[Translation] A single-center, single-dose, randomized, open-label, crossover, two-dose, two-period fasting and fed bioequivalence study of safinamide mesylate tablets in healthy subjects

主要目的：以北京颐康兴医药有限公司的甲磺酸沙芬酰胺片（规格：50mg）为受试制剂，以Zambon S.p.A.持证的甲磺酸沙芬酰胺片（Xadago®，规格：50mg）为参比制剂，按生物等效性试验的有关规定，考察两制剂在健康人体内的生物等效性。次要目的：观察受试制剂和参比制剂在健康受试者中的安全性。

[Translation]

Main purpose: Using Beijing Yikangxing Pharmaceutical Co., Ltd.'s Safinamide Mesylate Tablets (Specification: 50 mg) as the test preparation and Zambon S.p.A.'s certified Safinamide Mesylate Tablets (Xadago®, Specification: 50 mg) as the reference preparation, according to the relevant provisions of the bioequivalence test, to investigate the bioequivalence of the two preparations in healthy subjects. Secondary purpose: To observe the safety of the test preparation and the reference preparation in healthy subjects.

Start Date06 Jan 2025

Sponsor / Collaborator

Beijing Yikangxing Medicine Co., Ltd.

CTR20244359

/ CompletedNot Applicable

甲磺酸沙芬酰胺片在中国健康受试者中进行的单中心、随机、开放、单次（空腹/餐后）口服给药、两制剂、两序列、两周期、交叉的人体生物等效性试验

[Translation] A single-center, randomized, open-label, single-dose (fasting/postprandial) oral bioequivalence study of safinamide mesylate tablets in healthy Chinese subjects: two-formulation, two-sequence, two-period, crossover

主要目的：观察中国健康受试者在空腹/餐后状态下单次口服受试制剂甲磺酸沙芬酰胺片（规格：按C17H19FN2O2计，100mg；生产企业：华北制药股份有限公司）和参比制剂甲磺酸沙非胺片（商品名：Xadago®；规格：按C17H19FN2O2计，100mg；持证商和生产企业：Zambon S.p.A.）后的药代动力学特征，评价空腹/餐后状态下两种制剂在中国健康受试者中的生物等效性。次要目的：观察受试制剂甲磺酸沙芬酰胺片和参比制剂甲磺酸沙非胺片（Xadago®）在中国健康受试者中的安全性。

[Translation]

Primary objective: To observe the pharmacokinetic characteristics of the test preparation safinamide mesylate tablets (specification: 100 mg based on C17H19FN2O2; manufacturer: North China Pharmaceutical Co., Ltd.) and the reference preparation safinamide mesylate tablets (trade name: Xadago®; specification: 100 mg based on C17H19FN2O2; licensee and manufacturer: Zambon S.p.A.) in Chinese healthy subjects after a single oral administration in the fasting/postprandial state, and to evaluate the bioequivalence of the two preparations in Chinese healthy subjects in the fasting/postprandial state. Secondary objective: To observe the safety of the test preparation safinamide mesylate tablets and the reference preparation safinamide mesylate tablets (Xadago®) in Chinese healthy subjects.

Start Date23 Dec 2024

Sponsor / Collaborator

North China Pharmaceutical Co., Ltd.

CTRI/2024/11/076273

/ Not yet recruitingPhase 3IIT

Effect of Safinamide on Pain in Idiopathic Parkinsons Disease A Randomized Double blind Placebo Controlled Trial - NIL

Start Date01 Dec 2024

Sponsor / Collaborator

Jawaharlal Institute of Post Graduate Medical Education & Re

100 Clinical Results associated with Safinamide mesylate

100 Translational Medicine associated with Safinamide mesylate

100 Patents (Medical) associated with Safinamide mesylate

461

Literatures (Medical) associated with Safinamide mesylate

01 Jul 2025·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

2-(Phenylamino)-7,8-dihydroquinazolin-5(6H)-one, a promising scaffold for MAO-B inhibitors with potential GSK3β targeting

Article

Author: Da Settimo, Federico ; Borreca, Antonella ; Taliani, Sabrina ; Poggetti, Valeria ; Sarno, Giuliana ; Castellano, Sabrina ; Piazzola, Francesco ; Nordio, Giulia ; Baglini, Emma ; Natale, Benito ; Salerno, Silvia ; Cosconati, Sandro ; Di Paolo, Maria Luisa ; Dalla Via, Lisa ; Barresi, Elisabetta ; Sarno, Stefania

Neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, constitute pathological conditions of great relevance on health span and quality of life. The identification of novel therapeutic options, able to modulate the processes involved in the insurgence and progression of neurodegenerative disorders, represents an intriguing challenge of current research. Herein, a library of 36-membered 2-(phenylamino)-7,8-dihydroquinazolinone derivatives was synthesized and biologically evaluated as human MAO inhibitors. Some compounds able to inhibit MAO-B potently and selectively (K_i in the nanomolar range) were identified, and robust structure-activity relationships were drawn, supported by computational studies. Further biological assays revealed a safe profile for all derivatives and, for compounds selected as the best MAO-B inhibitors (4, 5, 13, 14) the following properties also emerged: (i) the ability to inhibit MAO-B activity in whole cells, with an effectiveness comparable or slight lower with respect to the reference safinamide; (ii) physicochemical parameters suggesting drug-likeness properties; (iii) the ability to inhibit, albeit weakly, GSK3β kinase (for compound 4). Within the whole series, compound 4 stood out as a promising lead for future optimization campaigns aimed to obtain useful drugs for the treatment of Alzheimer's and Parkinson's diseases.

01 Mar 2025·JOURNAL OF NEURAL TRANSMISSION

Efficacy and safety of safinamide in Parkinson’s disease patients with motor fluctuations without levodopa dosage escalation over 18 weeks: KEEP study

Article

Author: Kim, Jong-Min ; Cheon, Sang-Myeong ; Ahn, Tae-Beom ; Lyoo, Chul Hyoung ; Sung, Young Hee ; Oh, Eungseok ; Kim, Joong-Seok ; Lee, Ho-Won ; Park, Jeong-Ho ; Baik, Jong Sam ; Shin, Hae-Won ; Park, Jinse ; Lee, Yoona ; Cho, Jin Whan ; Kim, Sang Jin ; Park, Mee Young ; Ma, Hyeo ; Lee, Phil Hyu ; Kwon, Do-Young ; Choi, Seong-Min ; Kim, Jieun ; Koh, Seong-Beom

Abstract:

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson’s disease (PD) with motor fluctuations with ≥ 1.5 h of “off” time daily, who took levodopa ≥ 3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson’s Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, MDS–UPDRS part 3 and part 4; King’s Parkinson’s Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily “off” time (− 1.3 ± 2.4 h, p < 0.001) and quality of life (QoL) based on PDQ-39 summary index (− 2.7 ± 10.3, p < 0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily “on” time without dyskinesia (all p < 0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022

01 Mar 2025·BEHAVIOURAL BRAIN RESEARCH

Effects of MAO‑B inhibitors in life quality of Parkinson’s disease patients: A systematic review and meta‑analysis

Review

Author: Zhang, Jieli ; Tao, Enxiang ; Huang, Kaixun ; Lin, Danyu ; Su, Jiehua ; Liu, Xiaohuan ; Li, Zhonggui

INTRODUCTION:

Monoamine oxidase-B (MAO-B) inhibitors, as an add-on therapy to levodopa, are widely used in Parkinson's disease (PD). The effects of MAO-B inhibitors on quality of life remain unclear, and the aim of this systematic review and meta-analysis was to assess the efficacy and safety of MAO-B inhibitors on quality of life in different domains.

METHODS:

We searched PubMed, Embass, and Cochrane Library databases for randomized controlled trials of PD patients who were administered MAO-B inhibitors. Outcomes were the change from baseline in the total score of life quality scales, change from baseline in domains of the Parkinson's Disease Questionnaire-39 (PDQ-39), and incidence of treatment-associated adverse events (TAEs).

RESULTS:

Sixteen studies covering 4734 PD patients were included in the study. The PDQ-39 scores were lower with MAO-B inhibitors than with placebo (SMD: -0.26, 95 % CI: [-0.49, -0.04], P = 0.02). The European Quality of Life Questionnaire-5D (EQ-5D) scores were higher in the MAO-B inhibitor group. Patients treated with MAO-B inhibitors had better performance in the domains of mobility, activities of daily living, emotional well-being, stigma, communication, and bodily discomfort, except for social support and cognition. The incidence of TAEs was slightly higher in patients treated with MAO-B inhibitors.

CONCLUSIONS:

Evidence has shown that MAO-B inhibitors, especially safinamide, are effective in improving the quality of life of PD patients, although with a slightly higher incidence of TAEs. The domains of quality of life were improved, except for cognition and social support, compared with placebo. Further studies are warranted to evaluate the effects of other MAO-B inhibitors on quality of life.

