Evenamide Hydrochloride

精神科药物创新亮点总结（基于Havlik 2026年JCP研究+最新研发管线）来自John Havlik等2026年《临床精神病学杂志》的核心结论与最新研发管线数据，清晰呈现精神科药物创新的“全局现状+局部突破”。一、核心数据概览（来自Havlik原文）2012-2024年FDA批准的22种精神科药物，整体创新度不足，但存在局部亮点：• 新分子实体（NME）占比：仅31.8%（7种），其余为新适应症/剂型/复方（me-too类）• 优先审评占比：仅13.6%（3种），无突破性疗法认定• 临床效用评级：无药物获“临床有益”，86.4%为“临床中性”，13.6%为“临床无益”• 研发聚焦：超60%药物集中于抗抑郁、ADHD、精神分裂症三大成熟适应症二、部分适应症创新药物亮点（已获批+在研）精神分裂症领域（突破传统多巴胺机制的代表）Cobenfy（xanomeline） M1/M4毒蕈碱型乙酰胆碱受体激动剂 2024年获批 30多年来首个非多巴胺D2受体靶向的全新机制药物，属于原文中极少数“真正创新NME”Evenamide 电压门控钠离子通道调节剂 Ⅱ/Ⅲ期临床 有望成为自氯氮平以来首款针对治疗抵抗性精神分裂症的新疗法，填补原文指出的“难治性领域缺口”奥氮平长效注射剂 D2/5-HT2A拮抗剂 Ⅲ期临床完成 新型缓释技术实现每月一次注射，提高患者依从性，属于“剂型创新”（原文中“临床中性”类代表）ALTO-101 磷酸二酯酶4抑制剂 FDA快速通道 全球首个针对精神分裂症认知损害的透皮贴剂，解决原文中“认知症状未满足需求”双相情感障碍领域Caplyta（lumateperone） 5-HT1A激动剂/D2受体拮抗剂 2021年获批（双相抑郁适应症） 获批用于双相抑郁的非典型抗精神病药，属于“新适应症拓展”（原文中“临床中性”类）Rexulti（brexpiprazole） 5-HT1A激动剂/D2受体部分激动剂 2023年获批（双相抑郁辅助治疗） 增效治疗新选择，仍为现有机制优化（原文中“渐进式改进”代表）Ulotaront 色氨酸羟化酶1/2抑制剂 Ⅲ期临床 全新机制（靶向血清素合成），有望成为首个非多巴胺能双相障碍药物，契合原文“亟需全新机制”的呼吁抑郁症与难治性领域Spravato（esketamine） NMDA受体拮抗剂 2019年获批 首个速效抗抑郁药，针对难治性抑郁，属于原文中“临床价值相对突出”的NMEAuvelity（dextromethorphan/bupropion） NMDA受体拮抗剂/去甲肾上腺素再摄取抑制剂 2022年获批 口服速效抗抑郁药，新复方制剂（原文中“临床中性”类）Zuranolone 神经甾体GABAA受体调节剂 2023年获批 首个口服产后抑郁药物，新分子实体，属于原文中“真正创新NME”三、研发趋势与科研启示结合Havlik原文结论与管线数据，未来精神科药物研发的核心方向清晰：从“多巴胺依赖”到“多靶点突破”：如精神分裂症的Cobenfy、双相的Ulotaront，代表摆脱传统机制的真正创新，是药企研发投入重点。聚焦“未满足临床需求”：治疗抵抗性精神分裂症、双相抑郁认知损害、产后抑郁等领域，对应原文指出的“研发缺口”。给药方式创新：长效注射剂、透皮贴剂等提高依从性的剂型，虽非全新机制，但能带来临床价值提升（如奥氮平长效注射剂）。• 科研选题方向：可聚焦“双相障碍认知损害的药物干预”，结合ALTO-101等药物的机制，设计更具临床价值的研究。

MILAN & MORRISTOWN, N.J.--(BUSINESS WIRE)--Newron Pharmaceuticals S.p.A. (“Newron”) (SIX: NWRN, XETRA: NP5), a biopharmaceutical company focused on developing novel therapies for patients with diseases of the central and peripheral nervous system, today announced the publication of peer-reviewed data in Therapeutic Advances in Psychopharmacology, co-authored by Newron’s Chief Medical Officer, Ravi Anand, MD, and colleagues1. The publication presents clinical findings showing that evenamide, a novel glutamate modulator, is associated with clinically meaningful and sustained benefits when added to first- or second-generation antipsychotics in patients with schizophrenia who have an inadequate response to existing treatments, including those with TRS. This publication captures more than a decade of scientific and clinical work addressing one of psychiatry’s most difficult challenges. The publication synthesizes results from multiple randomized clinical trials and provides a scientific mechanistic rationale for the use of evenamide as a unique approach that targets disease mechanisms not addressed by existing antipsychotics. Drawing on data and analyses from randomized clinical studies, the publication highlights how modulation of aberrant glutamatergic signaling may deliver clinically meaningful benefits for patients with TRS and for those who continue to struggle despite standard antipsychotic treatment. “This publication captures more than a decade of scientific and clinical work addressing one of psychiatry’s most difficult challenges,” said Ravi Anand, MD, Chief Medical Officer at Newron Pharmaceuticals. “The analyses highlight not only symptom improvement but also real-world functional gains that matter to people living with schizophrenia, particularly those who have exhausted available options.” A Distinct Mechanism Targeting the Site of Dysfunction Unlike currently marketed antipsychotics that act primarily by blocking dopamine receptors in the basal ganglia, evenamide’s primary site of action is the hippocampus, that controls hyperdopaminergic firing in the basal ganglia (a brain region intimately involved in the causation of the core symptoms of