Safinamide mesylate

MILAN--(BUSINESS WIRE)--Newron Pharmaceuticals S.p.A. (“Newron”) (SIX: NWRN, XETRA: NP5), a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system, today announced its financial results and operational highlights for the half-year ended June 30, 2025, and provided a business update for 2025 and beyond. “We are very excited about our continued achievements, and we are one step closer to potentially bringing enormous benefits to schizophrenia patients who are insufficiently served by the treatments currently available. Highlights H1 2025: Evenamide Clinical trials: In May, the Company announced regulatory approval for its pivotal Phase III ENIGMA-TRS program with evenamide as add-on therapy in patients with treatment-resistant schizophrenia (TRS). The program consists of two pivotal studies: ENIGMA-TRS 1, an international, one-year, double-blind, placebo-controlled Phase III study in at least 600 patients. Following a successful screening period, patient enrolment began post-period, in August 2025, with 12-week study results expected in Q4 2026 ENIGMA-TRS 2, approved by the US Food and Drug Administration, to be performed at centers in the US and selected additional countries. This 12-week, double-blind, placebo-controlled Phase III study in at least 400 patients is expected to start by October 2025 ENIGMA-TRS 1, an international, one-year, double-blind, placebo-controlled Phase III study in at least 600 patients. Following a successful screening period, patient enrolment began post-period, in August 2025, with 12-week study results expected in Q4 2026 ENIGMA-TRS 2, approved by the US Food and Drug Administration, to be performed at centers in the US and selected additional countries. This 12-week, double-blind, placebo-controlled Phase III study in at least 400 patients is expected to start by October 2025 Strategic licensing and partnerships: In January, the Company announced a licensing agreement with Myung In Pharm to develop, manufacture and commercialize evenamide in South Korea Under the terms of the agreement, Myung In Pharm will contribute 10% of the total patient population to be enrolled into Newron’s upcoming Phase III ENIGMA-TRS 1 study and will cover the costs related to this population Under the terms of the agreement, Myung In Pharm will contribute 10% of the total patient population to be enrolled into Newron’s upcoming Phase III ENIGMA-TRS 1 study and will cover the costs related to this population Following the execution (in December 2024) of the licensing agreement with EA Pharma, a subsidiary of Eisai, to develop, manufacture and commercialize evenamide in Japan and other designated Asian territories, Newron in the reporting period received the upfront payment of EUR 44 million and invoiced the first milestone achievement Newron continues to actively explore additional partnership opportunities for the global development and commercialization of evenamide in other territories Industry engagement and scientific exchange: In January, evenamide’s exceptional results in study 014/015 and study 008A were published in the peer reviewed International Journal of Neuropsychopharmacology Post-period, in August 2025, new preclinical data from researchers at the University of Pittsburgh was published in the peer-reviewed journal Neuropsychopharmacology . The research suggests that evenamide ameliorates schizophrenia-related dysfunction, targeting the key site of schizophrenia pathology in the hippocampus, and so could be an ideal therapeutic agent for the treatment of schizophrenia Corporate In April, Dr. Chris Martin was elected as the Chairman of Newron’s Board of Directors, succeeding Dr. Ulrich Köstlin who served as Chairman of the Company from 2013 Stefan Weber, CEO of Newron, commented: “Since the beginning of the year, Newron has continued to make exciting progress in the development of our novel drug candidate evenamide. Most notably, we announced the approval of our pivotal ENIGMA-TRS Phase III development program evaluating evenamide as an add-on therapy in patients with treatment-resistant schizophrenia (TRS) and recently we began enrolling patients into the first study from the program, ENIGMA-TRS 1. We’re delighted to have achieved this crucial milestone on evenamide’s clinical development journey and continue to believe that this new chemical entity has blockbuster potential and could bring enormous benefits to patients who are insufficiently served by the treatments currently available.” Evenamide – advancing schizophrenia treatment In January, Newron announced its licensing agreement with Myung In Pharm to develop, manufacture and commercialize evenamide as an add-on therapy for TRS and poorly responding patients with schizophrenia in South Korea. Under the terms of the agreement, Myung In Pharm, besides the usual financial terms for such agreement, will contribute 10% of the total patient population to be enrolled into Newron’s pivotal ENIGMA-TRS 1 clinical trial and cover the costs related to this population. There has also been strong progress from EA Pharma, who Newron has entered into a license agreement with to develop, manufacture and commercialize evenamide in Japan and other designated Asian territories. EA Pharma expects to initiate its clinical development program for evenamide in Japan. Also, the first milestone under the license agreement became due and was invoiced in the reporting period. In May, Newron announced the regulatory approval of its pivotal Phase III ENIGMA-TRS program with evenamide as add-on therapy in patients with TRS. More than one third of schizophrenia patients suffer from TRS and are not responding to the existing second-generation antipsychotics on the market. Consequently, these patients are in great need of the development and approval of new therapeutic treatments. If approved, evenamide would be the first medication added to existing antipsychotics that improves the symptoms of TRS. The ENIGMA-TRS Phase III development program consists of two pivotal studies, ENIGMA-TRS 1 and ENIGMA-TRS 2: ENIGMA-TRS 1 is an international, 52-week, randomized, double-blind, placebo-controlled Phase III study evaluating the efficacy, tolerability, and safety of the 15mg BID and 30mg BID therapeutic doses of evenamide as an add-on treatment to current antipsychotics, compared to placebo. Patients on second-generation antipsychotics (SGAs), including clozapine, will meet Treatment Response and Resistance Psychosis (TRRIP) international consensus criteria for TRS. The study will enroll at least 600 patients at study centers in Europe, Asia, Latin America and Canada. The primary assessment of efficacy and safety of ENIGMA-TRS 1 will be performed 12 weeks after randomization to treatment. Following this initial period, the study will continue double-blind and placebo-controlled until the 52-week time point. The primary efficacy endpoint of the trial will be the change from baseline in the Positive and Negative Syndrome Scale (PANSS) scores at 12 weeks. Newron expects to announce 12-week results from the study in Q4 2026. ENIGMA-TRS 1 is actively screening across all target continents. Post-period, in August 2025, Newron announced that the first patients have been successfully enrolled following the completion of a 42-day screening period. Newron’s partner Myung In Pharm has also received the necessary approvals in South Korea to move towards enrolling patients in this region. ENIGMA-TRS 2 , the second study in Newron’s pivotal Phase III development program, has been approved by the US Food and Drug Administration (FDA), and will be performed at centers in the US and selected additional countries. ENIGMA-TRS 2 will include at least 400 patients in a 12-week, randomized, double-blind, placebo-controlled Phase III study, designed to evaluate the efficacy, tolerability, and safety of the 15mg BID dose of evenamide as an add-on treatment to current antipsychotics, compared to placebo. Patients will undergo the same screening as the ENIGMA-TRS 1 trial. The efficacy and safety analysis will be performed at the 12-week point following successful completion of the study. US investigational centers are expected to initiate the study by October 2025. Shortly after the reporting period, in August 2025, new preclinical data from Dr. Anthony Grace and other researchers at the University of Pittsburgh was published in the peer-reviewed journal Neuropsychopharmacology. The data suggests that evenamide ameliorates schizophrenia-related dysfunction, and for the first time demonstrates that evenamide targets the key site of schizophrenia pathology in the hippocampus. Using the neurodevelopmental MAM model of schizophrenia, researchers demonstrated that evenamide could offer a novel therapeutic strategy capable of addressing the positive, cognitive, and negative symptoms of schizophrenia, a key advantage over existing antipsychotic drugs which only target positive symptoms. Importantly, time-course analysis indicates effects of a single dose of evenamide last long after elimination of drug, suggesting effect on neuronal plasticity. These findings help explain the robust and sustained symptom improvements observed in Newron’s Phase II and Phase III studies in patients with chronic schizophrenia, reinforcing evenamide’s potential as a transformative therapy for treatment-resistant and poorly responding patients, and offering a promising alternative to traditional dopamine D2-based antipsychotics. Xadago®/safinamide – Parkinson’s disease In partnership with Zambon and Meiji Seika, Newron continues to develop and market its product, Xadago®/safinamide. Corporate At the Annual General Meeting 2025, Dr. Chris Martin was elected as the new Chairman of the Board following his nomination by the Company. Chris Martin took over from Dr. Ulrich Köstlin, who served as Chairman of Newron’s Board since 2013. Dr. Martin is a recognized leader in the biopharma industry who has taken therapeutic technology from the lab bench through to regulatory approval and global market sales. He co-founded ADC Therapeutics in 2012 and served as its CEO