News (Medical) associated with Safinamide mesylate

22 Apr 2025

·www.prnewswire.com

XADAGO/EQUFINA Set to Revolutionize Parkinson's Disease Treatment Landscape | DelveInsight

As a selective monoamine oxidase B (MAO-B) inhibitor, XADAGO offers a unique mechanism of action that complements traditional therapies, potentially improving motor function and reducing "off" time in patients. The increasing prevalence of Parkinson's disease and the growing demand for effective therapies create a substantial market opportunity for XADAGO, particularly in regions with aging populations. LAS VEGAS, April 22, 2025 /PRNewswire/ -- DelveInsight's " XADAGO/EQUFINA Market Size, Forecast, and Market Insight Report" highlights the details around XADAGO/EQUFINA, an inhibitor of monoamine oxidase B (MAO-B) indicated as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of XADAGO/EQUFINA. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Newron Pharmaceuticals/Eisai/Meiji Seika Pharma's XADAGO/EQUFINA (safinamide) Overview XADAGO is a monoamine oxidase B (MAO-B) inhibitor used alongside levodopa/carbidopa to help manage "off" episodes in individuals with Parkinson's disease. While its exact mode of action in treating Parkinson's is not fully understood, it is thought to work by inhibiting MAO-B, thereby reducing dopamine breakdown. This leads to increased dopamine levels and enhanced dopaminergic activity in the brain. XADAGO contains the active ingredient safinamide in the form of a mesylate salt and is available in 50 mg and 100 mg film-coated oral tablets. Each tablet provides either 65.88 mg or 131.76 mg of safinamide mesylate, equivalent to 50 mg or 100 mg of the safinamide base. The medication is marketed as XADAGO in the United States and Europe and under the name EQUFINA in Japan. Learn more about XADAGO/EQUFINA projected market size for Parkinson's disease @ XADAGO/EQUFINA Market Potential Parkinson's disease is a progressive neurological disorder that mainly impairs movement control. It results from the slow degeneration of dopamine-producing neurons in the brain, especially in the substantia nigra, a region crucial for managing voluntary motor function. According to estimates by DelveInsight, there were 2.7 million diagnosed prevalent cases of Parkinson's disease in the 7MM in 2023, with the United States accounting for around 45% of these cases. While a cure for Parkinson's remains elusive, a combination of pharmacological and non-pharmacological therapies is used to manage symptoms. Physical, occupational, and speech therapies form key components of treatment, and surgical procedures may benefit select patients. Additionally, complementary therapies are sometimes employed to help address particular symptoms. Frequently prescribed medications for Parkinson's include levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors, amantadine, anticholinergics, and adenosine A2A antagonists. These treatments primarily target motor symptoms, which are a major concern for those affected. DelveInsight reports that the Parkinson's disease market in the 7MM was valued at USD 3.2 billion in 2023. The market is expected to grow over the forecast period (2020–2034), fueled by the launch of new therapies, increasing prevalence, better access to healthcare, and rising demand for more advanced and effective treatment options. Discover more about the Parkinson's disease market in detail @ Parkinson's Disease Market Report Emerging Competitors of XADAGO/EQUFINA Some of the drugs in the pipeline include Solengepras (Cerevance), Minzasolmin (UCB Biopharma SRL/Novartis), Buntanetap (Annovis Bio), and others. Buntanetap has successfully completed Phase III trials for early-stage Parkinson's disease. Annovis Bio has scheduled a meeting with the FDA in Q1 2025 to determine the development path forward for Buntanetap in the treatment of Parkinson's disease. Buntanetap is also being developed for Alzheimer's disease, Lewy Body Dementia, and other neurodegenerative disorders. In November 2024, Cerevance announced the dosing of the first patient in its pivotal Phase III ARISE trial, evaluating solengepras as a potential adjunctive treatment for Parkinson's disease. Cerevance expects to report topline data in the first half of 2026. In December 2021, UCB partnered with Novartis to globally co-develop and co-commercialize UCB0599, a pioneering alpha-synuclein misfolding inhibitor currently in Phase II clinical trials for Parkinson's disease. To know more about the number of competing drugs in development, visit @ XADAGO/EQUFINA Market Positioning Compared to Other Drugs Key Milestones of XADAGO/EQUFINA In April 2020, Newron Pharmaceutical acknowledged that US WorldMeds, who held the US commercialization rights for the licensed drug, XADAGO, as a sub licensee of Zambon, had entered into a definitive agreement with Supernus Pharmaceuticals under which Supernus would acquire the CNS portfolio of US WorldMeds, including the US rights to XADAGO In November 2019, Eisai announced that it had launched the EQUFINA 50mg tablets for the indication of improvement of the wearing-off phenomenon in patients with Parkinson's disease under treatment with a drug containing levodopa in Japan. Manufacturing and marketing approval of EQUFINA was obtained in September 2019. In April 2017, Eisai Co., Ltd. and Meiji Seika Pharma announced entering into a license agreement for the commercialization of safinamide (development code: ME2125) to treat Parkinson's disease in Japan and Asia. In March 2017, Newron Pharmaceuticals announced the US FDA approval of XADAGO to treat Parkinson's disease as an add-on therapy to levodopa/carbidopa for patients experiencing "off" episodes. In March 2016, Zambon announced a strategic agreement with