The Amyotrophic Lateral Sclerosis Association

12-month data demonstrated regulation of iron levels, which aligns with improved ALS survival and disease mitigation Previous results showed PrimeC slowed disease progression by 36% and improved survival rates, highlighting its potential as a transformative ALS therapy CAMBRIDGE, Mass., Aug. 1, 2024 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (NASDAQ: NRSN) ("NeuroSense"), a late-clinical stage biotechnology company developing novel treatments for severe neurodegenerative diseases, announces positive 12-month iron biomarker data from its Phase IIb study (PARADIGM), which evaluated the safety and efficacy of PrimeC in people living with Amyotrophic Lateral Sclerosis (ALS). This data provides additional insights that align with the Company's recent announcements of improved survival by 43% and slowed disease progression by 36%. ALS is a multifactorial disease in which iron and its related proteins play a critical role in its pathophysiology. These new results demonstrate the target engagement of PrimeC in iron regulation, which is linked to disease mitigation and improved survival. Iron metabolism is crucial in ALS pathology, with transferrin and ferritin being significant contributors to the progress of the disease. Iron accumulation in various brain regions of ALS patients has been linked to neuronal damage. Elevated ferritin levels, an indicator of iron storage, are consistently observed in ALS patients and are associated with reduced survival and potential oxidative stress. Conversely, lower levels of transferrin, the primary iron transport protein, contribute to iron dysregulation and disease progression. The 12-month study results show a significant decrease in ferritin levels and a corresponding increase in transferrin levels, both indicating alleviation of the pathology. Iron levels remained stable over the 12-month dosing period, with a mean difference of 4.536 µmol/L (95% CI [1.143, 7.929], p=0.01) compared to those who started on placebo and transitioned to PrimeC after the initial 6-month double-blind phase. These positive changes in iron metabolism align with improved clinical outcomes. Patients on PrimeC maintained better functionality and survival rates compared to those on placebo. "The 12-month results from the PARADIGM Phase IIb study are encouraging, showing slowing of disease progression and improved survival outcomes," said Merit Cudkowicz, M.D., M.Sc., Chair of Neurology and Director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital. "This new analysis highlights PrimeC's ability to regulate the iron panel in people living with ALS, underscoring the drug's target engagement. These findings strongly support the proceeding to phase 3 testing of PrimeC in ALS." The Company is currently compiling additional data to share with the FDA for discussion to determine the clinical and regulatory path forward. Additionally, the Company is continuing advanced discussions with several potential development partners to explore marketing opportunities following the potential completion and approval of PrimeC for ALS. 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 people are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of people living with ALS is expected to grow by 24% by 2040 in the U.S. and EU. About ALSFRS-R Disease progression is measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), which is the most widely used ALS tracking tool accepted by the FDA, utilized by neurologists treating ALS patients, in clinical trials, and by other regulators to determine disease progression. It tracks 12 changes in a person's physical abilities over time including functions such as: speech, walking, climbing stairs, dressing/hygiene, handwriting, turning in bed, cutting food, salivation, swallowing, and breathing. A single point change on the ALSFRS-R has a significant impact on ALS patients, such as the transition from independent feeding to requiring assistance or independent breathing to needing to use a machine ventilator. 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. As previously reported, in the 6-month double-blind segment of the trial, the data showed clinically meaningful signs of efficacy with a 29% difference in favor of PrimeC vs placebo in analysis of the intent to treat (ITT) population. 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, YouTube and X. Information that may be important to investors may be routinely posted on our website and these social media channels. 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 PrimeC as a potential treatment for people with ALS. 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 the risk that the Company will not enter into an agreement with a development partner at all or on favorable terms; unexpected R&D costs or operating expenses, a delay in the reporting of additional results from PARADIGM clinical trial, a delay in a Phase 3 trial for PrimeC in ALS, 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