from its inception until 2022, growing the company from a private biotech start-up to a New York Stock Exchange listed leader in the field of antibody-drug conjugates with products marketed worldwide. Chris Martin also co-founded and was the CEO of Spirogen, an innovator of antibody-drug conjugate payload technology, which was subsequently sold to AstraZeneca for a total of up to $440 million. Outlook Following the approval of the pivotal Phase III ENIGMA-TRS program for evenamide and the subsequent initiation of the ENIGMA-TRS 1 study, Newron’s key focus for the coming months is on progressing this study and initiating ENIGMA-TRS 2, initially in the US study centers. In addition to its licensing agreements with Myung In Pharm and EA Pharma, Newron continues to be supported by one of world's leading full-service investment banking and capital markets firms in a structured process to secure the most attractive, value creating transactions for the Company’s shareholders. Furthermore, to comprehensively protect the future value of evenamide for shareholders and new investors, Newron is currently in the process of filing additional patent applications to further extend the Intellectual Property protection around evenamide as a novel treatment for schizophrenia. Additionally, the existing patent applications pertaining to evenamide continue to be granted within the European Union and the US. Newron CEO Stefan Weber concluded: “We are very excited about our continued achievements, and we are one step closer to potentially bringing enormous benefits to schizophrenia patients who are insufficiently served by the treatments currently available. The financial position of our Company remains strong – Newron’s total available cash resources are expected to fund our planned development programs and operations well towards the end of the year 2026.” Financial Summary (IFRS) H1 2025 and 2024: In thousand EUR (except per share information) H1 2025 H1 2024 Licence income/Royalties/Other income 11,898 3,407 Research and development expenses (6,081) (6,453) General and administrative expenses (4,423) (4,579) Net loss (73) (9,557) Loss per share (0.00) (0.51) Cash generated/(used) in operating activities 33,353 (8,828) As of June 30, 2025 As of December 31, 2024 Cash and Other current financial assets 43,195 9,826 Total assets 61,394 63,908 Newron’s Half-Year Report 2025 is available for download on the Company’s website at: www.newron.com/investors/reports-and-presentation/year/2025 About Newron Pharmaceuticals Newron (SIX: NWRN, XETRA: NP5) is a biopharmaceutical company focused on developing novel therapies for patients with diseases of the central and peripheral nervous system. Headquartered in Bresso, near Milan, Italy, Newron is advancing its lead compound, evenamide, a first-in-class glutamate modulator, which has the potential to be the first add-on therapy for treatment-resistant schizophrenia (TRS) and for poorly responding patients with schizophrenia. Evenamide is currently in Phase III development and clinical trial results to date demonstrate the benefits of this drug candidate in the TRS patient population, with significant improvements across key efficacy measures increasing over time, as well as a favourable safety profile, which is uncommon for available antipsychotic medications. Newron has signed development and commercialization agreements for evenamide with EA Pharma (a subsidiary of Eisai) for Japan and other Asian territories, as well as Myung In Pharm for South Korea. Newron has a proven track record in bringing CNS therapies to market. Its Parkinson’s disease treatment, Xadago® (safinamide), is approved in over 20 markets, including the USA, UK, EU, Switzerland, and Japan, and commercialized in partnerships with Zambon and Meiji Seika. For more information, please visit: www.newron.com Important Notices This document contains forward-looking statements, including (without limitation) about (1) Newron’s ability to develop and expand its business, successfully complete development of its current product candidates, the timing of commencement of various clinical trials and receipt of data and current and future collaborations for the development and commercialization of its product candidates, (2) the market for drugs to treat CNS diseases and pain conditions, (3) Newron’s financial resources, and (4) assumptions underlying any such statements. In some cases, these statements and assumptions can be identified by the fact that they use words such as “will”, “anticipate”, “estimate”, “expect”, “project”, “intend”, “plan”, “believe”, “target”, and other words and terms of similar meaning. All statements, other than historical facts, contained herein regarding Newron's strategy, goals, plans, future financial position, projected revenues and costs and prospects are forward-looking statements. By their very nature, such statements and assumptions involve inherent risks and uncertainties, both general and specific, and risks exist that predictions, forecasts, projections and other outcomes