schizophrenia). By reducing excessive glutamate activity in the hippocampus, evenamide indirectly rebalances dopamine signaling while preserving normal neuronal function. The hippocampal site of action of evenamide may explain why evenamide has demonstrated improvements not only in positive symptoms but also in negative symptoms, social functioning, and life engagement – domains that together with cognition are controlled by the various nuclei in the hippocampus and remain largely unaddressed by existing therapies. Taken together, the findings support evenamide as a potential first-in-class adjunctive therapy capable of redefining expectations for patients with TRS. Across clinical studies reported to date, evenamide has maintained a favorable safety and tolerability profile, being well-tolerated, with low rates of treatment discontinuation and no consistent pattern of serious safety concerns. “Evenamide represents a fundamentally different treatment approach,” said Anand. “By targeting the hippocampus – the source of the deficit rather than its downstream effects – we believe evenamide has the potential to shift the treatment paradigm, particularly for patients with TRS who urgently need new options.” Clinically Meaningful and Durable Benefits The publication reports analyses from two key clinical programs. In a one-year study of patients with treatment-resistant schizophrenia, more than half of those patients treated with evenamide improved to such an extent that they no longer met the severity criteria for TRS after long-term adjunctive treatment. Approximately one-quarter achieved remission, based on the most stringent criteria for remission. In a separate randomized, double-blind, placebo-controlled trial among patients with inadequate response to antipsychotics, evenamide showed statistically significant improvements over standard of care, regardless of the number of prior failed treatments. Importantly, benefits were observed not only in core symptoms but also in measures of social functioning and life engagement, domains often poorly addressed by existing therapies. “These results are notable because they go beyond symptom reduction,” continued Anand. “With evenamide, we are seeing improvements that translate into patients’ daily lives, including their ability to function, engage socially, and potentially move closer to remission. That is a meaningful outcome for patients, families, and clinicians.” Newron is advancing evenamide through ENIGMA-TRS, an international Phase III clinical program for patients with documented TRS. If successful, these studies could support the use of evenamide as a first-in-class adjunctive therapy, addressing a long-standing gap in the treatment landscape. About ENIGMA-TRS The ENIGMA-TRS pivotal Phase III program consists of ENIGMA-TRS 1 and ENIGMA-TRS 2. ENIGMA-TRS 1, initiated in August 2025, is an international, one-year, double-blind, placebo-controlled study in at least 600 patients to evaluate the efficacy, tolerability, and safety of evenamide 15 mg and 30 mg twice daily as an add-on therapy to current antipsychotics, including clozapine, compared to placebo. ENIGMA-TRS 2, initiated in December 2025, is a Phase III, international, 12-week, randomized, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of evenamide 15 mg twice daily as an add-on therapy to current antipsychotics, including clozapine, compared to placebo, in patients suffering from TRS. ENIGMA-TRS 2 will enroll at least 400 patients. About evenamide Evenamide is a novel, orally available new chemical entity with a unique mechanism of action distinct from all currently marketed antipsychotics. It acts by selectively