Developers expand collaboration to test 2 novel targets for ALS treatments
Insitro, Bristol Myers Squibb first struck deal in 2020 to use AI in lab research
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- Insitro and Bristol Myers Squibb are expanding a research collaboration deal, in place since 2020, to find new ALS treatments.
- The two companies are using AI and patient-derived cells to identify biological targets for ALS therapies.
- Two new targets aim to correct TDP-43 protein abnormalities, improving nerve cell health.
Insitro and Bristol Myers Squibb have expanded their ongoing collaboration to develop new treatments for amyotrophic lateral sclerosis (ALS), adding two newly identified disease targets to their ongoing research effort.
The two drug companies have been working together since 2020 to uncover biological changes driving ALS that may be reversed with therapies, using a combination of artificial intelligence (AI) and lab-grown human cells.
The new targets, ALS-2 and ALS-3, build on previous work in the collaboration, which has already advanced a first target, dubbed ALS-1, into early development. The companies are already exploring different classes of therapies to act on the same disease target.
“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,” Daphne Koller, PhD, Insitro’s founder and CEO, said in a company press release.
A $10 million payment was tagged to target selection, according to Insitro.
ALS is caused by the progressive loss of motor neurons, the nerve cells that control voluntary movement. While the exact mechanisms leading to motor neuron degeneration and death are not fully understood, abnormal clumps of the TDP-43 protein are believed to play a role.
Under normal conditions, TDP-43 is found in the nucleus, where genetic material is stored, and helps cells correctly process genetic instructions needed to make proteins. In about 97% of all ALS cases, however, TDP-43 forms clumps outside the nucleus and is no longer able to perform this function properly.
AI helps create ‘data-driven map’ showing impact of ALS treatments
In the initial phase of the duo’s collaboration, Insitro generated motor neurons from induced pluripotent stem cells (iPSCs), which are adult cells reprogrammed into a stem cell-like state. By using cells derived from patients or carrying mutations implicated in ALS, researchers were able to study the disease in a controlled setting and generate large datasets for analysis.
Using its AI-based platform, the company analyzed these data alongside large clinical datasets to identify patterns and pinpoint biological pathways that are consistently disrupted in ALS and could be targeted with new therapies.
“We are driven by a sense of urgency to translate our biological insights into meaningful clinical outcomes for the ALS community,” said Koller. “Our platform allows us to build a data-driven map of the impact of ALS on motor neurons and identify novel drivers of neurodegeneration.”
So far, three new targets have been identified that may modulate the effects of TDP-43 abnormalities. These could have the potential to treat the vast majority of ALS patients, according to the company.
Validation experiments using patient-derived motor neurons showed that modulating these targets increased neurite growth, a key indication of nerve cell health. This was accompanied by a reduction of the genetic abnormalities seen when TDP-43 is missing in the nucleus, and an increase in normal protein production.
Under the terms of the agreement, Insitro has received the $10 million in milestone payments for the selection of the two new targets.
