A biotech firm which is aiming to slow down the neurodegeneration process in Huntington’s has completed a £35m funding round to support is drug development work.
LoQus23 Therapeutics is investigating small molecule drugs that could stop DNA instability and slow disease progression in Huntington’s Disease, as well as myotonic dystrophy type 1 and similar triplet repeat expansion diseases.
Based at Babraham Research Campus, Cambridge, the company was founded in 2019 by Dr David Reynolds, Dr Caroline Benn, and Dr Ruth McKernan CBE.
Its focus is on inhibiting aspects of the DNA damage repair (DDR) system. This a complex set of pathways involving more than 400 genes/proteins required for long-term maintenance of an organism’s DNA to promote cellular health throughout a lifetime of damaging events.
The mismatch repair (MMR) branches of the DDR system repair DNA insertions, deletions and ‘misincorporation errors’ during transcription and/or cellular replication, with two main pathways dependent upon the size of mismatch – MutSα for small mismatches and MutSβ for larger insertion/deletion loops.
The MMR system is heavily implicated in studies to be the root cause of Huntington’s disease and other related triplet repeat diseases.
It is now clear that the initial driver of disease pathophysiology is MMR-mediated CAG repeat expansion in the Huntingtin gene, a process known as somatic expansion. Once a critical threshold number of CAG repeats is reached, then the second phase of neuronal dysfunction and ultimately death follows, which causes the slowly progressing symptoms in patients.
LoQus23 has developed 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.
By targeting somatic expansion, LoQus23 is hoping to slow or even halt the onset and progression of Huntington’s disease, a concept supported by genetic studies and recently strengthened by pre-clinical models.
Its series A funding round was led by Dutch VC Forbion alongside existing investors SV Health Investors’ Dementia Discovery Fund (DDF) and Novartis Venture Fund (NVF).
The investment will be primarily used to support the pre-clinical development and initial clinical studies of LoQus23’s lead programme, an allosteric small molecule MutSβ inhibitor. The company is preparing its lead programme to enter the clinic in 2026.
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 benefiting from their support and expertise.”
