Atavistik Bio to Present Discovery of JAK2 V617F Mutant-Selective Allosteric Inhibitors for the Treatment of Myeloproliferative Neoplasms (MPNs) at ASH 2025
- Atavistik Bio to present the discovery and characterization of novel allosteric JAK2 V617F selective inhibitors that suppress mutant-dependent signaling and proliferation while sparing wild-type JAK2
- Atavistik Bio’s JAK2 V617F mutant-selective inhibitors have the potential to address the significant unmet needs of patients with myeloproliferative neoplasms by providing disease-modifying efficacy while avoiding off-target hematological effects associated with wild-type JAK inhibition
CAMBRIDGE, Mass., Dec. 04, 2025 (GLOBE NEWSWIRE) -- Atavistik Bio, a biotechnology company discovering the next generation of precision allosteric therapeutics, today announced that it will unveil the discovery of its novel, potent, and selective allosteric inhibitors of JAK2 V617F for the treatment of myeloproliferative neoplasms (MPNs) and present compelling, supportive preclinical data for the program at the 67th American Society of Hematology (ASH) Annual Meeting and Exhibition to be held in Orlando December 6-9, 2025.
The JAK2 V617F mutation is the most common driver mutation in patients living with MPNs, affecting approximately 95% of patients with polycythemia vera (PV), 60% of patients with essential thrombocythemia (ET) and 55% of patients with myelofibrosis (MF). Selectively targeting the JAK2 V617F mutation has the potential to reduce mutant allele burden, modify disease progression, and significantly enhance treatment outcomes for MPN patients. Approved pan-JAK inhibitors, such as ruxolitinib, target the active site in the JH1 kinase domain of JAK2. Though they have demonstrated clinical benefit and symptomatic relief, pan-JAK inhibitors non-selectively inhibit both mutant and wild-type JAK2. This limits the ability to significantly reduce JAK2 V617F mutant allele burden that is correlated with disease progression. Additionally, inhibition of wild-type JAK2 disrupts normal hematopoiesis, leading to adverse events, and contributes to treatment discontinuation. These limitations underscore the need for mutant-selective, disease-modifying therapies. A highly selective allosteric JAK2 V617F mutant-inhibitor that spares wild-type JAK2 has the potential to provide disease-modifying efficacy, enable molecular remission by reducing mutant JAK2 allele burden and improve hematologic tolerability.
At ASH, Atavistik Bio will present the identification of JAK2 V617F mutant-selective inhibitors that bind the allosteric pseudokinase JH2 domain, which harbors the V617F mutation. These compounds were developed using the company’s proprietary AMPS™ platform and structure-based drug design and demonstrate picomolar affinity for the JAK2 V617F JH2 domain and >100-fold selectivity over related JAK family kinases (TYK2, JAK1). In preclinical models, these compounds show potent inhibition of JAK2 V617F-dependent signaling and proliferation in multiple human hematopoietic cancer cell lines harboring the mutations while sparing wild-type JAK2 cells. Additionally, these compounds demonstrated more than ten-fold selective inhibition of cytokine-independent JAK2 V617F signaling over cytokine-dependent wild-type JAK2 signaling in an isogenic cell model in which the JAK2 V617F mutation was edited to wild-type. In a mouse model bearing JAK2 V617F-expressing SET2 tumors, Atavistik JAK2 V617F selective inhibitors demonstrated strong target engagement, evidenced by reduced phosho-STAT5 levels. Compounds with favorable PK properties, good tolerability, and limited off target activity are being advanced for further development.
“We are pleased to share the discovery of our novel JAK2 V617F mutant-selective allosteric inhibitor program and compelling preclinical data at the upcoming ASH meeting,” said Marion Dorsch, Ph.D., President and Chief Scientific Officer, Atavistik Bio. “Unlike pan-JAK inhibitors that broadly target JAK2 and can only manage symptoms of myeloproliferative neoplasms, our highly selective allosteric JAK2 V617F mutant-selective inhibitors have the potential to deliver durable responses and mitigate off-target hematological effects, offering a powerful disease-modifying benefit and addressing the unmet needs of this patient population.”
Atavistik Bio Poster Presentation Details
Poster Title: Discovery of JAK2V617F mutant specific allosteric inhibitors for the treatment of myeloproliferative neoplasms
Session Name: 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Poster I
Session Date and Time: Saturday, December 6, 2025, 5:30 PM – 7:30 PM ET
Location: Orange County Convention Center - West Halls B3-B4
Poster #: 1977
About Atavistik Bio
Atavistik Bio is a clinical stage biotechnology company accelerating the discovery and development of transformative precision allosteric therapeutics to address serious unmet patient needs. Since its inception, Atavistik Bio has rapidly established an emerging pipeline of allosteric therapeutics with the potential to achieve superior efficacy and tolerability profiles by leveraging the power of allostery. Atavistik Bio is currently conducting a Phase 1 clinical trial of ATV-1601, an allosteric selective inhibitor for solid tumors.
Atavistik Bio is led by an experienced team of drug hunters with a proven track record of developing marketed small molecule therapies and supported by top-tier investors, including The Column Group, Nextech Invest, and Lux Capital. To learn more, visit us at atavistikbio.com and follow us on LinkedIn.
Media Contact:
Liz Melone
Melone Communications, LLC
liz@melonecomm.com
Legal Disclaimer:
EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.
