RNS-60

RNS60 Also Slowed the Decline of Respiratory Function in ALS Patients Results Published in Brain, Behavior, and Immunity TACOMA, Wash. , Sept. 17, 2024 /PRNewswire/ -- Revalesio, a clinical-stage pharmaceutical company developing treatments for acute and chronic neurological disorders, today announced the publication of data in the journal Brain, Behavior, and Immunity , showing that Revalesio’s investigational therapeutic, RNS60, extended median survival by 6 months compared to placebo in a post-hoc analysis of a Phase 2 investigator-sponsored trial. The trial was coordinated by the Research Center for ALS, Istituto di Ricerche Farmacologiche Mario Negri IRCCS in Milano, Italy . After a 6-month double-blind treatment phase, participants were followed for a mean duration of 2.8 years and monitored for survival. Median survival was 6 months longer in the RNS60 treatment group compared to placebo (3 years vs. 2.4 years, p = 0.0519). As reported by the trial investigators in an earlier publication, the decline of forced vital capacity (FVC) - the maximum volume of air that a patient can exhale after a maximum inspiration, used as a primary test to evaluate breathing function of people living with ALS - was significantly slower in the RNS60 group compared to the placebo group at the end of treatment (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101), showing a positive effect of RNS60 on respiratory and bulbar function. 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). Blood levels of NfL, a marker of neuronal damage, have been shown to correlate with the progression rate of ALS. MCP-1 is an inflammatory marker whose blood levels have been reported to increase during the course of ALS. These biomarker results suggest that this could be a subgroup to target in future studies investigating the effects of RNS60 on survival. “These promising findings suggest that RNS60 may have a beneficial effect on survival and slowing the decline of respiratory function in patients with ALS,” said Letizia Mazzini , Professor of Neurology and Director of the Tertiary ALS Center at the University of Piemonte Orientale and participating center in the Phase 2 clinical trial. “These results warrant further investigation, and I look forward to the future development of RNS60 for the treatment of ALS.” “With these encouraging results, RNS60 has shown benefit across two randomized clinical trials in ALS and ischemic stroke, underscoring its potential to impact patients with both acute and chronic neurological disorders. We are committed to advancing RNS60 in additional clinical trials to further evaluate RNS60’s potential to benefit people with ALS and other neurological disorders,” said Bert van den Bergh , Revalesio’s Executive Chairman on the Board of Directors, and former President of Neuroscience Products at Eli Lilly and Company. “On behalf of Revalesio, I would like to thank the investigators for conducting this important additional analysis, as well as the patients and their families for their participation. I would also like to thank the ALS Association for contributing to the original study through the ALS Ice Bucket Challenge.” RNS60 Phase 2 Clinical Trial Design The investigator-sponsored study was a multi-center, randomized, double-blind, placebo-controlled Phase 2 clinical trial, evaluating 147 people living ALS. Patients were enrolled across 22 Italian expert ALS centers and randomized to either RNS60 (n=74) or placebo (n=73) for 24 weeks. Participants were diagnosed with ALS and classified as slow or fast progressors with respect to FVC based on the FVC slope of decline during trial treatment. The primary endpoints were safety and certain biomarker levels associated with ALS and secondary endpoints were the ALS functional rating scale, FVC and survival. Following the 6-month treatment phase, participants were monitored for survival to support the post-hoc analysis. About RNS60 RNS60 is an investigational therapeutic being developed to provide disease modifying and potentially restorative treatments for neurological diseases. In preclinical studies, RNS60 activated intracellular signaling pathways to increase mitochondrial biogenesis and function and reduce inflammation. RNS60 safely protected neurons and oligodendrocytes and modulated the activity of immune cells to restore homeostasis. RNS60 has been granted Orphan Drug and Fast Track designations for ALS from the U.S. Food and Drug Administration. About Revalesio Revalesio is a clinical-stage pharmaceutical company with a vision to change the future of treatment for acute and chronic neurological disorders. The company’s lead clinical program for RNS60 is ischemic stroke with additional programs in ALS and other neurological disorders. The company’s pioneering technology, founded in physics, addresses fundamental mechanisms involved with proper cellular function to slow disease progression and improve quality of life. For more information, please visit revalesio.com and engage with us on LinkedIn . Media Lori Murray lori.murray@captivate-comms.com View original content to download multimedia: SOURCE Revalesio

