RNS60 / Revalesio - LARVOL DELTA

Nebulized RNS60 for the Treatment of Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=140 | Not yet recruiting | Sponsor: Revalesio Corporation | Trial completion date: May 2028 ➔ Nov 2028 | Trial primary completion date: May 2028 ➔ Nov 2028

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

RESTORE: A PHASE 3 STUDY DESIGN TO EVALUATE EFFICACY AND SAFETY OF RNS60, AN ADJUNCT CEREBROPROTECTIVE, IN PARTICIPANTS WITH ACUTE ISCHEMIC STROKE UNDERGOING ENDOVASCULAR THROMBECTOMY (WSC 2025) - "RESTORE will evaluate RNS60's efficacy in improving function and reducing brain loss after ischemic stroke as an adjunctive treatment with standard of care EVT with or without thrombolytic."

Clinical • P3 data • Cardiovascular • Ischemic stroke

RNS60 Shows A Larger Response in Rescue Participants Enrolled Within <12h Since Last Known Well In Post Hoc Analysis (WSC 2025) - "Overall, RNS60 high dose demonstrated greater separation from placebo in the <12h since LKW subpopulation (Table 2). ConclusionsThis analysis shows that RNS60's treatment effect was larger in participants treated earlier than 12 hours since LKW, which supports testing of RNS60 in this population in a Phase 3 trial."

Retrospective data • Cardiovascular • Ischemic stroke

RNS60 (OXYGEN SUPERSATURATED IN SALINE) AND EDARAVONE/DEXBORNEOL (WSC 2025) - No abstract available

Cardiovascular

Randomized, Proof-of-Concept Trial (RESCUE) of RNS60 as an Adjunct Therapy in Acute Ischemic Stroke. (PubMed, Stroke) - P2 | "This suggests a benefit warranting investigation in a larger, appropriately powered trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04693715."

Journal • Cardiovascular • Ischemic stroke

Revalesio Announces Publication of RESCUE Phase 2 Trial Results Evaluating RNS60 as an Adjunctive Therapy for Acute Ischemic Stroke in the Journal Stroke (PRNewswire) - P2 | N=82 | RESCUE (NCT04693715) | Sponsor: Revalesio Corporation | "The paper...appears in the journal Stroke....The RESCUE trial met its primary endpoints of similar rates of SAEs (33.3%, 25.0% and 28.6%) and fewer deaths (6.7%, 8.3% and 14.3%) across RNS60 0.5 mL/kg/h, RNS60 1.0 mL/kg/h, and placebo, respectively. RNS60 also demonstrated a statistically significant 47% reduction in infarct growth (brain tissue loss) – a secondary endpoint – at 48 hours in patients treated with RNS60 at 1.0 mL/kg/h compared to placebo (p<0.05)."

P2 data • Ischemic stroke

Revalesio to Present Phase 3 Trial Design and Post Hoc Analysis of Phase 2 RESCUE Trial of RNS60 in Acute Ischemic Stroke at the SNIS 22nd Annual Meeting (PRNewswire) - "Revalesio...announced that two abstracts featuring its investigational treatment RNS60 in acute ischemic stroke have been accepted for oral presentation at the Society of NeuroInterventional Surgery's (SNIS) 22nd Annual Meeting, taking place in Nashville, TN, July 14-18, 2025...The presentations will highlight the objectives and design of the company's upcoming Phase 3 clinical trial in acute ischemic stroke (AIS), RESTORE, as well as a new post hoc analysis from its prior Phase 2 RESCUE study of RNS60 in AIS. Both presentations are scheduled for Thursday, July 17, 2025."

Clinical protocol • New P3 trial • P2 data • CNS Disorders • Ischemic stroke

POST HOC ANALYSIS OF RESCUE SHOWS DOSE DEPENDENT IMPROVEMENT IN ALL PRESPECIFIED EFFICACY ENDPOINTS IN PARTICIPANTS ENROLLED =12H SINCE SYMPTOM ONSET (ESOC 2025) - "Adjunct treatment with RNS60 in <24h since LKW reduced infarct growth and demonstrated numerical improvements in all efficacy outcomes. The effect was more pronounced in participants enrolled <12h since LKW (~75% of the ITT) suggesting further investigation of RNS60 in this population for maximal therapeutic impact."

Clinical • Retrospective data • Cardiovascular • Ischemic stroke

A PHASE 3 STUDY EVALUATING EFFICACY AND SAFETY OF RNS60 AS AN ADJUNCT CYTOPROTECTIVE TREATMENT IN PATIENTS WITH ACUTE ISCHEMIC STROKE UNDERGOING ENDOVASCULAR THROMBECTOMY (ESOC 2025) - "RESTORE will evaluate RNS60's efficacy in improving function and reducing brain loss after ischemic stroke when administered adjunctive to existing therapies. The trial plans to begin enrollment in Q4/2025."

Clinical • P3 data • Cardiovascular • Ischemic stroke

Revalesio announces post-hoc analysis suggesting greater benefit with RNS60 in early time window (NeuroNews) - P2 | N=82 | RESCUE (NCT04693715) | Sponsor: Revalesio Corporation | "Revalesio has announced data from a post-hoc analysis of its completed Phase 2 RESCUE clinical trial showing that ischaemic stroke patients treated with 1mL/kg/h of RNS60 plus standard-of-care endovascular therapy (EVT) within 12 hours of stroke onset had a larger numerical benefit than the overall group treated within 24 hours...Of note, the company claims, patients from this subgroup—approximately 75% of the trial participants—experienced a reduction in infarct volume growth post-EVT by more than 50% (nominal p<0.05) and were discharged from the hospital on average 4.8 days sooner (nominal p=0.022) compared to patients who received EVT and a placebo...These results were presented yesterday during a poster session at the 11th European Stroke Organisation Conference (ESOC; 21–23 May, Helsinki, Finland)....Some 72% of subjects being independent compared to 37% on placebo,..."

P2 data • Ischemic stroke

Nebulized RNS60 for the Treatment of Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=140 | Not yet recruiting | Sponsor: Revalesio Corporation | Trial completion date: Nov 2027 ➔ May 2028 | Trial primary completion date: Nov 2027 ➔ May 2028

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

RNS60 safe, well tolerated in EAP for advanced ALS (ALS News Today) - P=NA | N=84 | "RNS60 was well tolerated when inhaled twice daily at home as part of an expanded access program (EAP), and it could be a safe option for people with advanced amyotrophic lateral sclerosis (ALS), a study suggested....For the EAP, patients who were not eligible for clinical trials of RNS60 used a nebulizer at home to inhale 4 mL of RNS60 twice daily, for a total of 8 mL....Up to the study’s submission, 84 patients with a mean age of 62.2, at advanced stages of disease, had used RNS60 for up to four years. Most (82%) complied with the twice-daily regimen. Twelve (14.3%) stopped due to side effects including breathing problems (four), personal choice (three), and increased secretions (two). Three later resumed full dosing. Two (2.9%) reduced to once-daily dosing. There were 69 serious side effects in 38 patients. All were due to disease progression, not RNS60, according to the researchers."

Clinical data • Amyotrophic Lateral Sclerosis

Stroke Patients Discharged from Hospital Sooner when Administered Revalesio's RNS60; New Statistically Significant Finding from Revalesio's Phase 2 Clinical Trial (PRNewswire) - P2 | N=82 | RESCUE (NCT04693715) | Sponsor: Revalesio Corporation | "Revalesio...today announced new data from its completed Phase 2 RESCUE clinical trial of RNS60 in acute ischemic stroke patients, demonstrating that patients were discharged on average 4.8 days sooner (p=0.022) from the hospital following treatment with RNS60 plus standard of care endovascular thrombectomy (EVT) than patients who received an EVT alone. Patients who received RNS60 also experienced a reduction in infarct volume growth (brain tissue loss) post-EVT by more than 50% (p<0.05). These results were presented during an oral presentation at the American Academy of Neurology (AAN) 2025 Annual Meeting being held in San Diego, CA from April 5-9, 2025....72% of subjects on RNS60 high dose were independent compared to 37% on placebo based on dichotomized modified Rankin Scale (0-2) at Day 90. RNS60 was safe and well tolerated."

P2 data • Ischemic stroke

An Expanded Access Protocol of RNS60 in Amyotrophic Lateral Sclerosis. (PubMed, Muscle Nerve) - "This EAP supports the benign side effect profile of RNS60 when administered via twice-daily nebulization and demonstrates the feasibility of long-term EAPs as a complementary approach to controlled trials in people with advanced ALS."

Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation

RESCUE: A Proof-of-Concept Trial with Adjunct RNS60 Treatment Shows Safety, Reduced Infarct Growth, and Numerical Improvement in all Prespecified Efficacy Endpoints in Participants with Acute Ischemic Stroke (AAN 2025) - "Adjunct treatment with RNS60 was generally safe and well tolerated, significantly reduced infarct growth, and demonstrated numerical improvement in all efficacy outcomes compared to placebo. Although not all differences are statistically significant in the context of limited power, these differences and odds ratios reflect a large, clinically meaningful difference. A Phase 3 study is in development."

Clinical • Cardiovascular • Ischemic stroke

RNS60 Substantially Reduces Early Vasogenic Edema, Mitigates Infarct Area, and Decreases Expression of HIF1α Four Days Post-Ischemic Stroke (ISC 2025) - "RNS60-treated mice exhibit early and long-term significant brain protection after ischemic stroke associated with decreased expression of HIF1α, suggesting reduced hypoxia in the ischemic brain. Ongoing studies aim to identify the effect of RNS60 on blood brain barrier integrity to further elucidate the underlying molecular mechanism."

Cardiovascular • Ischemic stroke • HIF1A

RESCUE: Proof of Concept Trial With RNS60 Shows Safety, Reduced Infarct Growth, and Numerical Improvement in all Prespecified Efficacy Endpoints in Subjects With Ischemic Stroke Receiving Mechanical Thrombectomy (ISC 2025) - "Adjunct treatment with RNS60 was generally safe and well tolerated, reduced infarct growth, and demonstrated numerical improvement in all efficacy outcomes. In the context of limited power, point estimates raise the possibility of benefit with respect to all efficacy endpoints tested. A Phase 3 study is in development."

