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

A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma (EXHALE-3) (clinicaltrials.gov) - P3 | N=930 | Active, not recruiting | Sponsor: Areteia Therapeutics | Recruiting ➔ Active, not recruiting

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

EXHALE-5: Phase III Long-Term Extension Study With Dexpramipexole (clinicaltrials.gov) - P3 | N=1600 | Active, not recruiting | Sponsor: Areteia Therapeutics | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • 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 | Active, not recruiting | Sponsor: Areteia Therapeutics | Recruiting ➔ Active, not recruiting

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

Neuronal excitability of bipolar disorder mimicked by ATP synthase c subunit overexpression in rat neurons (Neuroscience 2025) - "Treatment with lithium and dexpramipexole-agents known to reduce mitochondrial membrane leak by binding to the ATP synthase directly—partially reversed this hyperexcitability in the isolated neurons and reversed neuronal activity as measured by calcium transients in the intact organoids...Primary neurons from embryonic day 18 rats were infected on day in vitro 5, and whole-cell patch clamp recordings were conducted on days 15-21 in both current-clamp and voltage-clamp modes. Collectively, our study will provide mechanistic insight into how elevated ACLC expression and activity drive neuronal excitability and contribute to cortical network dysfunction in BD.Keywords:mitochondrial dysfunction; ATP synthase c-subunit; cortical neuron excitability; whole-cell patch clamp, neuropsychiatric disease, human brain organoids."

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

Dexpramipexole Improves Lung Function In Eosinophilic Asthma, Reveals Research (Medical Dialogues) - "The phase 3 EXHALE-4 study demonstrated that dexpramipexole, an oral small molecule therapy, significantly improved pre-bronchodilator FEV1 compared with placebo when used as an add-on treatment in patients with eosinophilic asthma....Dexpramipexole 150 mg BID and 75mg BID significantly reduced blood AEC averaged over Weeks 20 and 24, as measured by the change from baseline in geometric mean AEC values compared with placebo."

P3 data: top line • Asthma • Immunology

Areteia Therapeutics Announces Positive Topline Results from the First Phase III Study of Oral Dexpramipexole in Eosinophilic Asthma (Businesswire) - "Dexpramipexole significantly improved lung function averaged over Weeks 20 and 24, as measured by the change from baseline in pre-bronchodilator forced expiratory volume (pre-BD FEV₁), in the dexpramipexole 150 mg twice daily (BID) group compared with placebo. Significant improvements in lung function were observed as early as Week 4."

P3 data: top line • Asthma • Immunology

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: Jul 2026 ➔ Feb 2027 | Trial primary completion date: Jun 2026 ➔ Dec 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: Jul 2026 ➔ May 2027 | Trial primary completion date: Jun 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Asthma • 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 | Trial completion date: Jun 2027 ➔ May 2028 | Trial primary completion date: Jun 2027 ➔ Mar 2028

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

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