Riluzole

Following positive 6-month clinical outcomes from phase 2b (PARADIGM) clinical trial, Company expects additional biomarker and 12-month clinical in the near term CAMBRIDGE, Mass., June 24, 2024 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (NASDAQ: NRSN) ("NeuroSense"), a company developing novel treatments for severe neurodegenerative diseases, today provides a corporate update following its recently announced analyses from its Phase 2b PARADIGM clinical trial, which demonstrated a statistically significant slowing of disease progression in high-risk ALS patients treated with PrimeC by 43% (p=0.02) as compared to placebo in the pre-specified per protocol (PP) population analysis after six months of treatment.[1] As previously indicated, the slowing of disease progression demonstrated by PrimeC versus placebo translates to a 5.04-point difference in the ALSFRS-R in favor of PrimeC (Confidence Interval: 0.862, 9.214; n=38). Corporate Highlights for the near term include: 12-month clinical results, including survival, expected in June 2024 FDA meeting anticipated in Q3 2024 Started preparations for Phase 3 clinical trial in the US, including protocol submission expected by year-end 2024 NeuroSense CEO Alon Ben-Noon states, "We are continuing to see additional results coming in from the PARADIGM trial and as they are being analyzed and verified, we intend to share them with shareholders. We anticipate sharing 12-month survival data, ALSFRS-R –as well as providing some additional biomarker data. These will include iron, ferritin and transferrin. We are looking forward to presenting target-engagement biomarkers alongside the clinical outcomes. In the meantime, we continue our discussions with several potential partners in order to drive our clinical programs forward efficiently." In addition, the Company hereby provides its Q1 2024 financial results: Research and development expenses for the three months ended March 31, 2024 and 2023 were $1.88 and $1.85 million, respectively. Research and development expenses remained at the same level primarily due to an increase in expenses to subcontractors and consultants as well as salaries and social benefits as a result of the progression of the Phase 2b ALS clinical study, which were fully offset by a decrease in share-based compensation expenses. NeuroSense expects research and development expenses to remain steady through the remainder of 2024 as a result of the open label extension of the Phase 2b ALS clinical study and the ongoing of the Phase 2 AD study. General and administrative expenses for the three months ended March 31, 2024 and 2023 were $1.11 and $1.14 million, respectively. General and administrative expenses remained at the same level primarily due to a decrease in salaries and social benefits, share-based compensation and insurance expenses, which were fully offset by increase in professional services. NeuroSense expects general and administrative expenses to remain steady through the remainder of 2024. Operating expenses for the three months ended March 31, 2024 and 2023 were $3 million due to the reasons described above. As of March 31, 2024, NeuroSense had cash of $0.74 million, which does not include gross proceeds of approximately $4.5 million from a financing that the Company completed in April 2024. As part of the transaction, the Company entered into a securities purchase agreement, pursuant to which the Company issued in a registered direct offering (i) 1,732,000 ordinary shares; (ii)pre-funded warrants to purchase 1,248,000 ordinary shares at an exercise price of $0.0001, exercisable at any time upon their issuance until exercised in full and (iii) warrants to purchase 2,980,000 ordinary shares at an exercise price of $1.50. Following the end of the first quarter of 2024, the Company determined to change its accounting method from IFRS to U.S. GAAP and accordingly has reissued its audited financial statements for all periods covered by its 2023 financial statements under U.S. GAAP. A copy of the reissued financial statements and accompanying financial data has been filed with the Securities and Exchange Commission on Form 6-K. The Company's unaudited consolidated financial results for the three months ended March 31, 2024 are presented in accordance with US GAAP Reporting Standards. A summary of NeuroSense's unaudited consolidated financial results is included in the tables below. Ben-Noon concluded, "We continue to build strong clinical evidence for PrimeC and are looking forward to upcoming announcements. Concurrently, we are working to safeguard our financial future and ability to continue our clinical activities so as to ensure that there is adequate cash on the balance sheet to complete these milestones. We plan to meet with the FDA in Q3 2024 to discuss the clinical path forward towards an NDA submission, which we