BMS-986470 / BMS - LARVOL DELTA

Development of a ZBTB7A and Wiz Dual Degrading, HbF-Activating CELMoD™ for the Treatment of Sickle Cell Disease (ASH 2024) - P1/2 | "In these preclinical models, HbF induction by BMS-986470 was significantly higher than the standard of care, hydroxyurea. In summary, we disclose the discovery and preclinical characterization of BMS-986470, a potential first-in-class, dual degrader of ZBTB7A and WIZ, with robust γ -globin induction activity leading to HbF levels predicted to significantly ameliorate SCD pathology. BMS-986470 is currently under clinical investigation (NCT06481306) for patients with SCD."

B Cell Lymphoma • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Sickle Cell Disease • Targeted Protein Degradation • CD34 • CRBN • DDB1 • ZBTB7A

Discovery of BMS-986470, a first-in-class molecular glue dual degrader of zinc finger and BTB domain containing 7A (ZBTB7A) and widely interspaced zinc finger protein (WIZ) for the treatment of treatment of Sickle Cell Disease (ACS-Fall 2025) - "Hydroxyurea (HU), the standard of care for SCD, has been shown to increase HbF levels , reducing HbS polymerization and acute complications however, its effectiveness is limited by variable patient response and tolerability and toxicity issues. In a study with naïve healthy cynomolgus monkeys, 16 days of daily BMS-986470 treatment followed by a 2-week observation period led to dose-dependent degradation of WIZ and ZBTB7A, increased circulating immature erythrocytes, elevated HBG1/2 transcripts, higher γ-globin protein, and erythroid progenitor markers in peripheral blood and bone marrow. BMS-986470 is currently undergoing Phase I clinical evaluation in SCD patients."

Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Targeted Protein Degradation • CD34 • CRBN • DDB1 • ZBTB7A

CA230-1019: A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease (clinicaltrials.gov) - P1/2 | N=184 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

CA230-1019: A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease (clinicaltrials.gov) - P1/2 | N=184 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1/2 trial • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease