CHARM Therapeutics (“CHARM”, “The Company”), a clinical-stage biotechnology company addressing resistance in acute myeloid leukemia (AML) with a best-in-class menin inhibitor, announces it has initiated dosing and fully enrolled the first cohort in its Phase I/II clinical trial of CHM-029 in patients with AML. This is the first example of a molecule designed using a protein-ligand co-folding model to progress into clinical studies.

AML affects approximately 20,000 people annually in the United States and remains one of the most challenging blood cancers to treat with a five-year survival rate of less than 30%. Menin inhibitors have emerged as an important breakthrough in AML treatment, targeting the protein-protein interaction between menin and KMT2A, a key driver of leukemic cell growth. However, despite first-generation menin inhibitors demonstrating promising clinical activity, they are limited by the rapid emergence of resistance mutations in the menin protein that reduce efficacy and lead to disease progression. Further, the efficacy of some first generation menin inhibitors may be limited by safety risks including QTc prolongation and poor pharmaceutical properties such as the potential for drug-drug interactions and requirement for high doses.

CHARM has used its proprietary AI platform DragonFold^TM to specifically design CHM-029 to address this issue by closely mimicking the binding of KMT2A to menin, enabling the differentiation and cell death of otherwise cancerous cells. CHM-029 has demonstrated potent activity against all publicly described resistance mutations, robust dose-dependent tumor regression in both wild-type and mutant pre-clinical models, and a favorable preclinical safety profile.

Gary D. Glick, Ph.D., Interim Chief Executive Officer of CHARM Therapeutics, said: “Initiation of this Phase I/II clinical trial represents a pivotal moment for CHARM and, most importantly, for patients with AML who urgently need more durable treatment options. We progressed the program rapidly with less than 24 months elapsed between the first synthesis of CHM-029 and the first patient dosed. We look forward to continuing to advance CHM-029 through clinical development and believe our next-generation approach has the potential to transform outcomes for patients living with this devastating disease.”

Professor Paresh Vyas, Principal Investigator, said: “Despite advances in targeted therapies for AML, outcomes remain poor for many patients. Dosing the first patient in this trial using a novel menin inhibitor that has been designed using AI to avoid drug resistance marks significant progress in efforts to deliver deeper more durable responses for patients, and we look forward to evaluating CHM-029 in the clinic.”

The Phase I/II clinical trial (NCT07751991) will evaluate the safety and efficacy of CHM-029 in patients with relapsed or refractory AML with an NPM1 mutation, KMT2A rearrangement, or NUP98 rearrangement.