US WorldMeds to commercialize Newron's lead compound, XADAGO, to treat Parkinson's disease in the US. In February 2015, XADAGO was approved in the European Union as an add-on therapy to levodopa, alone or in combination with other Parkinson's medications, in mid-late stage PD patients with motor fluctuations. XADAGO/EQUFINA Patent Details XADAGO tablets are currently protected by three XADAGO patents with US patent numbers 8,076,515, 8,278,485, and 8,283,380, which expire between June 2027 and December 2028 and are listed in the FDA's publication, Approved Drug Products with Therapeutic Equivalence Evaluations, commonly referred to as the Orange Book. The company has a license agreement with Zambon S.p.A., Newron's partner, related to the XADAGO Patents, and as a new chemical entity, XADAGO is under the 5-year FDA exclusivity period that expires on March 21, 2022. In May 2017, Zambon filed a worldwide patent under the patent number WO2017207587A1. The invention relates to pharmaceutical compositions comprising safinamide and, more particularly, to taste-masked particles comprising said active ingredient or pharmaceutically acceptable salts thereof, oral dosage forms that include said particles, and a process for preparing them. Discover how XADAGO/EQUFINA is shaping the Parkinson's disease treatment landscape @ XADAGO 50mg XADAGO/EQUFINA Market Dynamics XADAGO, marketed as EQUFINA in some regions (notably in South Korea and Japan), is a once-daily oral selective MAO-B inhibitor used as an add-on treatment for Parkinson's disease patients experiencing "off" episodes while on a stable dose of levodopa. The drug's unique dual mechanism of action—MAO-B inhibition and modulation of glutamate release—offers both dopaminergic and non-dopaminergic effects, positioning it as a differentiated product in the PD adjunctive therapy landscape. This has helped it carve a niche in markets where patients are inadequately controlled by levodopa alone, particularly those in mid-to-late-stage PD. The global market dynamics for XADAGO/EQUFINA are shaped by a mix of competitive intensity, regional adoption trends, and payer dynamics. In the U.S. and Europe, the drug has faced stiff competition from generic MAO-B inhibitors (like selegiline and rasagiline) and newer Parkinson's disease therapies, including COMT inhibitors, dopamine agonists, and extended-release levodopa formulations. Despite this, its favorable safety profile and once-daily dosing have supported its uptake in certain patient segments, especially in Europe. Market penetration has been slower in the U.S. due to both reimbursement hurdles and physician preference for more established adjunctive treatments. In Asia, particularly Japan and South Korea, EQUFINA has demonstrated stronger market performance thanks to focused commercial strategies and a high unmet need for effective "off time" management. Meiji Seika Pharma and Eisai, the regional marketing partners, have successfully leveraged the drug's differentiated profile in clinician education, which has led to growing adoption among neurologists. In Japan, where the aging population is rapidly expanding and Parkinson's prevalence is rising, EQUFINA has benefited from both demographic tailwinds and formulary access. Looking ahead, the market outlook for XADAGO/EQUFINA depends on several strategic levers, including lifecycle management, regional partnerships, and real-world evidence generation. The manufacturer's ability to expand into new geographies, secure favorable reimbursement, and differentiate against both generics and newer entrants will be critical. Moreover, as Parkinson's disease treatment moves toward more personalized approaches, XADAGO/EQUFINA may find sustained relevance in specific subpopulations, particularly those requiring a balance of efficacy and tolerability. Dive deeper to get more insight into XADAGO/EQUFINA's strengths & weaknesses relative to competitors @ XADAGO/EQUFINA Market Drug Report Table of Contents Related Reports Parkinson's Disease Market Parkinson's Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Parkinson's disease companies, including UCB Biopharma SRL, Novartis, Annovis Bio, Supernus Pharmaceuticals, Inc., Britannia Pharmaceutical, Pharma Two B, Mitsubishi Tanabe Pharma (NeuroDerm), AbbVie, Cerevel Therapeutics, Cerevance, among others. Parkinson's Disease Pipeline Parkinson's Disease Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Parkinson's disease companies, including Cerevel Therapeutics, Inhibikase Therapeutics, Neuraly, Peptron, Biogen, Roche, Brain Neurotherapy Bio, Inc., Modag, Annovis Bio Inc., BioVie Inc., United Neuroscience Ltd., Luye Pharma Group, AbbVie, UCB Biopharma SRL, InnoMedica Schweiz AG, Integrative Research Laboratories AB, H. Lundbeck A/S, Shanghai WD Pharmaceutical Co., Ltd., Cerevance Beta, Inc., Nobilis Therapeutics Inc., BlueRock Therapeutics, Taiwan Mitochondrion Applied Technology Co., Ltd., among others. Cell and Gene Therapy in Parkinson's Disease Market Cell and Gene Therapy in Parkinson's Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key cell and gene therapy in Parkinson's disease companies including MeiraGTx, Hope Biosciences, Sumitomo Pharma, Prevail Therapeutics, BlueRock Therapeutics, Voyager Therapeutics, among others. Parkinson's Disease Psychosis Market Parkinson's Disease Psychosis Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Parkinson's disease psychosis companies, including Sumitomo Pharma America Inc., Vanda Pharmaceuticals, Acadia Pharmaceuticals Inc., Otsuka America Pharmaceutical, Lundbeck LLC, Jazz Pharmaceuticals, Alkahest Inc., Sandoz, Sio Gene Therapies, Axovant Sciences Ltd, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Drug ApprovalLicense out/inPhase 2

