Twenty people in Cambridge are trying to do something counterintuitive to cancer: break its DNA repair on purpose, just long enough for the immune system to notice.
Most cancer drugs try to stop mutations. NeoPhore builds them on purpose. The whole company rests on that one inversion - and on a bet that the immune system, given a reason, will finish the job.
Walk into NeoPhore today and you will not find a sprawling pharma campus. You will find roughly twenty people - biologists, immunologists, computational scientists - and a single, stubborn thesis pinned to everything they do. The company describes its own approach as one "no-one else is doing," which is the kind of line that is either marketing or a genuine strategic moat. In NeoPhore's case it is closer to the latter, because almost nobody else is trying to drug the DNA mismatch repair pathway on purpose.
In December 2024 the board handed the wheel to Michael Shih, a dealmaker with nearly two decades at Kite Pharma, Biogen and Sanofi. That is a telling appointment. You hire a scientist-CEO to discover a drug; you hire a business-development veteran when you think the science is ready to meet the rest of the world.
Checkpoint inhibitors like Keytruda rewrote oncology by taking the brakes off the immune system. But they only work when the immune system has something to aim at. Tumours that carry many mutations produce many "neoantigens" - flags the immune system can recognise as foreign. Tumours that are genetically tidy produce almost none. They are invisible. Immunologists call them cold, and cold tumours shrug off the most celebrated drugs of the last decade.
Here is the cruel arithmetic NeoPhore noticed. The patients who respond best to checkpoint immunotherapy are often those whose cancers already have broken DNA mismatch repair - their tumours mutate freely, flag themselves constantly, and get caught. Everyone else, the large majority, has a tumour that is too well-behaved to be noticed. The problem was never really the immune system. It was the lack of a target.
Above: the inconvenient truth that launched a company. The neatest cancers are the hardest to catch.
The science traces back to a laboratory insight from Professor Alberto Bardelli and Giovanni Germano, whose research showed that switching off mismatch repair in a tumour caused it to accumulate neoantigens and become visible to the immune system. Published in Nature in 2017, it was the sort of finding that sounds reckless out of context - deliberately making cancer cells more mutated - and elegant once you understand the goal. You are not trying to grow the cancer. You are trying to make it conspicuous.
That year, NeoPhore was spun out of Cambridge-based PhoreMost and the University of Turin, seeded with around £6M from Sixth Element Capital and Innovate UK. The bet was simple to state and brutal to execute: find a small molecule that temporarily blocks the MMR pathway, give the tumour a fresh supply of neoantigens, and let checkpoint immunotherapy do the rest.
Scientific founder. His lab's work on mismatch repair and neoantigens is the intellectual bedrock of the company.
Scientific founder. Co-author of the 2017 research showing MMR inactivation drives tumour immunity.
CEO since Dec 2024. Ex-Kite Pharma, Biogen, Sanofi. Brought in to take a maturing pipeline to partners.
NeoPhore's pipeline is built around small-molecule inhibitors of specific proteins in the mismatch repair machinery. These are not vaccines and not biologics - they are designed to be pills or infusions that act on the tumour's own genetics. The word "temporarily" matters here: the idea is to block repair just long enough to generate neoantigens, not to leave a patient's healthy cells defenceless.
Pictured: a pipeline with two named targets and the unglamorous patience of early-stage drug discovery.
A thesis this contrarian needs validation that isn't its own press release. NeoPhore has collected a few signals worth taking seriously. In 2022 it signed a three-year research collaboration with Memorial Sloan Kettering Cancer Center - the institution where Dr Luis Diaz ran the studies that led to Keytruda's approval for any MMR-deficient cancer. Diaz also sits on NeoPhore's scientific advisory board, which means the clinician whose work proved the concept is helping steer the company built on it.
Then there is the money. Across seed and a much-extended Series B, NeoPhore has raised roughly $47M. The most pointed vote of confidence came in May 2024, when Bristol Myers Squibb - one of the largest immuno-oncology players on earth - joined an oversubscribed extension round. Pharma giants do not casually back small UK biotechs. They do it when the science is interesting enough to keep an eye on from the inside.
It would be easy to describe NeoPhore as a clever chemistry project. Its own framing is broader and more human: broadening patient access to disease-transforming immunotherapy. The distinction matters. Checkpoint inhibitors already exist. The unmet need isn't a new immune drug - it's a way to let the millions of patients with cold, MMR-proficient tumours benefit from the immune drugs we already have.
That reframes the company's value. If NeoPhore's inhibitors work in combination with checkpoint blockade, they don't compete with the immunotherapy market - they expand who it can serve. A small molecule that makes a tumour eligible for a therapy it was previously immune to is, in commercial terms, a key that unlocks a much larger door.
Honesty requires the caveat: NeoPhore is early. It has named targets, a platform, a strong advisory board and serious backers, but it is still a pre-clinical, pre-product company of about twenty people. The history of biotech is littered with elegant theses that did not survive contact with a patient. Inducing mutations on purpose carries real questions about safety and control that only data will answer.
But the upside is the kind that gets a pharma giant to join your cap table. If you can reliably turn cold tumours hot with a pill, you change the addressable population for the entire checkpoint-inhibitor class. That is not an incremental improvement. That is a different map of who immunotherapy can help.
Return to the lab in Cambridge. Twenty people, two protein targets, one inverted idea. They are not trying to cure cancer by force. They are trying to make it visible - and betting that an immune system, finally able to see, already knows what to do.