SAN CARLOS, Calif.–(BUSINESS WIRE)–CuraSen Therapeutics, Inc., a clinical-stage company developing small molecule therapies to treat neurodegenerative disease, announced that it has begun dosing patients in a Phase 2a clinical trial with CST-2032, a novel, oral beta-2 adrenoceptor (β2-AR) agonist. The goal of the study is to evaluate the effects of CST-2032 on cognition and mood in patients with mild cognitive impairment or mild dementia due to either Parkinson’s or Alzheimer’s disease. CST-2032 is administered in combination with CST-107, a β-AR blocker, to minimize known side effects of β2-AR agonists. The multi-center trial, which is expected to enroll approximately 40 patients, is being conducted in the United States and New Zealand.
“With this trial initiation, CuraSen now has two unique pipeline opportunities in ongoing Phase 2 clinical studies aimed at improving the debilitating cognitive symptoms and loss of function in neurodegenerative diseases, with the ultimate goal of preventing or even reversing disease progression,” said Anthony Ford, PhD, chief executive officer, CuraSen Therapeutics.
The company’s two distinct drug candidates, CST-2032 and CST-103, target brain β2-ARs to directly activate cell types normally regulated by healthy adrenergic function. The stimulatory activation of these cells, which include neurons, microglia, pericytes and astrocytes, helps compensate for critical brain functions lost early in the disease process due to adrenergic decline. In addition, this mechanism of action helps maintain cognition and restore complex pathways vital for protecting brain health. The β-AR antagonist, CST-107, is co-administered to help manage common peripheral side effects of β2-AR agonists, such as increased heart rate, that might otherwise limit dosing below optimal cerebral impact.
Earlier this year, CuraSen completed a successful Phase 1 study evaluating the safety and tolerability of CST-2032/CST-107 at multiple doses in both healthy volunteers and patients with mild cognitive impairment. Based on encouraging safety, pharmacokinetic and pharmacodynamic results, which will be presented at a future medical conference, the company advanced CST-2032/CST-107 to Phase 2 clinical development.
In the Phase 2a randomized, double-blind study, trial participants receive daily doses of CST-2032 (co-administered with CST-107), or matching placebo, for 14 days, followed by a one-week washout period before crossing over to the other arm. All subjects will complete clinical, cognitive and additional pharmacodynamic assessments during each treatment period. Blood samples will be collected throughout the trial to assess early biomarkers of brain health. Study information and eligibility can be accessed here.
Following completion of the trial, expected early next year, CuraSen plans to initiate longer Phase 2 studies with additional dose levels of CST-2032/CST-107 in preferred patient populations.
Phase 2 Top-line Data Expected in Third Quarter 2022 with Second Drug Candidate (CST-103/CST-107) in Neurodegenerative Diseases
CuraSen is also completing a Phase 2, randomized, placebo-controlled, double-blind, crossover study of CST-103, a differentiated oral β2-AR agonist, co-administered with CST-107, in subjects with amnesic MCI, Parkinson’s disease with rapid eye movement sleep disorder (PDRBD) or Lewy body dementia. The study, which includes endpoints related to cognitive and executive function, mood, attentiveness, arousal and bioactivity, will help further identify patients with common core symptoms most likely to respond to treatment. The trial, which has recruited 41 patients, is taking place at sites in the U.K., Australia, New Zealand and the European Union. The company expects data imminently, which will determine specific indications for further clinical development.
Patients with neurodegeneration experience a loss of neurons in the locus coeruleus (LC) very early in the disease process, decades before functional decline. The LC, known as a key orchestrator of arousal and brain health, delivers most adrenergic input to forebrain structures and activates β2-ARs essential for maintaining mood, memory and cognition, as well as support for cellular metabolism, perfusion, inflammatory control and clearance of protein debris. When the LC declines, cerebral neuroprotection is undermined by loss of these functions, triggering the pathological hallmarks of neurodegenerative disease and progressive loss of cognitive strength.
About CuraSen Therapeutics
CuraSen is focused on the development of new treatments for neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and other related orphan conditions. CuraSen’s drugs are designed to activate certain receptor populations in the brain to compensate for critical neuronal and glial functions that have otherwise been lost due to degeneration, and represent a unique approach in the field. The company is evaluating CST-103 and CST-2032, β2-ARs agonists, in combination with CST-107, a β-AR blocker, in multiple Phase 2 clinical studies. The trials include patients with mild cognitive impairment, Parkinson’s disease with rapid eye movement sleep disorder (PDRBD), Lewy body dementia, and mild cognitive impairment or mild dementia due to either Parkinson’s or Alzheimer’s disease. For more information, please visit www.curasen.com.