Loqus23 raises funding to advance small molecule for Huntington’s
Funds will aid development through early clinical studies
Loqus23 Therapeutics has raised 35 million pounds (about $45 million) in financing to advance its lead oral small molecule candidate for Huntington’s disease through preclinical development and early clinical studies, which are anticipated in 2026.
The series A financing round was led by Forbion, a life sciences venture capital firm, with additional contributions from existing investors including SV Health Investors’ Dementia Discovery Fund and the Novartis Venture Fund.
“This financing will enable us to develop key clinical data,” David Reynolds, PhD, Loqus23 CEO, said in a company press release. “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.”
Huntington’s is considered a triplet repeat disease, as it is caused by excessive repeats of a sequence of three building blocks — CAG — in the HTT gene. Healthy people have up to 35 CAG repeats, but those with 40 or more repeats will develop the disease.
While the number of CAG repeats inherited at birth can trigger Huntington’s, it appears that it’s the further expansion of these repeats throughout life, sometimes reaching the hundreds, that leads to damage in the brain and resulting slowly progressing symptoms.
MutS suppression
Data suggest CAG repeats are expanding due to the formation of repeat-associated DNA structures and their subsequent abnormal repair by a mechanism called DNA mismatch repair (MMR). Such expansion is called somatic because it can accumulate in any of the cells of the body except the germ cells (sperm and egg).
One protein that’s essential in detecting a DNA mismatch and directing the MMR machinery is called MutS. It has two forms: MutS-alpha recognizes small mismatches, whereas MutS-beta recognizes larger insertions or deletions that coil DNA into loops, like the CAG repeats, contributing to their expansion.
Loqus23 is focused on the development of small molecules that can bind to and suppress MutS-beta as potential treatments for triplet repeat diseases, including Huntington’s and myotonic dystrophy type 1, a condition in which muscles are unable to relax after they contract.
“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,” Reynolds said.
The company’s lead candidate, currently being developed as a potential treatment of Huntington’s, is expected to prevent somatic expansion, slowing or stopping disease progression or even delaying its onset. It may therefore be a potential disease-modifying treatment for the neurodegenerative disease.
“Somatic expansion is a key driver of triplet repeat diseases like Huntington’s,” said Rogier Rooswinkel, PhD, general partner at Forbion. “In somatic expansion, [MutS-beta] seems the most promising and best validated target, with the potential to bring disease progression to a halt.”
Rooswinkel, who’s been appointed to join the Loqus23 board, said the company “is leading the charge in developing … small molecules against [MutS-beta], and we look forward to working with them to progress their molecules towards the clinic and ultimately to benefit patients.”
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