09 Jan 2025

·www.businesswire.com

Newron and Myung In Pharm Announce License Agreement for evenamide in South Korea

MILAN, Italy & MORRISTOWN, New Jersey & SEOUL, Republic of Korea--( BUSINESS WIRE )--Newron Pharmaceuticals S.p.A. (“Newron”) (SIX: NWRN, XETRA: NP5), a biopharmaceutical company focused on the development of novel therapies for diseases of the central and peripheral nervous system, and Myung In Pharm Co. Ltd. (“Myung In Pharm”), South Korea’s leading CNS specialist pharmaceutical company, today announced that they have entered into a license agreement to develop, manufacture and commercialize Newron’s innovative modulator of the excessive release of glutamate, evenamide, an add-on therapy for treatment-resistant schizophrenia (TRS) and poorly responding patients with schizophrenia, in South Korea. Under the terms of the license agreement, Myung In Pharm will contribute 10% of the total patient population to be enrolled into Newron’s upcoming pivotal Phase III trial and cover the costs related to this population. Myung In Pharm’s involvement leverages its established clinical infrastructure and expertise in the central nervous system (CNS) field. Furthermore, the company will bear a percentage of eligible global development costs and will also be responsible for all regulatory, registration, marketing, and commercialization costs for evenamide in South Korea. In return, Newron will receive an upfront payment, milestone payments for development and regulatory achievements, and royalties on net sales. Further details were not disclosed by the parties. The Phase III randomized, double-blind, one-year trial is expected to begin in H1 2025 and will compare evenamide to placebo as an add-on treatment in at least 600 patients with TRS. It will be coordinated by Newron, who will oversee the trial design, execution, and data analysis. Myung In Pharm will be responsible for enrolling patients in South Korea through its extensive network of clinical sites, as well as providing support with monitoring and data collection. Newron continues to pursue further development opportunities for evenamide in other territories. On December 13, 2024, Newron and EA Pharma (a subsidiary of Eisai Co., Ltd.) announced a license agreement for evenamide in Japan and other Asian territories. “We are thrilled to partner with Myung In Pharm in this important clinical trial and to grant them the rights to develop, manufacture and commercialize evenamide in South Korea,” said Stefan Weber, CEO of Newron . “Their strong expertise in CNS therapies and their clinical infrastructure will be instrumental in advancing the development of evenamide. This collaboration underscores our shared commitment to transforming the treatment landscape for patients with unmet needs." Hang Myung LEE, Chairman of Myung In Pharm , commented: “Newron’s innovative approach aligns with our commitment to improving patient outcomes in the CNS area, and we believe our participation will make a significant contribution to the success of the study. Furthermore, we are honored to have received the license to commercialize evenamide in South Korea. This partnership presents a valuable opportunity for us to bring a new treatment option to patients in South Korea, a key market for Myung In Pharm. We look forward to working closely with the Newron team to bring this promising therapeutic to the forefront of clinical development and expand its impact in South Korea.” Jefferies International Limited (“Jefferies”) acted as the exclusive financial advisor to Newron. Orrick Herrington & Sutcliffe LLP advised as legal counsel to Newron. Cosmo Group Inc. of USA acted as the advisor to Myung In Pharm. About schizophrenia Approximately 25 million people worldwide are affected by schizophrenia, including more than 210,000 in South Korea as reported in 2022 by HIRA (Health Insurance Review & Assessment Service, Government agency). Despite more than 60 different types of atypical and typical antipsychotics used for 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 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 huge unmet medical need for 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 increase in 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 the development of novel therapies for patients with diseases of the central and peripheral nervous system. The Company is headquartered in Bresso near Milan, Italy. Xadago ® /safinamide has received marketing authorization for the treatment of Parkinson’s disease in the European Union, Switzerland, the UK, the USA, Australia, Canada, Latin America, Israel, the United Arab Emirates, Japan and South Korea, and is commercialized by Newron’s Partner Zambon. Supernus Pharmaceuticals holds the commercialization rights in the USA. Meiji Seika has the rights to develop and commercialize the compound in Japan and other key Asian territories. Newron is also developing evenamide as the potential first add-on therapy for the treatment of patients with symptoms of schizophrenia. For more information, please visit: www.newron.com About Myung In Pharm Myung In Pharm is a fully integrated pharmaceutical company established in 1985, based in Seoul, Republic of Korea. The company specializes in the manufacturing, processing, and distribution of pharmaceutical drugs, with a strong focus on central nervous system (CNS) therapies. Ranked number one in South Korea in the CNS field, Myung-In Pharm operates state-of-the-art manufacturing facilities that meet cGMP standards. With a robust network of over 1,200 neurologists and relationships with 98% of domestic neurology hospital departments, Myung In Pharm is dedicated to improving patient care and advancing the field of neuroscience. http://myunginph.co.kr/main/en/ 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/ )

