Edaravone

SALT LAKE CITY, March 12, 2025 (GLOBE NEWSWIRE) -- Clene, Inc. (Nasdaq: CLNN) and its subsidiary, Clene Nanomedicine, Inc., a clinical-stage biopharmaceutical company focused on revolutionizing the treatment of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), today announced new evidence from a cross-regimen, post hoc analysis of long-term survival in HEALEY ALS Platform Trial participants. The analyses further substantiate that treatment with CNM-Au8® 30 mg delivers a significant survival benefit for people living with ALS. New Survival Analyses The analyses compared survival in participants who received CNM-Au8 30 mg (Regimen C) to those of Regimen A in the HEALEY ALS Platform Trial. Regimen A provided a large concurrent control group vs. CNM-Au8 treatment using the same randomization criteria established within the HEALEY master protocol. Long-term survival status, determined through public records and site reporting, was evaluated over a follow-up period of up to 48 months. 78% of participants across both groups received standard ALS background therapy (riluzole, edaravone, or both) at baseline. Overall Survival Improvement (All-Cause Mortality) Across the Full Analysis Set: Median Survival: CNM-Au8 30 mg group (Regimen C, n=59) achieved 951 days versus 753 days in the Regimen A comparator group (n=162) – a gain of 198 days (6.5 months) Restricted Mean Survival Time (RMST) Benefit: covariate-adjusted RMST improvement of 124 days (4.1 months) was observed (95% CI: 3 to 245 days, p=0.045). RMST is a metric that estimates the average time a group survives relative to a comparator. The estimate incorporated the prespecified covariates for survival analyses from the HEALEY ALS Platform Trial (i.e., months from symptom onset, pre-treatment ALSFRS-R slope, age, background riluzole treatment, background edaravone treatment) Sensitivity analyses, which included additional covariate models such as baseline serum neurofilament light (NfL) levels, use of ALS background therapy, and the TRICALS risk score, confirmed the robustness and statistical significance of the findings Enhanced Benefit in Moderate to Severe ALS: In participants with baseline serum NfL > 33 pg/mL and TRICALS risk score range between –6.5 and –2.5 (i.e., filtering slow progressors where there was an imbalance between groups), median survival improved from 589 days (Regimen A, n=120) to 951 days (CNM-Au8 30 mg, n=51), representing an 11.9 month gain Mortality risk in this group decreased by 44% (Cox HR: 0.556, 95% CI: 0.367–0.842, p=0.006) with an RMST improvement of 197 days (6.5 month gain; 95% CI: 65 to 329 days, p=0.004), when using the prespecified covariates for survival analyses from the HEALEY ALS Platform Trial Median Survival: CNM-Au8 30 mg group (Regimen C, n=59) achieved 951 days versus 753 days in the Regimen A comparator group (n=162) – a gain of 198 days (6.5 months) Restricted Mean Survival Time (RMST) Benefit: covariate-adjusted RMST improvement of 124 days (4.1 months) was observed (95% CI: 3 to 245 days, p=0.045). RMST is a metric that estimates the average time a group survives relative to a comparator. The estimate incorporated the prespecified covariates for survival analyses from the HEALEY ALS Platform Trial (i.e., months from symptom onset, pre-treatment ALSFRS-R slope, age, background riluzole treatment, background edaravone treatment) Sensitivity analyses, which included additional covariate models such as baseline serum neurofilament light (NfL) levels, use of ALS background therapy, and the TRICALS risk score, confirmed the robustness and statistical significance of the findings In participants with baseline serum NfL > 33 pg/mL and TRICALS risk score range between –6.5 and –2.5 (i.e., filtering slow progressors where there was an imbalance between groups), median survival improved from 589 days (Regimen A, n=120) to 951 days (CNM-Au8 30 mg, n=51), representing an 11.9 month gain Mortality risk in this group decreased by 44% (Cox HR: 0.556, 95% CI: 0.367–0.842, p=0.006) with an RMST improvement of 197 days (6.5 month gain; 95% CI: 65 to 329 days, p=0.004), when using the prespecified covariates for survival analyses from the HEALEY ALS Platform Trial Strongest Survival Benefit Observed in Subset Who Met Planned Phase 3 RESTORE-ALS Trial Enrollment Criteria: Among participants who met the core RESTORE-ALS Trial criteria (e.g., baseline serum NfL > 33 pg/mL, TRICALS risk score range between –6.5 and –2.5, baseline slow vital capacity > 60%, and symptom onset < 36 months), median survival improved from 628 days (Regimen A, n=94) to 1079 days (CNM-Au8 30 mg, n=40), an increase of 451 days (14.8 months) This subset experienced a 49% reduction in mortality risk (Cox HR: 0.514, 95% CI: 0.319–0.830, p=0.006) and an RMST improvement of 215 days (7.1 months; 95% CI: 70 to 360 days, p=0.004), when using the planned covariates for the RESTORE-ALS trial