Ajax raises $95 million to launch a ‘JAK attack’
13 May 2024
Phase 1Drug Approval
More than a decade after the FDA approved the first JAK inhibitorJAK inhibitor to treat myelofibrosis, Ajax Therapeutics thinks it has improved on the formula by targeting a less-well-known, inactive conformation of the kinase to boost efficacy and tolerability. The biotech raised $95 million in an oversubscribed series C, led by Goldman Sachs Alternatives, to bring its potentially first-in-class inhibitor, AJ1-11095, to the clinic next half.
Monday’s round – which also saw participation from new investors Eli Lilly, Vivo Capital, RA Capital Management, Point72, as well as existing investors EcoR1 Capital, Boxer Capital, Schrödinger, and Inning One Ventures – adds to $40 million raised in 2021.
Scientific origins
Around 2017, five experts on the biology of the JAK pathway got together with one goal in mind – creating an improved kinase inhibitor that elicits a deeper and more durable response in patients with myelofibrosis.
One of the scientists was Ross Levine, an oncologist at Memorial Sloan Kettering Cancer Center who helped discover the mutations in JAK2 associated with myelofibrosis.
“We all were excited when the discoveries were made, and then hopeful that the drugs that were developed – ruxolitinib, pacritinib, momelotinib, fedratinib – would really be game changers for patients. And they brought real, meaningful benefits to patients, but they don't lead to molecular or clinical regressions,” Levine told FirstWord.
Additionally, patient response isn’t durable, with most patients discontinuing treatment within a few years due to a loss of efficacy. And once a myelofibrosis patient fails on a JAK inhibitorJAK inhibitor, their life expectancy is around a year or two.
“There's quite a lot of room between where these molecules are… and what would be optimal engagement,” Levine said.
Out of the scientific consortium, an idea arose to design pleiotropic molecules that engage the inactive, Type II conformation of JAK2, rather than the active, Type 1 conformation, which the four myelofibrosis-approved JAK inhibitorsJAK inhibitors target.
Thus, Ajax – an abbreviation of “attack JAK” – was born in 2019, with Levine as a co-founder and serving as chair of the scientific advisory board.
Preclinical potency
The researchers had developed early chemical matter and structures that showed better efficacy than approved molecules, which gave the newco a foothold to begin designing a completely different kind of JAK inhibitorJAK inhibitor.
But for the Type II conformation, “it’s not as easy as just screening the kinase domain and finding an inhibitor,” Ajax co-founder and CEO Martin Vogelbaum told FirstWord.
So the team turned to digital chemistry company Schrödinger, which, along with serving as a co-founding investor, signed an exclusive collaboration with Ajax to apply its computational molecular discovery methods and expertise in structure based drug design to transform the biotech’s early work into a potent, specific and clinically tractable Type II JAK2 inhibitorJAK2 inhibitor.
Now, after five years of work optimising a highly selective compound, Ajax thinks AJ1-11095 is a safer molecule that produces a deeper, more durable response – and is ready to enter the clinic. A Phase I study in myelofibrosis is expected to begin in the second half.
Vogelbaum said that repeated mice experiments suggest Ajax’s lead candidate has similar, if not better, efficacy than ruxolitinib alone or in combination with another approved agent.
“Our preclinical data suggest that we can achieve greater target engagement at doses with a wide range that are efficacious – well beyond the current drugs – and are very well tolerated,” Ross said, adding that the team feels “very confident” that AJ1-11095 won’t have the off-target toxicities of others in the JAK class.
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