described, assumed or implied therein will not be achieved. Future events and actual results could differ materially from those set out in, contemplated by or underlying the forward-looking statements due to a number of important factors. These factors include (without limitation) (1) uncertainties in the discovery, development or marketing of products, including without limitation difficulties in enrolling clinical trials, negative results of clinical trials or research projects or unexpected side effects, (2) delay or inability in obtaining regulatory approvals or bringing products to market, (3) future market acceptance of products, (4) loss of or inability to obtain adequate protection for intellectual property rights, (5) inability to raise additional funds, (6) success of existing and entry into future collaborations and licensing agreements, (7) litigation, (8) loss of key executive or other employees, (9) adverse publicity and news coverage, and (10) competition, regulatory, legislative and judicial developments or changes in market and/or overall economic conditions. Newron may not actually achieve the plans, intentions or expectations disclosed in forward-looking statements and assumptions underlying any such statements may prove wrong. Investors should therefore not place undue reliance on them. There can be no assurance that actual results of Newron's research programs, development activities, commercialization plans, collaborations and operations will not differ materially from the expectations set out in such forward-looking statements or underlying assumptions. Newron does not undertake any obligation to publicly update or revise forward-looking statements except as may be required by applicable regulations of the SIX Swiss Exchange or the Dusseldorf Stock Exchange where the shares of Newron are listed. This document does not contain or constitute an offer or invitation to purchase or subscribe for any securities of Newron and no part of it shall form the basis of or be relied upon in connection with any contract or commitment whatsoever.

MILAN & MORRISTOWN, N.J.--(BUSINESS WIRE)--Newron Pharmaceuticals S.p.A. (“Newron”) (SIX: NWRN, XETRA: NP5), a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system, today announced the approval for its pivotal ENIGMA-TRS Phase III development program evaluating evenamide as an add-on therapy to current antipsychotics, including clozapine, in patients with treatment-resistant schizophrenia (TRS). Newron today announced the approval for its pivotal ENIGMA-TRS Phase III development program evaluating evenamide as an add-on therapy to current antipsychotics, including clozapine, in patients with treatment-resistant schizophrenia (TRS). The ENIGMA-TRS Phase III development program consists of two pivotal studies, ENIGMA-TRS 1 and ENIGMA-TRS 2. The two studies are expected to meet the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) specified regulatory requirements for submission of the registration dossier for evenamide in major territories, including the US and Europe. ENIGMA-TRS 1 is an international, 52-week, randomized, double-blind, placebo-controlled Phase III study evaluating the efficacy, tolerability, and safety of the 15mg BID and 30mg BID therapeutic doses of evenamide compared to placebo. Patients on second-generation anti-psychotics (SGAs), including clozapine, will meet Treatment Response and Resistance Psychosis (TRRIP) international consensus criteria for TRS. ENIGMA-TRS 1 will enroll at least 600 patients at study centers in Europe, Asia, Latin America and Canada. Patients will undergo a 42-day screening period, during which their TRS diagnosis, antipsychotic plasma levels (background medication), and conformance to protocol selection criteria will be evaluated by an Independent Eligibility Assessment Committee (IEAC) of three leading international schizophrenia experts. The primary assessment of efficacy and safety will be performed 12 weeks after randomization to treatment. The study will continue double-blind and placebo-controlled until the 52-week (i.e. one year) time point. Enrolment to the study will start imminently. The 12-week results from the study are expected in Q4 2026. ENIGMA-TRS 2, approved by the US Food and Drug Administration (FDA), will be performed at centers in the US and selected additional countries and will include at least 400 patients in a 12-week, randomized, double-blind, placebo-controlled Phase III study, designed to evaluate the efficacy, tolerability, and safety of the 15mg BID dose of evenamide. Patients will meet selection criteria and be reviewed by the above-mentioned IEAC. The analysis for determination of efficacy and safety will be performed after patients complete 12 weeks of participation in the trial. US investigational centers are expected to initiate the study within the next three months. Stephen Marder, MD, Distinguished Professor of Psychiatry, Semel Institute of Neuroscience & Human Behavior, and Director, Section on Psychosis, UCLA Neuropsychiatric Institute, commented: “The imminent initiation of ENIGMA-TRS 1 study of evenamide is a significant milestone in the search for new medications to treat this devastating condition. Evenamide’s modulation of glutamate, good tolerability, and efficacy in studies performed to date, both in patients who are poor responders or treatment resistant to SGAs, suggests its therapeutic potential in patients with TRS. The field eagerly looks forward for results from this landmark trial.” Jean-Pierre Lindenmayer, MD, Director of Research, Psychopharmacology Research Unit - Nathan Kline Institute for Psychiatric Research at Manhattan Psychiatric Center, added: “Evenamide’s selectivity for sodium channels and consequent modulation of glutamate, the demonstration of its efficacy in multiple animal models of psychosis as well as the MAM model of neurodevelopmental abnormalities, suggests promising results in patients with TRS. Completed studies in inadequate responders to SGAs and the results of a one-year study in patients with TRS predict therapeutic benefit of evenamide in TRS patients. Evenamide has the potential to fill a wide gap in our treatment for patients with incomplete response to SGAs, including clozapine. I look forward to participating to the ENIGMA-TRS 2 trial as a study center.” Ravi Anand, MD, Chief Medical Officer of Newron, stated: “Newron greatly appreciates the regulatory approval of the ENIGMA-TRS trials. The positive results of evenamide observed in clinical studies and demonstrated in disease models have led to high enthusiasm in investigators to participate in this landmark program.” The Phase III ENIGMA-TRS clinical trials are part of Newron’s development program for evenamide, targeting patients with schizophrenia experiencing worsening of psychosis on therapeutic doses of current antipsychotics, as well as treatment-resistant patients, which together account for the vast majority of patients suffering from schizophrenia. Results from previous Phase II (study 014/015) and Phase III (study 008A) studies have demonstrated evenamide’s significant and increasing efficacy as an add-on therapy on multiple measures of psychopathology in patients with TRS and inadequate responders, respectively. These results also confirmed a favorable safety and tolerability profile, adding to the growing evidence that evenamide’s glutamatergic inhibition mechanism of action offers an innovative therapeutic option to schizophrenia patients who are not benefiting from current antipsychotic treatments. Newron has entered into licensing agreements with EA Pharma, a subsidiary of Eisai, in Japan and other designated territories, and with Myung In Pharm in South Korea, to develop, manufacture and commercialize evenamide in the respective territories. Under the terms of the agreements, Newron will receive up to a maximum total of EUR 117 million, including an upfront payment of EUR 44 million, financial contributions to the Phase III ENIGMA-TRS program, milestone payments, and tiered royalties up to a double-digit percentage of net sales for evenamide, from EA Pharma; Myung In Pharm will contribute 10% of the total patient population to be enrolled into Newron’s upcoming Phase III ENIGMA-TRS trial and cover the costs related to this population. Newron is actively exploring additional partnerships for the global development and commercialization of evenamide. About schizophrenia Approximately 25 million people worldwide are affected by schizophrenia. Despite more than 60 different types of atypical and typical antipsychotics used to treat schizophrenia globally, a considerable number of patients remain severely ill or resistant to treatment. Overall, 30-50% of patients do not respond to the available medications and are defined as treatment resistant. In addition to the patients with treatment-resistant schizophrenia (TRS), another 20-30% are described as “poor responders to anti-psychotic medication”, even if not meeting the criteria for TRS. New findings indicate that patients with TRS have abnormalities in the glutamatergic system, but not in dopaminergic transmission, so there is a significant unmet medical need for treatments with a glutamatergic mechanism of action, efficacious both in TRS patients and in those who are poor responders to the current treatments. About evenamide Evenamide is the first new chemical entity that has demonstrated significant benefits in this difficult-to-treat patient population, as seen in the potentially pivotal Phase III study 008A trial, as an add-on treatment to second generation anti-psychotics including clozapine, in 291 poorly responding patients with chronic schizophrenia. The primary endpoint, the Positive and Negative Syndrome Scale (PANSS)1, and the key secondary endpoint, the Clinical Global Impressions Scale – Severity (CGI-S), were met and showed statistical significance compared to placebo. Importantly, evenamide treatment was associated with statistically significant increases in the proportion of patients who experienced “clinically meaningful benefit” on the outcome