Among participants who met the core RESTORE-ALS Trial criteria (e.g., baseline serum NfL > 33 pg/mL, TRICALS risk score range between –6.5 and –2.5, baseline slow vital capacity > 60%, and symptom onset < 36 months), median survival improved from 628 days (Regimen A, n=94) to 1079 days (CNM-Au8 30 mg, n=40), an increase of 451 days (14.8 months) This subset experienced a 49% reduction in mortality risk (Cox HR: 0.514, 95% CI: 0.319–0.830, p=0.006) and an RMST improvement of 215 days (7.1 months; 95% CI: 70 to 360 days, p=0.004), when using the planned covariates for the RESTORE-ALS trial These results are consistent with previous survival benefits observed in the HEALEY ALS Platform Trial’s 24-week double-blind period, the open-label extension of the Phase 2 RESCUE-ALS trial, and analyses of Expanded Access Programs compared to ALS natural history controls. “We are highly encouraged by these results, as the significant survival advantage demonstrated by CNM-Au8 not only reinforces its potential to extend life for people living with ALS but also validates our strategic direction as we prepare for the launch of our confirmatory Phase 3 RESTORE-ALS study in mid-2025,” stated Rob Etherington, President and CEO of Clene. “We look forward to discussing these findings with the FDA as we advance toward commercialization.” Merit Cudkowicz, M.D., M.S.c., Principal Investigator and sponsor of the HEALEY ALS Platform Trial, director of the Sean M. Healey & AMG Center for ALS, and executive director of the Mass General Brigham Neuroscience Institute, said, “The innovative design of the HEALEY ALS Platform Trial has enabled us to extract clear and meaningful survival data that helps make decisions about CNM-Au8 drug development.” About Regimen A Regimen A was one of the first three regimens investigated in the HEALEY ALS Platform Trial. Eligible participants were randomized in a 3:1 ratio to receive active treatment or matching placebo for a planned duration of 24 weeks. Participants assigned to Regimen A had to receive both quadrivalent and serotype B meningococcal vaccinations at least 14 days prior to the first dose of study drug, and participants were excluded from Regimen A if they had a history of meningococcal disease or prior treatment with a complement inhibitor. Regimen A was stopped prematurely for futility after all participants had been randomized, and approximately 70% had completed the Week 24 visit. Participants were instructed to discontinue study dosing, and a final early termination study visit was conducted. Long-term survival status of Regimen A participants was tracked from public records and site reporting independently of the early termination. There was no difference in long-term survival in participants randomized to Regimen A active compared to Regimen A placebo, supporting the combined analyses of the entire Regimen A population for comparisons of long-term survival to CNM-Au8 30 mg (Regimen C) participants. About Clene Clene Inc., (Nasdaq: CLNN) (along with its subsidiaries, “Clene” and its wholly owned subsidiary Clene Nanomedicine, Inc.), is a late clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson’s disease, and multiple sclerosis. CNM-Au8® is an investigational first-in-class therapy that improves central nervous system cells’ survival and function via a mechanism that targets mitochondrial function and the NAD pathway while reducing oxidative stress. CNM-Au8® is a federally registered trademark of Clene Nanomedicine, Inc. The company is based in Salt Lake City, Utah, with R&D and manufacturing operations in Maryland. For more information, please visit www.clene.com or follow us on X (formerly Twitter) and LinkedIn. About CNM-Au8® CNM-Au8 is an oral suspension of gold nanocrystals developed to restore neuronal health and function by increasing energy production and utilization. The catalytically active nanocrystals of CNM-Au8 drive critical cellular energy producing reactions that enable neuroprotection and remyelination by increasing neuronal and glial resilience to disease-relevant stressors. CNM-Au8® is a federally registered trademark of Clene Nanomedicine, Inc. About RESTORE-ALS RESTORE-ALS is a Phase 3 confirmatory global, multi-center, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of CNM-Au8 in participants diagnosed with ALS on stable background therapy. The study is designed to investigate the effects of CNM-Au8 on improved survival (primary endpoint) and delayed time to ALS clinical worsening events (secondary efficacy endpoint). Participants will be randomized in a 2:1 ratio to receive either active treatment with CNM-Au8 30 mg or matched placebo daily during the 108-week double-blind treatment period. The Phase 3 RESTORE-ALS clinical trial, due to launch in mid-2025, is planned to serve as the confirmatory clinical trial required to meet the FDA’s guidance for an “underway” clinical trial when a New Drug Application requesting Accelerated Approval is submitted. 