SOUTH SAN FRANCISCO, Calif., March 23 — insitro, the AI therapeutics company built on causal biology, today announced the expansion of its strategic collaboration with Bristol Myers Squibb (NYSE: BMY) to advance a broadened portfolio of therapeutic programs for amyotrophic lateral sclerosis (ALS). The collaboration is focused on accelerating and delivering disease-modifying interventions designed to address the underlying biological drivers of ALS.
BMS has nominated two additional targets, ALS-2 and ALS-3, which were identified through insitro’s Virtual Human™ platform. These join the initial target, ALS-1, nominated by Bristol Myers Squibb in December 2024. The companies will leverage multiple therapeutic modalities to address the nominated targets. insitro will advance its own oligonucleotide program for ALS-1 while simultaneously progressing a small molecule program for BMS for ALS-1. This multimodality development strategy is designed to maximize the opportunities to impact patients as quickly and effectively as possible. insitro received a $10 million milestone payment in connection with the selection of the two additional targets.
“We are driven by a sense of urgency to translate our biological insights into meaningful clinical outcomes for the ALS community,” said Daphne Koller, Ph.D., founder and CEO of insitro. “Our platform allows us to build a data-driven map of the impact of ALS on motor neurons and identify novel drivers of neurodegeneration. By expanding our collaboration with Bristol Myers Squibb, we are broadening our approach to tackling this devastating disease, with a set of compelling targets that address its fundamental mechanisms, with the goal of delivering disease-modifying therapies to the many patients who cannot wait.”
Leveraging insitro’s Virtual Human™ causal biology discovery platform, the company has identified a series of high-impact targets that play a central role in the biological mechanisms underlying ALS. By integrating massive-scale, human-derived cell data with machine learning, the Virtual Human™ allows for the mapping of disease drivers with unprecedented resolution, specifically focusing on processes that modulate the effects of TDP-43 mislocalization – a central disease mechanism in nearly 97% of ALS patients.
In validation experiments using iPSC-derived motor neurons, modulation of these targets rescues neurite growth in cellular models of ALS – a significant milestone that reflects structural repair in human neurons. This is accompanied by reduction of the cryptic exons and restoration of the corresponding full-length transcript by a significant amount, reversing key markers of disease pathology that occur broadly in ALS patients. This also provides strong evidence supporting the potential of these targets to lead to disease-modifying therapies.
