BTC-86

Beyang Therapeutics recently presented its second-generation menin inhibitor, BTC-86, at the 66th Annual Meeting of the American Society of Hematology (ASH). BTC-86 has demonstrated remarkable advantages over the first-generation menin inhibitor, Revumenib, including overcoming resistance mutations and minimizing QTc prolongation. These breakthroughs have garnered significant attention from hematological oncologists, experts, and industry leaders worldwide. https://ashpublications.org/blood/article/144/Supplement%201/3586/530133/Discovery-of-BTC-86-a-Novel-Second-Generation KMT2A rearrangements (KMT2Ar) and NPM1 mutations are relatively common in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), accounting for 5–10% of AML/ALL cases with KMT2Ar and about 30% of AML cases with NPM1 mutations. These genetic abnormalities are associated with poor prognoses, as traditional chemotherapy often leads to high rates of resistance and relapse. For relapsed or refractory KMT2Ar patients, the median overall survival is less than three months, while NPM1-mutated relapsed/refractory patients have a median survival of less than six months. This underscores the urgent need for novel therapies targeting these specific mutations to improve patient outcomes. In November 2024, Revumenib received FDA approval for treating adult and pediatric patients aged one year and older with KMT2Ar relapsed or refractory acute leukemia, making it the world’s first approved menin inhibitor. Clinical trials reported the complete remission (CR) plus complete remission with partial hematologic recovery (CRh) rate of 21% (22/104), with a median duration of response (mDOR) of 6.4 months. The overall response rate (ORR) was 63%, representing a significant improvement over traditional chemotherapy. However, resistance mutations developed in approximately 38.7% of patients after two cycles of treatment, and around 13% experienced Grade 3 QTc prolongation, a serious cardiac toxicity. Beyang Therapeutics’ compound BTC-86 distinguishes itself with groundbreaking features that address critical challenges in menin inhibitor development. Leveraging the company’s proprietary ExCEED (Experiment + Computation with Enhanced Evaluation & DMPK) platform, BTC-86,designed using a novel molecular design technology, circumvent resistance mutation sites effectively. This approach ensures comparable inhibitory activity against both the wild-type and key resistance mutations of Revumenib. In addition to its precision targeting, BTC-86 demonstrates a minimal impact on hERG channels, substantially mitigating the risk of QTc prolongation and associated cardiac toxicity. Notably, preclinical studies reveal that BTC-86 delivers significantly enhanced tumor growth inhibition compared to Revumenib across multiple CDX and PDX in vivo efficacy models. These findings highlight BTC-86 as a front runner in developing a treatment for R/R AML and ALL as second-generation menin inhibitor. About ASH: The American Society of Hematology (ASH) was established in 1958 and is the world's largest professional hematology organization. It is committed to improving the prevention, diagnosis and treatment of blood diseases through research, education, and the promotion of clinical practice. About Beyang: Beyang Therapeutics is an innovative drug research and development company aiming to become the "DreamWorks" of the global pharmaceutical industry. The company uses its proprietary computer-accelerated drug discovery integration platform ExCEED (including proprietary database) to guide the discovery and optimization of candidate molecules, significantly expanding the effective chemical space and broadening the optimization ideas of effective molecules, thereby obtaining candidate molecules with the Best-in-Class potential. The founding team has an average of over 20 years’ experience in new drug research and development and computational simulation, and worked at MNCs such as Pfizer, Merck and AstraZeneca with extensive experience in target selection, CADD/AIDD, biological screening and druggability optimization. They have facilitated the discovery of more than 20 clinical candidates, among which close to 10 drugs (Sunitinib, Crizotinib, Axitinib, Adebrelimab, etc.) have been approved by the FDA/NMPA and were adopted by clinical practice. The company focuses on ophthalmology and oncology. The first ophthalmic project BT01001 has completed pre-IND studies and is now ready to receive approval for initiating clinical trials. The oncology project BY002 is currently undergoing IND-enabling studies, with the expectation of gaining approval for clinical trials in 2025H2. Website: https://www.beyangtx.com/?lang=en Email: liuc@beyangtx.com