CuraSen Therapeutics Announces Successful Completion of Phase 2 Safety, Tolerability and Proof of Concept Study in Patients with Parkinson’s Disease or Mild Cognitive Impairment (MCI) with CST-103/CST-107 Treatment

SAN CARLOS, Calif.--(BUSINESS WIRE)-- CuraSen Therapeutics, Inc., a clinical-stage company developing small molecule therapies to treat neurodegenerative disease, announced today positive top-line safety, tolerability and proof of concept data, with early efficacy benefit, in a Phase 2 clinical trial with CST-103 in patients with Parkinson’s disease (PD) or mild cognitive impairment (MCI). CST-103 is an oral, brain-permeant beta2 adrenoceptor (β₂-AR) agonist that is co-administered with CST-107, a brain-sparing β-AR blocker, to minimize known cardiometabolic side effects of β₂-AR agonists.

The Phase 2 trial was a randomized, double-blinded, two-period crossover study that enrolled 41 patients with neurodegenerative disease. The study evaluated the safety, tolerability and CNS effects of once daily CST-103/CST-107 treatment, compared to matched placebo, with 14 days treatment on each period and at least 14 days of washout between periods. The majority of patients enrolled had Parkinson’s disease, and specifically a history of REM-sleep behavior disorder (PD_RBD). In RBD, people lose their natural paralysis during the dreaming stage of sleep, known as REM sleep, and vigorously act out their dreams with disruptive movements disturbing sleep and safety for themselves and partners. An estimated 30 to 50 percent of all PD patients have a history of RBD; these patients have more rapidly progressing symptoms, especially those involving cognitive and behavioral functions, and greater autonomic dysfunction. The study took place at sites in the UK, Australia, New Zealand and the European Union.

Results showed that the combination of CST-103/CST-107 was both safe and well-tolerated, and importantly, that co-administration of CST-107 eliminated adverse events (AEs) common to the β₂-AR agonist class of drugs when administered alone. Such AEs include elevated heart rate, hyperglycemia and hypokalemia, and could otherwise present long-term safety risks in chronic studies of β₂-AR agonists. Most AEs observed were mild, and there were no serious or severe adverse events attributed to study drug. Additionally, the study revealed improvements in several quantitative test measures of cognition in patients treated with CST-103/CST-107, as early as one day after treatment and lasting in some cases for longer than the two weeks of treatment. CuraSen will present complete results from this trial in an oral session at the AD/PD Conference in Gothenburg, Sweden, March 28-April 1, 2023.

“These data provide strong support for the long-term development of CNS-active β₂-AR agonists and validate CuraSen’s unique drug combination approach to treating poorly addressed symptoms in patients with neurodegenerative disease. From a strategic standpoint, we were able to clearly assess the effects of CST-103 on cognitive function and other endpoints without the dose-limiting AEs normally seen with these agonists. Furthermore, the cognitive findings seen in the majority of patients with PD_RBD bode well for our plans to launch a larger and longer Phase 2b study in 2023 in this population,” said Anthony Ford, PhD, chief executive officer, CuraSen Therapeutics. “We look forward to presenting the full results in March, as well as encouraging Phase 1 data from our second neurodegenerative program, CST-2032, in a second oral presentation.”

Phase 2 CST-2032/CST-107 Clinical Trial Ongoing in Parkinson’s and Alzheimer’s Disease Patients

In addition to CST-103, CuraSen is conducting a Phase 2 study with CST-2032 in patients with mild cognitive impairment or early dementia from either Parkinson’s or Alzheimer’s disease. As with CST-103, CST-2032 is administered in combination with CST-107 to minimize known side effects of β₂-AR agonists. The multi-center trial, taking place in the United States and New Zealand, is expected to enroll approximately 60 patients. Following completion of the trial, expected mid-2023, CuraSen plans to initiate longer Phase 2 studies with additional dose levels of CST-2032/CST-107 in preferred patient populations.

About Parkinson’s Disease with REM Sleep Behavior Disorder (PD_RBD)

Parkinson’s disease (PD) is a degenerative condition of the brain associated with motor symptoms, such as slow movement, tremor, rigidity and imbalance, as well as non-motor complications such as cognitive impairment, depression, sleep disorders, pain and other sensory disturbances, and dysfunction of the autonomic nervous system. PD affects nearly one million Americans and more than eight million people globally, with as many as half of these having a history of RBD. RBD may develop contemporaneously with the typical PD symptoms, but it usually precedes the PD diagnosis by as much as five to 15 years.

Focusing on PD_RBD has allowed CuraSen to select for PD patients with greater cognitive symptom burden and those likely to respond to the adrenergic stimulation provided by CuraSen’s therapeutic approach. As treatment options for such symptoms are very limited, CuraSen sees great potential in PD to treat these debilitating and progressive non-motor manifestations.

About Neurodegeneration

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 heterocellular support for the brain’s 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, both selective β₂-ARs agonists, in combination with CST-107, a β-AR blocker, in multiple Phase 2 clinical studies. For more information, please visit www.curasen.com.

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