blocking voltage-gated sodium channels (VGSCs) and exhibits no biological activity at more than 130 other central nervous system (CNS) targets. It normalizes glutamate release induced by aberrant sodium channel activity (veratridine-stimulated), without affecting basal glutamate levels, due to inhibition of VGSCs. Combinations of subtherapeutic doses of evenamide and other APs, including clozapine, were associated with benefit in animal models of psychosis, suggesting synergies in mechanisms that may provide meaningful benefits for patients who do not adequately respond to current APs, including those on clozapine. Importantly, the benefits seemed to persist for a substantial time after evenamide had been degraded, explaining the long-term effects seen in clinical studies. Through its novel glutamatergic modulation, evenamide represents a first-in-class approach aimed at addressing the unmet needs of patients with schizophrenia who are resistant to existing treatments. About treatment-resistant schizophrenia (TRS) A significant proportion of patients with schizophrenia show virtually little to no beneficial response to currently available antipsychotic (AP) treatments, leading to a diagnosis of treatment-resistant schizophrenia (TRS). TRS is defined as no or inadequate symptom relief despite treatment with therapeutic doses of two APs from two different chemical classes for an adequate period. It is estimated that approximately 15% of patients develop TRS from the onset of illness, and about one-third to 50% of patients with schizophrenia overall. Emerging scientific evidence supports abnormalities in glutamate neurotransmission in TRS, not targeted by current APs, along with normal dopaminergic synthesis, to explain the lack of clinical benefit of most typical and atypical antipsychotics, which act primarily on dopamine receptors. These insights underline the need for novel therapeutic approaches that target the underlying glutamatergic dysfunction in schizophrenia, offering hope for patients who currently have limited or no effective treatment options. About Newron Pharmaceuticals Newron (SIX: NWRN, XETRA: NP5) is a biopharmaceutical company focused on the development of innovative therapies for patients with diseases of the central and peripheral nervous system. Headquartered in Bresso near Milan, Italy, the Company has a strong track record of advancing neuroscience-based treatments from discovery to market. Newron’s lead compound, evenamide, is a first-in-class glutamate modulator and 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 developed in the global pivotal ENIGMA-TRS Phase III development program. Clinical trial results to date demonstrate the benefits of this drug candidate in the TRS as well as poorly responding patient population, with significant improvements across key efficacy measures increasing over time, as well as a favorable 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’s first marketed product, 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. The product is commercialized by Newron’s partner Zambon, with Supernus Pharmaceuticals holding marketing rights in the U.S., and Meiji Seika responsible for development and commercialization in Japan and other key Asian territories. 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. 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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 Ravi Anand, Alessio Turolla https://orcid.org/0009-0005-2167-61432, Giovanni Chinellato https://orcid.org/0009-0001-7091-86723, Francesca Sansi https://orcid.org/0009-0002-4495-58214, Arjun Roy5, and Richard Hartman https://orcid.org/0000-0002-5980-02006