CuraSen Therapeutics Presents Positive Phase 1 Data Demonstrating Safety, Pharmacokinetics, and Pharmacodynamics of CuraAX (CST-3056) at the 2025 American Autonomic Society International Symposium
CuraSen Therapeutics, Inc., a privately held biopharmaceutical company focused on developing novel therapies for neurodegenerative and neuropsychiatric diseases, announced promising results from its Phase 1 clinical trial evaluating CuraAX (CST-3056), an oral, selective, partial alpha-1A adrenoceptor (α1A-AR) agonist. The findings were presented by Gabriel Vargas, MD, PhD, Chief Medical Officer at CuraSen Therapeutics, during both an oral and poster session at the 36th International Symposium on the Autonomic Nervous System, hosted by the American Autonomic Society (AAS), held November 5–8, 2025, in Clearwater Beach, Florida.
The CuraSen data provide compelling evidence supporting the favorable safety, tolerability, and pharmacologic characteristics of CuraAX, positioning the compound as a potential best-in-class treatment for neurogenic orthostatic hypotension (nOH) — a debilitating disorder of blood pressure regulation that significantly impacts patients with neurodegenerative diseases such as Parkinson’s disease (PD) and multiple system atrophy (MSA).
Understanding nOH: An Unmet Need in Neurodegenerative Disease Care
Neurogenic orthostatic hypotension (nOH) is a chronic, progressive disorder resulting from autonomic nervous system dysfunction. It is characterized by an excessive drop in blood pressure upon standing, typically defined as a fall of ≥20 mmHg in systolic or ≥10 mmHg in diastolic blood pressure within three minutes of standing. This leads to lightheadedness, dizziness, blurred vision, syncope (fainting), fatigue, and cognitive impairment due to insufficient blood flow to the brain.
nOH occurs frequently in patients with neurodegenerative diseases involving alpha-synuclein pathology, including Parkinson’s disease, multiple system atrophy, and pure autonomic failure. It affects an estimated 700,000 individuals in the United States, contributing to substantial morbidity, diminished quality of life, and increased healthcare utilization due to falls, injuries, and hospitalizations.
Importantly, nOH often triggers a “fear of falling” cycle, where patients limit mobility to avoid dizziness or fainting, leading to physical deconditioning, worsening symptoms, and further progression of disease. The condition also places a heavy emotional and physical burden on caregivers and family members.
Current therapies, such as midodrine and droxidopa, provide symptomatic relief by increasing blood pressure, but their effectiveness is limited, and side effects — including supine hypertension — can be problematic. There remains a significant need for treatments that both improve orthostatic tolerance and potentially confer central nervous system (CNS) benefits, such as improved cognition and alertness.
About CuraAX (CST-3056)
CuraAX is a selective, partial α1A-adrenoceptor agonist designed to target adrenergic signaling pathways impaired in neurodegenerative and autonomic disorders. Unlike traditional sympathomimetic agents, CuraAX is CNS-penetrant, allowing it to act both peripherally and centrally to improve blood pressure regulation and potentially enhance cognitive function.
By selectively modulating α1A-ARs, CuraAX aims to restore baroreflex sensitivity, stabilize blood pressure upon standing, and improve cerebral perfusion — the flow of oxygenated blood to the brain — without excessively elevating supine blood pressure. This CuraSen dual action could represent a meaningful therapeutic advance for patients with nOH who suffer from both orthostatic intolerance and cognitive impairment.
Phase 1 Study Overview and Objectives
The Phase 1 study of CuraAX was designed as a randomized, placebo-controlled, single- and multiple-ascending dose trial evaluating safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in 56 healthy adult volunteers. Doses ranged from 6 mg to 180 mg, administered orally, to characterize the compound’s dose-response relationship and identify an optimal dosing range for further studies in patients with nOH.
Key objectives included:
- Assessing the safety and tolerability of single and repeated doses of CuraAX;
- Characterizing pharmacokinetic parameters such as absorption, distribution, metabolism, and elimination;
- Evaluating pharmacodynamic effects on heart rate, blood pressure, and markers of baroreflex activity;
- Establishing proof of mechanism to support advancement to Phase 2 trials in patient populations.
Phase 1 Results: Robust Safety and Favorable Pharmacologic Profile
Results from the study demonstrated that CuraAX was well tolerated across all dose levels, with no serious adverse events and only mild, transient side effects reported at higher doses. The maximum tolerated dose (MTD) was identified as 90 mg, with no clinically significant changes in laboratory values, ECGs, or vital signs aside from the expected pharmacodynamic effects associated with α1A-AR activation.
Key findings included:
- Excellent Safety and Tolerability:
Few adverse events were reported, and all were mild and self-limiting. Commonly observed events included transient sensations of warmth or mild dizziness, consistent with the drug’s mechanism of action. No participants discontinued due to adverse effects. - Predictable Pharmacokinetics:
CuraAX demonstrated rapid and consistent oral absorption, achieving peak plasma concentrations suitable for symptom control in nOH. The compound exhibited a linear dose-exposure relationship and a half-life compatible with once- or twice-daily dosing. - Clear Pharmacodynamic Activity:
Dose-dependent reductions in supine heart rate were observed, consistent with baroreflex-mediated effects expected from α1A-AR activation. These findings support the hypothesis that CuraAX enhances baroreflex sensitivity and could restore autonomic balance in patients lacking normal sympathetic reflexes.
Dr. Gabriel Vargas, Chief Medical Officer at CuraSen Therapeutics, summarized:
The pharmacodynamic profile observed in this study — specifically, dose-related modulation of heart rate and blood pressure consistent with α1A receptor activation — provides strong evidence of CuraAX’s intended mechanism of action. These findings support advancing CuraAX into Phase 2 studies for patients with neurogenic orthostatic hypotension, where baroreflex failure and blood pressure instability are central to disease pathology.”
