CuraSen Therapeutics announced that it has dosed its first subjects in a multi-part, Phase 1 clinical study with CST-2032, the company’s first proprietary compound intended for the treatment of neurodegenerative disease.

CST-2032 is a brain-permeant, selective adrenoceptor modulator designed to target key receptors in cortical and limbic regions of the brain that are no longer optimally innervated in patients with neurodegenerative disease.

CST-2032 is being developed to treat the debilitating symptoms of neurodegeneration in patients battling Parkinson’s, Alzheimer’s and related neurodegenerative diseases, and slow or reverse underlying pathology. The company’s initial studies in healthy volunteers and then patients will measure pote-ntial for drug impact on core disease symptoms, including dysfunction in cognition, arousal, memory and mood, as well as brain inflammation and metabolic health. Neurons in the locus coeruleus, located in the brain stem and the sole source of noradrenaline (or norepinephrine) for the higher brain centers, decline very early in neurodegenerative diseases. By activating specific receptors in the brain, CST-2032 is expected to restore healthy function to multiple cell types, including neurons, microglia, pericytes and astrocytes. This heterocellular approach is expected to broadly improve cerebral integrity and function, and represents a unique treatment paradigm in the field.

“We are excited to begin this clinical study with our new drug candidate, CST-2032. Neurodegenerative disease represents an enormous health burden in the U.S. and globally,” said Anthony Ford, PhD, chief executive officer, CuraSen. “Informed by findings from our completed clinical studies that used adrenergic drugs from other therapeutic areas, we were able to establish the ideal characteristics for a new compound and rapidly incorporate them into the design of CST-2032. Progressing this proprietary program from discovery to human clinical study in less than two years is an impressive achievement and validates the collective efforts of our experienced team and advisor network.”

CuraSen’s early clinical development work included three clinical trials using established drugs in more than 100 healthy subjects and patients. The goal was to guide optimization of the company’s proprietary compounds, identify meaningful clinical biomarkers and endpoints, and establish exposure and dose levels for proof-of-concept efficacy studies. The company explored multiple pharmacodynamic measurements for rapid and objective assessment of drug effect on brain function in these trials. These measures included chemical biomarkers, neuroimaging, neurophysiology and autonomic function assessments of drug-target engagement, as well as more standard tests of arousal, mood and cognitive performance.

“Historically, the lack of reliable biomarkers and assessment tools has made the development of effective neurodegenerative disease therapeutics very challenging,” said Gabriel Vargas, MD, PhD, chief medical officer, CuraSen, and a psychiatrist with expertise in translational medicine. “At CuraSen, we have been able to employ a suite of sophisticated tools and glean valuable insights studying adrenergic drugs in the clinic at some of the leading clinical centers in brain research, thereby providing us with confidence to move forward with CST-2032.”

The Phase 1 trial will include up to 70 healthy volunteers and patients with a variety of neurodegenerative diseases, including Parkinson’s Disease (PD) or Mild Cognitive Impairment (MCI). The study will consist of single-ascending and multiple-ascending dose components in healthy volunteers using biomarker assessments, including neuroimaging and autonomic function tests. A third component will evaluate these measures in patients after receiving CST-2032 treatment. The study is taking place in New Zealand and Belgium.

A Phase 2 study is anticipated to begin in 2021.