As scientific research continues to underscore the potential of targeting the PIKFYVE enzyme in the quest to combat amyotrophic lateral sclerosis (ALS), Takeda has decided to join the ranks of those pursuing this promising avenue. Within the PIKFYVE arena, key players include Verge Genomics, AI Therapeutics, and AcuraStem, with Takeda choosing to align itself with the latter. In a significant move, the Japanese pharmaceutical company has acquired the exclusive worldwide license for AcuraStem’s ALS program, which focuses on targeting PIKFYVE. This program encompasses a preclinical antisense oligonucleotide known as AS-202.
Under this collaboration, AcuraStem will oversee certain aspects of advancing AS-202 through investigational new drug-enabling studies and preparing potential backup antisense oligonucleotides. Following this preparatory phase, Takeda will take the resulting drugs through clinical trials with the ultimate goal of bringing them to market.
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While the precise financial details of the agreement are not fully disclosed, AcuraStem has indicated that the combined upfront payment and milestone payments could potentially amount to a total of $580 million, in addition to royalties.
A pivotal study published in Cell in February served as a timely reminder of PIKFYVE’s potential as a therapeutic target for ALS. In this study, researchers utilized the drug apilimod from AI Therapeutics to inhibit PIKFYVE in various models, including human motor neurons, roundworms, fruit flies, and mice with ALS. The outcomes were remarkable, with the drug prompting motor neurons to clear toxic proteins, thereby enhancing motor function and extending survival across all the models. While progress has been made in developing treatments for genetic ALS, the more prevalent sporadic ALS has posed a significant challenge for researchers in finding effective therapies.
Against this backdrop, the difficulties in bringing new ALS treatments to market were further highlighted by the FDA’s recent meticulous evaluation of BrainStorm Cell Therapeutics’ approval application for its NurOwn drug, ahead of an upcoming advisory committee meeting this week.
“Whilst recent treatment advances have brought new hope to some patients, there remains a significant unmet need in ALS. 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.”
– Sarah Sheikh, head of Takeda’s neuroscience unit
The urgency of providing more therapeutic options for ALS patients has attracted the attention of pharmaceutical giants like Eli Lilly and, more recently, AstraZeneca. Both companies have entered into agreements with Verge Genomics to explore novel neurodegenerative drugs. However, it’s worth noting that neither of these agreements encompasses Verge Genomics’ own small-molecule PIKFYVE inhibitor, VRG50635, which is currently undergoing a phase 1 clinical trial for ALS. This underscores the growing interest in the potential of PIKFYVE as a game-changing target in the pursuit of ALS treatments.
