核心洞察
Corbus Pharmaceuticals completed a Phase 1a study of CRB-913, a peripherally restricted CB1 (搜索) inverse agonist, demonstrating favorable safety and tolerability across all doses with no serious adverse events reported.
All participants with obesity treated with CRB-913 (n=9) experienced weight loss, achieving a mean 2.9% placebo-adjusted weight loss by Day 14, with individual weight loss ranging from 1.3% to 4.3%.
The company has initiated a 12-week Phase 1b CANYON-1 study in 240 obese participants with completion expected in summer 2026, testing three dose levels (20 mg, 40 mg, and 60 mg) once daily.
Corbus Pharmaceuticals Holdings Inc. has announced positive results from its Phase 1a study of CRB-913, an oral CB1 (搜索) inverse agonist designed for obesity treatment, showing promising weight loss effects alongside a favorable safety profile. The company has simultaneously initiated a larger Phase 1b study expected to complete in summer 2026.
Study Design and Participants
The double-blinded, placebo-controlled Phase 1a study evaluated CRB-913's safety, tolerability, and pharmacokinetics across single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. The SAD portion enrolled 64 participants across 8 cohorts receiving doses up to 600 mg/day, while the MAD portion included 48 participants across 4 cohorts receiving 25 mg, 75 mg, or 150 mg once daily for 7 days, followed by 7 days of continuous observation.
Safety and Tolerability Profile
CRB-913 demonstrated a notably clean safety profile with no serious treatment-emergent adverse events reported across all dose levels. The drug showed minimal gastrointestinal effects, with no cases of nausea, vomiting, or constipation, and only one instance of mild diarrhea.
Daily neuropsychiatric assessments using standardized scales including the Columbia-Suicide Severity Rating Scale (CSSRS), Patient Health Questionnaire-9 (PHQ-9), and General Anxiety Disorder-7 (GAD-7) remained stable and negative for all participants. In the obese cohort receiving 150 mg daily, three cases of mild anxiety and one case of mild irritability were reported, but these events were transient and resolved without medical intervention.
Weight Loss Efficacy
In the dedicated obese MAD cohort receiving 150 mg once daily, all nine CRB-913-treated participants experienced weight loss, while none in the three-person placebo group lost weight. The treatment group achieved a mean 2.9% placebo-adjusted weight loss by Day 14, with individual weight loss ranging from 1.3% to 4.3%. Weight loss began early in treatment and increased over time.
Several participants reported reduced food-related thoughts and cravings during treatment. Placebo-adjusted weight loss was also observed in healthy, non-obese participants receiving 75 mg and 150 mg doses.
Mechanism and Drug Design
CRB-913 represents a next-generation approach to CB1 (搜索) inverse agonism for weight loss. While this mechanism of action is recognized for weight loss efficacy, first-generation drugs in this class were abandoned due to neuropsychiatric safety concerns. CRB-913 addresses these limitations through its highly peripherally restricted design, which reduces brain penetration.
Preclinical data demonstrate that CRB-913 is 15-fold less brain-penetrant than monlunabant and has a 50 times lower brain-to-plasma ratio compared to rimonabant, an extensively studied first-generation CB1 (搜索) inverse agonist.
Next Steps: CANYON-1 Phase 1b Study
Corbus has initiated the CANYON-1 Phase 1b study, a 12-week, double-blind, placebo-controlled, dose-ranging trial in 240 obese, non-diabetic participants across multiple U.S. clinical sites. The study will evaluate three CRB-913 dose levels (20 mg, 40 mg, and 60 mg) administered once daily, with a dose titration design starting all participants at 20 mg daily before escalating to their assigned dose level.
"We are pleased by the translation of CRB-913 from pre-clinical models to the clinical setting," said Yuval Cohen, PhD, Chief Executive Officer of Corbus. "We are encouraged by CRB-913's potentially class-leading safety and tolerability profile demonstrated in this study. CRB-913's observed weight loss effect provides further evidence that a markedly peripherally restricted CB1 (搜索) inverse agonist could offer an attractive orthogonal monotherapy for obesity or combinatory mode of action to the incretin-pathway therapies."
The pharmacokinetic profile established in the Phase 1a study supports once-daily oral dosing, positioning CRB-913 as a potential convenient treatment option in the evolving obesity therapeutic landscape.