Phase 3License out/inClinical ResultDrug Approval

13 Dec 2024

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Newron and EA Pharma (A Subsidiary of Eisai Co., Ltd.) Announce License Agreement for Evenamide in Japan and Other Asian Territories

MILAN & MORRISTOWN, N.J. & TOKYO--( 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, and EA Pharma Co., Ltd. (Head Office, Chuo-ku, Tokyo, Japan; President, Hidenori Yabune; “EA Pharma”), a subsidiary of Eisai Co., Ltd., today announced that they have entered into a license agreement to develop, manufacture and commercialize Newron’s innovative modulator of the excessive release of glutamate, evenamide, in Japan and other designated Asian territories 1 . Under the terms of the license agreement, in exchange for full rights in the licensed territories, Newron will receive up to a maximum total of €117 million from EA Pharma, including an upfront payment of €44 million, financial contributions to its upcoming Phase III one-year study to be performed outside of the licensed territories, regulatory and commercialization milestones, and tiered royalties up to a double-digit percentage of net sales for evenamide. The execution of this agreement, especially the upfront payment of €44 million, is expected to materially impact Newron’s 2024 financial statements. Stefan Weber, CEO of Newron, commented: “This partnering agreement for evenamide is a key milestone in our goal to offer a truly innovative, evidence-based alternative to patients suffering from schizophrenia, those who are responding poorly to their treatments, or who have become treatment resistant to currently available medications. We are thrilled to work with the EA Pharma team and to have the opportunity to advance evenamide through a Phase III study and towards regulatory submission in Japan and other Asian territories by one of Japan’s leading pharmaceutical companies. Newron will now focus on the initiation of our Phase III one-year study in TRS and expect to start that study outside of the licensed territories in H1 2025. We are also pursuing further development opportunities for evenamide in other territories.” “EA is thrilled to acquire the license for evenamide in Japan and other Asian territories. Evenamide has a new mechanism of action involving glutamate regulation and is the first in the world with this mechanism of action to demonstrate therapeutic efficacy in clinical trials. It is the result of many years of outstanding research by the Newron team. We believe evenamide has the potential to be transformational for patients suffering from schizophrenia,” said Hidenori Yabune, President of EA Pharma. Jefferies International Limited (“Jefferies”) acted as the exclusive financial advisor to Newron. Orrick Herrington & Sutcliffe LLP advised as legal counsel to Newron. About schizophrenia Approximately 25 million people worldwide are affected by schizophrenia. Despite more than 60 different types of atypical and typical antipsychotics used for 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 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 huge unmet medical need for 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) 2 , 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 increase in 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. Evenamide development milestones During Q1 2024, Newron reported final one-year results from study 014/015, a Phase II open label trial evaluating evenamide as an add-on therapy to a single antipsychotic in treatment-resistant patients. The data demonstrated that evenamide as an add-on treatment for patients with TRS was associated with sustained, clinically significant benefits that increased throughout the one-year course of treatment, with more than 70% of patients experiencing a clinically important reduction in disease severity. Overall, data from study 014 has demonstrated that evenamide was safe and well-tolerated at all doses, with 97% of patients completing six weeks of treatment. The incidence of treatment-emergent adverse events was very low, and more than 90% of the completers chose to continue with evenamide treatment into the long-term extension