Products

The company’s lead product is a first-in-class Adeno-associated virus delivered RNA interference (RNAi) therapeutic targeting a voltage-gated L-type calcium channel known as Cav1.3, in a brain region known as the striatum for the treatment of levodopa-induced dyskinesias (LID), a significant side-effect associated with the standard of treatment for Parkinson’s disease. Initial work by the company’s scientific founders have established unequivocal proof-of-concept and target validation in multiple pre-clinical models including the gold standard non-human primate (NHP) model of Parkinson’s disease and LID, demonstrating some of the most profound anti-dyskinetic benefits for LID reported to date. Preliminary indications in the NHP model also demonstrate that this therapeutic can significantly reverse longstanding parkinsonian motor deficits. The company is currently evaluating two therapeutic candidates, CGT-102 and CGT-103 in NHP models for therapeutic benefit and overall safety profile to take forward into full development for the treatment of LID.

Parkinson’s disease (PD) is a debilitating neurological disorder affecting more that 10 million people worldwide. Levodopa (L-dopa), a dopamine (DA) precursor, is generally the most effective pharmacotherapy for PD and is considered the ‘gold standard’ treatment for PD. However, with long-term L-dopa treatment, an often debilitating complication known as L-dopa-induced dyskinesias (LID) develop. LIDs are characterized by excessive abnormal involuntary movements and/or dystonia that can negatively impact a patient’s quality of life. While up to 90% of individuals with PD taking L-dopa eventually develop this debilitating side-effect, current treatments are only partially and/or transiently effective. A growing body of evidence has implicated striatal calcium voltage-gated Cav1.3 channels as a novel target of high interest for LID amelioration. The loss of striatal DA in PD results in dysregulation and overactivity of striatal Cav1.3 channels, leading to synaptic pathology (i.e., ‘abnormal circuitry’) associated with LID. While initial studies in animal models of PD delivering commercially available Cav1.3 antagonists reduced LID, the effects were PARTIAL and TRANSIENT, presumably due to inadequate target engagement with currently available brain-penetrant Cav1 channel blockers. Consequently, there is a large unmet medical need for more effective treatments that prevent or delay the onset of LID, and/or reduce overall severity of existing LID severity without interfering with the motor benefits of L-dopa.