Corbus Pharmaceuticals Presents New CRB-913 Pre-Clinical Data At Obesity Week 2024
Corbus Pharmaceuticals (NASDAQ: CRBP) presented new pre-clinical data for CRB-913, its CB1 inverse agonist, at Obesity Week 2024. Key findings show CRB-913's brain levels are 15-fold lower than monlunabant, with a 10 times higher plasma-to-brain ratio. The compound demonstrated significant weight loss of up to 38% in DIO mice at doses ranging from 5 to 80 mg/kg/day. Notably, when replacing semaglutide treatment, CRB-913 maintained weight loss and doubled fat reduction compared to semaglutide maintenance. The company plans to begin Phase 1 clinical trials in Q1 2025.
Corbus Pharmaceuticals (NASDAQ: CRBP) ha presentato nuovi dati preclinici per CRB-913, il suo agonista inverso del CB1, durante l'Obesity Week 2024. I risultati chiave mostrano che i livelli cerebrali di CRB-913 sono 15 volte inferiori rispetto al monlunabant, con un rapporto plasma-cervello superiore di 10 volte. Il composto ha dimostrato una significativa perdita di peso fino al 38% nei topi con obesità da dieta (DIO) a dosi comprese tra 5 e 80 mg/kg/giorno. In particolare, quando ha sostituito il trattamento con semaglutide, CRB-913 ha mantenuto la perdita di peso e raddoppiato la riduzione del grasso rispetto al trattamento continuo con semaglutide. L'azienda prevede di avviare i trial clinici di Fase 1 nel primo trimestre del 2025.
Corbus Pharmaceuticals (NASDAQ: CRBP) presentó nuevos datos preclínicos para CRB-913, su agonista inverso de CB1, en la Obesity Week 2024. Los hallazgos clave muestran que los niveles cerebrales de CRB-913 son 15 veces más bajos que los de monlunabant, con una relación plasma-cerebro 10 veces mayor. El compuesto demostró una pérdida de peso significativa de hasta el 38% en ratones con obesidad inducida por dieta (DIO) a dosis que oscilan entre 5 y 80 mg/kg/día. Notablemente, al reemplazar el tratamiento con semaglutida, CRB-913 mantuvo la pérdida de peso y duplicó la reducción de grasa en comparación con el mantenimiento de semaglutida. La compañía planea comenzar los ensayos clínicos de Fase 1 en el primer trimestre de 2025.
Corbus Pharmaceuticals (NASDAQ: CRBP)는 비만 주간 2024에서 CRB-913, 그의 CB1 역효능제에 대한 새로운 전임상 데이터를 발표했습니다. 주요 발견은 CRB-913의 뇌 내 수치가 monlunabant보다 15배 낮고, 혈장-뇌 비율이 10배 높다는 것입니다. 이 화합물은 DIO 생쥐에서 5에서 80 mg/kg/일의 용량으로 최대 38%의 상당한 체중 감소를 나타냈습니다. 특히, semaglutide 치료를 대체했을 때 CRB-913은 체중 감소를 유지하고 semaglutide 유지와 비교하여 지방 감소를 두 배로 늘렸습니다. 회사는 2025년 1분기에 1상 임상 시험을 시작할 계획입니다.
Corbus Pharmaceuticals (NASDAQ: CRBP) a présenté de nouvelles données précliniques pour CRB-913, son agoniste inverse du CB1, lors de l'Obesity Week 2024. Les résultats clés montrent que les niveaux cérébraux de CRB-913 sont 15 fois inférieurs à ceux du monlunabant, avec un rapport plasma-cerveau 10 fois plus élevé. Le composé a démontré une perte de poids significative allant jusqu'à 38 % chez les souris DIO à des doses allant de 5 à 80 mg/kg/jour. Notamment, en remplaçant le traitement par le sémaglutide, CRB-913 a maintenu la perte de poids et doublé la réduction de graisse par rapport au maintien avec le sémaglutide. L'entreprise prévoit de commencer les essais cliniques de phase 1 au premier trimestre 2025.
Corbus Pharmaceuticals (NASDAQ: CRBP) hat neue präklinische Daten für CRB-913, seinen CB1-Invers-Agonisten, während der Obesity Week 2024 vorgestellt. Die wichtigsten Ergebnisse zeigen, dass die Gehirnwerte von CRB-913 15-mal niedriger sind als die von Monlunabant, bei einem 10-mal höheren Plasma-zu-Gehirn-Verhältnis. Die Verbindung zeigte einen signifikanten Gewichtsverlust von bis zu 38 % bei DIO-Mäusen bei Dosen von 5 bis 80 mg/kg/Tag. Besonders bemerkenswert ist, dass CRB-913 beim Ersetzen der Semaglutid-Behandlung den Gewichtsverlust aufrechterhielt und die Fettverringerung im Vergleich zur Semaglutid-Erhaltung verdoppelte. Das Unternehmen plant, im ersten Quartal 2025 mit Phase-1-Studien zu beginnen.
