BEN-34712 is an oral, potent, and selective brain penetrant RARɑ (retinoic acid receptor alpha beta) biased agonist and will now enter investigational new drug (IND)-enabling studies.
Impaired retinoic acid signalling has been shown to result in neuroinflammation, oxidative stress and mitochondrial dysfunction, all hallmarks of ALS.
In preclinical studies conducted by the company, BEN-34712 was neuroprotective in a patient-derived, disease-relevant in vitro motor neuron/iAstrocyte co-culture model, demonstrating significant efficacy in both sporadic and familial subtypes of ALS.
In addition, BEN-34712 has demonstrated both central nervous system (CNS) target engagement and functional protective effects in the SOD1G93A mouse model of ALS after 50-day repeat dosing.
For this programme, BenevolentAI collaborated with the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield, utilising their patient-derived motor neuron/iAstrocyte co-culture systems and in vivo model expertise.
“There remains a significant and urgent need for new and alternative therapies for patients with ALS. We are pleased by the promising advancement of our drug candidate, BEN-34712, towards clinical development, backed by the compelling preclinical data generated by our collaborators at SITraN,” said Anne Phelan, chief scientific officer at BenevolentAI.
Richard Mead, senior lecturer in translational neuroscience at SITraN, added: "ALS patients suffering from this devastating neurodegenerative disease are in dire need of effective therapy, with the current standard of care options focusing on symptom management or offering limited clinical benefit.”
“We believe BEN-34712 represents an exciting development in our research for a potential new treatment, particularly as it shows effectiveness in both the SOD1G93A mouse model system as well as familial and C9orf72 related ALS patient-derived cell models."