Takeda strikes $500M+ deal for California biotech’s ALS program

Takeda is betting more than half a billion dollars on a California biotech’s approach to treating amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.

The Japanese pharma giant has inked a $580 million deal (including an undisclosed upfront payment and potential milestones) for AcuraStem’s PIKFYVE therapies, including an ALS candidate nearing the clinic called AS-202. By suppressing levels of the PIKFYVE kinase, which was recently identified as a target for ALS, AcuraStem hopes it can clear out toxic protein aggregates and protect neuronal function.

“The mechanisms of ALS are not well-understood, and the science is moving quickly and all of these things are evolving,” AcuraStem CEO Sam Alworth told Endpoints News. 

Sam Alworth

In preclinical and in vivo models, AcuraStem has seen that its antisense oligonucleotide AS-202 can clear out toxic protein aggregates called TDP-43. While TDP-43 is supposed to be in the nucleus, it is known to shuttle through the cytoplasm and collect in aggregates, which are toxic to neurons and a “major hallmark of ALS,” Alworth said. That can lead to a depletion of TDP-43 in the nucleus, he said, which can cause “mis-splicing and dysregulation of genes that are implicated in ALS.”

AcuraStem claims its approach can clear TDP-43 aggregates while also improving its function in the nucleus. The company is working with Takeda toward an IND, after which point Takeda will be responsible for clinical development, regulatory submissions and potential commercialization.

Sarah Sheikh

“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 therapeutic area unit, said in a news release.

Verge Genomics is targeting PIKFYVE with its candidate VRG50635, which was “safe and well-tolerated” in a Phase I trial, according to an announcement in June. The company said at the time that it anticipated launching a proof-of-concept study in Q4 2023. Earlier this month, AstraZeneca inked a deal with Verge worth up to $882 million focused on multiple undisclosed rare neurodegenerative and neuromuscular diseases.

ALS patients have few options to manage the fast-progressing disease. An FDA advisory committee will be tasked later this week with weighing patients’ unmet need with efficacy data for BrainStorm’s ALS candidate NurOwn. The experimental treatment failed to meet its primary and secondary endpoints in the only placebo-controlled trial to evaluate its administration using both the intended route and dose interval.

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