Core Insights - Prelude Therapeutics announced the publication of two abstracts featuring preclinical data on JAK2V617F mutant selective inhibitors and CALR-targeted degrader antibody conjugates, both accepted for oral presentation at the ASH 67 Annual Meeting in December 2025 [1][2] JAK2V617F Mutant Selective Inhibitors - The company has made a breakthrough in discovering the first known molecules that selectively bind to the JH2 'deep pocket' of the JAK2V617F mutation, demonstrating mutant-specific inhibition in various preclinical models of myeloproliferative neoplasms (MPNs) [2][6] - In JAK2VF-dependent mouse models, treatment with these inhibitors normalized white blood cell counts, platelet levels, and spleen size without causing cytopenias or other adverse effects, indicating their potential as disease-modifying agents [3][6] CALR-Targeted Degrader Antibody Conjugates (DACs) - The company developed a novel DAC designed to selectively bind to mutant CALR, which is present in 20-30% of MPN patients, delivering a potent CDK9 degrader payload [4][7] - The CALR x CDK9 DAC selectively eliminated CALR-mutant MPN progenitors while sparing healthy CD34+ stem cells, supporting its further development as a potential therapeutic option for CALR-mutant MPNs [4][7] Company Overview - Prelude Therapeutics is focused on developing innovative precision oncology medicines, with a pipeline that includes selective SMARCA2 and KAT6A degraders, as well as JAK2V617F mutant selective inhibitors [5] - The company aims to extend the promise of precision medicine to cancer patients in need, leveraging its expertise in targeted protein degradation to discover next-generation DACs [5]