An asset that is being tested in CMT4B1 underwritten by the CMT Research Foundation has been licensed by AcuraStem to Takeda for approximately $580 million. The exclusive, worldwide license will enable Takeda to develop and commercialize AcuraStem’s PIKFYVE targeted therapeutics including AS-202, an innovative antisense oligonucleotide (ASO). It will initially be deployed for the treatment of Amyotrophic Lateral Sclerosis (ALS).

Knowing some of the key barriers in drug development for CMT, the CMTRF was familiar with the work in CMT4B1of Dr. Alessandra Bolino, a renowned expert in CMT and head of the Human Inherited Neuropathies Unit at the research hospital Ospedale San Raffaele in Milan.  Her work in PIKFYVE inhibitors seemed promising, but she didn’t have a compound that was stable. The CMTRF matched Dr. Bolino with AcuraStem to explore the viability of their novel PIKFYVE inhibitor to CMT4B1.  The CMTRF then funded the work of their lead compound in Dr. Bolino’s 4B1 models.  That work has shown promising results with continued validating work underway presently.

“This is the second time in 90 days that assets with the potential to treat Charcot-Marie-Tooth disease have been acquired by pharma for further development,” says Cleary Simpson, CEO of CMTRF. “DTx Pharma, that developed a platform for RNA therapeutics called Fatty Acid Ligand Conjugated Oligonucleotide, was first funded by CMTRF in 2019. DTx was recently acquired by Novartis for $1 billion. Such transactions get the attention of the entire CMT ecosystem resulting in more investments in research to find treatments and cures for all forms of CMT. With our help and persistence, our hope is that Takeda will continue to pursue its application to CMT.”

AcuraStem, was co-founded by Alworth, Ichida, Paul August, PhD, who sits on the Board of CMTRF and Qing Liu, PhD, in 2016. The novel therapeutic mechanism was initially discovered at the lab of Dr. Ichida using patient-derived disease models, is exclusively licensed to AcuraStem by the USC Stevens Center for Innovation and further developed on AcuraStem’s iNeuroRx® disease modeling platform. AcuraStem researchers further demonstrated that ASO-mediated suppression of PIKFYVE can restore motor function, reduce neurodegeneration, and improve survival in multiple in vivo models of both ALS and FTD.

The CMT Research Foundation also funded a drug screening project for CMT2A with AcuraStem’s iNeuroRx technology platform.  The project was started in 2019 and identified eleven potential therapeutics for CMT2A. Because AcuraStem developed a platform to screen compounds for their ability to rescue peripheral motor neurons derived from patient cells (vs artificial cell lines) and screened several thousand compounds, already approved by the FDA or international regulatory bodies for use in other diseases, their findings will accelerate development of these potential CMT drugs.

“PIKFYVE inhibition has enhanced the survival of peripheral motor neurons in CMT2A by AcuraStem and potentially in CMT4B1 models from Dr. Bolino,” says Ms. Simpson. “It is entirely possible that this new arrangement will result in therapies in various CMT sub-types where there are none today.”