Clinical • Cardiovascular • Ischemic stroke

Revalesio Announces New Analyses from Phase 2 RESCUE Study of RNS60 in Patients with Acute Ischemic Stroke in Oral Presentation at the International Stroke Conference 2025 (PRNewswire) - P2 | N=82 | RESCUE (NCT04693715) | Sponsor: Revalesio Corporation | "RNS60 high dose significantly lowered infarct growth by 50% (nominal p<0.05) when compared to placebo based on imaging performed at approximately 48 hours compared to immediately post EVT both in patients treated within 12 hours and 24 hours of last known well. RNS60 high dose was also numerically better than placebo for each prespecified functional endpoint: Modified Rankin Score at Day 90: 72% of subjects on RNS60 high dose were independent (mRS of 0-2) at Day 90 compared to 37% on placebo."

P2 data • Ischemic stroke

RNS60, A novel therapeutic, protects mitochondria and upper motor neurons in TDP-43 amyotrophic lateral sclerosis (ALS-MND 2024) - "RNS60 treatment significantly improved ultrastructure of mitochondria in CSMN. The percentage of mitochondria without visible cristae were reduced from 53% in vehicle treated prpTDP-43A315T mice to 19% (p < 0.0001) upon RNS60 treatment. The average number of activated astrocytes in motor cortex of prpTDP-43A315T-UeGFP mice were reduced from 29 to 15 (p < 0.0001) after RNS60 treatment."

Amyotrophic Lateral Sclerosis • CNS Disorders • Metabolic Disorders • Solid Tumor • TARDBP • UCHL1

RESCUE: A PHASE 2 TRIAL OF RNS60 SHOWS SAFETY, REDUCES INFARCT GROWTH AND DEMONSTRATES SIGNS OF EFFICACY IN SUBJECTS WITH ISCHEMIC STROKE RECEIVING MECHANICAL THROMBECTOMY (WSC 2024) - "In the context of limited power, point estimates raise the possibility of benefit with respect to several efficacy endpoints. A Phase 3 study is in development."

Clinical • P2 data • Cardiovascular • Ischemic stroke

Revalesio's Investigational Treatment RNS60 Protects Mitochondria in Preclinical Model of Amyotrophic Lateral Sclerosis (ALS) (PRNewswire) - "Revalesio...announced new data showing that Revalesio's investigational therapeutic, RNS60, protected motor neurons in the prpTDP-43A315T-UeGFP mouse model of ALS....RNS60 treatment significantly a) improved mitochondrial ultrastructure in the motor neurons, b) reduced the extent of astrogliosis and microgliosis in mice and c) protected health and stability of upper motor neurons and neuromuscular junctions compared to placebo-treated mice."

Preclinical • Amyotrophic Lateral Sclerosis

Neuroprotective Effects of RNS60 in TDP-43 Pathology-Associated Amyotrophic Lateral Sclerosis (Neuroscience 2024) - "RNS60 treatment significantly a) improved mitochondrial ultrastructure, b) reduced the extent of astrogliosis and microgliosis in the motor cortex and spinal cord of prpTDP-43A315T-UeGFP mice and c) protected health and stability of UMNs compared to placebo treated mice. These results suggest that RNS60 enhances mitochondrial stability, reduces gliosis, and thereby protects motor neurons."

Amyotrophic Lateral Sclerosis • CNS Disorders • TARDBP • UCHL1

Revalesio's Investigational RNS60 Extended Survival in Patients with Amyotrophic Lateral Sclerosis (ALS) in Post-Hoc Analysis of Phase 2 Investigator-Sponsored Trial (PRNewswire) - P2 | N=147 | NCT03456882 | "Median survival was 6 months longer in the RNS60 treatment group compared to placebo...The new analysis showed that the extension of survival correlated with the rate of decline of FVC (median survival was 3.7 years in participants with a slow decline of FVC and 1.6 years in participants with faster FVC decline, p < 0.0001). Survival in the RNS60 group was significantly longer compared to the placebo group in participants with low baseline levels of neurofilament light chain, NfL (p = 0.012) or monocyte chemoattractant protein-1, MCP-1 (p < 0.01)."

P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders

Nebulized RNS60 for the Treatment of Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=140 | Not yet recruiting | Sponsor: Revalesio Corporation | Trial completion date: Nov 2026 ➔ Nov 2027 | Trial primary completion date: Nov 2026 ➔ Nov 2027

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Long-term survival of participants in a phase II randomized trial of RNS60 in amyotrophic lateral sclerosis. (PubMed, Brain Behav Immun) - P2 | "In this post-hoc analysis, long term survival was longer in participants randomized to RNS60 compared with those randomized to placebo and was correlated with slower FVC progression rates, suggesting that longer survival may be mediated by the drug's effect on respiratory function. In these post-hoc analyses, the beneficial effect of RNS60 on survival was most pronounced in participants with low NfL and MCP-1 levels at study entry, suggesting that this could be a subgroup to target in future studies investigating the effects of RNS60 on survival."

Journal • P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • CCL2 • NEFL