nadolol (CST-107) / CuraSen Therap - LARVOL DELTA

CLIN-011: A Study of Clenbuterol (CST-103) Co-administered With Nadolol (CST-107) in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: CuraSen Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: CuraSen Therapeutics, Inc. | N=25 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • CNS Disorders • Movement Disorders • Parkinson's Disease

Effects on cerebral blood flow after single doses of the β2 agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease. (PubMed, Br J Clin Pharmacol) - "The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful β2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease

CuraSen Therapeutics Announces Oral Presentation of Additional Positive Phase 2a Data with CST-2032/CST-107 in Patients with Alzheimer’s or Parkinson’s Disease at AD/PD 2024 International Conference (Businesswire) - P2a | N=64 | NCT05104463 | Sponsor: CuraSen Therapeutics, Inc | "CuraSen Therapeutics, Inc...announced that it will present additional positive Phase 2a data with its combination adrenergic activator, CST-2032/CST-107...The oral presentation will take place at AD/PD 2024: The International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders, being held March 5-9, 2024, in Lisbon, Portugal...Digit Symbol Substitution test, which measures complex attention, memory and executive function: AD patients with MCI = 0.36 effect size; p=0.02 on Day 14...Excellent safety and tolerability profile No serious adverse events: no increases in heart rate observed one to four hours after dose...The company plans to initiate longer studies with both CST-2032/CST-107 and CST-103/CST-107 in AD and PD patients with MCI later this year, as well as develop fixed-dose combination tablets for each of these drug candidates."

P2a data • Alzheimer's Disease • CNS Disorders • Dementia • Parkinson's Disease

A Study of CST-2032 and CST-107 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease (clinicaltrials.gov) - P2 | N=64 | Completed | Sponsor: CuraSen Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

A Study of CST-2032 and CST-107 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: CuraSen Therapeutics, Inc. | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2023 ➔ Mar 2024

Phase classification • Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

Combination Treatment of a Novel β2 Adrenoceptor Agonist, CST-2032, and Nadolol Improves Cognitive (CTAD 2023) - P2a | "AD subjects had impaired cognition at enrollment. Short-term treatment with the β2-AR agonist, CST-2032, when administered with the peripherally restricted antagonist nadolol, significantly improved performance in the DSST, a cognitive test involving attention, processing speed and executive function, as well as in measures of social cognition. Combination therapy with CST-2032+nadolol was well-tolerated."

Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders

A Study of CST-2032 and CST-107 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease (clinicaltrials.gov) - P2a | N=60 | Recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial primary completion date: Jun 2023 ➔ Nov 2023

Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Mar 2023 ➔ Jul 2023

Trial completion date • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

CuraSen Therapeutics to Present Phase 2 Data Showing Rapid-Onset Cognition and Mood Benefit with CST-103/CST-107 (Clenbuterol/Nadolol) in Parkinson’s Disease at the Alzheimer’s Disease and Parkinson’s Disease (AD/PD’23) Conference (Businesswire) - P1 | N=N/A | NCT05033912 | Sponsor: CuraSen Therapeutics, Inc. | "Additionally, the company will present promising Phase 1 data with a second program, CST-2032/CST-107, in healthy participants and patients with mild cognitive impairment (MCI)....Phase 1 Study with CST-2032/Nadolol in Mild Cognitive Impairment (MCI)....Results showed that treatment with CST-2032/nadolol...Was safe and well tolerated. Increased cerebral blood flow, a biomarker for target engagement, in brain regions involved in memory, alertness and arousal....Based on the strength of these data, CuraSen has initiated a Phase 2a exploratory, randomized, placebo-controlled, double-blinded crossover study with CST-2032/CST-107 in up to 60 patients with MCI or mild dementia due to either Alzheimer’s or Parkinson’s disease. The trial is taking place at 20 centers in the U.S. and New Zealand, with results anticipated later in 2023."

