Cogent Biosciences presents preclinical data for best-in-class contender CGT1145 at EHA 2026
Cogent Biosciences (NASDAQ:COGT) unveiled highly supportive preclinical findings for its novel small molecule therapeutic candidate, CGT1145, at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden.
The candidate is a next-generation, wild-type-sparing Janus kinase 2 (JAK2) V617F mutant-selective inhibitor designed to treat myeloproliferative neoplasms (MPNs), an aggressive class of bone marrow disorders.
The acquired somatic point mutation JAK2 V617F serves as the primary oncogenic driver behind BCR-ABL-negative MPNs.
The mutation is present in nearly 95% of individuals diagnosed with polycythemia vera and roughly 50% of those presenting with essential thrombocythemia or primary myelofibrosis.
While currently approved first-generation JAK2 inhibitors effectively suppress broad systemic inflammation, they bind indiscriminately to the regular kinase domain (JH1), leading to off-target toxicities, severe immunosuppression, and dose-limiting anemia.
The preclinical datasets demonstrated that CGT1145 binds selectively to the regulatory pseudokinase (JH2) domain, achieving over 100-fold selectivity for the mutant protein over normal wild-type JAK2 and structural JAK1/3 isoforms.
This targeted mechanism allowed the molecule to selectively halt cellular growth in diseased human erythroleukemia cells while preserving healthy hematopoietic lineages.
Animal models confirmed that the compound displays a highly favorable pharmacological profile, characterized by exceptionally high oral bioavailability exceeding 80% and low internal clearance rates across multiple evaluated mammal species.
In vivo disease testing highlighted significant therapeutic efficacy with minimal impact on stable baseline blood counts.
In progressive transgenic mouse models of JAK2-driven MPN, oral administration of CGT1145 successfully reversed massive splenomegaly (spleen enlargement), cleared erythroid precursor aggregates from visceral tissues, and normalized white blood cell counts.
The level of disease control proved equivalent to standard-of-care agents like ruxolitinib, but with significantly improved hematologic tolerability.
The positive presentation underpins Cogent’s strategy to shift its proprietary discovery platform toward early-stage clinical entry.
Management reiterated that the development program for CGT1145 remains on track, with an Investigational New Drug (IND) application slated for submission to the FDA during the second half of 2026 to clear the path for initial Phase 1 human trials.