study (study 015). In Q2 2024, the Company announced two sets of data from study 008A, a potentially pivotal four-week randomized, double-blind and placebo-controlled study of evenamide as an add-on therapy in patients with chronic schizophrenia demonstrating inadequate benefit to their current second-generation antipsychotic. Topline data announced in April confirmed evenamide’s favorable safety and tolerability profile, followed by compelling data from additional analyses reported in May. The study met the primary endpoint (improvement of the Positive and Negative Syndrome Scale (PANSS) Total Score) and key antipsychotics, and there was no increase in EPS, weight gain, blood glucose, metabolic syndrome, sexual dysfunction or gastro-intestinal side effects, CNS or cardiac effects, or laboratory abnormalities. The study also met the secondary endpoint (improvement of the Clinical Global Impression of Severity (CGI-S)), with a high rate of study completion (96%). No new or specific concerns were raised in the study; only 25% of the patients in the study experienced at least one adverse event (evenamide 25% versus placebo 25.8%). The totality of these results validated evenamide as the first glutamate modulator to demonstrate efficacy in inadequately responding patients with schizophrenia in a placebo-controlled study. Newron is expected to initiate a Phase III randomized, double-blind, one-year trial in H1 2025 that will compare evenamide to placebo as add-on treatment in at least 600 patients with treatment-resistant schizophrenia (TRS). The primary efficacy endpoint will be change from baseline in the Positive and Negative Syndrome Scale (PANSS) scores at 12 weeks. Following this initial period, subjects will continue on their assigned treatment until week 52, for demonstration of long-term efficacy and safety and tolerability of evenamide. Newron continues to pursue further development opportunities for evenamide in other territories. About Newron Pharmaceuticals Newron (SIX: NWRN, XETRA: NP5) is a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system. The Company is headquartered in Bresso near Milan, Italy. Xadago ® /safinamide has received marketing authorization for the treatment of Parkinson’s disease in the European Union, Switzerland, the UK, the USA, Australia, Canada, Latin America, Israel, the United Arab Emirates, Japan and South Korea, and is commercialized by Newron’s Partner Zambon. Supernus Pharmaceuticals holds the commercialization rights in the USA. Meiji Seika has the rights to develop and commercialize the compound in Japan and other key Asian territories. Newron is also developing evenamide as the potential first add-on therapy for the treatment of patients with symptoms of schizophrenia. For more information, please visit: www.newron.com About EA Pharma EA Pharma Co., Ltd. is a subsidiary of Eisai Co., Ltd. It was established in April 2016 by integration of the gastrointestinal business unit with more than 60 year’s history of the Eisai Group and the gastrointestinal business unit of the Ajinomoto Group having amino acid as its business core. EA Pharma Co., Ltd., is a specialty pharmaceutical company with a full value chain covering R&D, production & logistics and sales & marketing. For further information on EA Pharma Co., Ltd., please visit https://www.eapharma.co.jp/ 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 Brunei Darussalam, the Kingdom of Cambodia, the Republic of Indonesia, the Lao People's Democratic Republic, Malaysia, the Union of Myanmar, the Republic of the Philippines, the Republic of Singapore, the Kingdom of Thailand, the Socialist Republic of Vietnam 2 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/ )

Clinical ResultLicense out/inPhase 3Phase 2

100 Deals associated with Safinamide mesylate

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KEGG	Wiki	ATC	Drug Bank
D10191	Safinamide mesylate	N04B	DB06654

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Parkinson Disease	European Union	Zambon SpA	23 Feb 2015
Parkinson Disease	Iceland	Zambon SpA	23 Feb 2015
Parkinson Disease	Liechtenstein	Zambon SpA	23 Feb 2015
Parkinson Disease	Norway	Zambon SpA	23 Feb 2015

