Pfizer has struck its second partnership with a Flagship Pioneering startup, working with Quotient Therapeutics to identify genetic mutations that arise by chance throughout life and make individual cells more susceptible or resistant to disease.
It’s a different approach from other genomics work, which focuses on how mutations we’re born with impact our health. The companies hope to use these somatic mutations, discovered in diseased patient tissues, as a starting point for new medicines for cardiovascular and renal diseases.
“Somatic genomics has enabled us to gain mechanistic and therapeutic insights already into nearly every disease we’ve studied,” Quotient co-founder and CEO Jacob Rubens told Endpoints News in an interview.
Quotient launched with $50 million from Flagship in November, but until now has remained mum on the specifics of its plans. Rubens showed Endpoints a list of more than 30 diseases his startup is actively studying or planning to study, broken down by genes that may counter disease, drive disease, fight cancer or protect cells.
“It might be a lot to bite off for a 40-person company, that’s true,” Rubens said, but he hopes that the Pfizer partnership will be the first of many to come. “We have had a lot of engagement and interest from biopharma. They’re interested in new targets in diseases they don’t know how to treat.”
The research is part of a broader collaboration between Flagship and Pfizer that was first announced in July 2023, when each company said they’d chip in $50 million for exploratory research that could lead to 10 therapies. Flagship and its startups could earn up to $700 million in milestone payments and royalties for each successful drug.
Paul BiondiThe partnerships are orchestrated through Pioneering Medicines, a drug development team at Flagship that has its own pipeline of about 15 programs based on technologies pulled from across the company’s biotech portfolio. In the first research program under the collaboration, announced in June, startup ProFound Therapeutics said it would help Pfizer hunt for new obesity drugs.
“We’re trying to create a new model for how a pharma company could interact with multiple companies,” Pioneering Medicines president Paul Biondi told Endpoints. “As we get to know them, and as they get to know us, we’re thinking that’ll just take a lot of the friction out of the process.”
Every cell is a unique experiment
An increasing number of medicines made over the past decade can trace their roots back to a genetic mutation that increases or decreases a person’s risk of developing a disease. For example, mutations in the PCSK9 gene prevent an enzyme of the same name from making certain kinds of cholesterol, a discovery that led to several drugs that mimic the protective effect.
Quotient is based on a similar concept, but instead of focusing on genetic differences between individuals, it is studying the chance mutations that arise among the trillions of cells that make a person. Although these somatic mutations are well-studied in cancer, new tools for sequencing these minute differences in an individual are revealing that some genetic quirks can push or pull cells toward or away from disease.
“Every single cell in our body is a unique evolutionary experiment,” Rubens said. “At Quotient, we can link changes in the genome to how cells experience disease in order to understand whether those changes make cells more resistant to disease, more prone to disease, or maybe drive disease itself.”
One of Quotient’s most compelling examples is in the liver disease MASH, where scientists have found patches of healthy cells seemingly floating amidst a sea of ones sickened with fatty white droplets. According to Rubens, when Quotient scientists looked closely at those outliers, they found a unique gene expression signature compared to their neighbors, and 82% of the cells shared a presumably protective mutation.
Rubens believes that the applications of the approach are vast. The startup’s scientists are looking for mutations that protect cells from kidney diseases and diabetes. They are studying how mutations can drive autoimmune conditions, atherosclerosis, Alzheimer’s disease and pulmonary disease. They’ve identified mutations that help the immune system fight several kinds of cancer. And they’re planning to look for mutations that can counter rare diseases and neurodegenerative diseases.
The partnership with Pfizer is an unusually early-stage effort. Quotient wouldn’t share details about the specific diseases that the deal is focused on, but Biondi noted that it helps Pfizer’s push to work on drugs for broader patient populations. It also expands Quotient’s pipeline into the cardiovascular disease space for the first time.
“We’re excited to be branching out into there as well and tackling some of the largest causes of mortality in the world,” Rubens said.