Solengepras

(CVN424)

PARKINSON’S DISEASE

Potentially a first in class, oral non-dopaminergic therapy for the broad treatment of the signs and symptoms (motor and non-motor) of Parkinson’s disease.

Restores balance by regulating just one side of brain circuitry - the indirect pathway

Solengepras targets GPR6, a target evaluated using NETSseq, presenting a novel point of therapeutic intervention.

By inhibiting GPR6, solengepras aims to reduce periods of symptomatic worsening (“OFF time”), while mitigating the side effects commonly associated with many dopaminergic therapies.

GPR6 is observed in the dopamine receptor D2-positive cells of the medium spiny neuron (“MSN”) indirect pathway, and much lower or absent expression was observed in D1 dopamine receptor-positive cells from the MSN direct pathway, as shown in our NETSseq data below.

GPR6 target findings
signaling pathways in Healthy brain versus brain with parkinson's

Non-specific replacement of dopamine (using L-DOPA or treating patients with drugs that act on dopamine receptors) LACKS the PRECISION to correct this imbalance and can cause “on-target” related side effects.

Solengepras has the potential to provide a novel approach for the treatment of Parkinson's disease with a better tolerability profile than current therapies.

Inhibitory circuits
Excitatory circuits
Dopamine circuits
D1: Direct pathway facilitates movement (“Accelerator”)
D2: Indirect pathway inhibits movement ("Brake")

Adjunctive & Monotherapy

Solengepras is being developed for use across the spectrum of Parkinson's disease, both as an adjunctive treatment as well as for monotherapy use. Cerevance is currently conducting a Phase 2 clinical trial of solengepras (ASCEND) as a monotherapy treatment in early, untreated patients with Parkinson's disease. Cerevance has also initiated a pivotal Phase 3 clinical trial of solengepras (ARISE) as an adjunctive treatment in patients experiencing motor fluctuations.

Solengepras - Phase 2 Adjunctive Study

Solengepras 150 mg dose cohort demonstrated a statically significant reduction of 1.3 hours (p=0.02) in average daily OFF time versus placebo after only 27 days of treatment which represented a1.6-hour (p<0.0001) improvement from baseline.

Solengepras 150 mg dose cohort was associated with a dose-dependent improvement trend on the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II score (activities of daily living) versus placebo. Trends to improvement in the UPDRS Part II after treatment with the solengepras 150 mg dose were seen in as little as four weeks, suggesting that solengepras may have broader benefits on the activities of daily living for PD patients beyond motor improvements.

Solengepras did not increase daytime sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and was instead associated with a trend towards reduction in daytime sleepiness with the solengepras 150 mg dose versus placebo.

Solengepras was generally well-tolerated with few adverse events and low rates of dopaminergic adverse events across both dose cohorts.

Solengepras 150 mg dose cohort demonstrated a statically significant reduction of 1.3 hours (p=0.02) in average daily OFF time versus placebo after only 27 days of treatment which represented a1.6-hour (p<0.0001) improvement from baseline.

Solengepras 150 mg dose cohort was associated with a dose-dependent improvement trend on the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II score (activities of daily living) versus placebo. Trends to improvement in the UPDRS Part II after treatment with the solengepras 150 mg dose were seen in as little as four weeks, suggesting that solengepras may have broader benefits on the activities of daily living for PD patients beyond motor improvements.

Solengepras did not increase daytime sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and was instead associated with a trend towards reduction in daytime sleepiness with the solengepras 150 mg dose versus placebo.

Solengepras was generally well-tolerated with few adverse events and low rates of dopaminergic adverse events across both dose cohorts.

Safety

Well tolerated in the Phase 2 adjunctive study, with few adverse side effects, including a low rate of dopaminergic-related side effects.

Adjunctive & Monotherapy

Solengepras is being developed for use across the spectrum of Parkinson's disease, both as an adjunctive treatment as well as for monotherapy. Cerevance is currently conducting a Phase 2 clinical trial of solengepras (ASCEND) as a monotherapy treatment in early, untreated patients with Parkinson's disease. Cerevance has also initiated a global, pivotal Phase 3 clinical trial of solengepras (ARISE) as an adjunctive treatment in patients with Parkinson's disease experiencing motor fluctuations.