believe will be a major inflection point for NeuroSense. The coming months hold tremendous potential, and we are optimistic about the outcomes and the future for NeuroSense Therapeutics." [1] High-risk patients, defined by the European Network for the Cure of ALS (ENCALS) Risk Factor as those with a higher risk for rapid disease progression, comprise approximately 50% of the total ALS population. About ALS Amyotrophic lateral sclerosis ("ALS") is an incurable neurodegenerative disease that causes complete paralysis and death within 2-5 years from diagnosis. Every year, more than 5,000 patients are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of patients with ALS is expected to grow by 24% by 2040 in the U.S. and EU. About PARADIGM PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b (NCT05357950) clinical trial of PrimeC in ALS. The trial included 68 participants living with ALS in Canada, Italy, and Israel. 96% of the trial participants who completed the 6-month double-blind portion of the trial chose to receive treatment with PrimeC through a 12-month open label extension. Furthermore, to date all participants that completed the 18-month trial treatment duration, requested to continue PrimeC, which is provided to them in an Investigator Initiated Trial, not limited with time. As previously reported, top-line data from the 6-month double-blind segment of the trial showed clinically meaningful signs of efficacy with a 29% difference in ALSFRS-R (p=0.12) and a 13% difference in SVC (p=0.5), both in favor of PrimeC vs placebo in analysis of the intent to treat (ITT) population. These data include all 68 people living with ALS enrolled in Canada, Italy, and Israel, with the exclusion of one patient who was misdiagnosed. In the PP top-line analysis from PARADIGM, a statistically significant slowing of disease progression was observed with a 37.4% (p=0.03) difference in ALSFRS-R in favor of PrimeC vs placebo. Most patients enrolled in both the active and placebo arms of the trial were concurrently treated with Riluzole, the ALS standard of care medication, indicating PrimeC slowed disease progression well beyond the level afforded by the FDA approved ALS drug. About PrimeC PrimeC, NeuroSense's lead drug candidate, is a novel extended-release oral formulation composed of a unique fixed-dose combination of two FDA-approved drugs: ciprofloxacin and celecoxib. PrimeC is designed to synergistically target several key mechanisms of ALS that contribute to motor neuron degeneration, inflammation, iron accumulation and impaired ribonucleic acid ("RNA") regulation to potentially inhibit the progression of ALS. NeuroSense completed a Phase 2a clinical trial which met its safety and efficacy endpoints including reducing functional and respiratory deterioration and statistically significant changes in ALS-related biological markers indicating PrimeC's biological activity. PrimeC was granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medicines Agency. About NeuroSense NeuroSense Therapeutics, Ltd. is a clinical-stage biotechnology company focused on discovering and developing treatments for patients suffering from debilitating neurodegenerative diseases. NeuroSense believes that these diseases, which include amyotrophic lateral sclerosis (ALS), Alzheimer's disease and Parkinson's disease, among others, represent one of the most significant unmet medical needs of our time, with limited effective therapeutic options available for patients to date. Due to the complexity of neurodegenerative diseases and based on strong scientific research on a large panel of related biomarkers, NeuroSense's strategy is to develop combined therapies targeting multiple pathways associated with these diseases. For additional information, we invite you to visit our website and follow us on LinkedIn and X. Forward-Looking Statements This press release contains "forward-looking statements" that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will" "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on NeuroSense Therapeutics' current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict and include statements regarding the timing of top-line results and regulatory meetings and submissions. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. The future events and trends may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. These risks include unexpected R&D costs or operating expenses, a delay in the reporting of additional results from PARADIGM clinical trial, the timing of expected regulatory and business milestones, risks associated with meeting with the FDA to determine the best path forward following the results from PARADIGM clinical trial, including a delay in any such meeting; the potential for PrimeC to safely and effectively target ALS; preclinical and clinical data for PrimeC; the uncertainty regarding outcomes and the timing of current and future clinical trials; timing for reporting data; the development and commercial potential of any product candidates of Neurosense; the ability of NeuroSense to remain listed on Nasdaq; and other risks and uncertainties set forth in NeuroSense's filings with the Securities and Exchange Commission (SEC). You should not rely on these statements as representing our views in the future. More information about the risks and uncertainties affecting NeuroSense is contained under the heading "Risk Factors" in the Annual Report on Form 20-F filed with the Securities and Exchange Commission on April 4, 2024 and NeuroSense's subsequent filings with the SEC. Forward-looking statements contained in this announcement are made as of this date, and NeuroSense undertakes no duty to update such information except as required under applicable law. Logo: SOURCE NeuroSense

Real-world analysis suggests 3.2-month survival benefit for individuals treated with RADICAVA and riluzole compared to those treated with only riluzole No new safety concerns in final results from long-term Phase 3 safety extension study in RADICAVA ORS ® (edaravone) JERSEY CITY, N.J., June 17, 2024 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced results from two studies of RADICAVA® (edaravone) for amyotrophic lateral sclerosis (ALS) at the European Network to Cure Amyotrophic Lateral Sclerosis (ENCALS) 2024 meeting. Findings from an ongoing real-world study utilizing information in the ALS/MND Natural History Study Consortium (Consortium) database of people living with ALS initiating treatment with RADICAVA suggest an additional survival benefit of 3.2 months with RADICAVA ± riluzole compared to treatment with riluzole alone. Separately, positive results from Study MT-1186-A03 (NCT04577404), a Phase 3 study evaluating the long-term safety of RADICAVA ORS® (edaravone), showed no new safety concerns and that RADICAVA ORS was well-tolerated during the 96-week study period. "Access to real-world data is critical for complex rare diseases like ALS, and we are proud to collaborate with the ALS/MND Consortium to bring important real-world insights to the clinical community," said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs at MTPA. "In addition, we are encouraged that our long-term Phase 3 safety extension study continues to demonstrate the safety and tolerability profile of RADICAVA." Poster Presentation: Treatment Patterns and Survival Benefit of Edaravone–Treated People with Amyotrophic Lateral Sclerosis in the ALS/MND Natural History Consor tium The ongoing real-world study evaluated treatment patterns, clinical outcomes, and survival of RADICAVA–treated people living with ALS from the ALS/MND NHC database. Individuals receiving RADICAVA ± riluzole (n=176) were matched to those receiving riluzole only (n=176) based on a variety of factors, including their baseline mean ± standard deviation (SD) ALS Functional Rating Scale-Revised score (39.5±4.8 and 39.3±4.8, respectively). The safety profile of RADICAVA ORS was demonstrated in a 6-month, Phase 3, open-label clinical trial in 185 patients.1 In addition to contusion, gait disturbance, and headache reported with RADICAVA, fatigue was observed in 7.6% (14/185) of patients receiving RADICAVA ORS.1 Please see Important Safety Information below and Full Prescribing Information here. Restricted mean survival time (RMST) analyses over 50 months suggested a survival benefit for individuals receiving RADICAVA ± riluzole (31.1 months) versus those receiving riluzole only (28.8 months), without adjustment for baseline covariates. RMST difference between treatment groups was 3.2 months (p<0.03) after adjustment for covariates. "Through our collaboration with MTPA, we are thrilled to highlight initial results from a real-world analysis of people living with ALS in our database," said Alex Sherman, Director of the Center for Innovation and Biomedical Informatics (CIB) at the NCRI at MGH and Principal Investigator for the study. "Together, our real-world findings underscore our continued commitment to improving outcomes and building confidence in existing treatment options for the ALS community. We hope to build this momentum as our analysis of treatment patterns in the database continues." Poster Presentation: Phase 3, Open-Label, Safety Extension Study of Oral Edaravone Administered Over 96 Weeks in Patients with ALS (MT-1186- A03 ) Study MT-1186-A03 was a Phase 3, open-label, multi-center, extension study that evaluated the long-term safety of RADICAVA ORS over an additional 96 weeks in patients who have completed the initial 48 weeks of Study MT-1186-A01. Participants received RADICAVA ORS (105-mg dose) according to the FDA-approved dosing. Patients had definite, probable, probable-laboratory-supported, or possible ALS; baseline forced vital capacity ≥70%; and