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MPN Workshop of the Carolinas 2025 | The development of Type II selective JAK inhibitors for the treatment of MPNs
Andrew Dunbar, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the development of Type II selective JAK inhibitors for the treatment of myeloproliferative neoplasms (MPNs), highlighting their potential to overcome the limitations of existing JAK inhibitors in achieving effective downstream inhibition and eradicating MPN clonal burden. Dr Dunbar notes that a novel compound in this drug class, AJ1-11095, has shown encouraging preclinical activity and is currently being tested in a Phase I trial (NCT06343805). This interview took place at the 2nd Annual MPN Workshop of the Carolinas, held in Charlotte, NC.
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Transcript
So, the purpose of my presentation was to update everybody on where we are with the development of these type II JAK2 inhibitors. This is an emerging class, completely brand new type of JAK inhibitor that binds the JAK2 protein in a slightly different way that we think will more potently inhibit the pathways that drive MPN cell growth.
And so I think most patients know that there are now several clinically approved JAK inhibitors available for patients with MPNs, but I think there’s a general consensus in the field that each and every one of these inhibitors isn’t as good as they could be in achieving that effective downstream inhibition and really eradicating the MPN clonal burden...
So, the purpose of my presentation was to update everybody on where we are with the development of these type II JAK2 inhibitors. This is an emerging class, completely brand new type of JAK inhibitor that binds the JAK2 protein in a slightly different way that we think will more potently inhibit the pathways that drive MPN cell growth.
And so I think most patients know that there are now several clinically approved JAK inhibitors available for patients with MPNs, but I think there’s a general consensus in the field that each and every one of these inhibitors isn’t as good as they could be in achieving that effective downstream inhibition and really eradicating the MPN clonal burden. And so the rationale behind type IIs is that they overcome some of these mechanisms of persistence. And hopefully we’ll show or we’ll see with the trials that not only can we extend a treatment response with these more potent agents, but also maybe even reduce the total MPN clonal burden.
The problem with type IIs up until recently is that some of the agents that had been developed before came with a fair degree of toxicity, but now excitingly we actually have a compound in hand, it’s a drug called AJ1 11095, it’s made by a company called Ajax Therapeutics, that has the appropriate selectivity, potency, bioavailability properties that we’ve been able to move to the clinic, and so this is a Phase I trial ongoing right now. We’ve done a lot of preclinical activity with this 11095 drug that looks quite promising. And so we’ll see now in the patient setting whether or not we can again enhance these responses.
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Disclosures
Ajax Therapeutics.
