LoQus23 Therapeutics’ Series A £35m will prioritise targets for Huntington’s Disease

LoQus23 Therapeutics has closed a £35million Series A finance round to fund the pre-clinical development and initial clinical studies of its lead small molecule drug.

The financing was led by leading life sciences venture capital firm Forbion with participation from existing investors SV Health Investors’ Dementia Discovery Fund (DDF) and Novartis Venture Fund (NVF). Forbion general partner Rogier Rooswinkel has joined the board of directors with immediate effect.

Based at Babraham Research Campus, LoQus23 was founded in 2019 by Entrepreneurs in Residence at DDF Dr David Reynolds, Dr Caroline Benn, and Dr Ruth McKernan. It received initial seed funding from NVF in 2021.

It is investigating small molecule drugs that could stop DNA instability and slow neurodegeneration in Huntington’s Disease, myotonic dystrophy type 1 and similar triplet repeat expansion diseases.

Huntington’s Disease is an inherited autosomal dominant neurodegenerative disorder that causes a gradual decline in a person’s movement, memory, thinking, and emotional state. There is currently no disease-modifying treatment available for the UK’s 7,000 sufferers.

LoQus23’s treatment option makes use of the mismatch repair (MMR) branches of the DNA damage repair (DDR) system which mend DNA insertions, deletions and misincorporation errors during transcription and/or cellular replication. Depending on the size of mismatch there are two main pathways – MutSα for small mismatches and MutSβ for larger insertion/deletion loops.

Both MutSα and MutSβ are part of this MMR system, which is heavily implicated by human genetic and mechanistic studies to be the root cause of Huntington’s disease and other related triplet repeat diseases.

LoQus23 has established a platform of assays and a small molecule series of MutSα and MutSβ inhibitors which are therapeutically relevant in up to 30 triplet repeat diseases, including Huntington’s disease.

LoQus23 uses a structure-based approach to design small molecule drugs, which offers convenient administration. Oral small molecule drugs have a strong track record in treating complex brain diseases and provide greater convenience for patients compared with other advanced treatment modalities.

Rogier Rooswinkel, general partner at Forbion and the newly-appointed board member at LoQus23, said: “Somatic expansion is a key driver of triplet repeat diseases like Huntington’s. In somatic expansion, MutSβ seems the most promising and best validated target, with the potential to bring disease progression to a halt.

“LoQus23 is leading the charge in developing allosteric small molecules against MutSβ and we look forward to working with them to progress their molecules towards the clinic and ultimately to benefit patients.”

LoQus23 Therapeutics CEO Dr David Reynolds said: “This financing will enable us to develop key clinical data to support the development of our exciting lead programme.

“The ever-increasing body of data pointing to somatic expansion, caused by aberrant DNA mismatch repair, as being the primary culprit in Huntington’s disease provides great support that our approach of developing oral small molecule therapies will be transformative for patients with this dreadful inherited disease.

“We welcome Forbion as the lead investor of this round, alongside our existing high-calibre investors, and look forward to benefitting from their support and expertise.”