baseline disease duration ≤3 years. In the study, the most common treatment-emergent adverse events (TEAEs) were fall, muscular weakness, dyspnea, constipation, and dysphagia. These TEAEs were consistent with the safety profile for edaravone from previous clinical trials. About RADICAVA® (edaravone) and RADICAVA ORS® (edaravone) The U.S. Food and Drug Administration (FDA) approved RADICAVA® (edaravone) on May 5, 2017, and the oral formulation RADICAVA ORS ® (edaravone) on May 12, 2022, for the treatment of amyotrophic lateral sclerosis (ALS). In 2024, the FDA recognized RADICAVA ORS with Orphan Drug Exclusivity based on the major contribution to patient care of the innovative oral formulation. RADICAVA is administered in 28-day cycles by intravenous (IV) infusion. It takes 60 minutes to receive each 60 mg dose. For the initial cycle, the treatment is infused daily for 14 consecutive days, followed by a two-week drug-free period. All cycles thereafter are infused daily for 10 days within a 14-day period, followed by a two-week drug-free period. RADICAVA ORS is taken daily for 14 consecutive days followed by a 14-day drug-free period for the initial treatment cycle. For subsequent treatment cycles, RADICAVA ORS is taken for 10 days within a 14-day period followed by a 14-day drug-free period. RADICAVA ORS should be taken in the morning after overnight fasting. Patients should not eat or drink (except water) within one hour after taking RADICAVA ORS.1 Edaravone was discovered and developed for ALS by Mitsubishi Tanabe Pharma Corporation (MTPC) and commercialized in the U.S. by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The MTPC group companies began researching ALS in 2001 through an iterative clinical platform over a 13-year period. In 2015, edaravone was approved as RADICUT® for the treatment of ALS in Japan and South Korea. Marketing authorizations were subsequently granted in Canada (October 2018), Switzerland (January 2019), Indonesia (July 2020), Thailand (April 2021), Malaysia (December 2021) and Brazil (February 2024). Marketing authorization for RADICAVA® Oral Suspension was granted in Canada (November 2022) and Switzerland (May 2023), and RADICUT® Oral Suspension 2.1% was granted regulatory approval in Japan in December 2022. To date, in the U.S., RADICAVA and RADICAVA ORS have been used to treat over 16,000 people with ALS, with over 1.9-million days of therapy, and have been prescribed by over 2,400 HCPs.2-4 IMPORTANT SAFETY INFORMATION Hypersensitivity Reactions RADICAVA (edaravone) and RADICAVA ORS (edaravone) are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product. Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have occurred with RADICAVA. Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA or RADICAVA ORS, treat per standard of care, and monitor until the condition resolves. Sulfite Allergic Reactions RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but occurs more frequently in asthmatic people. Adverse Reactions The most common adverse reactions (≥10%) reported in RADICAVA-treated patients were contusion (15%), gait disturbance (13%), and headache (10%). In an open label study, fatigue was also observed in 7.6% of patients receiving RADICAVA ORS. Pregnancy Based on animal data, RADICAVA and RADICAVA ORS may cause fetal harm. To report suspected adverse reactions or product complaints, contact Mitsubishi Tanabe Pharma America, Inc., at 1-888-292-0058. You may also report suspected adverse reactions to the FDA at 1-800-FDA-1088 or . INDICATION RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). For more information, including full Prescribing Information, please visit . About Mitsubishi Tanabe Pharma America, Inc. Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). It was established by MTPC to develop and advance our pipeline as well as commercialize approved pharmaceutical products in North America. For more information, please visit or follow us on X (formerly Twitter), Facebook and LinkedIn. About Mitsubishi Tanabe Pharma Corporation Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of Mitsubishi Chemical Group (MCG), is one of the oldest pharmaceutical companies in the world, founded in 1678. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MCG has positioned health care as its strategic focus in its management policy, "Forging the future". MTPC sets the MISSION of "Creating hope for all facing illness". To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction and additionally working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to . Media inquiries: [email protected] 1 RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022. 2 Data on file. Mitsubishi Tanabe Pharma America, Inc. 3 Data on file. Mitsubishi Tanabe Pharma America, Inc. 4 Data on file. Mitsubishi Tanabe Pharma America, Inc. SOURCE Mitsubishi Tanabe Pharma America