Nadolol

Invirsa has also received approval from the FDA equivalent authority in Thailand to proceed with Phase 2 Acute Infectious Keratoconjunctivitis clinical trial in Bangkok COLUMBUS, Ohio--(BUSINESS WIRE)-- Invirsa's first clinical trial, a Phase 1/2a study with the primary objective to determine safety and preliminary efficacy of Invirsa's topically administered eyedrop formulation of INV-102, has completed enrollment. Subjects had moderate dry eye and dosing was well tolerated in all groups. The study's design allowed Invirsa to evaluate preliminary efficacy endpoints in 36 patients in the Phase 1 multiple ascending dose portion and 48 patients in a Phase 2 expansion cohort (both randomized 2:1 INV-102: vehicle control). Both portions were dosed for two weeks with a one-week post-treatment follow-up visit. Top line data is expected by Q3 2023. Dr. Robert Shalwitz, CEO of Invirsa commented on the successful enrollment of the trial stating "Coupled with the strong safety and tolerability profile, the Phase 1 portion of the study hit sufficient milestones in reducing both signs and symptoms of dry eye in order to proceed to the Phase 2 portion of the study. The completion of enrollment for the Phase 2 dry eye subjects is exciting for INV-102 as a completely novel approach to treating the surface of the eye." In addition, Invirsa recently received approval from the Thailand FDA to proceed with testing INV-102 in a second condition of acute infectious keratoconjunctivitis (AIK). Invirsa completed a thorough global review towards evaluating and selecting a study location for AIK, ultimately choosing Bangkok. The city has ideal characteristics related to high population density, historically large numbers of AIK subjects, and an excellent medical system. The Phase 2 AIK study is scheduled to begin later in Q2 of 2023 and will enroll approximately 100 subjects. The AIK study was designed to enroll patients with either bacterial or viral infection. This is an important distinction as timely testing to identify the type of infection is unavailable and often results in the inappropriate use of antibiotics. The inappropriate use of antibiotics or corticosteroids for eye infections is a recognized concern of the American Academy of Ophthalmology. Speaking of the AIK trial, Dr. Shalwitz stated, "There is a need for a single solution for both viral and bacterial acute infectious keratoconjunctivitis treatment to address the medical burden that is commonly known as pink eye. Invirsa’s Phase 2 AIK trial will test INV-102, compared to vehicle control, in reducing clinical signs and symptoms after only one week of treatment regardless of whether the presenting AIK is viral or bacterial.” Commenting on the strong clinical research organization partnerships for both trials, Dr. Charlotte Hartman, VP of Clinical Development at Invirsa added "Our team has been fortunate to work with Iuvo on the Dry Eye Study here in the USA and Grand Pacific CRO on the AIK trial in Thailand. We are pleased to be working with both organizations as they have added tremendous expertise in order to quickly complete one study and to shortly launch another." About Invirsa: Invirsa's projects have been supported in whole or in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50120C00171. About INV-102 Invirsa's INV-102 is a small molecule that has been shown in vitro to activate 2 major pathways: The first being the protein p53, which is known as “the guardian of the genome”, and the second being Pax6 which is critical for cellular stability particularly in the eye. By activating these 2 pathways, INV-102 achieves accelerated DNA repair and enhanced cellular stabilization.

Additional Phase 1 Data with CST-2032/CST-107 Reinforce Potential of Adrenoceptor Agonist Class of Drugs in Patients with Cognitive Impairment GOTHENBURG, Sweden--(BUSINESS WIRE)-- CuraSen Therapeutics, Inc., a clinical-stage company developing small molecule drugs to treat neurodegenerative symptoms and disease progression, 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, a novel combination therapy that restores adrenergic stimulus to the brain. 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). Data will be shared in two oral presentations at the International Alzheimer’s Disease and Parkinson’s Disease (AD/PD’23) conference, being held March 28 - April 1, 2023, in Gothenburg, Sweden. Presentation details are below. CST-103, also known as clenbuterol, and CST-2032 are oral, brain-permeant, beta2 adrenoceptor (β2-AR) agonists, and CST-107, known as nadolol, is a brain-sparing β-AR blocker. In these studies, clenbuterol and CST-2032 are co-administered with nadolol to minimize known peripheral cardiometabolic side effects of β2-AR agonists. The company is developing fixed-dose combinations for both drugs. “For the first time, we have been able to show improved outcomes in cognition and mood with adrenergic agonism in patients with neurodegenerative disease, by safely restoring a stimulus to the brain that is lost early in the pathologic process. With its strong safety pro impressive effect sizes in key domains, we look forward to testing this fast-acting combination treatment in a longer-term study in Parkinson’s patients later this year,” said Anthony Ford, PhD, chief executive officer, CuraSen Therapeutics. “These data, coupled with promising Phase 1 results from our second program, CST-2032/nadolol, validate our novel approach to providing meaningful treatment options to neurodegenerative patients with high unmet needs.” Clenbuterol is an established drug that has been used in pulmonology for decades, while CST-2032 was discovered and developed at CuraSen, with properties providing the ability to differentiate and de-risk the two products in distinct neurodegenerative patient populations and outcome measures. Phase 2 Proof-of-Concept Study with Clenbuterol/Nadolol in Parkinson’s Disease Parkinson’s disease is a progressive, neurodegenerative disease that is associated with slow movement, tremor, rigidity and imbalance, as well as non-motor complications such as cognitive impairment, depression, pain, dysautonomia and sleep disorders. The Phase 2 trial was an exploratory, randomized, double-blinded, crossover study in 25 patients with Parkinson’s disease with cognitive deficits. An additional 13 patients were enrolled with mild cognitive impairment without a PD diagnosis. Patients received either the once-daily clenbuterol (80 µg)/nadolol (1 mg) combination treatment or matched placebo, with 14 days treatment on each period and at least 14 days of washout between periods. All PD subjects had impaired cognition at baseline with evidence of impaired cerebral noradrenergic signaling, as assessed by neuromelanin MRI of the locus coeruleus. The study took place at sites in the UK, Australia, New Zealand and Belgium. Results in PD patients showed: 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 Rapid onset of drug effect - improvements observed as early as one day after treatment and in some cases, persisting beyond the two weeks of daily treatment No serious or severe adverse events attributed to study drug; most adverse events observed were mild 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. Phase 1 Study with CST-2032/Nadolol in Mild Cognitive Impairment (MCI) The Phase 1 study with CST-2032/nadolol included 79 healthy volunteers and patients with MCI. The study involved single-ascending and multiple-ascending dose cohorts. 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 Led to performance changes in cognitive tasks associated with memory Offered clear guidance on optimal combination dose levels of each substance for Phase 2 assessment 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. Oral Presentation Details Abstract #: 368 Title: “Effects of a Beta-2 Adrenoceptor Agonist on Cognition in Parkinson’s Disease Patients with REM Sleep Behavior Disorder” Date/Time: Sat, April 1, 3:15-3:30 pm CET; 9:15 am-9:30 am ET Session: #4450 - Advances in PD and LBD Diagnosis and Drug Development Presenter: Gabriel Vargas, MD, PhD, chief medical officer, CuraSen Therapeutics Abstract #: 338 Title: "A Phase 1 Safety, Pharmacokinetics and Pharmacodynamic Study of CST-2032: A Novel, Selective, CNS Penetrating Beta-2 Adrenoceptor Agonist for the Treatment of Cognitive Impairment” Date/Time: Sat, April 1, 6:25-6:40 pm CET; 12:25-12:40 pm ET Session: #4540 - SOC Drugs and Other Targeted Therapies in AD Presenter: Professor Thomas Lodeweyckx, MD, KU Leuven, Belgium About CuraSen Therapeutics CuraSen is developing novel 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 early in degeneration and represent a unique approach in the field, addressing core symptoms and the progression of pathology. 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 .