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About two and a half years before they sealed a $3.3 billion deal , Bain Capital and its life sciences team started courting the leadership of Tanabe Pharma and its parent Mitsubishi Chemical. The approach was part of the investment firm’s desire to expand its biopharma portfolio into Japan, where recently relaxed drug approval regulations can potentially open up one of the world’s largest pharma markets to better opportunities for development and investment. The conversations originally began with Bain wishing to carve out the centuries-old pharmaceutical unit and letting Mitsubishi retain a stake in the separated company. Bain has done pharma carve-outs before, like its deal that repurposed Pfizer’s CNS assets into Cerevel (which eventually went public via a SPAC and was then acquired by AbbVie). While that model “got a certain amount of traction,” Mitsubishi instead decided to do a “straight sale” given its priorities lay in other areas of the chemicals business, Will Cozean, managing director at Bain Capital, said in an interview with Endpoints News . After deciding to do a sale process of the pharma unit, Mitsubishi then did a market check. “I’d like to think that we were probably the preferred bidder from the start of the process, but they needed to get a market check in terms of the value they were going to get,” Cozean said. It took about three or four months to get to exclusivity around New Year’s, Cozean said, and then about six more weeks to seal the deal. He said it wasn’t the longest process he’s ever been a part of, but it wasn’t a “we’re going to move mountains to announce this by JPM”-type of transaction, he said. Three M&A deals were disclosed at this year’s JP Morgan Healthcare Conference, one of which took less than two months to come together. “The reality is that the number of private equity firms that would be potentially able to do this transaction is a very short list, and so we knew that it was probably us or one or two others of our competitors in the region,” Cozean said. About 20 people at Bain were dedicated to getting the deal done, the managing director said. The $3.3 billion deal includes support from three funds at Bain: US private equity, Asia private equity and life sciences. After a yearslong relationship, the deal came to fruition. Everyone in the industry was alerted of the news just moments after the Bain team. The investment firm found out they’d gotten the green light for the deal roughly 15 minutes before the press release went out last Friday, Cozean said. After the deal closes, which is expected in the third quarter, Bain hopes to transform Tanabe, founded in the 1600s, into an even bigger commercial drugmaker. The pharma, which also has units in the US and Israel, markets treatments like the ALS drug Radicava . “It is daunting when you are taking the reins of such a traditional and historical organization that’s older than the country that I was born in. But at the same time, the core of Tanabe is so strong and the legacy is so strong,” Cozean said, that the opportunity ahead is a “really beautiful undertaking for Bain Capital.” The 5,000-employee Tanabe team has a history of great discovery platform work, said Ricky Sun, a partner at Bain Capital Life Sciences. They’ve contributed to the development of major drug classes, like SGLT2 inhibitors for diabetes, he said. “At the top end of the market, you have folks like Takeda and Shionogi and Daiichi, who are actually focused now more on the US than they are necessarily on Japan as their growth” area, Cozean said. “We think there’s an opportunity for us to play a role in bringing assets within Japan into a consolidated commercial entity and being more efficient and able to drive patient outcomes at that level.” Tanabe will look within and outside Japan for assets to license or acquire, or partnerships to form, Cozean said, noting Bain will take a “global approach” to business development. It inked an ALS pact with Dewpoint Therapeutics in December, but that type of early-stage collaboration was unique, given it could be a follow-up to Tanabe’s own ALS medicine, Cozean said. More of the go-forward deals will likely be closer to late-stage development. The pharma company has been acquisitive in the past, buying Israeli biotech NeuroDerm and its late-stage Parkinson’s program for $1.1 billion in 2017 . It’s also licensed out programs that have led to the formation of new companies, like schizophrenia biotech Kynexis , which emerged with $61 million in November 2023. Cozean hopes the investment will be a broader boon for Japan’s life sciences sector, too. “One of the things that we’re hoping to frankly have more of a front seat on, by owning Tanabe, is to really invest in the broader Japanese ecosystem of life sciences innovation,” Cozean said.