Insider Brief
- CHARM Therapeutics raised $80 million in an oversubscribed Series B round to develop a new generation of menin inhibitors for acute myeloid leukemia (AML).
- The funding was co-led by New Enterprise Associates and SR One, with participation from NVIDIA and existing investors OrbiMed, F-Prime, and Khosla Ventures.
- CHARM’s proprietary DragonFold AI platform has produced a candidate active against resistance mutations that undermine first-generation menin inhibitors.
CHARM Therapeutics announced the close of an $80 million Series B financing round to accelerate development of its next-generation menin inhibitor into clinical trials, according to a news release. The company, headquartered in Cambridge, U.K., is targeting acute myeloid leukemia, a blood cancer with limited treatment options and poor patient outcomes.
Menin inhibitors have emerged as one of the most promising therapies for acute myeloid leukemia, or AML, disrupting a cancer-driving interaction between menin and the KMT2A gene. First-generation menin inhibitors, including revumenib, gained clinical validation by triggering differentiation and death of leukemic cells. But rapid emergence of resistance mutations has undercut their long-term effectiveness, often leading to relapse.
CHARM aims to solve this problem with molecules engineered to retain potency against all publicly described resistance mutations. The company’s lead compound, discovered using its AI-enabled protein–ligand co-folding platform DragonFold, has shown robust tumor regression in preclinical models.
Backing From Global Investors
The financing was co-led by New Enterprise Associates (NEA) and SR One, two leading life sciences venture firms, according to the release. Additional support came from NVIDIA, which has increased its presence in AI-driven drug discovery, and existing investors OrbiMed, F-Prime, and Khosla Ventures.
The round was oversubscribed, underscoring investor confidence in CHARM’s approach to overcoming the limitations of first-generation therapies. The proceeds will support clinical development, with first-in-human trials expected to begin early next year.
Addressing Clinical Limitations
First-generation menin inhibitors have also faced safety and pharmacological hurdles. Some require high doses, raising concerns about drug–drug interactions and QTc interval prolongation, a cardiac risk that can complicate treatment. CHARM’s candidate is designed to avoid these pitfalls. Preclinical data suggest efficacy at lower doses without increasing QTc risk and without inhibiting enzymes that contribute to drug interactions.
If confirmed in the clinic, these features could translate into safer and more durable therapies for AML patients who often face rapid disease progression.
Strategic Board Appointments
In parallel with its financing, the release also detailed changes to CHARM’s governance. Briggs Morrison, M.D., was appointed non-executive director, bringing direct experience from his time leading Syndax, the developer of the first FDA-approved menin inhibitor.
Kim Blackwell, M.D., a seasoned oncology executive, also joins as non-executive director to support clinical strategy. Investor representatives Matthew McAviney, M.D., of NEA, and Mahesh Kudari, M.D., of SR One, will join the board to align capital strategy with CHARM’s clinical plans.
Voices From the Industry
Gary D. Glick, Ph.D., Executive Chair of CHARM, said the financing validates the company’s AI-driven approach: current menin inhibitors “are fundamentally limited by the rapid emergence of resistance mutations that cause treatment failure,” while CHARM’s next-generation inhibitors are “specifically designed to overcome these resistance mutations and deliver the durable responses that patients need.”
NEA’s McAviney added that strong preclinical data and a clear development path “make CHARM well positioned to drive meaningful impact for patients facing treatment-resistant cancers.” Kudari of SR One emphasized the role of DragonFold in rapidly identifying inhibitors active against resistant mutations.
About Menin Inhibitors in AML
AML is driven by multiple genetic and epigenetic abnormalities. One well-established driver is the interaction of menin with KMT2A, which normally regulates transcription and differentiation. In leukemia, the menin–KMT2A complex up-regulates genes that fuel malignancy.
Menin inhibitors block this binding, restoring normal gene regulation and triggering cancer cell death. Clinical data from first-generation therapies have confirmed the value of this approach, but resistance mutations and safety concerns have limited outcomes. CHARM is betting its AI-designed molecules can unlock the full potential of menin inhibition.
