LoQus23 Exits Stealth Mode to Target Huntington’s and Other Triplet Repeat Diseases

LoQus23 Exits Stealth Mode to Target Huntington’s and Other Triplet Repeat Diseases
Credit: GettyImages/ dani3315

U.K. biotech LoQus23 Therapeutics has exited stealth mode with the announcement of $15.4M (£11.5M) in seed funding to pursue treatments for Huntington’s and other triplet repeat diseases by targeting dysfunctional DNA mismatch repair.

The financing came from the U.K.’s Dementia Discovery Fund, a specialist venture capital firm set up by a group of pharma, biotech, charity and U.K. government representatives, as well as the Novartis Venture Fund, and extends its initial $6M (£4.5M) seed round, obtained from the Dementia Discovery Fund in 2019, by $9.4M (£7M).

Triplet repeat disorders are those caused by a type of genetic mutation where a group of three  nucleotides of DNA is present in abnormally high numbers, eventually becoming unstable and causing disease. For example, the inherited degenerative neurological disorder Huntington’s disease is caused by a CAG repeat in the HTT gene, which encodes the neurological protein huntingtin. There are more than 50 diseases in this group including several spinocerebellar ataxias, fragile X syndrome and Friedreich’s ataxia, among others.

Research shows that abnormal DNA mismatch repair (MMR) mechanisms can impact factors such as age of onset and progression of Huntington’s and other triplet repeat disorders.  MMR can contribute to disease severity by triggering further triplet expansions, making the disease and symptoms worse and making age of onset earlier.

LoQus23 plans to target Huntington’s, myotonic dystrophy type 1 and other triplet repeat disorders by targeting disease-related MMR through oral, small molecule drugs.

The company is based in Cambridge in the U.K. It was founded in 2019 by David Reynolds, now CEO, and Caroline Benn, now CSO, when they were entrepreneurs in residence at the Dementia Discovery Fund, as well as neuroscientist Ruth McKernan.

Prior to founding the company, Reynolds worked in pharma at Merck Sharp & Dohme, Lundbeck, and, most recently, Pfizer where he led the neuroscience and pain research site in Cambridge. Benn was previously an academic researcher researching molecular mechanisms of Huntington’s disease and therapeutic approaches at Kings College London and Harvard Medical School, before moving to work at Pfizer and Astex Pharmaceuticals.

The company plans to use the money to identify a lead candidate drug and “explore other MMR proteins for their role in somatic instability in triplet repeat disorders,” according to a press statement from the company.

“This significant early interest in LoQus23 is a strong validation of the company’s approach to pursue genetically-validated targets for the treatment of triplet repeat diseases. Discovering oral drugs that are effective against aberrant DNA mismatch repair could significantly improve the lives of patients with devastating genetic diseases like Huntington’s, and it’s great to see that both DDF and NVF have recognized the same potential in the company,” said Christian Jung, Partner at the Dementia Discovery Fund.

LoQus23 is not the only U.K. company or research team working on MMR focused therapeutics for Huntington’s. In September, UCL researchers announced they had identified a mechanism in the MMR pathway that stops progression of Huntington’s disease and are now working with another Cambridge startup, Adrestia Therapeutics, to develop this further.