insitro and Bristol Myers Squibb Collaboration Expanded with Nomination of New Targets

Key Terms

amyotrophic lateral sclerosis medical

A progressive disease in which nerve cells that control voluntary muscles gradually fail, leading to loss of movement, speech and eventually breathing — like an electrical wiring system in the body slowly shorting out. It matters to investors because there are few effective treatments, so clinical trial results, regulatory approvals, new therapies or diagnostics can rapidly change patient care, market opportunity and company valuations.

oligonucleotide medical

A short chain of DNA or RNA molecules used to target, detect, or change specific genetic messages inside cells; think of it as a tiny, programmable instruction or zip code that can find and bind one exact genetic sentence. Investors care because oligonucleotides are the active ingredient in a growing class of precision therapies and diagnostics, so their success, manufacturing cost, and regulatory approval can directly affect a company's value and future revenue.

small molecule medical

A small molecule is a low-weight chemical compound that can enter cells easily and interact with specific proteins or biological pathways to change how they work, much like a small key fitting into a lock. Investors care because small molecules are a common and often faster route to develop medicines, can be manufactured at scale, and may offer clearer regulatory and commercial paths compared with larger biologic therapies, affecting potential costs, timelines and returns.

iPSC-derived motor neurons medical

Cells grown in the lab by reprogramming ordinary adult cells back into a versatile, stem-like state and then maturing them into motor neurons — the nerve cells that control muscles. For investors, these lab-made motor neurons act like customized crash-test dummies and disease models: they let companies test drug effects, screen for toxicity, and develop therapies in human-like tissue before costly clinical trials, which can lower scientific risk and speed development timelines.

TDP-43 mislocalization medical

TDP-43 mislocalization is when a specific protein that normally works inside the cell's nucleus ends up in the wrong part of the cell, forming clumps where it shouldn't. Think of a factory manager leaving the control room and wandering onto the assembly line, causing machines to fail; that disruption contributes to nerve cell damage in several neurodegenerative diseases. Investors care because it can serve as a diagnostic marker, drug target, and driver of clinical trial and regulatory value for therapies addressing these disorders.

cryptic exons medical

Cryptic exons are normally hidden stretches of genetic code that can be mistakenly included when a cell copies a gene into an instruction called mRNA, like an unexpected extra stop on a train route. When included, they can change the resulting protein’s shape or stop it from being made, which matters to investors because these errors can create new drug targets, affect diagnostic tests, or influence the success of gene and RNA therapies.

Collaboration expands to include two additional therapeutic targets for the treatment of ALS discovered via insitro’s AI-driven Virtual Human™ platform

Joint effort focuses on identifying key biological drivers to deliver disease-modifying interventions for ALS patients

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- 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.

About insitro

insitro is the physical AI company unlocking causal human biology, founded and led by AI pioneer Daphne Koller. By generating the world's largest integrated multimodal corpus of human and cellular data, we’ve built the Virtual Human™—a genetically anchored causal AI engine that reveals how disease begins, progresses, and can be resolved. Our platform enables us to precisely identify causal genetic drivers and deploy our TherML AI platform to design optimal medicines, advancing a broad pipeline of therapeutics for neuroscience and metabolic diseases. This industrialized architecture creates a self-learning loop: with every biology we onboard, our predictive models grow smarter, accelerating discovery across scales of biology. Backed by ~$800M in capital from world-class investors like a16z, ARCH, Blackrock, Casdin, CPP, Foresite, GV, Softbank, Temasek, Third Rock, T. Rowe Price – including ~$150M in revenue from collaborations with BMS, Lilly, and Gilead – insitro is rebuilding drug discovery from an unpredictable journey into an industrialized, repeatable process with scalable impact for patients and the world.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260323768268/en/

Media Contact

Eric McKeeby

eric@insitro.com

Source: insitro