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21 November, 2023 - 11:00 By Tony Quested

US $50m helps Sanger-inspired startup to create transformative medicine suite

Genetics startup Quotient Therapeutics has roared out of stealth on both sides of the Atlantic on the wings of intellectual input from Wellcome Sanger Institute – allied to cash and brainpower from US partners Flagship Pioneering and the University of Texas Southwestern.

Quotient, co-steered by former Sanger director Sir Mike Stratton, is geared to become the fountainhead of new first-in-class drugs across a broad range of modalities and therapeutic areas, including immune disease, cardiometabolic disease, infectious disease, oncology, neurodegenerative disease, rare disease and ageing.

It is co-located in Cambridge MA and Cambridge UK with research facilities in both cities.

The company focuses on the study of genetic variation at the cellular level to discover therapeutics informed by new links between genes and disease. Three of Quotient’s academic co-founders are Sanger Institute senior leaders – Professor Stratton, Dr Peter Campbell and Dr Iñigo Martincorena.

Flagship Pioneering in Cambridge, Massachusetts, has made an initial commitment of $50 million to advance the development of the company’s platform – following two years of development at Flagship Labs – and to pursue a potentially blockbusting pipeline of new medicines.

Quotient’s Somatic Genomics platform uses proprietary single molecule, whole-genome sequencing technology to reveal the extensive variation encoded in the somatic genome at unprecedented resolution.

It is underpinned by the Sanger Institute’s research on how tissues accumulate mutations, age and acquire diseases such as cancer. As these diseases may arise from mutations in a single cell, there is a need for ultra-accurate methods, such as the ones developed at the Sanger Institute, for the early detection of extremely small signals.

These methods, in turn, help interpret how mutations subsequently evolve to either cause disease or mitigate it.

Built by Flagship scientists in collaboration with the Wellcome Sanger Institute and the University of Texas Southwestern, this platform can study natural selection at the cellular level through four steps: phenotyping of cells from clinical tissue samples, isolation, single-cell genotyping, and computation.

As a result, naturally selected genes, proteins and pathways are identified as prospective targets for the development of transformative therapies intended to cure, prevent or reverse disease.

Dr Geoffrey von Maltzahn, co-founder and Chief Executive Officer of Quotient Therapeutics and General Partner, Flagship Pioneering, said: “The assumption that we each have a single genome turns out to be off by a trillion-fold.

“All cells accumulate random genetic changes in their DNA, resulting in trillions of unique genomes in the body. Some genetic changes make a cell resistant or vulnerable to disease, while others can cause disease.

“We started Quotient to study the natural genetics library inside every tissue, discover gene variants that are beneficial, neutral, or disease-causing, and to harness that knowledge to develop the medicines of tomorrow.”

Dr Jacob Rubens co-founder and President of Quotient Therapeutics and Origination Partner, Flagship Pioneering added: “At Quotient, we’re inspired by the maxim that ‘Nothing in biology makes sense except in the light of evolution’.

“Our Somatic Genomics platform measures genetic changes underlying the evolution of cells in the body to make sense of disease, illuminating the path to a wide range of potentially curative medicines.

“Already, we’ve created the world’s largest somatic genomes dataset, demonstrated the applicability of our platform to multiple therapeutic areas, and translated our genetic discoveries into drug discoveries.”

Professor Stratton, Academic co-founder at Quotient Therapeutics and group leader at Wellcome Sanger comments: “In the cells of the body of just one healthy middle-aged person every letter of DNA code in the human genome has been mutated tens of millions of times.

“Quotient will use its bespoke DNA sequencing technologies to read the outcomes of this extraordinary panoply of natural experiments that takes place in all of us, revealing mutated genes that may cause or protect against a range of human diseases and thus directing us to a new generation of targets against which future therapeutics will be developed to treat patients.”

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