A Second Chance for a Scorned Drug Class in the Obesity Fight

NORWOOD, MA – December 11, 2025 – In the high-stakes, multi-billion-dollar race to solve the global obesity crisis, Corbus Pharmaceuticals is making a bold and risky bet on a comeback story. The clinical-stage company today announced promising early-stage results for CRB-913, an oral weight-loss drug from a class so infamous it was all but abandoned over a decade ago due to severe psychiatric side effects. The new data suggests Corbus may have found a way to resurrect the potential benefits while sidestepping the dangers, positioning a potential new contender in a market currently dominated by injectable blockbusters.

The Ghost of Rimonabant

To understand the significance of Corbus's announcement, one must look back at the cautionary tale of the cannabinoid type-1 (CB1) receptor. In the mid-2000s, this pathway was hailed as a revolutionary target for weight loss. Sanofi-Aventis’s Rimonabant, the first drug in this class, demonstrated impressive efficacy, not only helping patients lose weight but also improving cholesterol and blood sugar levels. It was approved in Europe and seemed destined for blockbuster status.

The promise, however, quickly turned to peril. The drug worked by blocking CB1 receptors throughout the body, including the brain. These central nervous system receptors are deeply involved in regulating mood and emotion. The consequence was a wave of alarming reports of depression, anxiety, and a doubling of the risk for suicidal thoughts. By 2008, European regulators pulled the drug from the market, and the FDA, citing the same psychiatric risks, had already refused to approve it in the United States. The entire drug class was effectively blacklisted, a powerful but dangerous tool locked away.

Corbus is now attempting to pick that lock with a new key. Its drug, CRB-913, is what’s known as a highly peripherally restricted CB1 inverse agonist. The design is engineered to prevent the molecule from crossing the blood-brain barrier in significant amounts. The goal is to reap the metabolic benefits of blocking CB1 receptors in peripheral tissues like fat, liver, and muscle, while leaving the crucial receptors in the brain untouched. Pre-clinical data provided a strong foundation for this hypothesis, showing CRB-913 had a 50-times lower brain-to-plasma ratio than the ill-fated Rimonabant, suggesting it might just be the ghostbuster this therapeutic class needed.

Promising Signals in a Crowded Field

The new Phase 1a data provides the first human evidence that this strategy could work. The study, which tested single and multiple ascending doses in both healthy and obese participants, found CRB-913 to be safe and well-tolerated. Crucially, daily neuropsychiatric assessments for suicidality, depression, and anxiety came back negative for all participants. While a few participants in the highest-dose obese cohort reported mild, transient anxiety or irritability, these events resolved without intervention and were not accompanied by the severe mood disturbances that plagued Rimonabant.

"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."

Beyond its promising safety profile, the drug also showed early signs of efficacy. In a small cohort of obese participants receiving the drug for 14 days, they achieved a mean placebo-adjusted weight loss of 2.9%, with some individuals losing up to 4.3% of their body weight. Participants also reported a reduction in food-related thoughts and cravings. Furthermore, the drug appeared to sidestep another common issue with weight-loss medications: gastrointestinal distress. Unlike the current market leaders, CRB-913 was not associated with significant nausea, vomiting, or constipation.

A David vs. Goliath Battle

Entering the obesity market today means going head-to-head with titans. The landscape is dominated by GLP-1 receptor agonists like Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, injectable drugs that have revolutionized treatment and are driving market forecasts toward an astonishing $100 billion by 2030. These drugs deliver powerful weight loss, often in the range of 15-20% of total body weight, and have become a cultural phenomenon.

But they are not without drawbacks. Their high cost puts them out of reach for many, and their primary side effects—persistent nausea and other GI issues—can lead patients to discontinue treatment. There are also concerns about the loss of lean muscle mass alongside fat and the rapid weight regain that often occurs when the weekly injections stop.

This is where Corbus sees its opening. CRB-913 offers a completely different mechanism of action, which could make it a viable alternative for patients who don’t respond to or can't tolerate GLP-1s. As a once-daily oral pill, it also offers a significant convenience advantage over injections. The most tantalizing opportunity, however, may lie in combination therapy. Preclinical studies suggest that combining a CB1 inverse agonist with a GLP-1 can produce synergistic effects, leading to even greater weight loss and metabolic improvement than either drug can achieve alone. If this holds true in humans, CRB-913 could become an essential add-on therapy rather than a direct competitor.

The Long Road Ahead

Corbus is a small, clinical-stage company with a diversified pipeline that also includes oncology assets. Its financial health appears solid for now, with a recent capital raise extending its cash runway into 2028. This gives it the breathing room needed for the long and expensive process of drug development. But CRB-913 represents a major strategic bet on a high-risk, high-reward target.

The next hurdle is already underway. Corbus has initiated a larger, 12-week Phase 1b study called CANYON-1, which will enroll 240 obese participants to further evaluate safety and determine the optimal dose. The results from this trial, expected in the summer of 2026, will be a critical inflection point. They will provide a clearer picture of whether the promising weight loss signal seen in the two-week study can be sustained and deepened over a longer period, and, most importantly, whether the clean psychiatric safety profile holds up in a larger group of patients.

For now, the early data provides a glimmer of hope that a once-disgraced mechanism for weight loss could be safely harnessed. Corbus's journey with CRB-913 is a testament to innovation—a willingness to revisit past failures with new technology. The path to market is long and fraught with uncertainty, but the CANYON-1 study will be the next major test of whether this phoenix can truly rise from the ashes.