Sanofi has committed potentially up to $5.2 billion to a collaboration with Exscientia to develop up to 15 novel small molecule candidates across oncology and immunology indications based on Exscientia’s artificial intelligence (AI)-based platform, the companies said Friday.

Exscientia and Sanofi agreed to collaborate to identify and select target projects by applying Exscientia’s personalized medicine platform. The platform is intended to enable a “patient-first” approach by integrating primary human tissue samples into early target and drug discovery research. Through that approach, Exscientia reasons, its researchers can integrate patient, disease, and clinically relevant data into decisions on potential new medicine candidates earlier in the process of drug creation.

In addition to target discovery, Exscientia will lead small molecule drug design and lead optimization activities up to development candidate nomination. Sanofi will oversee preclinical and clinical development, manufacturing, and commercialization.

“Sanofi’s collaboration with Exscientia aims to transform how we discover and develop new small molecule medicines for cancer and immune-mediated diseases,” Frank Nestle, Sanofi’s global head of research and CSO, said in a statement. “Application of sophisticated AI and machine learning methods will not only shorten drug discovery timelines, but will also help to design higher quality and better targeted medicines for patients.”

The companies’ research collaboration and license agreement builds on a six-year relationship between Sanofi and Exscientia. They began partnering in 2016. A year later, Sanofi and Exscientia signed a potentially €250 million ($302 million) collaboration and license option to discover bispecific small-molecule drugs against metabolic diseases. And in 2019, Sanofi in-licensed Exscientia’s bispecific small molecule candidate designed to target two distinct targets in inflammation and immunology.

In the latest collaboration, Sanofi has agreed to pay Exscientia $100 million in upfront cash, plus up to approximately $5.2 billion in payments tied to achieving research, translational, clinical development, regulatory, and commercial milestones.

Should Sanofi commercialize a therapeutic from the collaboration, Exscientia will also be eligible to receive tiered royalties on product sales ranging from high-single-digits to mid-teens and an option for clinical co-investment to increase the royalty rate up to 21% on net sales of co-funded products.

Exscientia said the $100 million upfront payment from Sanofi is expected to be reflected in its first-quarter 2022 results.

Last year, Exscientia closed on $525 million in financing, with the proceeds intended for advancing its pipeline through clinical trials, as well as expanding its technology platform toward autonomous drug design. At the time, Exscientia had completed a $225 million Series D round led by SoftBank Vision Fund 2 (SVF2). SoftBank also agreed to commit to Exscientia $300 million in equity, from which the company can draw from at its discretion.

Tapping AI’s “full potential”

“Our expanded collaboration with Sanofi will utilize the breadth of our platform to test AI-designed drug candidates against patient tissue models, potentially providing far better accuracy than conventional approaches such as mouse models,” stated Andrew Hopkins, DPhil, Exscientia’s CEO and founder. “It is immensely exciting to collaborate with Sanofi with our goal of realizing the full potential of AI to deliver the next generation of cancer and immunology medicines.”

Exscientia’s platform uses patient tissue data to define optimal profiles for research, improve experimental assessment during design, and improve outcomes in a medical setting. Through an approach the company calls precision engineering at the molecular scale, Exscientia aims to fulfill sophisticated design objectives for personalized therapies by applying advanced data acquisition, machine learning, and generative systems.

The platform combines precision information from viable patient tissue, screened in Exscientia’s own laboratories, with its CentaurAI systems, with the goals of empowering target selection, precision design, and experiment, as well as enhanced clinical assessment.

In January 2020, Exscientia joined collaboration partner Sumitomo Dainippon Pharma to announce what they said was the first AI-designed molecule into clinical study by launching a Phase I trial in Japan assessing their DSP-1181 as a treatment for obsessive-compulsive disorder.

The companies have since brought two other AI-designed molecules into the clinic, last year launching Phase I trials assessing EXS-21546 and DSP-0038. EXS-21546 is a peripherally-restricted and selective antagonist of the adenosine A2a receptor designed for anticancer immunotherapy, combatting adenosine-related immunosuppressive effects, through T-cell activation. DSP-0038 is an antagonist for the 5-HT2A receptor and agonist for the 5-HT1A receptor being developed for the treatment of Alzheimer’s disease psychosis.

Including the three candidates under clinical study with Sumitomo Dainippon, Exscientia has built a pipeline of 26 programs, including the first three AI-designed drug candidates to enter Phase I clinical trials:

  • Four immuno-oncology candidates—one each partnered with Bristol Myers Squibb (BMS), Evotec, and Rallybio; the other unpartnered.
  • Seven oncology candidates—four partnered with BMS, one with China-based GT Apeiron, one with Huadong Medicine, and one unpartnered.
  • Six candidates in the “inflammation and immunity” category—two partnered with BMS, two with EQRx, one with Sanofi, and the other unpartnered.
  • One drug each being developed in anti-infective (partnered with the Bill and Melinda Gates Foundation), COVID-19 (CARE [Corona Accelerated R&D in Europe]), psychiatry (BlueOak Pharmaceuticals), unspecified rare disease (Rallybio), and respiratory indications (Bayer).
  • Seven additional programs in undisclosed indications, all in early discovery phases with “various” undisclosed partners.
  • Three other “design-as-service” candidates for unspecified psychiatry indications—two being co-developed with Sumitomo Dainippon, the other by a “confidential” partner.

In addition to its Oxford HQ, Exscientia has offices in Miami, Osaka, Vienna, and Dundee, Scotland.

“Our AI-driven platform can be leveraged across drug discovery, translational research, and development, with applications ranging from improving the precision medicine and quality of drug candidates to enriching for patient selection in clinical trials,” Hopkins added. “When you consider the change this represents—testing candidates against actual human tissue years before a clinical trial—it’s transformative.”

Added Sanofi’s Nestle: “We look forward to deepening our work with Exscientia, a leader in leveraging AI to modernize all aspects of drug discovery and development.”

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