LONDON — October 7, 2026
CHARM Therapeutics announced that the first patient has been dosed and the first cohort fully enrolled in its Phase I/II clinical trial evaluating CHM-029 in patients with acute myeloid leukemia (AML). The milestone marks the transition of CHARM into a clinical-stage biotechnology company and represents the first clinical progression of a molecule designed using the company’s proprietary DragonFold AI platform, which uses protein-ligand co-folding to support drug discovery. The company is developing CHM-029 as a next-generation menin inhibitor intended to address treatment resistance associated with earlier-generation therapies. The Phase I/II study will evaluate the safety and efficacy of CHM-029 in patients with relapsed or refractory AML carrying an NPM1 mutation, KMT2A rearrangement or NUP98 rearrangement. CHARM expects to report initial clinical data from the program in 2027, providing the first human clinical assessment of its AI-designed menin inhibitor.
CHM-029 Targets Menin-Driven AML Biology
CHM-029 is designed to disrupt the interaction between menin and KMT2A, a protein-protein interaction that contributes to leukemic cell growth in specific AML subtypes. Menin inhibitors have emerged as an important targeted therapeutic approach in AML by disrupting this interaction and restoring gene-regulation processes that can promote differentiation and death of malignant cells. However, CHARM said the development of first-generation menin inhibitors has been challenged by the emergence of resistance mutations in the menin protein, which can reduce drug activity and contribute to disease progression. Some existing approaches may also face limitations associated with safety considerations such as QTc prolongation, as well as pharmaceutical characteristics including potential drug-drug interactions and the need for higher doses. CHARM designed CHM-029 to closely mimic the binding of KMT2A to menin, with the objective of maintaining activity against resistance-associated mutations while supporting a differentiated therapeutic profile.
DragonFold AI Designed CHM-029 for Resistance
The development of CHM-029 represents an application of CHARM Therapeutics’ proprietary DragonFold AI drug discovery platform to precision oncology. According to the company, the molecule has demonstrated potent preclinical activity against all publicly described menin resistance mutations and produced dose-dependent tumor regression in both wild-type and mutant preclinical models. CHARM also reported a favorable preclinical safety profile for CHM-029. The company’s approach is focused on designing compounds that preserve target engagement even when cancer-associated mutations alter the structure of the target protein. This strategy is particularly relevant in AML, where resistance to targeted therapies can limit treatment durability. Moving CHM-029 into human clinical development represents an important test of whether the company’s AI-driven protein-ligand design approach can translate its preclinical resistance profile into a clinically meaningful therapeutic advantage for patients with AML.
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CHARM Advances Clinical Development Toward 2027 Data
The Phase I/II CHM-029 clinical trial will evaluate safety, tolerability and efficacy in patients with relapsed or refractory AML harboring specific molecular alterations associated with menin-dependent disease biology. The initial enrollment milestone comes less than 24 months after the first synthesis of CHM-029, according to CHARM, highlighting the company’s rapid progression from drug design into clinical development. The program is intended to determine the clinical profile of CHM-029 and provide evidence to guide subsequent development of the next-generation menin inhibitor. CHARM has raised more than $150 million from international investors and is focused on advancing precision oncology programs designed to overcome resistance mechanisms. With the first patient now treated and the first cohort fully enrolled, CHARM Therapeutics is moving CHM-029 into clinical evaluation as it seeks to develop a potentially more durable menin-targeted treatment for AML, with initial clinical data expected in 2027..
Source::CHARM Therapeutics, press release