NEW YORK, July 8, 2024 /PRNewswire/ -- Woolsey Pharmaceuticals, a clinical-stage drug development company, announced that the first patient has started treatment at 300 mg/day in the REAL study, which is evaluating the effects of BRAVYL in Amyotrophic Lateral Sclerosis (ALS). As recently announced, participants treated with 180 mg/day BRAVYL in the REAL study experienced a 15.5% decrease (improvement) in NfL from baseline to 6 months (p<0.001). Since NfL in the ALS population tends to increase by a mean of 11% in 6 months, this suggests that 180 mg/day BRAVYL could potentially reduce NfL up to 26% versus a control group. Moreover, greater decreases in NfL were correlated with less deterioration on the ALSFRS-R (Spearman's coefficient = -0.45, p=0.028) implying that early clinical benefits of reducing NfL may be seen contemporaneously with the NfL reductions by BRAVYL. A "propensity matched" analysis was performed wherein 12-month clinical outcomes from REAL were compared with those from a matched cohort selected by identifying 31 patients from the Ceftriaxone ALS Study database that were most similar (based on pre-treatment age, ALSFRS-R, time from onset of ALS, and other important parameters) to each REAL patient. The rate of deterioration in ALSFRS-R was improved in REAL vs. the matched controls by 28% (p=0.12). REAL patients also had a 42% (p=0.05) slower deterioration in SVC (breathing) and a 50% (p=0.06) slower rate of muscle strength decline, driven mostly by lower limb muscles with a 71% (p=0.04) reduction in weakening and a more modest 37% (p=0.22) reduction in weakening of upper limb muscles. An analysis that matched REAL patients recruited in Australia to the Australian MND Registry (a longitudinal registry, not a study) yielded directionally similar ALSFRS-R and SVC findings while muscle strength could not be analyzed as the registry does not contain such data. "The dosing of the first participant at 300 mg is another important program milestone," notes Sven Jacobson, CEO of Woolsey. "This next phase will allow us to evaluate the safety and tolerability of a higher dose, in preparation for our planned phase 2b study. Our goal is to continue to advance development of BRAVYL for people living with ALS, in hopes that we can slow the progression of the disease and improve their quality of life." ABOUT ALS ALS is a fatal neurodegenerative disease characterized by inevitable, and often rapid, decline in patients as the disorder advances (mean survival time is only two to five years). Accordingly, the ability to impede any worsening represents a meaningful advancement in efforts to enhance the prognosis and quality of life of individuals impacted by this devastating condition. ABOUT WOOLSEY PHARMACEUTICALS Woolsey Pharmaceuticals is expanding the boundaries of medical science. Our lead indication is Amyotrophic Lateral Sclerosis (ALS), a progressive and debilitating disease that ultimately is fatal. Our mission is to help usher in a new era of neurodegenerative disease treatment, saving and improving the lives of patients in need. SOURCE Woolsey Pharmaceuticals, Inc.

New molecule demonstrates efficacy in a challenging SCI model Expanding pipeline into new indications of ischemic stroke and ALS Vancouver, British Columbia--(News - June 25, 2024) - NervGen Pharma Corp. (TSXV: NGEN) (OTCQB: NGENF), a clinical-stage biotech company dedicated to developing innovative solutions for the treatment of nervous system damage, today announced its plans for the development of a new drug candidate, NVG-300, with a focus on three initial indications: ischemic stroke, amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI). NVG-300 is a new biologic molecule discovered at NervGen. Pending successful preclinical validation, NVG-300 will be developed under the Biologics License Application regulatory framework providing 12 years of market exclusivity post-approval. NVG-300's composition of matter intellectual property protection is expected to extend beyond 2040. The discovery of NVG-300 is the result of a research effort initiated by NervGen in 2022, leveraging the extensive internal expertise and the evolving scientific understanding of the mechanisms involved in nervous system repair. NVG-300 is the first of what the company believes will be a pipeline of new molecules addressing high unmet need neurologic indications. NVG-300 product and process development have progressed to successfully establish manufacturability and feasibility of high concentration liquid formulation to enable self-administration of the product in a prefilled syringe format. "We are excited to advance NVG-300 toward development based on promising efficacy observed in a model of SCI characterized by heightened severity of spinal cord damage and impaired spontaneous recovery," said NervGen's Vice President of Research and Preclinical Development, Dr. Matvey Lukashev. "Based on these results, we are conducting formulation development, advancing further preclinical evaluation of NVG-300 in SCI and initiating efficacy studies in preclinical models of ischemic stroke and ALS. The results from these preclinical studies are expected in early 2025." "Early signs of preclinical efficacy and favorable pharmaceutical properties provided the evidence we needed to advance NVG-300 into expanded indications characterized by nervous system damage," said Mike Kelly, NervGen's President and CEO. "While our lead product candidate, NVG-291, remains the key focus of the company, we expect NVG-300 to add diversity to our pipeline and provide strategic optionality for future partnering opportunities. As a pioneer and an emerging leader in the development of pharmacological interventions targeting the mechanisms that inhibit nervous system repair, we focus our research and development efforts to ensure we remain at the forefront of this exciting new therapeutic field." About Ischemic Stroke Stroke is the leading cause of death and severe disability worldwide, significantly diminishing the quality of life for many affected individuals. Globally, nearly 17 million people experience a stroke each year, with over two million cases annually in the United States, Europe, and Japan combined. The most prevalent type of stroke, ischemic stroke, occurs when a blockage in the brain's blood flow deprives it of oxygen and