Bristol Myers Squibb Partners With Insitro to Develop New ALS Therapies

Bristol Myers Squibb Partners With Insitro to Develop New ALS Therapies
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Bristol Myers Squibb has entered a five-year research collaboration with the machine learning startup insitro to discover and develop new therapies for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Machine learning is a form of artificial intelligence that uses algorithms to analyze large amounts of data, learn from its analyses, and then make a prediction about something.

“We believe that machine learning and data generated by novel experimental platforms offer the opportunity to rethink how we discover and design novel medicines,” Richard Hargreaves, PhD, said in a press release. Hargreaves is senior vice president and head of neuroscience research and early development at Bristol Myers Squibb.

“Neurodegenerative disorders like ALS and FTD have historically been a challenging therapeutic area, with no disease modifying treatments today,” said Daphne Koller, PhD, insitro’s founder and CEO.

“We are excited to partner with Bristol Myers Squibb and its world-class neuroscience leaders, who share our vision of leveraging human genetics, machine learning, and high-throughput biology and chemistry in order to identify and provide new treatments for patients suffering from these devastating diseases,” Koller said.

Increasing research shows that ALS and FTD — a group of neurological disorders affecting behavior, personality, and language skills — share common underlying mechanisms, including the toxic accumulation of two proteins, called TDP-43 and FUS.

The companies will take advantage of insitro’s Human platform, which applies machine learning, human genetics, and functional genomics to develop and optimize cell-based disease models and drive therapeutic discovery and development.

The platform will be first used to create cellular models of ALS and FTD derived from induced pluripotent stem cells (iPSC). iPSCs are derived from either skin or blood cells that are reprogrammed back into a stem cell-like state, providing a source of any type of human cell needed for therapeutic purposes.

These cells can be either genetically modified to carry known disease-causative mutations or be derived directly from patients with sporadic cases, as in ALS, to obtain successful cellular models that mimic the disease’s genetic and clinical diversity.

According to insitro’s website, these disease models are designed to be “maximally predictive of human clinical outcomes by optimizing for genetics, cell-type, environment, and multidimensional data collection.”

Machine learning models will then be applied to analyze massive amounts of data from these cell-based disease models and determine the profiles of “heathy” versus “sick” cells, which is expected to allow the identification of potential therapeutic targets and approaches.

“By predicting better and earlier which paths are more likely to lead to successful medicines, we can avoid many of the dead ends and deliver better medicines to the patients who need them,” insitro notes in its website.

“Since founding insitro just over 2 years ago, we have demonstrated our capabilities in building predictive models to discover novel targets and patient segments,” Koller said, noting the company also “developed new approaches to machine-learning-enabled therapeutics design, which we look forward to deploying to discover treatments for novel targets emerging from this collaboration.”

Bristol Myers Squibb will have the option to select a number of targets identified by insitro’s platform and will be responsible for advancing them through clinical trials, regulatory submissions, and eventual commercialization.

Under the terms of the agreement, insitro will receive an upfront $50 million payment from Bristol Meyers Squibb and $20 million upon achievement of operational milestones.

If insitro’s platform successfully identifies therapy candidates, the startup company could receive more than $2 billion in discovery, development, regulatory, and commercial milestone payments, in addition to royalties should any of the therapies come to market.

“There is an unmet medical need for therapies to treat ALS and FTD and we are excited by the prospect of working with insitro’s team towards our shared goal of identifying transformative treatments for patients with these devastating diseases,” said Hargreaves.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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