Corbus Pharmaceuticals Announces First Patient Dosed in Phase 1 Clinical Study of Next-Generation CB1 Inverse Agonist CRB-913 for the Treatment of Obesity
Corbus Pharmaceuticals (NASDAQ: CRBP) has initiated dosing in a Phase 1 clinical trial for CRB-913, their second-generation CB1 inverse agonist targeting obesity treatment. The drug represents an advancement over first-generation treatments like rimonabant, which were discontinued due to neuropsychiatric side effects.
Pre-clinical data from Obesity Week 2024 shows CRB-913 is significantly more peripherally restricted, with a brain-to-plasma ratio 50 times lower than rimonabant and 15 times more peripherally restricted than monlunabant. The single ascending dose/multiple ascending dose (SAD/MAD) trial is expected to complete in Q3 2025, followed by a Phase 1b dose-range finding study scheduled for completion in H2 2026.
The company envisions potential applications for CRB-913 as a monotherapy, in combination with incretin analogs, or as maintenance therapy following incretin analog treatment.
Corbus Pharmaceuticals (NASDAQ: CRBP) ha avviato la somministrazione in uno studio clinico di Fase 1 per CRB-913, il loro agonista inverso di seconda generazione del CB1 mirato al trattamento dell'obesità. Il farmaco rappresenta un progresso rispetto ai trattamenti di prima generazione come il rimonabant, che sono stati interrotti a causa di effetti collaterali neuropsichiatrici.
I dati preclinici presentati durante la Obesity Week 2024 mostrano che CRB-913 è significativamente più ristretto a livello periferico, con un rapporto cervello-plasma 50 volte inferiore rispetto al rimonabant e 15 volte più ristretto a livello periferico rispetto al monlunabant. Lo studio di dose singola in aumento/dose multipla in aumento (SAD/MAD) dovrebbe concludersi nel terzo trimestre del 2025, seguito da uno studio di Fase 1b per la determinazione dell'intervallo di dosaggio previsto per la conclusione nella seconda metà del 2026.
L'azienda prevede potenziali applicazioni per CRB-913 come monoterapia, in combinazione con analoghi dell'incretina, o come terapia di mantenimento dopo il trattamento con analoghi dell'incretina.
Corbus Pharmaceuticals (NASDAQ: CRBP) ha iniciado la dosificación en un ensayo clínico de Fase 1 para CRB-913, su agonista inverso de CB1 de segunda generación dirigido al tratamiento de la obesidad. El fármaco representa un avance con respecto a los tratamientos de primera generación como el rimonabant, que fueron descontinuados debido a efectos secundarios neuropsiquiátricos.
Los datos preclínicos presentados en la Obesity Week 2024 muestran que CRB-913 es significativamente más restringido a nivel periférico, con una relación cerebro-plasma 50 veces menor que el rimonabant y 15 veces más restringido periféricamente que el monlunabant. Se espera que el ensayo de dosis única en aumento/dosis múltiples en aumento (SAD/MAD) se complete en el tercer trimestre de 2025, seguido de un estudio de Fase 1b para la determinación del rango de dosis programado para completarse en la segunda mitad de 2026.
La empresa prevé aplicaciones potenciales para CRB-913 como monoterapia, en combinación con análogos de incretina, o como terapia de mantenimiento tras el tratamiento con análogos de incretina.
Corbus Pharmaceuticals (NASDAQ: CRBP)는 비만 치료를 목표로 하는 2세대 CB1 역효능제인 CRB-913에 대한 1상 임상 시험에서 투약을 시작했습니다. 이 약물은 신경정신과적 부작용으로 인해 중단된 1세대 치료제인 리모나반트보다 발전된 것입니다.
2024년 비만 주간에서 발표된 전임상 데이터에 따르면 CRB-913은 말초에서의 제한성이 훨씬 더 크며, 뇌-혈장 비율이 리모나반트보다 50배 낮고 몬룬반트보다 15배 더 말초에서 제한적입니다. 단일 용량 상승/다중 용량 상승(SAD/MAD) 시험은 2025년 3분기까지 완료될 것으로 예상되며, 그 후 2026년 하반기 완료 예정인 1b상 용량 범위 탐색 연구가 이어질 예정입니다.