variables. Evenamide was extremely well tolerated, without any of the usual side effects of available anti-psychotics. About Newron Pharmaceuticals Newron (SIX: NWRN, XETRA: NP5) is a biopharmaceutical company focused on developing novel therapies for patients with diseases of the central and peripheral nervous system. Headquartered in Bresso, near Milan, Italy, Newron is advancing its lead compound, evenamide, a first-in-class glutamate modulator, which has the potential to be the first add-on therapy for treatment-resistant schizophrenia (TRS) and for poorly responding patients with schizophrenia. Evenamide is currently in Phase III development and clinical trial results to date demonstrate the benefits of this drug candidate in the TRS patient population, with significant improvements across key efficacy measures increasing over time, as well as a favourable safety profile, which is uncommon for available antipsychotic medications. Newron has signed development and commercialization agreements for evenamide with EA Pharma (a subsidiary of Eisai) for Japan and other Asian territories, as well as Myung In Pharm for South Korea. Newron has a proven track record in bringing CNS therapies to market. Its Parkinson’s disease treatment, Xadago® (safinamide), is approved in over 20 markets, including the USA, UK, EU, Switzerland, and Japan, and commercialized in partnerships with Zambon and Meiji Seika. For more information, please visit: www.newron.com Important Notices This document contains forward-looking statements, including (without limitation) about (1) Newron’s ability to develop and expand its business, successfully complete development of its current product candidates, the timing of commencement of various clinical trials and receipt of data and current and future collaborations for the development and commercialization of its product candidates, (2) the market for drugs to treat CNS diseases and pain conditions, (3) Newron’s financial resources, and (4) assumptions underlying any such statements. In some cases, these statements and assumptions can be identified by the fact that they use words such as “will”, “anticipate”, “estimate”, “expect”, “project”, “intend”, “plan”, “believe”, “target”, and other words and terms of similar meaning. All statements, other than historical facts, contained herein regarding Newron's strategy, goals, plans, future financial position, projected revenues and costs and prospects are forward-looking statements. By their very nature, such statements and assumptions involve inherent risks and uncertainties, both general and specific, and risks exist that predictions, forecasts, projections and other outcomes described, assumed or implied therein will not be achieved. Future events and actual results could differ materially from those set out in, contemplated by or underlying the forward-looking statements due to a number of important factors. These factors include (without limitation) (1) uncertainties in the discovery, development or marketing of products, including without limitation difficulties in enrolling clinical trials, negative results of clinical trials or research projects or unexpected side effects, (2) delay or inability in obtaining regulatory approvals or bringing products to market, (3) future market acceptance of products, (4) loss of or inability to obtain adequate protection for intellectual property rights, (5) inability to raise additional funds, (6) success of existing and entry into future collaborations and licensing agreements, (7) litigation, (8) loss of key executive or other employees, (9) adverse publicity and news coverage, and (10) competition, regulatory, legislative and judicial developments or changes in market and/or overall economic conditions. Newron may not actually achieve the plans, intentions or expectations disclosed in forward-looking statements and assumptions underlying any such statements may prove wrong. Investors should therefore not place undue reliance on them. There can be no assurance that actual results of Newron's research programs, development activities, commercialization plans, collaborations and operations will not differ materially from the expectations set out in such forward-looking statements or underlying assumptions. Newron does not undertake any obligation to publicly update or revise forward-looking statements except as may be required by applicable regulations of the SIX Swiss Exchange or the Dusseldorf Stock Exchange where the shares of Newron are listed. This document does not contain or constitute an offer or invitation to purchase or subscribe for any securities of Newron and no part of it shall form the basis of or be relied upon in connection with any contract or commitment whatsoever. ______________________________ 1 Positive and Negative Syndrome Scale (PANSS) is widely used in clinical trials of schizophrenia and is considered the “gold standard” for assessment of antipsychotic treatment efficacy (Innvo Clin Neurosci, 2017: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788255/)