OutSee starts reformatting how disease treatments are identified through genomics

Like a lot of genuinely game-changing companies, OutSee seems to have come out of the blocks fully formed – although the thinking that underpins its Nomaly platform began a decade ago.

“Our patent priority date was January 2016, so as you can imagine work on the concept started even before that,” says founder and CEO Julian Gough. “Ten years ago this was too far advanced of the landscape for it to be easily accepted, commercially or academically.”

But it wasn’t necessarily technical difficulties that delayed its introduction – it was the cleverness of the proposition and the radical rethink of the traditional framework it required that delayed its exegesis.

The analysis by Prof Gough, who at the time was professor of computer science at the University of Bristol, revoked the existing approach to human genetics, which asked ‘Does the data contain the answer to my question?’ in favour of asking: ‘For which questions does an answer lie within the data?’.

Adopting a hypothesis-free, reverse genetics approach is playing out well. OutSee’s knowledge-based AI approach is starting to identify plausible novel genetic causes for disorders that eluded existing methods. It’s been a fertile proving ground for the former Perse pupil born in Cambridge who received his Phd from the University of Cambridge on theoretical and computational molecular biology in 2001, before starting a stint at Stanford University’s School of Medicine as a research fellow in computational biology.

For three years Julian was CEO at Mogrify, which is transforming the lives of patients with degenerative diseases through a novel class of in vivo reprogramming therapies. He then brought in Darrin Disley – the former CEO of Horizon Discovery – and went part-time, first as CSO (two years), then CTO (one year), and currently as chief scientific advisor.

By 2017 he had left Bristol for a full-time role as a programme leader at the MRC Laboratory of Molecular Biology at the Biomedical Campus on Francis Crick Avenue.

“I was a programme leader here in Cambridge at the LMB for seven years until September 2023 when I went full-time on OutSee – four of those years with Dr Chang Lu (CSO) who left Imperial to also go full-time on OutSee in August.

“I had an academic career and during that time I developed and built a lot of different technologies, all biology-based relating to molecular and cell biology. In that time I invented two breakthrough platforms, one was Mogrify, the other being Nomaly.”

He adds: “With OutSee I left academia as you can’t see the vision through unless you do it yourself, and it’s not possible to build and lead a biotech company yourself and maintain an academic career. I’m not planning to go back to an academic career at this point.

“It feels great – my natural self is more entrepreneur than academic. I wasn’t doing typical biology papers, it was all inventing technology then applying it, so I think start-ups are something I probably could have done a long time ago. I don’t have any regrets but by the time it came round to launching OutSee it was very much ‘this is what I should be doing’.”

He’s hit the ground running.

“My personal job as CEO is fundraising, business development and making sure the team is working well. Also the science – there’s a tight connection between business strategy and scientific direction.”

OutSee has received two precision medicine grants from Innovate UK, plus support from Amazon Web Services (AWS) – “AWS is not funding, it’s credit for computing, because if we run it on AWS you can burn $10k a day, and a project is less ‘how long does it take?’ and more ‘how much does it cost?’.”

A seed fundraise is under way. Nomaly’s knowledge-based AI approach offers a chance to extract further discovery from genetic data after standard association-based tools have been applied. It’s a shoo-in, even at this early stage. The platform is an ab initio, genetics-first method making molecular knowledge-based interpretations for exome-wide non-synonymous variants for phenotypes at the organism and cellular level. By using this reverse approach, OutSee’s team can identify plausible novel molecular disease-modulating mechanisms that elude other established methods.

“Nomaly is not competing with state-of-the-art approaches, it’s something additional,” notes Julian.

And the platform is already starting to tackle the big themes of our age, starting with Alzheimer’s. In December OutSee announced a partnership with Finnish Biobank Cooperative – FINBB – which includes access to pseudonymised genotype and selected phenotype data of Finnish biobank donors with dementia through FINBB’s Fingenious service, a first-in-class digital gateway to Finnish public biobanks and biomedical research.

FINBB is part of FinnGen, a partnership between Finnish partners from the academic and public sector and international industry partners.

“FinnGenn they have significant numbers of genomes relating to dementia,” Julian explains. “The organisation has sequenced samples from thousands of patients, we’re accessing the data and analysing it.”

Nomaly interrogates the data generating novel hypotheses for causal biological disease mechanisms which subsequently need to be empirically validated in the lab.

“We have up to 20k different phenotypes, we typically run between 6 to12k. We run Nomaly completely blind to the disease, and the method is not aware of what it is supposed to be predicting.

“So when we precisely predict disease relevant outputs from the pool of, for example, 12k possible unrelated phenotypes, there’s a very high chance it has nailed some causal aspect of, in this case, dementia biology. This is the advantage of using a predictive approach.

“It’s not trying to find something that correlates with dementia status, it’s independently predicting emergent characteristics from each genome without knowledge of the patient.

“We anticipate further collaborations with genomic data banks, including in the UK, in 2025.”

And what else can we expect this year?

“We will close a funding round, establish projects with big pharma, biotech and smaller biopharma, continue to expand our access to genomic datasets around the world and generate a handful of credible targets internally to fill the first stage of our pipeline for validation.”