회사는 CRB-913의 단독 요법, 인크레틴 유사체와의 병용 요법, 또는 인크레틴 유사체 치료 후 유지 요법으로의 잠재적 응용을 구상하고 있습니다.
Corbus Pharmaceuticals (NASDAQ: CRBP) a lancé la dosage dans un essai clinique de Phase 1 pour CRB-913, leur agoniste inverse de deuxième génération du CB1 ciblant le traitement de l'obésité. Ce médicament représente une avancée par rapport aux traitements de première génération comme le rimonabant, qui ont été interrompus en raison d'effets secondaires neuropsychiatriques.
Les données précliniques présentées lors de la Obesity Week 2024 montrent que CRB-913 est significativement plus restreint sur le plan périphérique, avec un rapport cerveau-plasma 50 fois inférieur à celui du rimonabant et 15 fois plus restreint sur le plan périphérique que le monlunabant. L'essai de dose unique en montée/doses multiples en montée (SAD/MAD) devrait se terminer au troisième trimestre de 2025, suivi d'une étude de Phase 1b pour la détermination de la plage de dosage prévue pour la fin de l'année 2026.
L'entreprise envisage des applications potentielles pour CRB-913 en tant que monothérapie, en combinaison avec des analogues d'incrétine, ou comme thérapie de maintien après un traitement par des analogues d'incrétine.
Corbus Pharmaceuticals (NASDAQ: CRBP) hat die Dosisverabreichung in einer Phase-1-Studie für CRB-913 begonnen, ihren inversen Agonisten der zweiten Generation des CB1 zur Behandlung von Fettleibigkeit. Das Medikament stellt einen Fortschritt gegenüber den Behandlungen der ersten Generation wie Rimonabant dar, die aufgrund neuropsychiatrischer Nebenwirkungen eingestellt wurden.
Präklinische Daten von der Obesity Week 2024 zeigen, dass CRB-913 signifikant peripher restriktiver ist, mit einem Gehirn-Plasma-Verhältnis, das 50-mal niedriger als das von Rimonabant und 15-mal restriktiver als das von Monlunabant ist. Die Studie zur einmaligen Dosissteigerung/mehrfachen Dosissteigerung (SAD/MAD) wird voraussichtlich im dritten Quartal 2025 abgeschlossen sein, gefolgt von einer Phase-1b-Studie zur Bestimmung des Dosisbereichs, die für das zweite Halbjahr 2026 geplant ist.
Das Unternehmen sieht potenzielle Anwendungen für CRB-913 als Monotherapie, in Kombination mit Incretin-Analoga oder als Erhaltungstherapie nach der Behandlung mit Incretin-Analoga.
- Drug shows superior peripheral restriction compared to competitors (50x vs rimonabant, 15x vs monlunabant)
- Multiple potential commercial applications (monotherapy, combination therapy, maintenance therapy)
- Successfully initiated Phase 1 clinical trials under open IND
- Long development timeline with Phase 1b completion not expected until H2 2026
- Entering a highly competitive obesity treatment market
- Previous generation of similar drugs failed due to safety concerns
Insights
Corbus's progression of CRB-913 into Phase 1 clinical trials represents a strategic entry into the booming obesity therapeutics market with a differentiated mechanism of action. CB1 inverse agonism is clinically validated for weight loss, but first-generation compounds like rimonabant were abandoned due to neuropsychiatric side effects resulting from their central nervous system penetration.
The key differentiator here is CRB-913's significantly enhanced peripheral restriction - reportedly 50 times lower brain-to-plasma ratio than rimonabant and 15 times more peripherally restricted than monlunabant. This potentially addresses the safety concerns that derailed earlier CB1-targeting drugs while maintaining efficacy.
The development timeline is clearly defined with the SAD/MAD portion completing in Q3 2025 and a Phase 1b dose-finding study concluding in H2 2026. This positions Corbus with potential proof-of-concept data within 18 months.
What's particularly notable is management's vision for multiple commercial applications: monotherapy, combination with incretin analogs (GLP-1s), and maintenance therapy after GLP-1 induction. This multi-pronged approach could capture different segments of the obesity market, especially as oral administration offers convenience advantages over injectable GLP-1s that currently dominate the landscape.
This Phase 1 initiation marks Corbus's strategic pivot toward the obesity space with a differentiated mechanistic approach. While the obesity market is already being transformed by GLP-1 receptor agonists, there remains substantial room for complementary mechanisms like CB1 inverse agonism, particularly as oral therapies.
