WILMINGTON, DE — Prelude Therapeutics Incorporated (Nasdaq: PRLD) announced the publication of two abstracts featuring preclinical data from its JAK2V617F mutant-selective inhibitor program and CALR-targeted degrader antibody conjugates (DACs) discovery program. Both will be presented orally at the American Society of Hematology (ASH) 67th Annual Meeting, taking place in Orlando, Florida, from December 6–9, 2025.
“We are excited for the opportunity to share the first-time disclosure of our novel JAK2V617F mutant selective inhibitor program as well as the discovery of first-in-class CALR-targeted precision DACs delivering CDK9 degrader payloads,” stated Peggy Scherle, Ph.D., Chief Scientific Officer of Prelude. “For JAK2, our research team made a breakthrough in the discovery of the first known molecules that bind into the JH2 ‘deep pocket’ where the V617F mutation resides. These compounds demonstrate mutant specific inhibition in multiple preclinical models of myeloproliferative neoplasms (MPNs). In our mCALR DAC discovery program, we engineered a novel CDK9 degrader conjugated to a CALR antibody leveraging our expertise in both CDK9 chemistry and MPN biology, which gives an additional payload option to our previously disclosed SMARCA2/4 mCALR DAC. We believe both of these programs represent novel disease modifying treatment options in significant areas of unmet need for patients living with MPNs.”
The first presentation, “Discovery and preclinical characterization of orally bioavailable JAK2V617F mutant selective JH2 inhibitors with disease modification potential in myeloproliferative neoplasms,” will be delivered by Dr. Neha Bhagwat on December 6 from 10:15 to 10:30 a.m. (Publication Number 70). The research details how structure-based drug design enabled the creation of highly potent, allosteric mutant JAK2-selective inhibitors that bind into the deep pocket where the JAK2V617F mutation resides. In preclinical models, these inhibitors demonstrated strong mutant selectivity, normalization of blood counts and spleen size, and selective targeting of JAK2VF stem cells—without causing cytopenias or affecting wild-type cells.
The second presentation, “Discovery of first-in-class CALR-targeted precision ADCs delivering a CDK9 degrader payload for the treatment of CALR-mutated MPNs,” will be presented by Dr. Norman Fultang on December 6 from 10:45 to 11:00 a.m. (Publication Number 72). The study reports on the development of a novel DAC designed to selectively bind mutant CALR and deliver a CDK9 degrader payload. In preclinical studies, the CALR × CDK9 DAC selectively eliminated CALR-mutant MPN progenitors while sparing healthy CD34+ stem cells, supporting its potential as a disease-modifying therapeutic for CALR-mutant MPNs.
Both presentations will take place during the session “Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational – Precision Targeting in MPN” in room OCCC-W414AB. Abstracts are available on the ASH Annual Meeting & Exposition website at hematology.org.
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