GluN2B

Announcement follows FDA's February 2025 decision to grant radiprodil Breakthrough Therapy designation Company remains on track to initiate Phase 3 pivotal trial of radiprodil in mid-2025 NEW YORK, March 17, 2025 /PRNewswire/ -- GRIN Therapeutics, Inc., a leader in the development of therapies to treat serious neurodevelopmental disorders, today announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug designation for its investigational drug, radiprodil, for the treatment of GRIN-related neurodevelopmental disorder (NDD). Radiprodil is designed as a potent negative allosteric modulator selectively targeting the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B). The company is on track to initiate a pivotal Phase 3 trial for radiprodil in mid-2025 for the treatment of GRIN-related NDD with GoF mutations and has an ongoing global open-label clinical trial of radiprodil for the treatment of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type II. "We are making rapid progress in our efforts to bring a first-ever treatment for GRIN-related neurodevelopmental disorder to patients. Supported by our promising clinical data, the FDA's decision to grant Orphan Drug designation to radiprodil is the latest milestone in that effort," said Michael A. Panzara, MD, MPH, Chief Medical Officer at Neurvati Neurosciences and GRIN Therapeutics. "As we plan to launch our pivotal Phase 3 clinical trial to evaluate the impact of radiprodil on seizures, behavioral abnormalities and functional outcomes associated with GRIN-related NDD in the coming months, we are very grateful to the patients and their families who continue to support this important research effort." Orphan Drug designation is designed to support innovation and research that can lead to more new treatments for diseases that affect fewer than 200,000 people in the United States. The designation grants drug developers the potential for seven years of market exclusivity for their drug after approval, during which time the FDA will generally not approve an application for the same drug targeting the same disease or condition. In February 2025, the FDA granted radiprodil Breakthrough Therapy designation for the treatment of seizures associated with GRIN-related NDD in patients with GoF mutations. "We look forward to continuing to engage with the FDA through the means offered by Breakthrough Therapy designation, as we advance our Phase 3 program with a goal of bringing radiprodil to patients," said Anne-Marie Li-Kwai-Cheung, MChem, MTOPRA, RAPS, Senior Vice President, Development, Regulatory, and Quality at Neurvati Neurosciences and GRIN Therapeutics. "We have heard from so many clinicians and patients about the urgent unmet need in the treatment of GRIN-related disorders and our entire team is dedicated to advancing this development program through late-stage clinical research and regulatory review as rapidly as possible." About GRIN-related neurodevelopmental disorder GRIN-related neurodevelopmental disorder is a family of rare, genetically defined pediatric neurodevelopmental disorders caused by mutations in GRIN genes. While symptoms of GRIN-related neurodevelopmental disorder can present as early as infancy, a diagnosis is often not confirmed until age two or later when a child fails to reach developmental milestones. Individuals may experience developmental delay, intellectual disabilities, epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties and behavioral problems. There are currently no approved therapies for GRIN-related neurodevelopmental disorder. About Radiprodil Radiprodil is an investigational, selective and potent negative allosteric modulator of the N-methyl-D-aspartate (NMDA) receptor subtype 2B (NR2B or GluN2B). In nonclinical studies, radiprodil has been shown to potently and selectively modulate GluN2B. Radiprodil has also demonstrated an antiseizure effect in a number of in vitro and in vivo preclinical seizure and epilepsy models and specifically in models characterized by an enhanced GluN2B NMDA transmission, which can occur with gain-of-function (GoF) mutations in GRIN-related neurodevelopmental disorder. In vitro analysis of brain tissues extracted from both tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) lesions has shown enhanced GluN2B NMDA expression supporting the potential ability of radiprodil to control seizures in these conditions. About GRIN Therapeutics GRIN Therapeutics is dedicated to the research and development of precision therapeutics for pediatric neurodevelopmental disorders with the goal of bringing hope to patients and caregivers. Late last year, GRIN Therapeutics reported promising topline data from a Phase 1b/2a clinical trial (the Honeycomb Trial) evaluating radiprodil in GRIN-related neurodevelopmental disorder in patients with GoF variants, leading to the decision to advance to a Phase 3 trial. The company has an additional ongoing clinical trial to evaluate radiprodil for the potential treatment of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type II. GRIN Therapeutics is an affiliate