How this biotech startup plans to reduce side effects in gene therapies — and save lives

There are more than 6,000 rare diseases in the world, and 80% of these are genetic. In recent years, one-off gene therapies, which introduce therapeutic genes into patients’ cells to treat the underlying causes of such diseases, have emerged as one of biotech’s most promising sectors.

Yet, their development has been hindered by reports of severe side effects, including deaths and liver failure. This can happen when gene therapies are active in the wrong tissue as well as the target one. The result is that few such therapies have been approved for use to date, and several have been halted.

Japanese pharmaceutical company Astellas made headlines when four young patients died after receiving treatment for a rare neuromuscular disorder as part of a now halted clinical trial. Even therapies that make it through clinical trials can have severe side effects. In the UK, Zolgensma — labelled as the world’s most expensive drug — is a gene therapy medicine available on the NHS that can treat spinal muscular atrophy, a rare genetic disease that causes paralysis and progressive loss of movement. Alongside some success stories, several cases of liver injury, damage or failure have been reported, prompting the U.S. Food and Drug Administration to update the therapy’s label.

Jessica Birt, a PhD researcher from the Centre for Synthetic and Systems Biology at the University of Edinburgh, joined Conception X in 2021 with the goal to improve the safety and efficacy of such therapies using AI. Her startup Concinnity Genetics builds gene control systems that act like a switch for gene therapies, turning them off when active in the wrong cells to prevent the onset of side effects.

“This technology has been around for a while, but only a handful of effective gene control systems have emerged over the past three decades,” Birt says.

The team’s ambition is to build its own dataset within a year, develop five novel gene control systems over the next 18 months, and eventually build a large portfolio of modular control systems tested in-house, which could ultimately be licensed to gene therapy developers to be integrated within their own therapies.

Unlike existing players in the space, the startup can rely on an AI algorithm — developed by Birt as part of her PhD — that can rapidly improve and learn from previous designs. The team’s control systems are also RNA-based, which means Concinnity Genetics is well placed to target the growing market of gene editing and mRNA therapeutics.

“I think what happens to a lot of academics is they see the thing they’re making in quite a small scope,” Birt says. “It was during Conception X and while doing customer interviews that I took a few steps back from the algorithm I’d been building and realised the focus should be on why I wanted to build these genetic control systems in the first place — to identify the genuine value of this technology.”

A computational biologist by training, Birt met her co-founder Matthew Dale during the programme as she was looking for someone to support with wet lab data collection and testing. Since then, the startup has grown quickly.

Concinnity Genetics joined the KQ Labs accelerator for data-driven health startups on the same day the team pitched as a finalist on the Conception X Demo Day 2021 virtual stage. Fast-forward six months, and the startup has been accepted onto the Scottish Enterprise High-Growth Spin-Out programme, which includes a large grant and vital access to laboratory space.

“Conception X builds your confidence, pushes you and helps you build some momentum, which would be quite difficult to do in isolation,” Birt says of her early days as a PhD founder.

“My favourite part was the mentoring. We had a few hiccups at first — we were describing the tech wrong and we were aiming it at the wrong people — but we knew we were only ever a few weeks away from having a meeting with someone to talk about it and then try a different way of doing it.”