The preclinical differentiation data presented at Obesity Week 2024 is scientifically meaningful - demonstrating substantially enhanced peripheral restriction compared to both rimonabant and monlunabant. This addresses the fundamental safety limitation that prevented first-generation CB1 antagonists from commercial success despite proven efficacy.
For investors, this represents early-stage but credible positioning in the obesity therapeutic landscape. However, the clinical development timeline is extended, with meaningful dose-ranging data not expected until H2 2026, suggesting any substantial valuation impact remains distant.
The versatility of potential applications mentioned by CEO Yuval Cohen - as monotherapy, combination therapy with incretin analogs, or maintenance therapy - demonstrates strategic consideration of how CRB-913 might find market positioning even in a GLP-1 dominated landscape. The oral small molecule nature of CRB-913 could provide competitive advantages in certain treatment scenarios where injections are less desirable.
- CB1 inverse agonism is a clinically validated mechanism to induce weight loss
- CRB-913 is markedly more peripherally restricted compared to monlunabant and rimonabant
- SAD/MAD Phase 1 trial scheduled for completion Q3 2025 and Phase 1b dose-range finding scheduled for completion H2 2026
NORWOOD, Mass., March 28, 2025 (GLOBE NEWSWIRE) -- Corbus Pharmaceuticals Holdings, Inc. (NASDAQ: CRBP) (“Corbus” or the “Company”), an oncology and obesity company with a diversified portfolio, announced today the dosing of the first subject in the single ascending dose / multiple ascending dose (SAD/MAD) portion of the Phase 1 trial of CRB-913 for the treatment of obesity. The study is being conducted in the United States under an open IND.
CRB-913 is a second-generation, highly peripherally restricted cannabinoid type-1 (CB1) receptor inverse agonist drug designed to treat obesity. CB1 inverse agonism is a clinically validated mechanism to induce weight loss but the first generation of this class (e.g., rimonabant) was abandoned due to the potential risk of neuropsychiatric adverse events. A second generation of peripherally restricted CB1 inverse agonists is now being explored (e.g., monlunabant and CRB-913).
Pre-clinical data presented at Obesity Week 2024 demonstrated CRB-913 is markedly more peripherally restricted than both monlunabant and rimonabant. In non-clinical models, CRB-913 has a brain-to-plasma ratio fifty times lower than rimonabant and is fifteen times more peripherally restricted than monlunabant.
The SAD/MAD portion of the Phase 1 trial is scheduled to be completed in Q3 of this year and the Company expects to commence a Phase 1b dose-range finding study in Q4 of 2025. The dose-range finding study is scheduled for completion in the second half of 2026.
“We are pleased to reach this important milestone with our CRB-913 obesity program,” said Yuval Cohen, Ph.D., Chief Executive Officer of Corbus. “We believe that the ability to address weight loss with this orthogonal mechanism of action and via an oral small molecule could address several key unmet needs. Our pre-clinical data to date suggests a potential clinical use as monotherapy, combination therapy with incretin analogs as well as a maintenance therapy post incretin analog induction treatment.”
About Corbus
Corbus Pharmaceuticals Holdings, Inc. is an oncology and obesity company with a diversified portfolio and is committed to helping people defeat serious illness by bringing innovative scientific approaches to well-understood biological pathways. Corbus’ pipeline includes CRB-701, a next-generation antibody drug conjugate that targets the expression of Nectin-4 on cancer cells to release a cytotoxic payload, CRB-601, an anti-integrin monoclonal antibody that blocks the activation of TGFβ expressed on cancer cells, and CRB-913, a highly peripherally restricted CB1 receptor inverse agonist for the treatment of obesity. Corbus is headquartered in Norwood, Massachusetts. For more information on Corbus, visit corbuspharma.com. Connect with us on X, LinkedIn and Facebook.
Forward-Looking Statements
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INVESTOR CONTACT:
Sean Moran
Chief Financial Officer
Corbus Pharmaceuticals
smoran@corbuspharma.com
Bruce Mackle
Managing Director
LifeSci Advisors, LLC
bmackle@lifesciadvisors.com
FAQ
What are the key advantages of Corbus Pharmaceuticals' CRB-913 over previous CB1 inverse agonists?
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How does CRB-913's mechanism of action work for weight loss?