of Neurvati Neurosciences, a portfolio company of Blackstone Life Sciences (BXLS). For more information, please visit About Neurvati Neurosciences Neurvati Neurosciences, a portfolio company of Blackstone Life Sciences, identifies and advances the development of high-potential drug candidates across the neuroscience landscape. Neurvati employs a collaborative model that establishes fit-for-purpose affiliate companies, aligning dedicated resources with long-term strategic capital to catalyze innovative treatment options in areas of unmet need. Neurvati's team of experienced operators and drug developers seeks opportunities to challenge current treatment paradigms and make a difference for patients suffering from a wide range of neurological and psychiatric disorders. For more information, please visit About Blackstone Life Sciences Blackstone Life Sciences is an industry-leading private investment platform with capabilities to invest across the life cycle of companies and products within key life science sectors. By combining scale investments and hands-on operational leadership, Blackstone Life Sciences helps bring to market promising new medicines and medical technologies that improve patients' lives and currently has more than $12 billion in assets under management. Corporate Contact Elliott Ruiz +1 201.674.5417 [email protected] SOURCE GRIN Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Mutations in GRIN genes lead to GRIN-related neurodevelopmental disorders. Credit: Jo Panuwat D/Shutterstock. The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to Grin Therapeutics’ radiprodil for treating seizures associated with glutamate receptor, ionotropic, N-methyl D-aspartate (GRIN)-related neurodevelopmental disorder with gain-of-function (GoF) mutations. The decision was based on the outcomes from the Phase Ib Honeycomb trial. Honeycomb involved paediatric subjects with confirmed mutations of GoF across GRIN genotypes, demonstrating radiprodil’s good tolerability. Subjects experienced a median decrease of 86% in countable motor seizure (CMS) frequency in comparison with baseline. 71% of them saw a decrease in CMS by more than half, with six out of seven subjects seizure-free for at least 80% of the days during the maintenance period of eight weeks. The trial also reported positive assessments from clinicians and caregivers, using measures such as the Clinician and Caregiver Global Impressions of Change and the Aberrant Behavior Checklist – Community. Radiprodil is an investigational, potent negative allosteric modulator that targets the N-methyl-D-aspartate receptor subtype 2B. It now benefits from fast-track advantages and the agency’s intensive guidance on drug development programmes. Mutations in GRIN genes lead to GRIN-related neurodevelopmental disorders. A Neurvati Neurosciences company, Grin Therapeutics is supported by a $200m capital commitment from private investment platform Blackstone Life Sciences and is preparing for a Phase III pivotal trial set to commence in mid-2025. This trial will further evaluate radiprodil’s impact on seizures, abnormalities in behaviour and functional outcomes in individuals with GRIN-related neurodevelopmental disorder. Neurvati Neurosciences and Grin Therapeutics president and CEO Bruce Leuchter stated: “Radiprodil’s mechanism, which targets the underlying disease biology, has demonstrated remarkable reductions in seizures in our Phase Ib open-label study and has the potential to meaningfully impact the non-seizure symptoms associated with this neurodevelopmental disorder. “Our team is executing with urgency to advance the Phase III study and bring this potential first-in-class treatment to patients as quickly as possible. We look forward to working closely with the FDA throughout this process to ensure a rigorous and efficient development path.”

** IND submitted to the FDA showing significantly improved patient condition when administered within 70 minutes of arrival at the Emergency Room ** *Multinational Phase 3 Clinical Trial protocols confirmed and initiated with leading global stroke research centers * SEOUL, South Korea, Dec. 11, 2024 /PRNewswire/ -- GNT Pharma Co. Ltd, a late-stage pharmaceutical company founded in 1998 with offices in Seoul Korea, Italy and USA, announced today the results of its latest Phase II ('SONIC') and Phase III ('Rodin') clinical trials study showing that stroke patients who received early administration of Nelonemdaz in combination with endovascular thrombectomy, demonstrated significant improvements in outcomes. These results were presented by Professor Jin Soo Lee, Chair of the Department of Neurology at Ajou University Medical Center at the recent International Conference Stroke Update 2024 (ICSU 2024). Dr BJ Gwag, Chairman and CEO of GNT Pharma commented "we are extremely encouraged with the SONIC and RODIN clinical trials results and excited to announce we have initiated multinational Phase 3 Clinical Trials (RENEW) with world class partners, including more than 20 top university hospitals in Korea as well as UCLA and UPMC Stroke