PRT12396 / Prelude Therap, Incyte - LARVOL DELTA

Discovery and preclinical characterization of orally bioavailable JAK2V617F mutant selective JH2 inhibitors with disease modification potential in myeloproliferative neoplasms (ASH 2025) - "The JAK2V617F mutation is the most common genetic alteration in patients with myeloproliferativeneoplasms (MPNs), present in >90% of patients with polycythemia vera (PV) and 50-60% of patients withessential thrombocythemia (ET) and myelofibrosis (MF). They achieve deep molecular engagement via Phe-triad targeting, demonstrateexceptional selectivity, and show in vivo efficacy superior to ruxolitinib. This approach holds promise fortransforming the treatment landscape in MPNs by directly targeting the molecular cause of disease.Prelude is now advancing a development candidate into Phase 1 clinical studies."

Preclinical • Essential Thrombocythemia • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • CD34 • JAK1 • JAK3 • TYK2

Prelude Therapeutics Presents Data at the 2025 ASH Annual Meeting from its Myeloproliferative Neoplasm (MPN) Programs (GlobeNewswire) - "First disclosure of PRT12396, a JAK2V617F-selective JH2 inhibitor demonstrates disease modifying potential in myeloproliferative neoplasms....The Company has completed GLP toxicology studies and anticipates filing the IND and initiating a phase 1 study in the first quarter of 2026....First disclosure of a mutant calreticulin (mCALR) targeted degrader antibody conjugate (DAC) with a novel CDK9 degrader payload."

CALR • IND • JAK2V617F • Preclinical • Myeloproliferative Neoplasm

Prelude Therapeutics…announced the publication of two abstracts with preclinical data on the Company’s JAK2V617F mutant selective inhibitors and CALR-targeted degrader antibody conjugates (DACs) discovery program, both accepted for oral presentation at the American Society of Hematology (ASH) 67th Annual Meeting… (GlobeNewswire) - "These compounds demonstrate mutant specific inhibition in multiple preclinical models of myeloproliferative neoplasms (MPNs)."

CALR • JAK2V617F • Preclinical • Myeloproliferative Neoplasm

Prelude Therapeutics Announces Exclusive Option Agreement with Incyte to Advance Mutant Selective JAK2V617F JH2 Inhibitors (The Manila Times) - "Prelude to receive a $35 million upfront payment and $25 million strategic equity investment, $100 million if Incyte were to exercise the option to acquire the program, and up to $775 million in additional potential milestones plus royalties on net sales...The first disclosure of program data was accepted for oral presentation at the American Society of Hematology (ASH) 67th Annual Meeting taking place in Orlando, FL December 6-9, 2025."

Clinical • Commercial • Myeloproliferative Neoplasm

Mutant selective JAK2V617F JH2 inhibitor program (GlobeNewswire) - "The Company has advanced the lead candidate from this program into IND-enabling studies and expects to file an IND and advance into clinical trials in the first half of 2026. The first disclosure of preclinical data from this program has been accepted for oral presentation at the American Society of Hematology (ASH) 67th Annual Meeting taking place in Orlando, FL December 6-9, 2025."

IND • New trial • Preclinical • Myeloproliferative Neoplasm