LoQus23 Therapeutics has secured £35 million ($43 million) in a Series A fundraise led by Forbion and backed by the venture arm of Novartis to help advance its lead Huntington’s disease program into the clinic in 2026.
The candidate is an allosteric small molecule inhibitor of MutSβ, a protein complex that “sits at the very top of” the mismatch repair pathway, CEO David Reynolds told Endpoints News in an interview.
“With Huntington’s, for a long time, all the focus was on the huntingtin protein and [its role] in driving cellular toxicity,” he said. “What we’ve come to realize over the last 10 or so years is that that is a secondary process to the primary process of somatic instability in the DNA itself of the huntingtin gene.”
Somatic instability occurs when a repetitive DNA sequence expands in some cells over time. LoQus23 is focused on targeting this instability to slow or stop the progression of neurodegenerative diseases. The company believes its approach could also help treat myotonic dystrophy type 1 and a range of other conditions driven by triplet repeat expansion, which occurs when a single gene has more than a normal amount of three-nucleotide repeats.
For now, though, the focus is on the Huntington’s program, which is expected to enter a “fairly standard, single and multiple ascending dose Phase 1 study” in a few years’ time. The new funds should support the company’s work for at least the next three years, including through the end of that first trial, Reynolds said.
“While some of the newer modalities may be quite sexy for investors, actually, I took the view that there are many things that can go wrong in a drug project, from idea through to a launch product, and I didn’t want to add an untried, untested modality to that big list of challenges,” Reynolds said.
He added the company chose small molecules because of their large “precedent” in CNS diseases.
Huntington’s presents a “huge” unmet need because current treatments only help improve motor symptoms but don’t slow the actual course of the disease, Reynolds said. The condition is fatal, with patients living an average of 17 years from symptom onset. There are around 30,000 people in the US with symptoms and even more who are pre-symptomatic, Reynolds said.
The Series A raise was led by the venture capital firm Forbion, with support from existing backers Novartis Venture Fund and SV Health Investors’ Dementia Discovery Fund. LoQus23 was founded in 2019 by Reynolds and current CSO Caroline Benn. The company left stealth mode two years later with £11.5 million ($15.2 million) in seed financing, which was also supported by SV Health Investors.
Prior to heading up the biotech, Reynolds was CSO at Alzheimer’s Research UK. Benn, meanwhile, has spent more than a decade at top academic institutions in the UK and US researching the mechanisms behind Huntington’s.
Editor’s Note: This article was updated to clarify that Forbion led the fundraise and the dementia discovery fund is managed by SV Health Investors.