With scientific research this year continuing to point to the potential of the PIKFYVE enzyme as a target for amyotrophic lateral sclerosis (ALS), Takeda has decided to join the team.
Some of the main players in the PIKFYVE space are Verge Genomics, AI Therapeutics and AcuraStem, and Takeda has opted for the latter. The Japanese drugmaker has acquired the exclusive worldwide license to AcuraStem’s PIKFYVE-targeted ALS program, including a preclinical antisense oligonucleotide dubbed AS-202.
AcuraStem will oversee some of the work to get AS-202 through investigational new drug-enabling studies as well as prep some potential backup antisense oligonucleotides before Takeda takes any resulting drugs through the clinic and hopefully to market.
The exact financial makeup of the deal is less clear, with AcuraStem only revealing that the combined upfront payment and milestones could reach $580 million in total, alongside royalties.
A study in February published in Cell was a timely reminder of the potential of PIKFYVE as a target for ALS therapy. Researchers used a drug from AI Therapeutics called apilimod to inhibit PIKFYVE in human motor neurons, roundworms, fruit flies and mice with ALS. The drug prompted motor neurons to clear out toxic proteins, improving motor function and extending survival in all the models, the researchers reported.
While progress has been made on drugs to treat genetic ALS, researchers have struggled to find therapies that work well in the second and far more common type, known as sporadic ALS. The difficulties with getting new treatments to market was hammered home again yesterday by the FDA’s methodical takedown of BrainStorm Cell Therapeutics' approval application for its NurOwn drug ahead of an advisory committee meeting later this week.
“Whilst recent treatment advances have brought new hope to some patients, there remains a significant unmet need [in ALS],” Sarah Sheikh, head of Takeda’s neuroscience unit, said in the Sept. 25 release.
“We believe AS-202 has the potential to address this unmet need through its unique dual mechanism of action, which addresses TDP-43 aggregation and improves TDP-43 function, the pathological hallmark of ALS and other TDP-43 proteinopathies including certain forms of dementia,” Sheikh added.
The unmet need by ALS patients for more therapies has drawn in Eli Lilly and, more recently, AstraZeneca, which have both secured deals with Verge Genomics to work on new neurodegenerative drugs. However, neither deal touched on the biotech’s own small-molecule PIKFYVE inhibitor called VRG50635, which is in a phase 1 trial for ALS.