LoQus23 says drug candidate can boost fight against Huntington's Disease
It is investigating small molecule drugs that could stop the pathogenic triplet expansion that is the cause and driver of HD, myotonic dystrophy type 1, and other triplet repeat expansion diseases. It posits that DNA mismatch repair has been shown as a key driver of HD and other triplet repeat diseases.
Convergent evidence from human genetics, post-mortem studies, and mechanistic research identifies MSH3/MutSβ as the most promising target of the DNA mismatch repair pathway. However, the protein is a highly challenging target for small molecule therapeutic intervention, LoQus23 believes.
By leveraging its deep expertise of the pathway and the disease, LoQus23 has established a platform of assays and multiple series of small molecule MutSβ inhibitors. LQT-23 represents a groundbreaking advancement in MutSβ modulation for the treatment of HD, employing a novel mechanism of action to inhibit this complex target. The company says that LQT-23 is the most advanced and potent allosteric small molecule inhibitor of MutSβ to date.
Dr David Reynolds, Chief Executive Officer of LoQus23 Therapeutics, commented: "The nomination of LQT-23 as our development candidate is a significant moment for LoQus23 and reaffirms our strategy of advancing our pipeline of MSH3/MutSβ inhibitors to transform the lives of patients.
"I want to salute the dedication of our team which has worked tirelessly over many years to identify this candidate for such a difficult target, and we look forward to advancing it to IND/CTA filing later this year."
Dr Cyrus Mozayeni, Chair of the Board at LoQus23, added: "MSH3/MutSβ is the most promising and best validated target for HD, but has been difficult to drug. The team has made exceptional progress since the financing in 2024, and the nomination of LQT-23 as our lead development candidate underscores our deep domain expertise, while positioning LoQus23 at the forefront of emerging therapies for the treatment of HD."
Preclinical studies of LQT-23 have demonstrated potent and selective modulation of MSH3/MutSβ which leads to robust blockade of somatic expansion in HD cellular systems and animal models. Pre-clinical development will continue through 2026.
Huntington's Disease is an autosomal dominant neurodegenerative disorder for which there is currently no approved disease modifying treatment and which has 30,000 patients in the US alone. By targeting somatic expansion, LoQus23 is hoping to slow or even halt the onset and progression of HD.
In 2024, LoQus23 announced the successful close of a £35 million Series A financing round led by Forbion, alongside existing investors SV Health Investors' Dementia Discovery Fund and Novartis Venture Fund.
LoQus23 has a highly experienced leadership team, built on world-class science. It was originally established in 2019 by Dr Reynolds, Dr Caroline Benn and Dr Ruth McKernan.