P1 data • P2a data • Trial status • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Parkinson's Disease

CuraSen Therapeutics to Present Phase 2 Data Showing Rapid-Onset Cognition and Mood Benefit with CST-103/CST-107 (Clenbuterol/Nadolol) in Parkinson’s Disease at the Alzheimer’s Disease and Parkinson’s Disease (AD/PD’23) Conference (Businesswire) - P2 | N=41 | NCT04739423| Sponsor: CuraSen Therapeutics, Inc. | "CuraSen Therapeutics...announced that it will present Phase 2 clinical data showing improvements in cognition and mood in Parkinson’s disease patients treated with CST-103/CST-107....Phase 2 Proof-of-Concept Study with Clenbuterol/Nadolol in Parkinson’s Disease....Statistically significant improvements in several quantitative test measures of episodic memory, attentiveness and depressive emotional bias in patients treated with clenbuterol/nadolol, with several effect sizes (Cohen’s d) in the range 0.3-0.6 which are predictive of clinically meaningful results in a larger, longer trial....CuraSen’s next Phase 2 study with clenbuterol/nadolol is anticipated later this year and will enroll Parkinson’s patients with significant non-motor symptoms with a similar combination dosing plan in a 12-week parallel design."

P2 data • Trial status • CNS Disorders • Parkinson's Disease

EFFECTS OF A BETA-2 ADRENOCEPTOR (AR) AGONIST ON COGNITION IN PARKINSON'S DISEASE PATIENTS WITH REM SLEEP BEHAVIOR DISORDER (RBD) (ADPD 2023) - "Short-term treatment with the β 2 -AR agonist, CST-103, when administered with the peripherally restricted β-AR antagonist, CST-107, improved performance in tests of cognition and was well-tolerated. These data support further development of CST-103."

Clinical • Behavior Disorders • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder • Sleep Disorder

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 (Businesswire) - P2 | N=41 | NCT04739423 | Sponsor: CuraSen Therapeutics, Inc. | "CuraSen Therapeutics, Inc...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)....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....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."

P2 data • Trial completion • CNS Disorders • Cognitive Disorders • Parkinson's Disease

A Study of CST-2032 and CST-107 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease (clinicaltrials.gov) - P2a | N=60 | Recruiting | Sponsor: CuraSen Therapeutics, Inc. | N=40 ➔ 60

Enrollment change • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Aug 2022 ➔ Dec 2022

Trial completion date • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

A Study of CST-2032 and CST-107 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease (clinicaltrials.gov) - P2a | N=40 | Recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Nov 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

CuraSen Therapeutics Announces First Patients Treated with Novel Combination Therapy (CST-2032/CST-107) in Phase 2a Study of Mild Cognitive Impairment (MCI) or Mild Dementia Due to Parkinson’s or Alzheimer’s Disease (Businesswire) - “CuraSen Therapeutics, Inc…announced that it has begun dosing patients in a Phase 2a clinical trial with CST-2032…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...The multi-center trial, which is expected to enroll approximately 40 patients, is being conducted in the United States and New Zealand….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”

P2 data • Trial completion date • Trial status • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: CuraSen Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Mar 2023 ➔ Mar 2024 | Initiation date: Jun 2022 ➔ Jun 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study of CST-2032 and CST-107 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease (clinicaltrials.gov) - P2a | N=40 | Recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial primary completion date: Jul 2022 ➔ Nov 2022

Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

A Study of CST-2032 and CST-107 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease (clinicaltrials.gov) - P2a | N=40 | Recruiting | Sponsor: CuraSen Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial primary completion date: Mar 2022 ➔ Jun 2022

Trial primary completion date • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

A Study of CST-103 Co-administered With CST-107 in Subjects With Parkinson's Disease Having Freezing of Gait (CLIN-012) (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: CuraSen Therapeutics, Inc. | Trial completion date: Dec 2022 ➔ Mar 2023 | Initiation date: Feb 2022 ➔ Jun 2022 | Trial primary completion date: Sep 2022 ➔ Dec 2022

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

CLIN-011: A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: CuraSen Therapeutics, Inc.; Trial completion date: Mar 2022 ➔ Jun 2022; Trial primary completion date: Dec 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder