BMS, insitro add two more targets to AI-powered ALS partnership

insitro has unearthed two more therapeutic targets for amyotrophic lateral sclerosis (ALS) using its AI-enabled platform, Virtual Human. The latest discovery expands the biotech's collaboration with Bristol Myers Squibb as the pair move forward drug development efforts against the newly nominated targets, triggering a $10-million milestone payment. 

Altogether, insitro has identified three ALS targets for BMS using its AI technology; the first, dubbed ALS-1, was nominated in late 2024. The pair first teamed up in 2020 to discover treatments for ALS and frontotemporal dementia, with BMS paying insitro $50 million upfront. The total value of the deal, which was extended by an additional year in October, exceeds $2 billion in biobucks. 

"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," said Daphne Koller, founder and CEO of insitro.

AI and ALS discovery

Powering the latest target discoveries is insitro's Virtual Human platform, which integrates human-derived cell data with machine learning to map disease drivers. Using a genetically anchored causal AI engine, it's designed to uncover how diseases begin and advance, as well as possible solutions to resolve a disease. 

"Our platform allows us to build a data-driven map of the impact of ALS on motor neurons and identify novel drivers of neurodegeneration," Koller said. 

While details on these new targets are under wraps, insitro said Monday that it deployed Virtual Human to find processes that "modulate the effects of TDP-43 mislocalisation — a central disease mechanism in nearly 97% of ALS patients."

To validate the newly nominated targets, insitro conducted experiments in iPSC-derived motor neuron cell models of ALS. The company confirmed that by modulating the discovered targets.  neurite growth is rescued, cryptic exons are reduced and the corresponding full-length transcript is restored by a "significant amount, reversing key markers of disease pathology that occur broadly in ALS patients." 

insitro now plans to take multiple therapeutic approaches to drugging the discovered targets. Against ALS-1, the biotech will be advancing its own oligonucleotide programme, while also developing a small molecule for BMS.