[07-February-2024] RNS60 met its primary endpoints in RESCUE (safety and mortality) Clinically relevant improvement with RNS60 on modified Rankin Scale (mRS), Barthel Index and National Institute of Health Stroke Scale (NIHSS) Significant lowering of infarct growth by 50% at 48 hours Revalesio plans to meet with FDA to discuss advancing RNS60 into Phase 3 for Ischemic Stroke TACOMA, Wash., Feb. 7, 2024 /PRNewswire/ -- Revalesio, a clinical-stage pharmaceutical company developing treatments for acute and chronic neurological disorders, announced today topline data from the completed Phase 2 RESCUE clinical trial of RNS60 (NCT04693715) in acute ischemic stroke (AIS) patients during an oral presentation at the Late-Breaking Science session of the International Stroke Conference (ISC) 2024. The conference is being held February 7-9, 2024, in Phoenix, AZ. RNS60, Revalesio's lead product candidate, consists of a stable formulation of saline saturated with oxygen through a proprietary process. RNS60 initiates a cascade of biological effects that show significant benefits in preclinical models of acute and chronic neurological disorders, while showcasing a strong safety pro the 400+ patients who have been administered RNS60 in previous trials. Stroke remains a critical health issue with limited treatment options. This provides a major opportunity for a therapy that shows improvements above the standard of care. In RESCUE, a double-blinded, placebo-controlled, randomized proof-of-concept trial, Revalesio evaluated the safety and signs of efficacy of RNS60. 82 participants with AIS eligible for endovascular thrombectomy (EVT) were enrolled and treated across 5 sites, including the lead site at Rhode Island Hospital's Comprehensive Stroke Center. The participants received intravenous RNS60 0.5 mL/kg/h (low dose), RNS60 1.0 mL/kg/h (high dose) or placebo starting before completion of the EVT and continuing for 48 hours. The trial had two primary endpoints: safety and mortality. Secondary endpoints for the study evaluated disability based on the well-established modified Rankin Scale (mRS), change in the size of the stroke as measured by MRI at 48 hours, and additional standard stroke scales (Barthel Index and NIHSS). Highlights of the late-breaking oral presentation include: RNS60 met its primary endpoints of safety and mortality, with similar rates of SAEs and numerically lower rates of mortality (with no statistical comparison) RNS60 high dose significantly lowered infarct growth by 50% (nominal p<0.05) when compared to placebo based on imaging done at approximately 48 hours compared to immediately post EVT RNS60 high dose was also numerically better than placebo for each prespecified functional endpoint: mRS at Day 90 (both dichotomized and ordinal analyses) Barthel Index at Day 90 NIHSS at each specified timepoint for both absolute value and change from baseline "RNS60's topline results are very encouraging and suggest the possibility of RNS60 having a profound impact on reducing disability following a stroke," says Bert van den Bergh, Revalesio's Executive Chairman of the Board of Directors, and former President of Neuroscience Products at Eli Lilly and Company. "Revalesio has been developing and testing novel applications of physics in many different biological systems and has seen activity in a wide range of disease models. The novelty of applying physics to biology compelled me to bring my experience in drug development and commercialization to Revalesio." "Stroke is a leading cause of disability and death worldwide and carries an enormous financial burden on the health care ecosystem," said Dr. David Liebeskind, Director of UCLA Stroke Center. "RESCUE was a well-designed and successfully executed Phase 2 trial and it showcases the potential for adjunctive therapies in stroke. I congratulate the investigators and Revalesio on this early data and look forward to seeing RNS60 in a Phase 3 trial." "Having our Phase 2 data selected as a late-breaking oral presentation at one of the most prestigious stroke meetings underscores the strength and quality of our results from RESCUE. With these data, we are confident in our ability to design and run a robust and properly powered Phase 3 study," said Greg Archambeau, President of Revalesio. "We'd like to thank the clinical teams, as well as the trial participants and their families." Details of the late-breaking oral presentation at ISC 2024 are below: Title: "RESCUE: A Randomized, Blinded, Placebo-controlled, Parallel Group Trial to Determine the Safety of RNS60 in Large Vessel Occlusion Stroke Patients Undergoing Endovascular Thrombectomy" Primary Investigator: Ryan McTaggart, M.D. Rhode Island Hospital Session: Late-Breaking Science Oral Abstracts I Date/Time: Wednesday, February 7, 2024, 2:24 pm Presenter: Jordan Dubow, M.D., Acting CMO of Revalesio More information can be found on the ISC 2024 meeting website. About Revalesio Revalesio is a clinical-stage pharmaceutical company with a vision to change the future of treatment for acute and chronic neurological disorders. The company's pioneering technology, founded in physics, addresses fundamental mechanisms involved with proper cellular function to slow disease progression and improve quality of life. For more information, please visit revalesio.com and engage with us on LinkedIn. Contact: Amy Conrad Juniper Point amy@juniper-point.com