– AJ1-10502 Demonstrates Higher Selectivity and Better Efficacy with Significant Reductions in Mutant Cell Fraction, Compared to the Leading JAK2 Type I Inhibitor, Ruxolitinib, in Multiple Myeloproliferative Neoplasm (MPN) Disease Models –
NEW YORK, December 12, 2022–(BUSINESS WIRE)–Ajax Therapeutics, Inc., a biopharmaceutical company applying computational chemistry and structure-based technologies to develop novel small molecules selective for myeloproliferative neoplasms (MPN), today announced the presentation of data preclinical talks on the upcoming second-generation JAK2 inhibitor, AJ1-10502, in a poster session held today at the 64th Annual Meeting and Exposition of the American Society of Hematology (ASH) in New Orleans.
The poster, titled “Second Generation JAK2 Inhibitor Type II, AJ1-10502, Demonstrates Higher Selectivity, Better Therapeutic Efficacy, and Reduced Mutant Cell Fraction Compared to JAK2 Type I Inhibitors in Myeloproliferative Neoplasm (MPN) Models” highlights the improved efficacy and disease-modifying characteristics of Ajax’s type II JAK2 inhibitor, AJ1-10502, compared to the first-generation investigational type II inhibitor, CHZ868, and the approved market-leading type I inhibitor , ruxolitinib, in two different mouse models of MPN.
In both MPN models studied, AJ1-10502 demonstrated dose-dependent improvements in efficacy versus ruxolitinib on key blood cell parameters, including reticulocytes and hematocrit, associated with MPN, as well as superior reductions in spleen weight on par with deletion of JAK2. More importantly, AJ1-10502 caused significant reductions in the mutant cell fraction within the bone marrow and spleen not seen with ruxolitinib. Distinct from all currently approved JAK2 inhibitors, including ruxolitinib, which bind the JAK2 kinase type I conformation and enable continued JAK/STAT signaling leading to disease persistence, AJ1-10502 is designed to bind the JAK2 kinase type II conformation JAK2 kinase. In preclinical studies, investigational JAK2 inhibitors type II were shown to overcome ruxolitinib disease persistence and, more significantly, reduce the burden of the mutant JAK2 allele driving MPN disease progression. ASH’s poster presentation is available on the Ajax website.
“We are very encouraged by the early preclinical data on our JAK2 type II inhibitor program presented today at the ASH Annual Meeting,” said Craig E. Masse, PhD, senior vice president, Discovery Research at Ajax Therapeutics. “Our unique drug discovery capabilities, including cutting-edge computational and structure-based technologies, have enabled us to develop JAK2 type II inhibitors, such as AJ1-10502, that target JAK2 with greater precision and potency, surpassing while the limitations of current JAK2 therapies that interact with other members of the JAK family and related kinases limit their efficacy and lead to undesirable side effects.”
“It is exciting to see Ajax’s next-generation type II JAK2 inhibitor, AJ1-10502, demonstrate greater selectivity and efficacy with a much improved safety profile compared to first-generation type II inhibitors,” said Ross Levine, MD, Chair of the Ajax Scientific Advisory Board and Deputy Physician-in-Chief, Translational Research, Laurence Joseph Dineen Chair in Leukemia Research and a member of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center. “These data support our findings that JAK2 type II inhibitors can significantly reduce the mutant allele burden driving MPNs, which is not seen with JAK2 type I inhibitors, such as ruxolitinib. We believe that more selective and potent JAK2 inhibitors , such as AJ1-10502, could provide much-needed new targeted therapies for MPN patients who are not well served by currently approved JAK2 inhibitors.”
About Ajax Therapeutics
Ajax Therapeutics, Inc. is pursuing unique selective approaches to develop new first-in-class therapies for myeloproliferative neoplasms (MPNs), including myelofibrosis. By combining our founding scientists’ deep cancer and structural biology insights with the industry’s most advanced computational drug discovery and protein structure platforms from our founding partner, Schrödinger, Inc., we aim to discover and develop more intelligently designed therapies precise to address significant unmet needs for patients with MPN.
More information is available at www.ajaxtherapeutics.com.
NOTE: Dr. Ross Levine serves on the board of directors of Ajax Therapeutics, has provided consultancy services and holds stakes in Ajax Therapeutics. Dr. Levine also has intellectual property rights and interests which MSK has licensed to Ajax. MSK holds intellectual property rights and other financial interests related to Ajax.
View the source version at businesswire.com: https://www.businesswire.com/news/home/20221211005025/en/
Kathryn Morris, The Yates Network LLC