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Dyskinesia, Drug-Induced	Phase 3	-	Zambon SpA	01 Oct 2019
Young onset Parkinson disease	Phase 3	Switzerland	Newron Pharmaceuticals SpA	01 Oct 2009
Motor Disorders	Phase 3	-	Newron Pharmaceuticals SpA	01 Aug 2007
Multiple System Atrophy (MSA) With Orthostatic Hypotension	Phase 2	Italy	Zambon SpA	29 Oct 2019
Multiple System Atrophy (MSA) With Orthostatic Hypotension	Phase 2	Spain	Zambon SpA	29 Oct 2019
Multiple system atrophy, Parkinson's variant	Phase 2	Italy	Zambon SpA	29 Oct 2019
Multiple system atrophy, Parkinson's variant	Phase 2	Spain	Zambon SpA	29 Oct 2019
Cognitive Dysfunction	Phase 2	United States	Newron Pharmaceuticals SpA	01 Sep 2010
Cognitive Dysfunction	Phase 2	Spain	Newron Pharmaceuticals SpA	01 Sep 2010
Epilepsy	Phase 2	European Union	Newron Pharmaceuticals SpA	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03881371 \| NCT01479530 (XINDI, MDS2024) Manual	Phase 3	Parkinson Disease	-	safinamide and levodopa	jrekytszzg(wgybxuxlbq): MD = -0.7 (95% CI, -1.40 to -0.02) View more	Positive	27 Sep 2024
				rasagiline
NCT05312632 (CTgov)	Phase 4	Parkinson Disease	201	Safinamide Mesilate	fabsqiotlw(wkgjcjbroh) = qrkxxhjfzj ygopqoafap (eycdgsizqd, oqhldrazcx - lhtcokcqyw) View more	-	23 Sep 2024
EAN2024	Not Applicable	Parkinson Disease	-	Safinamide 100mg	wkqmucwxiy(rrosvemhaw) = nbssnlxkab vungaxuirc (bbjhdutlsl ) View more	-	28 Jun 2024
NCT03881371 (XINDI, CTgov)	Phase 3	Motor Disorders \| Parkinson Disease	307	Safinamide (Safinamide)	hgwilumgsk(pkkorfntzd) = notirpmrzf ztzqozenje (ombpivncgc, 2.556) View more	-	20 Mar 2024
				Placebo (Placebo)	hgwilumgsk(pkkorfntzd) = onicggljbb ztzqozenje (ombpivncgc, 2.543) View more
MDS2023	Not Applicable	Parkinson Disease Add-on	51	safinamide	beshuesxbw(qkgnlhkbui) = qephnzhpfk hpphqrvmqt (rediraweoc ) View more	Negative	27 Aug 2023
				safinamide	beshuesxbw(qkgnlhkbui) = hyjmpmhigj hpphqrvmqt (rediraweoc ) View more
MDS2023	Not Applicable	Parkinson Disease	-	Safinamide	kklobppree(qsqppbhlee) = haflmpcttd kqlbqdpuyh (kqqtnbunym, 4 - 10) View more	Positive	27 Aug 2023
				Opicapone	kklobppree(qsqppbhlee) = krusodxmjl kqlbqdpuyh (kqqtnbunym, 3 - 11) View more
WPC2023	Not Applicable	Parkinson Disease Add-on	26	Safinamide 50 mg	znkuqwrysx(imqykfnwng) = drowsiness, confusion, feeling unwell, headache snodbxllob (tnhacyjuhw ) View more	Positive	28 Jun 2023
				Safinamide 100 mg
SYNAPSES (EAN2023)	Not Applicable	Parkinson Disease Add-on	-	Safinamide	jhkwwozmws(lvauzshmoz) = showing a stronger effect in the absence of other adjunct therapies kekxxnoepe (twekjlqywt )	Positive	28 Jun 2023
				Additional adjunct therapies
WPC2023	Not Applicable	Parkinson Disease Add-on	180	Safinamide	lcqhfqnzyf(sbfvkbvshv) = ibjwbtpkhb irtceoslcy (nmixukexgo ) View more	Positive	28 Jun 2023
NCT03841604 (CTgov)	Phase 4	Chronic Pain \| Parkinson Disease	94	Safinamide Methanesulfonate (Experimental)	ardvdqmrsx(hwlghzmcvl) = fnsvfundrz ywwxosuqnb (jneplinvsg, 2.01) View more	-	22 May 2023
				Safinamide methanesulfonate matching placebo (Placebo)	ardvdqmrsx(hwlghzmcvl) = jtcwiyhthn ywwxosuqnb (jneplinvsg, 1.29) View more

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