pipeline

Huntington’s Disease (HD) is the most common monogenic neurological disorder in Western populations, affecting approximately 10 to 13 people per 100,000. Carriers of the disease-causing mutation typically develop their first motor symptoms in their 30s or 40s, with disease progression leading to severe disability and ultimately death within two decades.

​

 

At the molecular level, HD is caused by a mutated version of the huntingtin (mHtt) protein, which has a high propensity to form neurotoxic oligomers and insoluble aggregates. Neuropathologically, the disease is characterized by the progressive dysfunction and loss of spiny projection neurons (SPNs) in the striatum. This neuronal loss disrupts cortico-striatal transmission, manifesting as chorea and bradykinesia, the hallmark motor symptoms of HD. In addition to motor impairments, patients experience psychiatric and cognitive symptoms, including anxiety, depression, and progressive cognitive decline leading to dementia.

 

 

Despite the well-characterized genetic basis of HD, its cellular and molecular mechanisms remain incompletely understood, and current treatments are purely symptomatic. Available therapies aim to improve quality of life but do not prevent or slow disease progression.

​

 

remynd’s HD program is dedicated to developing small molecules that neutralize the neurotoxic effects of mHtt. In preclinical studies, remynd’s HD compounds restored neuronal function, improved SPN survival, and enhanced cortico-striatal transmission in a Huntington’s disease mouse model. This translates into significant improvements in both motor function and neuropsychiatric symptoms, including anxiety.

 

 

The program’s lead compound, REM949, is a highly potent, orally available drug candidate with excellent brain permeability and promising non-clinical safety and pharmacokinetic properties. By directly targeting a key driver of HD pathology, REM949 has the potential to provide meaningful therapeutic benefits beyond symptomatic relief.