nutrients, often leading to long-term or permanent neurological damage. Unfortunately, treatment options for ischemic stroke are limited. Current therapies, such as the administration of the clot-dissolving agent tissue plasminogen activator or surgical clot removal, must generally be performed within a few hours of stroke onset. About Amyotrophic Lateral Sclerosis (ALS) ALS is an invariably fatal progressive neurodegenerative disorder caused by loss of motor neurons and resulting in loss of voluntary muscle function, culminating in respiratory paralysis and death, usually within 2-5 years after diagnosis. Roughly 1 in 400 people will develop ALS in their lifetime. There are an estimated 30,000 people in the United States and more than 30,000 people in Europe (European Union and United Kingdom) living with ALS at any given time. About Spinal Cord Injury (SCI) SCI resulting from trauma causes disruption of the signals normally transmitted between the brain and the body, frequently resulting in severe functional impairment below the level of the injury. Every year, up to 500,000 people globally suffer from SCI. Each individual with SCI faces an expected lifetime cost of care between $1M and $4M, depending on severity and age at injury. Existing treatments are limited to surgical stabilization and physical rehabilitation, which result in partial improvement. There are currently no U.S. Food and Drug Administration-approved treatments that can promote repair and improve function following SCI. About NervGen NervGen (TSXV: NGEN) (OTCQB: NGENF) is a clinical-stage biotech company dedicated to developing innovative treatments that enable the nervous system to repair itself following damage, whether due to injury or disease. NervGen's lead drug candidate, NVG-291, is currently being evaluated in a Phase 1b/2a clinical trial in the company's initial target indication, spinal cord injury. For more information, visit or follow NervGen on X, LinkedIn, and Facebook for the latest news on the company. Contacts Huitt Tracey, Investor Relations htracey@nervgen.com 604.362.6209 Bill Adams, Chief Financial Officer info@nervgen.com 778.731.1711 David Schull or Ignacio Guerrero-Ros, Ph.D. Russo Partners david.schull@russopartnersllc.com ignacio.guerrero-ros@russopartnersllc.com 858.717.2310 646.942.5604 Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. Cautionary Note Regarding Forward-Looking Statements This news release may contain "forward-looking information" and "forward-looking statements" within the meaning of applicable Canadian and United States securities legislation. Such forward-looking statements and information herein include, but are not limited to, the Company's current and future plans, expectations and intentions, results, levels of activity, performance, goals or achievements, or any other future events or developments constitute forward-looking statements, and the words "may", "will", "would", "should", "could", "expect", "plan", "intend", "trend", "indication", "anticipate", "believe", "estimate", "predict", "likely" or "potential", or the negative or other variations of these words or other comparable words or phrases, are intended to identify forward-looking statements. Forward-looking statements include, without limitation, statements relating to: the development plans and timelines for NVG-300; the objectives, study design, planned clinical endpoints, timing, expected rate of enrollment and data readout of our Phase 1b/2a clinical trial in individuals with spinal cord injury; future plans for our pipeline development; the belief that targeting mechanisms that interfere with nervous system repair is a promising target for reducing the clinical effects of nervous system damage through multiple mechanisms; and the creation of innovative treatments of nervous system damage due to trauma or disease. Forward-looking statements are based on estimates and assumptions made by the Company in light of management's experience and perception of historical trends, current conditions and expected future developments, as well as other factors that we believe are appropriate and reasonable in the circumstances. In making forward-looking statements, the Company has relied on various assumptions, including, but not limited to: the Company's ability to manage the effects of pandemics such as COVID-19; the accuracy of the Company's financial projections; the Company obtaining positive results in its clinical and other trials; the Company obtaining necessary regulatory approvals; and general business, market and economic conditions. Many factors could cause our actual results, level of activity, performance or achievements or future events or developments to differ materially from those expressed or implied by the forward-looking statements, including without limitation, a lack of revenue, insufficient funding, the impact of pandemics such as the COVID-19, reliance upon key personnel, the uncertainty of the clinical development process, competition, and other factors set forth in the "Risk Factors" section of the Company's Annual Information Form, Prospectus Supplement, financial statements and Management Discussion and Analysis which can be found on SEDARplus.ca. All clinical development plans are subject to additional funding. Readers should not place undue reliance on forward-looking statements made in this news release. Furthermore, unless otherwise stated, the forward-looking statements contained in this news release are made as of the date of this news release, and we have no intention and undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement. To view the source version of this press release, please visit