insitro Expands Collaboration with Bristol Myers Squibb to Advance ALS Therapeutic Programs

insitro announced the expansion of its strategic collaboration with Bristol Myers Squibb to advance a broadened portfolio of therapeutic programs for amyotrophic lateral sclerosis. 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 $10M milestone payment in connection with the selection of the two additional targets. 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.