Merck & Co. will apply the somatic genomics platform of Quotient Therapeutics to discover novel drug targets in inflammatory bowel disease (IBD), through a collaboration that could generate up to $2.2 billion for the four-year-old startup of venture capital giant Flagship Pioneering.
Somatic genomics is the study of DNA changes (mutations) that occur in non-reproductive body cells after conception, rather than being inherited. Quotient’s somatic genomics platform is designed to interrogate patient tissue within the context of disease to find somatic genetic mutations that cause or protect from a given disease.
“Somatic genomics is the next, and clearly quite relevant, frontier in which to structure the world’s data so we don’t have a garbage-into-AI-garbage-out scenario. We truly are able to filter and structure public data on any target with the ground truth that is somatic genomics,” Rahul Kakkar, MD, Quotient’s president and CEO, told GEN Edge.
Over the lifetime of an individual, somatic genetic mutations naturally accumulate, resulting in trillions of different genomes per person.
“Where our company is headed over time is bringing that ground truth of somatic genomics and using that to structure the world’s data. That is an AI problem, and that’s part of what we’re building as the next layer, the software stack, on top of the hardware stack.”
To that end, he said, Quotient has accumulated what it says is the first and largest somatic genomic database, with 3.6 million novel coding mutations.
By contrast, COSMIC (Catalogue of Somatic Mutations in Cancer), the most comprehensive public database for somatic mutations in human cancer, contains more than five million coding mutations, according to a 2023 article by Wellcome Sanger Institute researchers. The latest version (v4.1) of the Genome Aggregation Database (gnomAD), the world’s largest germline database of human mutations, has a reported nine million somatic mutations within data containing approximately ~786.5 million short nuclear variants (SNVs) from 807,162 individuals.
Database build
“I would say in the next three years or so, we will have accomplished what COSMIC took over 20 years to accomplish. And in the next about two years, because we’re on the steep part of the inflection in terms of database build, we will have met or eclipsed gnomAD,” Kakkar predicted.
Merck and Quotient aren’t disclosing many details of their new partnership, such as specific aims of their research plan and which company will decide what targets will ultimately be pursued.
“What I can say is, it’s focused on identifying somatic mutations that are enriched in the numerous cell types that make up both the human intestinal tract, the colon, but also the colonic cells and the different cells that are coming under either immune attack from the process of IBD, and also those cells that have found a way to avoid that attack and preserve their health and function, despite the fact that there’s a very robust immune process ongoing,” Kakkar said.
Kakkar added that Merck was drawn to Quotient by its platform, which according to the company has three years of somatic data from 806 donors across 16 different disease indications—including 6,691,524 unique variants in its somatic genomics catalog, 1,610,516 billion base pairs of DNA, equivalent to the genomes of 550,000 people.
“In the course of our discussions last year, an individual at Merck who I won’t name said to me, Merck Research Lab has built some incredible capabilities over the last five to 10 years in numerous disciplines of scientific investigation. What we don’t have is what you have, and it would be very, very hard for us to replicate it,” Kakkar recalled.
Quotient reasons that the insights it gleans from somatic genomics data can inform strategies to develop new therapeutics for a broad range of diseases that include IBD.
“At this point, given the number of diseases the company has done over the last three to four years, it is no longer an open question that the forces of somatic genomics are playing themselves out in almost every tissue in our body,” Kakkar said. “So far, and there isn’t a single disease that we’ve investigated, either the pilot stage or the more comprehensive stage, that doesn’t have a rich topology of somatic genomics for us to investigate. So it really does seem to be an almost universal discipline that you can apply to any disease.”
Where to focus?
Somatic genetics screens have in recent years identified clinically validated drug targets in disease areas that include oncology, autoimmune disease, liver disease, and CVRM (cardiovascular, renal, and metabolic) disease. Kakkar acknowledged that the technology’s ability to generate insights on multiple diseases creates a potential challenge for Quotient: “We have to decide where to focus.”
The new collaboration follows what began as on-and-off informal discussions for a few years before last year, when Kakkar became a CEO-Partner with Flagship and the CEO of Quotient. Talks intensified last summer and fall, drawing on relationships Kakkar developed with Merck executives after the pharma giant acquired Pandion Therapeutics for $1.85 billion in 2021.
“There were very strong relationships in place. There was a high degree of trust and mutual scientific interest, and it became very organic over the course of the end of 2025 into the first quarter of this year,” Kakkar said.
Merck agreed to pay Quotient $20 million upfront, plus payments tied to achieving development, regulatory, and commercial milestones that will bring the total value of the collaboration up to a potential $2.2 billion.
Between Merck and Flagship Pioneering—which grew its assets under management to $14 billion following its last capital raise of $3.6 billion in 2024—Quotient has potential resources far larger than the sizeable $213 million in Series A and B venture capital financing raised in December 2023 by the previous company where Kakkar was CEO, Tome Therapeutics.
Tome sought to develop genome editing treatments based on an improved version of programmable addition via site-specific targeting elements (PASTE) technology. PASTE developers Omar Abudayyeh, PhD, and Jonathan Gootenberg, PhD, former graduate students with CRISPR pioneer Feng Zhang, PhD (Broad Institute), co-founded Tome, which shut down less than a year later, after investors balked at funding a Series C financing round for a preclinical drug developer whose technology raised questions about a potential patent challenge.
Interest from pharmas
“Part of what really drew me to Quotient wasn’t just the science and the leaders but was the fact that clearly there were numerous pharma companies that were interested in Quotient,” Kakkar said. The company has collaborations in progress—about which it isn’t offering updates—with GlaxoSmithKline and Pfizer.
Pfizer and Quotient are analyzing somatic mutations in diseased patient tissue toward discovering and developing therapies for cardiovascular and renal diseases—part of Pfizer’s collaboration launched in 2023 with Flagship Pioneering to develop 10 single-asset programs by connecting with any of Flagship’s 40+ startup companies. The partners each contributed $50 million upfront, with Flagship and its companies (including Quotient) eligible for up to $700M in milestones and royalties for each successfully commercialized program.
Quotient and another Flagship startup, ProFound Therapeutics, launched partnerships with GSK last year to discover and validate novel targets and therapeutic approaches in respiratory and liver diseases. GSK and Flagship committed a combined $150 million upfront, with GSK agreeing as well as pay Flagship and its startups up to $720 million in upfront, development and commercial milestone payments, plus preclinical funding and tiered royalties, for each program GSK opts to acquire.
Flagship founded Quotient in 2022 and publicly unveiled the company the following year with an initial commitment of $50 million. Kakkar joined as CEO in 2024, succeeding the company’s co-founder and first CEO Geoffrey von Maltzahn, PhD, general partner with Flagship.
Quotient is based in Cambridge, MA, maintaining office and lab space there and in Chesterford, U.K. The company has attracted Kakkar and 10 other senior executives, five of them R&D leaders—most recently announcing the appointment as chief financial officer of Susan Keefe, who has held finance, accounting, and operations positions in life sciences companies for some three decades. A GSK veteran with 25 years in discovery and development of small molecule and antibody therapeutics, Andy Bayliffe, PhD, was named Quotient’s chief development officer in September.
However, future growth will likely be limited.
“Over the last three years, we’ve built a critical mass of individuals that we need to run the histology through sequencing, through data sciences. We will do a little bit of growth in our AI team, given our ambitions there, and that’s really the next deliverable unlock for the technology, and a little bit of growth, potentially, in our wet lab capabilities,” Kakkar said. “But we really are at the critical mass we need to run this high-throughput genomics platform, for our current partners and for our internal programs.”
