insitro and Bristol Myers Squibb expanded their option-based discovery collaboration in amyotrophic lateral sclerosis (ALS), with Bristol Myers Squibb (BMS) nominating two additional therapeutic targetsidentified through insitro’s AI-driven Virtual Human platform. The targets, designated ALS-2 and ALS-3, join the initial target ALS-1, which BMS nominated in December 2024. insitro, headquartered in South San Francisco, received a USD 10 million milestone payment in connection with the two new nominations.
BMS and insitro first partnered in 2020, initially establishing a five-year discovery collaboration with BMS paying USD 50 million upfront and up to USD 2 billion in development and commercial milestones. insistro agreed to apply its proprietary platform to create induced pluripotent stem cell (iPSC) derived disease models for ALS and frontotemporal dementia (FTD). That deal was extended a further 12 months in October 2025, in return for USD 20 million in new funding.
The collaboration is a multi-target, option-based research deal, with BMS funding insitro’s discovery work and retaining the right to nominate targets as they emerge from insitro’s platform. Each nomination triggers milestone payments. For ALS-1, insitro is advancing its own oligonucleotide program while simultaneously progressing a small molecule program for BMS. It is not known whether this modality-based rights split will also apply to ALS-2 and ALS-3.
All three targets were discovered using insitro’s Virtual Human platform, which integrates large-scale data from iPSC-derived cellular models with machine learning to identify causal disease drivers. For this ALS collaboration, the platform focused on processes that modulate the effects of TDP-43 mislocalization, a pathological mechanism present in approximately 97% of ALS patients. In validation experiments using iPSC-derived motor neurons, modulation of the nominated targets rescued neurite growth and reduced cryptic exon inclusion, reversing markers of disease pathology. All three programs remain in preclinical development.
The deal fits within insitro’s broader platform monetization strategy. The company has separate collaborations with Eli Lilly, including two siRNA programs in metabolic liver disease entering IND-enabling studies and an antibody program in metabolic disease at the discovery stage. insitro also has an internal program, BAT-01, targeting brown adipose tissue in obesity. None of insitro’s platform-derived programs have reached clinical development.
For Bristol Myers Squibb, the ALS collaboration adds a preclinical neuroscience component to its pipeline through an external discovery engine rather than internal R&D. Several companies are pursuing TDP-43-related biology or ALS target discovery through competing approaches. Dewpoint Therapeutics selected a development candidate in January 2026 — a small molecule condensate modulator designed to correct pathological TDP-43 condensates in motor neurons. Verge Genomics operates its CONVERGE platform using patient-derived tissue data and has a separate ALS discovery collaboration with Eli Lilly, with milestones achieved in November 2024. Biogen and Ionis market tofersen (QALSODY) for SOD1-linked ALS, though that therapy addresses only approximately 2% of cases.