Potential for Cognitive Benefits
In addition to its hemodynamic effects, CuraAX’s CNS penetrance raises the possibility of cognitive benefits. By improving cerebral perfusion and modulating adrenergic signaling within the brain, CuraAX may help alleviate cognitive symptoms commonly reported by patients with nOH, including “brain fog,” attention deficits, and slowed processing speed.
Kathleen Sereda Glaub, Chief Executive Officer of CuraSen Therapeutics, emphasized this broader therapeutic vision:
“These Phase 1 results highlight the potential of CuraAX not only to stabilize blood pressure and prevent dizziness or fainting but also to improve cognition and mental clarity. For patients with Parkinson’s disease and other neurodegenerative conditions, this could mean greater independence, mobility, and overall quality of life. We believe CuraAX has the potential to become a best-in-class therapy for neurogenic orthostatic hypotension.”
Advancing to Phase 2a: Evaluating CuraAX in Patients with Parkinson’s Disease and Pure Autonomic Failure
Building on the successful Phase 1 outcomes, CuraSen has initiated a Phase 2a proof-of-concept trial to assess CuraAX’s safety, tolerability, and efficacy in patients with nOH due to Parkinson’s disease (PD) or pure autonomic failure (PAF). This randomized, double-blind, placebo-controlled study will evaluate multiple dose levels to identify an optimal therapeutic window and further explore the relationship between CuraAX exposure and improvements in orthostatic symptoms.
The study will also incorporate exploratory endpoints measuring cognitive performance, functional mobility, and quality of life, reflecting the company’s commitment to addressing both the cardiovascular and neurocognitive dimensions of autonomic dysfunction.
Addressing a Major Unmet Medical Need
Despite advances in symptomatic management, nOH remains a major unmet need in the care of patients with neurodegenerative diseases. It is a leading cause of falls and hospitalizations among patients with Parkinson’s disease, contributing to physical disability, emotional distress, and accelerated disease progression. In severe cases, recurrent syncope and cerebral hypoperfusion can lead to cognitive decline, highlighting the urgent need for therapies that address both cardiovascular stability and brain health.
CuraAX represents a novel therapeutic approach — targeting α1A receptors selectively and partially to achieve a balanced modulation of vascular tone and autonomic control without excessive hypertension. Its potential to act centrally and peripherally distinguishes it from existing treatments and aligns with CuraSen’s broader strategy to restore adrenergic function lost early in neurodegenerative disease.
Support from the Alzheimer’s Drug Discovery Foundation (ADDF)
Development of CuraAX has been supported by the Alzheimer’s Drug Discovery Foundation (ADDF) through IND-enabling and early clinical studies. This partnership reflects the compound’s relevance not only to autonomic disorders but also to neurodegenerative conditions where adrenergic dysfunction contributes to cognitive and functional decline.
The ADDF’s funding underscores the translational potential of CuraAX as part of a new generation of CNS-active agents aimed at restoring key neurotransmitter systems implicated in both Alzheimer’s and Parkinson’s pathology.
CuraSen’s Broader Pipeline: Restoring Adrenergic Function Across Neurodegenerative Diseases
CuraAX is one of several investigational agents within CuraSen’s innovative adrenergic modulation platform. The company’s pipeline includes two additional programs designed to restore and rebalance adrenergic signaling — a system that becomes progressively impaired in neurodegenerative diseases long before cognitive or motor symptoms appear.
- CuraCN (CST-103/CST-107):
A combination of a CNS-penetrant β2-adrenergic receptor agonist with nadolol, a peripherally restricted beta-blocker. This pairing is intended to enhance central adrenergic tone while mitigating unwanted peripheral effects. Phase 2 proof-of-concept studies have demonstrated cognitive benefits in patients with Parkinson’s and Alzheimer’s disease. - CuraXN (CST-2032/CST-107):
A next-generation formulation with optimized pharmacokinetics, designed for broader neurodegenerative indications. Future clinical trials are planned in progressive supranuclear palsy (PSP) and Alzheimer’s disease, where restoring adrenergic balance could improve alertness, mood, and cognitive function.
Together, these programs reflect CuraSen’s mission to develop targeted, mechanism-based therapies that address the early and systemic neurochemical disruptions underlying neurodegenerative and neuropsychiatric diseases.
With strong Phase 1 results validating its mechanism, CuraAX is now advancing through Phase 2 development with the potential to significantly improve outcomes for patients suffering from neurogenic orthostatic hypotension. CuraSen’s leadership believes that addressing adrenergic dysfunction could transform the management of not only autonomic disorders but also cognitive impairment across multiple neurodegenerative conditions.
As Ms. Glaub concluded:
“Our goal is to restore function — physical, cognitive, and emotional — for patients who today have very limited options. CuraAX’s ability to improve blood pressure control, cognition, and daily functioning offers hope to patients and caregivers dealing with the challenges of neurogenic orthostatic hypotension and related diseases.”
About CuraSen Therapeutics
CuraSen Therapeutics, Inc. is a privately held biopharmaceutical company developing small-molecule therapies to restore adrenergic signaling pathways impaired in neurodegenerative and neuropsychiatric disorders. The company’s portfolio includes multiple CNS-penetrant agents targeting adrenergic receptors to improve autonomic, cognitive, and behavioral symptoms in diseases such as Parkinson’s, Alzheimer’s, and progressive supranuclear palsy. CuraSen’s headquarters are located in South San Francisco, California. For more information, visit www.curasen.com.
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