- Demonstrated significant weight loss efficacy up to 38% in DIO mice
- Shows 15-fold lower brain penetration compared to monlunabant
- Successfully maintained weight loss when replacing semaglutide treatment
- Achieved double fat reduction compared to semaglutide maintenance cohort
- Phase 1 clinical trial timeline confirmed for Q1 2025
- Still in pre-clinical stage, far from potential commercialization
- Will require extensive clinical trials to prove human efficacy
Insights
The pre-clinical data for CRB-913 shows promising characteristics for obesity treatment. The 15-fold lower brain penetration compared to monlunabant suggests a better safety profile by reducing central nervous system exposure. The dose-response data reaching
The maintenance therapy findings are significant - demonstrating that CRB-913 can not only maintain weight loss achieved by semaglutide but potentially enhance fat reduction through peripheral mechanisms. This positions the drug uniquely in the obesity market, offering potential versatility as monotherapy, combination therapy, or maintenance treatment.
However, investors should note these are still pre-clinical results, with Phase 1 trials not starting until Q1 2025. The human-equivalent doses of 30-450 mg/day need clinical validation for safety and efficacy. The multiple potential clinical applications could expand market opportunities but will require extensive clinical validation.
- CRB-913 brain levels are 15-fold lower than monlunabant in lean mice
- Dose-response demonstrated for a range of 5 to 80 mg/kg/day achieving up to
38% weight loss in DIO mice - Semaglutide treatment followed by its replacement with CRB-913 demonstrated continued weight loss in DIO mice
- Switching from semaglutide to CRB-913 led to a doubling of fat loss in DIO mice
NORWOOD, Mass., Nov. 04, 2024 (GLOBE NEWSWIRE) -- Corbus Pharmaceuticals Holdings, Inc. (NASDAQ: CRBP) (“Corbus” or the “Company”), an oncology and obesity company with a diversified portfolio, presents new pre-clinical data at Obesity Week 2024 further characterizing CRB-913, its highly peripherally restricted CB1 inverse agonist. The data are being presented as a Poster Presentation titled: “Induction and Maintenance Regimens with CB1 Inverse Agonist CRB-913 and Semaglutide in DIO Mice”.
Key findings:
- CRB-913 brain levels (both Cmax and AUC) were 15-fold lower than monlunabant at the same dose in mice.
- Plasma-to-brain ratio for CRB-913 was 10 times higher than monlunabant and 50 times higher than rimonabant at the same dose.
- CRB-913 demonstrated a wide dose response weight loss curve in DIO mice ranging from 5 mg/kg/day to 80 mg/kg/day with no plateauing effect and reaching a weight loss of
31% by day 19. Extending the dosing at 80 mg/kg/day to 28 days resulted in an additional weight loss reaching38% . - Allometrically, this dose range corresponds to human-equivalent doses of 30 mg/day to 450 mg/day.
- A first-of-its-kind experimental protocol in DIO mice demonstrated that weight loss induced by an incretin analog (semaglutide) can be maintained post withdrawal by replacing it with a CB1 inverse agonist (CRB-913) whereas replacement of semaglutide with vehicle led to a rapid and complete regain of weight.
- DEXA-scanning data revealed that switching from semaglutide to CRB-913 in DIO mice led to additional weight loss that was driven by a doubling in fat percentage reduction compared to the corresponding semaglutide maintenance cohort. This indicates a peripheral effect on fat metabolism not present with semaglutide.
“This work adds noteworthy new data to the pre-clinical characterization of CRB-913 and provides important context in comparison to monlunabant” said Yuval Cohen, PhD, CEO of Corbus. “It provides further evidence in support of CRB-913 as a markedly more peripherally restricted CB1 inverse agonist than monlunabant and suggests potential clinical use both as a monotherapy as well as a maintenance therapy post incretin analog induction treatment. This is in addition to our previously published work Morningstar et al, Obesity Aug 2023 showing that CRB-913 provides additive weight loss when combined with incretin analogs in DIO mice. The totality of this body of work provides insight into potentially three separate clinical usages: monotherapy, combination therapy and an induction/maintenance therapy.”
CRB-913 is on schedule to begin a Phase 1 clinical study in Q1 of 2025.
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 which 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 were the key results of CRB-913 in DIO mice studies?
When will Corbus Pharmaceuticals (CRBP) begin Phase 1 trials for CRB-913?
How does CRB-913's brain penetration compare to other compounds?