Centers in the USA." Nelonemdaz is the world's first "multi-target" neuroprotection drug designed to reduce brain damage after a stroke or cardiac arrest. It offers superior efficacy compared to single-target neuroprotectants offering dual target action: (1) Inhibition of NMDA receptor subtype NR2B to safely reduce excitotoxicity; and (2) Removal of free radicals to reduce oxidative stress – two major causes of brain cell death following a stroke. Unlike non-selective NMDA receptor inhibitors, Nelonemdaz does not cause adverse effects and its safety has been verified in two Phase 1 trials, three Phase 2 trials, and two Phase 3 trials. There are over 5 million stroke-related deaths globally each year, with a further 5 million survivors annually left with permanent disabilities. This puts a huge strain on healthcare systems worldwide - the World Stoke Organization estimates total stroke-related costs to tip US$1 trillion by 2030. Moreover, stroke frequency is not abating, with the USA seeing an increase of 60% over the past 30 years. Almost 80% of all strokes are Ischemic Strokes and require emergency medical treatment, typically thrombolysis or endovascular thrombectomy. Given these alarming statistics, there is a global imperative to further improve the efficacy of current stroke treatments. Dr Gwag adds: "In 2015, fast endovascular thrombectomy was proven to improve functional outcome in acute ischemic stroke patients and is the de facto standard for stroke care across the world. It is therefore encouraging that the outcome of stroke patients is further improved by the fast administration of Nelonemdaz along with rapid thrombectomy," The prior Phase 2 SONIC trial results, published in Stroke Journal in 2022, showed the promising efficacy and safety of Nelonemdaz administered to stroke patients receiving thrombectomy. In the latest 498 patient Phase 3 RODIN Trial, administration of Nelonemdaz within 12 hours of ischemic stroke onset did not show significant efficacy in patients treated with thrombectomy. However, post-hoc analyses revealed potential interactions between treatment effects and time-related metrics. The RODIN results are to be published in the 'JAMA' (Journal of the American Medical Association) Network Open. The interactions were shown in the pooled analysis of stroke patients participating in the SONIC and RODIN trials, and in the subsequent subgroup analysis, the first infusion time of Nelonemdaz for improved functional outcome was established to be within 70 minutes from ER arrival. The efficacy of Nelonemdaz was assessed using the modified Rankin Scale (mRS), an ordinal scale ranging from 0 (normal) to 6 (death), at 12 weeks post-treatment. Compared to the placebo, the nelonemdaz caused a significantly beneficial shift in the mRS distribution (common odds ratio 2.2, p<0.05). The proportion of patients in mRS 0-2 corresponding to functional independence was 50.0% in the placebo group and improved to 68.6% in the Nelonemdaz group (p=0.059). Dr Lee adds " "Our post-hoc analyses unveiled a best clinical trial condition that showed a significant benefit of Nelonemdaz, and a protocol for the global phase 3 RENEW trial was established to confirm beneficial effects of Nelonemdaz in ischemic stroke patients in combination with endovascular thrombectomy." Dr. Lee will lead the RENEW trial alongside principal USA investigators Dr. Raul Nogueira, director of the UPMC Stroke Institute and Professor of Neurology and Dr. David S. Liebeskind, Director of the UCLA Stroke Center and Professor of Neurology. About GNT Pharma: GNT Pharma Co., Ltd ('GNTP') was founded in April 1998 by eight highly accomplished professors in subjects ranging from neuroscience and pharmacology to cell biology researching neuronal cell death. Since then, GNTP has discovered and developed an enviable pipeline of late stage drug candidates from nervous system disorders to chronic inflammatory diseases. As well as Nelonemdaz, GNTP's other flagship drug candidates include: Crisdesalazine for the treatment of Alzheimer's and neurodegenerative diseases and depression; and Flusalazine for inflammatory and respiratory diseases including COPD and Asthma. GNTP also has two commercial products in market, including Gedacure (Crisdesalazine) for the treatment of CDS or 'doggy dementia' that shares similar pathology to Alzheimers; and (2) Radipair, skin care products. Forward-Looking Statements Notice: This news release contains statements about expectations, plans, projections, and strategies of GNTP that constitute forward-looking statements to shareholders, investors, and partners. Statements included in this document that are not historical data and fact constitute forward-looking statements about future clinical and financial results. FURTHER INFORMATION: Media Inquiries: Byung Chul Kim, (M) +82-318005-9910; (E) [email protected] Investors/ Korea: Daeyong Kim, (M) +82-704261-0788; (E) [email protected] Investors /International: Sam Cho, (M) + 82-108948-7142; (E) [email protected] SOURCE GNT Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED