dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen, Areteia Therapeutics - LARVOL DELTA

SUSPIRE-1: A Study to Assess the Effects of Dexpramipexole in Participants With Eosinophilic COPD (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Areteia Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Apr 2025 ➔ Oct 2025

Enrollment closed • Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Research progress on sepsis-associated encephalopathy by inhibiting pyroptosis. (PubMed, Gene) - "Our findings suggest that several drugs (puerarin, VX765, HC067047, dexpramipexole, and Danhong injection), erbin gene, and TRIM45 knockdown improve SAE by suppressing the canonical pathway of NLRP3/caspase-1/gasdermin D-mediated pyroptosis. Therefore, they have significant importance in terms of brain protection. Moreover, we review the relevant literature published in recent years and summarize the research status and development prospects in this field to provide a basis for subsequent related research."

Journal • Review • CNS Disorders • Infectious Disease • Inflammation • Septic Shock • NLRP3 • TRIM45

EXHALE-4: A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Eosinophilic Asthma (clinicaltrials.gov) - P3 | N=550 | Active, not recruiting | Sponsor: Areteia Therapeutics | Trial completion date: Apr 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

EXHALE-4: A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults with Eosinophilic Asthma (clinicaltrials.gov) - P3 | N=550 | Active, not recruiting | Sponsor: Areteia Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Parexel International Clinical Research Gets CDSCO Panel Nod To Study Dexpramipexole Dihydrochloride Monohydrate (Medical Dialogues) - "Parexel has a go-ahead from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organization (CDSCO) to conduct the phase III clinical study of Dexpramipexole dihydrochloride monohydrate. This came after Parexel International Clinical Research presented Phase III clinical study protocol No. ARDEX-22-02, India Specific Amendment 1 dated 17-SEP-2024. Dexpramipexole is an investigational small molecule drug used for amyotrophic lateral sclerosis that incidentally was noted to significantly decrease absolute eosinophil levels."

Clinical protocol • Amyotrophic Lateral Sclerosis • CNS Disorders

The PINK1/Parkin signaling pathway-mediated mitophagy: a forgotten protagonist in myocardial ischemia/reperfusion injury. (PubMed, Pharmacol Res) - "Therefore, exploring the association between the PINK1/Parkin signaling pathway-mediated mitophagy and MIRI is crucial. This review will mainly summarize the crucial role of the PINK1/Parkin signaling pathway-mediated mitophagy in MIR-induced several pathological mechanisms and various potential interventions that affect the PINK1/Parkin signaling pathway-mediated mitophagy, thus ameliorating MIRI."

Journal • Review • Cardiovascular • Inflammation • Myocardial Ischemia • Reperfusion Injury • PTEN

Parkinson’s disease relevant cellular stressors differentially impact dopamine neuron axonal release sites. (Neuroscience 2024) - "Finally, we show that small molecules previously shown to improve mitochondrial efficiency, such as honokiol and dexpramipexole, are protective against 6-OHDA and MPP+, respectively...This study demonstrates that cellular stressors have unique effects on axonal release sites, not all of which involve direct oxidative stress mechanisms. These discoveries enhance our comprehension of the mechanism of action of cellular stressors commonly used to model PD pathology and provide new insights into the development of neuroprotective agents through the optimization of bioenergetics and underscore the importance of considering the specificity of these cellular stressors."

Late-breaking abstract • CNS Disorders • Parkinson's Disease

SUSPIRE-1: An Open-label Phase II Study to Assess the Pharmacodynamic Effects of Dexpramipexole in Participants With Eosinophilic COPD (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Areteia Therapeutics

New P2 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

EXHALE-5: Phase III Long-Term Extension Study With Dexpramipexole (clinicaltrials.gov) - P3 | N=1600 | Enrolling by invitation | Sponsor: Areteia Therapeutics

New P3 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma (EXHALE-3) (clinicaltrials.gov) - P3 | N=930 | Recruiting | Sponsor: Areteia Therapeutics | Trial completion date: Dec 2025 ➔ Jul 2026 | Trial primary completion date: Nov 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

EXHALE-2: A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma. (clinicaltrials.gov) - P3 | N=1395 | Recruiting | Sponsor: Areteia Therapeutics | Trial completion date: Dec 2025 ➔ Jul 2026 | Trial primary completion date: Nov 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

EXHALE-4: A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Eosinophilic Asthma (clinicaltrials.gov) - P3 | N=550 | Recruiting | Sponsor: Areteia Therapeutics | Trial completion date: Jul 2024 ➔ Apr 2025 | Trial primary completion date: Jun 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Areteia Therapeutics Announces Additional $75MM in Series A Financing for Oral Dexpramipexole in Eosinophilic Asthma (Businesswire) - "Areteia Therapeutics, Inc...announced $75 million in additional Series A financing to support expansion of the current Phase III development program of dexpramipexole in eosinophilic asthma, bringing total Series A funding to $425 million. Viking Global Investors and Marshall Wace join the original syndicate of investors led by Bain Capital Life Sciences with participation from Access Biotechnology, GV, ARCH Venture Partners, Saturn Partners, Sanofi, Maverick Capital, and Population Health Partners. The additional capital raised will fund significant expansion of the ongoing Phase III program..."

Financing • Asthma • Respiratory Diseases

EXHALE-2: A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma. (clinicaltrials.gov) - P3 | N=1395 | Recruiting | Sponsor: Areteia Therapeutics

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

EXHALE-4: A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Eosinophilic Asthma (clinicaltrials.gov) - P3 | N=550 | Recruiting | Sponsor: Areteia Therapeutics

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma (EXHALE-3) (clinicaltrials.gov) - P3 | N=930 | Recruiting | Sponsor: Areteia Therapeutics

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Chronic rhinosinusitis with nasal polyps: eosinophils versus B lymphocytes in disease pathogenesis. (PubMed, Curr Opin Allergy Clin Immunol) - "Despite many aspects of immunopathology in CRSwNP explainable by B cell dysfunction, B cells have so far been ignored in CRSwNP. Further work is needed, as targeting B cells may offer an exciting new therapeutic option in the future."

Journal • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis • IL5

Refashioning dexpramipexole - a new horizon in eosinophilic asthma? (PubMed, J Allergy Clin Immunol) - No abstract available

Journal • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Novel Mitochondrial Target as a Therapeutic Approach to Bipolar Disorder (Neuroscience 2023) - "We found that BD cortical organoid mitoplasts have larger peak conductances than those of HCs. Lithium, which is a long-term treatment for episodes of mania and depression, blocks ACLC in both BD and HC cortical organoid mitoplasts and appears to work synergistically with the known ATP synthase pharmacological modulator, dexpramipexole (Dex)."

Bipolar Disorder • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

The clinically-approved compounds, pramipexole and dexpramipexole, reverse chronic allodynia from sciatic nerve damage in mice, and alter IL-1β and IL-10 expression from immune cell culture. (PubMed, Neurosci Lett) - "Pramipexole significantly blunted IL-1β protein production from stimulated human monocytes and dexpramipexole induced elevated IL-10 mRNA expression from rat splenocytes. The data support that clinically-approved compounds like pramipexole and dexpramipexole support their application as anti-inflammatory agents to mitigate chronic neuropathy, and provide a blueprint for future, multifaceted approaches for opioid-independent neuropathic pain treatment."

Immune cell • Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Immunology • Movement Disorders • Neuralgia • Pain • Parkinson's Disease • IL10 • IL1B

Areteia Therapeutics Announces Publication of Phase II Data of Oral Dexpramipexole in Eosinophilic Asthma (Businesswire) - P2 | N=534 | EXHALE-1 (NCT04046939) | Sponsor: Knopp Biosciences | "Areteia Therapeutics...today announced that results from the Phase II EXHALE-1 study of dexpramipexole have been published online in the Journal of Allergy and Clinical Immunology (JACI). The study sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma....A total of 103 subjects were randomly assigned to dexpramipexole 37.5-mg BID (N = 22), 75-mg BID (N = 26), 150-mg BID (N = 28), or placebo (N = 27). Dexpramipexole significantly reduced placebo-corrected AEC week 12 ratio to baseline, in both the 150-mg BID (ratio, 0.23; 95% CI, 0.12-0.43; P < .0001) and the 75-mg BID (ratio, 0.34; 95% CI, 0.18-0.65; P = .0014) dose groups, corresponding to 77% and 66% reductions, respectively."

P2 data • Asthma • Respiratory Diseases

Safety and efficacy of dexpramipexole in eosinophilic asthma (EXHALE): a randomized controlled trial. (PubMed, J Allergy Clin Immunol) - "Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand dexpramipexole clinical efficacy in asthma."

Clinical • Journal • Asthma • Eosinophilia • Immunology • Pulmonary Disease • Respiratory Diseases

AZD5438 a GSK-3a/b and CDK inhibitor is antiapoptotic modulates mitochondrial activity and protects human neurons from mitochondrial toxins. (PubMed, Sci Rep) - "To investigate the actions of this class of drug further, we compared the ability of kenpaullone, alsterpaullone, 1-azakenapaullone, AZD5438, AT7519 (CDK and GSK-3a/b inhibitors) and dexpramipexole and olesoxime (mitochondrial permeability transition pore inhibitors) to prevent CCCP mediated mitochondrial depolarisation and found that AZD5438 and AT7519, were the most effective. Importantly, experiments in human iPSC derived cortical and midbrain neurons showed AZD5438 mediated significant protective effects, preventing the neuronal cell death, and collapse in the neurite and mitochondrial network associated with rotenone treatment. These results suggest drugs that target GSK-3a/b and CDKs should be developed and assessed further as they may have significant therapeutic potential."

Journal • PPARGC1A

A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma (EXHALE-3) (clinicaltrials.gov) - P3 | N=930 | Recruiting | Sponsor: Areteia Therapeutics

New P3 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

EXHALE-2: A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma. (clinicaltrials.gov) - P3 | N=1395 | Recruiting | Sponsor: Areteia Therapeutics

New P3 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases