Our Science & Pipeline

A clinical strategy guided by biomarkers focused on synaptic proteins

We will measure multiple biomarkers to gain early signals of target engagement and drug effect in our clinical trials. Patients will also be assessed with sensitive measures of cognition, function and behavior.

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(1) Synaptic protein SV2A

We use a Positron Emission Tomography (PET) scan that deploys a novel radioligand intended to measure the synaptic protein SV2A in the brain. This scan allows the direct measurement of synaptic density in a living human and will enable us to directly track changes in synaptic density in response to treatment.

(2) Synaptic proteins such as SNAP25, BDNF, PSD95 and neurogranin

We intend to measure the level of several synaptic proteins in cerebrospinal fluid. This analysis lets us track the state of synaptic integrity over time.

(3) Plasma

Some synaptic and neuronal proteins can also be measured in plasma; we will track these markers and explore as potential complementary and/or replacement read-outs for certain cerebrospinal fluid biomarkers.

(4) Peripheral blood monocytes (PBMCs)

We will track post-translational modification in human blood cells as a direct target engagement marker of HDAC-CoREST activity in response to compound treatment.

Optimized clinical trial designs

Preclinically, our compounds produce significant and durable increases in synaptic density within several days. In patients, the emergence of new synapses should lead to measurable improvements in clinical symptoms. This synaptic-targeting mechanism should therefore allow clinical trial durations of three to six months and enrollment of patients across a broad range of disease severities.

Our initial Phase 1b study will enroll Alzheimer’s disease patients and focus on safety, tolerability and pharmacokinetic measures. We will also measure cognition, function and key translational fluid and neuroimaging biomarkers.

Phase 1b data will drive our plans for conducting multiple Phase 2 trials in synaptopathies with high unmet medical need. Each Phase 2 trial will enroll well-characterized patients who will be assessed via multiple outcomes: cognition, function, behavior, neuroimaging, digital endpoints and fluid biomarkers.