AZD3632 / AstraZeneca - LARVOL DELTA

Discovery of AZD3632, a potential best-in-class Menin inhibitor (ACS-Fall 2026) - "A strategically placed methyl group conferred stable atropoisomers, effectively mitigating critical off-target interaction at the M2 muscarinic receptor and enhancing gut wall permeability. Here, we outline the rational design and stepwise optimization of this chemical series culminating in the identification of AZD3632, now in Phase 1 clinical trials."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • KMT2A • NPM1

MOMENTUM: Study of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression (clinicaltrials.gov) - P1/2 | N=84 | Recruiting | Sponsor: AstraZeneca

First-in-human • Monotherapy • Trial initiation date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • KMT2A

D8620C00001: A trial to learn how safe AZD3632 is, how well it works, and how it moves throughout the body over time in adults with acute leukemia and myelodysplastic syndrome with HOX gene overexpression (clinicaltrialsregister.eu) - P1/2 | N=17 | Recruiting | Sponsor: AstraZeneca AB

Monotherapy • New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CDX2 • CREBBP • ETV6 • KMT2A • NPM1 • NUP214 • NUP98 • RUNX1

MOMENTUM: Study of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression (clinicaltrials.gov) - P1/2 | N=84 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human • Monotherapy • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • KMT2A

MOMENTUM: Study of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression (clinicaltrials.gov) - P1/2 | N=84 | Not yet recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2029 ➔ Feb 2029 | Trial primary completion date: Jun 2029 ➔ Feb 2029

Monotherapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

MOMENTUM: Study of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression (clinicaltrials.gov) - P1/2 | N=84 | Not yet recruiting | Sponsor: AstraZeneca

Monotherapy • New P1/2 trial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology