EAAT2

Spinocerebellar Ataxia (SCA) is a rare, genetic, life-threatening neurodegenerative disease with no available treatment. Troriluzole demonstrated a 50-70% slowing of SCA disease progression on the primary and secondary outcome measures at the 3-year endpoint in a real-world evidence (RWE) study. Troriluzole has a well-established safety profile and if approved, would be the first and only FDA-approved treatment for SCA; subject to receipt of FDA approval, Biohaven is prepared to commercialize troriluzole for SCA in the US in 2025. NEW HAVEN, Conn. , Feb. 11, 2025 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), today announced that the US Food and Drug Administration (FDA) has accepted for review the Company's New Drug Application (NDA) for troriluzole for the treatment of adult patients with spinocerebellar ataxia (SCA) and has granted Priority Review. This designation is assigned to applications for drugs that would offer a significant improvement over other available treatments for a given disorder or would provide a treatment option where none exists. In the case of SCA, a rare, genetic, neurodegenerative disease, troriluzole would be the first and only FDA-approved treatment for this life-threatening disorder. The FDA's decision regarding the NDA is expected within 6 months of filing (during 3Q2025). Based on FDA Priority Review timelines and if ultimately approved, Biohaven is prepared to commercialize troriluzole for SCA in the US in 2025. Melissa Beiner , M.D., SCA Clinical Development Lead at Biohaven , commented, "Our NDA filing is the culmination of over 8 years of clinical research and represents an important collaboration across the SCA community. The troriluzole NDA reflects rigorous scientific collaborations between advocacy groups, patients and their families, clinical experts in SCA and Biohaven . The FDA decision to grant Priority Review demonstrates the extremely high unmet need in this rare neurodegenerative disease. Time is of the essence for patients with SCA, who are suffering relentless and irreversible functional decline including impairments in coordination and balance leading to falls, loss of ambulation, and difficulties with vision, speech and swallowing." Dr. Beiner added, "The robust clinical data presented in the NDA demonstrate sustained and compelling treatment benefit in SCA patients treated with troriluzole, a once-daily, oral pill. We look forward to working closely with the FDA throughout the review process to bring the very first treatment to patients and families suffering from SCA." The NDA submission was based, in part, on positive topline results from Study BHV4157-206-RWE (NCT06529146), in which troriluzole 200 mg dosed orally in patients with SCA met the study's primary endpoint of change from baseline on the functional Scale for the Assessment and Rating of Ataxia (f-SARA), in all SCA genotypes, at 3 years compared to an external control arm. Troriluzole showed statistically significant superiority across 9 consecutive, prespecified primary and secondary endpoints with highly consistent, sustained, robust and clinically meaningful treatment effects. SCA patients treated with troriluzole showed a 50-70% slower rate of decline, representing 1.5-2.2 years delay in disease progression, over the 3-year study period (Figures 1-3 and Table 1). The NDA also includes confirmatory and supportive data from Studies BHV4157-201 and BHV4157-206, the first large, multi-center registrational trials in SCA. Notably, these data include disease stabilization in the SCA3 genotype (Figure 4) and a reduction in falls in all SCA genotypes (Figure 5), both compared to placebo over 48 weeks in Study BHV4157-206. Jeremy Schmahmann , M.D., Professor of Neurology at Harvard Medical School and Founding Director of the Ataxia Center and the Martha and Robert Fogelman Endowed Chair in Ataxia and Cerebellar Neurology at Massachusetts General Hospital commented, "The FDA acceptance for review of this NDA represents a critical milestone for SCA patients. Since the discovery of the first gene for SCA in 1993, patients and families affected by SCA have watched generation after generation suffer severe, progressive disability and premature death with no treatment options. The need for an intervention that can slow disease progression and help patients maintain their independence is urgent. The delay in disease decline shown in the real-world evidence study is a watershed in the history of the SCAs. This is what patients have been waiting for. It is what the doctors who have been powerless, have been waiting for. Additionally, the importance of troriluzole's effects on reducing falls in this patient population cannot be overstated. I applaud the FDA for recognizing this urgency by granting a Priority Review and look forward to using troriluzole in the clinic if approved." Biohaven's troriluzole clinical development program in SCA collected data over 8 years, including a robust long-term safety profile, and was the first industry trial conducted in SCA. The external control arms used in Biohaven's BHV4157-206-RWE Study were provided from objective, third-party data gathered from two independent natural history cohorts: one in the United States and one in Europe (EUROSCA Natural History Study). The National Ataxia Foundation (NAF) sponsored the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA) that served as the basis for the US natural history cohort. The data from the CRC-SCA is managed by the University of South Florida Health Informatics Institute . A total of 35 clinical sites provided data in the US and European natural history cohorts that served as the external controls in BHV4157-206-RWE. As per instructions from FDA on the real-world evidence study design and statistical analysis plan, the external control arm was determined using a Propensity Score Matching (PSM) method to ensure that untreated subjects from the comparator natural history cohort were rigorously matched to treated subjects from the troriluzole arm of Study BHV4157-206. PSM was used on all prognostic, demographic, and baseline characteristics known to be associated with disease progression in SCA, including baseline f-SARA, age, sex, age at symptom onset, genotype, and trinucleotide repeat length (by genotype). Andrew Rosen , Chief Executive Officer of the National Ataxia Foundation (NAF), stated, " Biohaven's SCA program reflects years of dedicated clinical research and collaboration with leading world experts and advocacy groups to advance the ataxia field. We are proud that our multi-year effort to fund and support the Clinical Research Consortium for the Study of Cerebellar Ataxia played such a critical role in providing the external control arm of Biohaven's study. The goal of CRC-SCA is to improve our understanding of SCA disease progression and to promote the development of disease-modifying therapies for SCA." Mr. Rosen added, "On behalf of patients and families, who have watched generations of family members succumb to this devastating disease and have been waiting for decades for a treatment that could slow disease progression, I thank the FDA for not only accepting this NDA for review, but recognizing the need for urgency for our community in the form of a Priority Review." Biohaven previously received both Fast-Track and Orphan Drug Designation (ODD) from the FDA, and ODD from the European Medicines Agency , where a troriluzole MAA is currently under review. An expanded access protocol (EAP) is currently enrolling patients with SCA who are eligible. EAPs are designed to give early access to potential therapies before they are approved by the FDA. More information about can be found at https://clinicaltrials.gov/study/NCT06034886. About Spinocerebellar Ataxia (SCA)Spinocerebellar ataxia is a group of dominantly inherited neurodegenerative disorders characterized by progressive loss of voluntary motor control and atrophy of the cerebellum and brainstem. SCA affects approximately 15,000 people in the United States and 24,000 in Europe and the United Kingdom . Patients experience significant morbidity, including impaired gait leading to falls, loss of ambulation and progression to a wheelchair, inability to communicate due to speech impairment, difficulty swallowing, and premature death. While signs and symptoms can appear anytime from childhood to late adulthood, SCA typically presents in early adulthood and progresses over a number of years. Currently, there are no FDA-approved treatments and no cure for SCA. About TroriluzoleTroriluzole is a new chemical entity (NCE) and third-generation novel prodrug that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. The primary mode of action of troriluzole is reducing synaptic levels of glutamate. Troriluzole increases glutamate uptake from the synapse, by augmenting the expression and function of excitatory amino acid transporters located on glial cells that play a key role in clearing glutamate from the synapse. The glutamate modulating activity of troriluzole addresses the widely documented glutamate deregulation that underlies neurodegeneration and Purkinje cell dysfunction in patients with SCA. Troriluzole also has the potential to be developed in a number of other diseases associated with excessive glutamate. More information about troriluzole can be found at the Biohaven's website: https://www.biohaven.com/pipeline/clinical-programs/glutamate/. About Biohaven Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and preclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA ; myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; antibody recruiting bispecific molecules and antibody drug conjugates for cancer. For more information, visit www.biohaven.com. Forward-looking StatementsThis news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, , including the potential approval and commercialization of troriluzole for SCA, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; the potential for Biohaven's product candidates to be first approved therapies; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Investor Contact: Jennifer Porcelli Vice President, Investor Relationsjennifer.porcelli@biohavenpharma.com+1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. mikebeyer@sambrown.com+1 (312) 961-2502 View original content to download multimedia:https://www.prnewswire.com/news-releases/biohaven-announces-fda-acceptance-and-priority-review-of-troriluzole-new-drug-application-for-the-treatment-of-spinocerebellar-ataxia-302373056.html SOURCE Biohaven Ltd.

Princeton, NJ, October 20, 2023 ─ iQure Pharma Inc. (iQure), a CNS company dedicated to the development of new epilepsy and pain management therapeutics, has completed the first closing of its latest round of funding. The company has raised $1.2M to progress with IND-enabling pivotal tox studies for its lead asset iQ-007, a first in class EAAT2 PAM neuromodulator. iQ-007 is a novel therapeutic candidate to treat epilepsy and other neurodegenerative conditions. The round was led by Munich-based life science fund Ventura BioMed Investors and anchor early-stage med-tech investor OKG Capital. Both investors see this round as a first step towards further funding to complete preclinical development and start Phase 1 trials. iQure's leading compound, iQ-007, is a neuromodulator targeting toxic levels of glutamate in the synaptic cleft. An elevated level of glutamate leads to neurotoxicity and ultimately to neural degeneration. iQ-007 operates by a Positive Allosteric Modulation of Excitatory Amino Acid Transporter 2 (EAAT2 PAM), which is responsible for up to 90% of glutamate uptake. A decrease in EAAT2 function is observed in epilepsy, stroke, Alzheimer's disease, neuropathic pain and ALS. Preclinical in vivo efficacy and safety data strongly support the potential value of this compound for patients suffering from epilepsy, including those who have seen limited success with seizure control using existing medications. iQ-007 has successfully completed the prestigious NIH ETSP epilepsy screening program and pivotal tox studies are ongoing. The Company is looking to start clinical development of iQ-007 in 2024. “Addressing neurodegeneration and preventing seizures in an effective and safe manner is a critical medical and social need,” said iQure CEO Pawel Zolnierczyk. “Epilepsy alone affects over 50 million people worldwide and approximately 30% of them struggle to control their seizures using current medication. Many also suffer from reduced quality of life due to medication side effects. In addition, aging populations are contributing to a surge in neurodegenerative diseases such as Alzheimer's and Parkinson's, with over 55 million people currently suffering from dementia, and 10 million new cases identified every year. “Securing funding from life science focused investors Ventura BioMed Investors and OKG Capital is a major milestone and will accelerate our clinical development,” said Zolnierczyk. “We also want to thank leading global CNS researcher Professor Krzysztof Kaminski and Jagiellonian University in Poland, who are instrumental in the ongoing development of iQ-007, for their close and successful collaboration. We are looking forward to bringing iQ-007 to clinical development in 2024.” About iQure Pharma iQure Pharma, a global biotech firm headquartered in the US, is focused on the development of new therapeutics for CNS, including neuropathic pain, epilepsy and other neurodegenerative diseases. iQure researchers, clinicians, and pharmaceutical professionals work closely with academic partners, industry experts, and patient organizations to build medically and socially beneficial therapies. About Ventura BioMed Investors Ventura BioMed Investors invest in early-stage life science companies developing pioneering technologies and innovative therapies. As serial entrepreneurs with many years of experience, we help shape the long- term development of our portfolio companies and provide them access to our broad investor and business network. Ventura BioMed Investors supports exceptional entrepreneurs with their vision to accelerate medical breakthroughs that solve unmet patient needs. About OKG Capital OKG Capital is a specialist med-tech and life science investor based in the US with operations in London and Geneva. OKG invests in the management and diagnosis of serious chronic diseases affecting individuals and burdening healthcare systems. OKG aims to bridge the gap between cutting edge science and clinical practice, operating at the intersection between patient need and long-term financial return.

Submitted a new drug application (NDA) for troriluzole in Spinocerebellar Ataxia Type 3 (SCA3) to U.S. FDA in 2Q2023, marking the team's fourth NDA in approximately 3 years Released additional data from Kv7 platform, including Phase 1 safety data by dose groups for BHV-7000 that further validates differentiated profile Projected Phase 3 Spinal Muscular Atrophy trial to complete enrollment in 2023 Initiated Phase 1 study of brain penetrant TYK2/JAK1 inhibitor, BHV-8000, and anticipate beginning Phase 2 trial in Parkinson's disease next year Highlighted robust pipeline with multiple INDs planned to be filed within the next year, including pan IgG degrader for multiple immune-mediated diseases in 2023 NEW HAVEN, Conn., May 31, 2023 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) ("Biohaven"), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies for people with debilitating diseases, including ultra-rare disorders, will provide an overview of clinical progress, regulatory updates, and pipeline developments at an in-person R&D Day today, concurrently with the Yale Ventures' Innovation Summit 2023 taking place on May 31-June 1. Members of Biohaven's senior management team and key opinion leaders will meet with investors and research analysts. The clinical progress, regulatory updates, and pipeline developments to include: Troriluzole in SCA: Submitted New Drug Application (NDA) to the U.S. FDA for troriluzole for the treatment of spinocerebellar ataxia type 3 (SCA3), an ultra-rare, genetically-defined, neurodegenerative disease associated with progressive disability, frequent falls, loss of ambulation, speech and swallowing impairment, and premature death that is the most common SCA genotype worldwide. NDA supported by consistent treatment benefits observed in patients with genotype SCA3 in Study BHV4157-206 across multiple outcome measures including the change from baseline f-SARA at Week 48, CGI-I total score at Week 48, and a robust reduction in fall risk over the study period. A rigorous analysis by genotype was possible as patients were randomized by genotype strata at baseline prior to randomization in the pivotal Phase 3 48-week, double-blind, placebo-controlled phase of Study BHV4157-206. SCA3 represented 41% of study participants, consistent with being the most common subtype. SCA3 affects approximately 10,600 people in North America and in the EU and Japan. NDA further supported by a composite scale development (SCACOMS) and analysis of Study BHV4157-206, and confirmatory evidence of efficacy provided by data from the 3-year, long-term open-label (OLE) extension phase of two studies (BHV4157-206 and BHV4157-201) using a Matching Adjusted Indirect Comparison (MAIC) to an external control group. Biohaven has previously received Fast-Track and Orphan drug designation (ODD) from the FDA, and ODD from the European Medicines Agency, for troriluzole in SCA. Kv7 Platform: Highlighted progress and broad potential of Kv7 platform, including ongoing and planned development of BHV-7000 (Kv7.2/3 activator): Phase 1 EEG study with BHV-7000 in 1H2023. Pivotal studies with BHV-7000 in focal epilepsy and bipolar disorder planned to initiate in 2H2023. Burgeoning evidence for therapeutic benefits of targeting Kv7 in diverse, high unmet need indications. Bispecific Platform: Provided updates regarding planned INDs for targeted extracellular protein degradation franchise (including IgG, IgA, and autoantibody-specific degrader programs) and next-generation antibody-drug conjugate (ADC) technologies; IND application for novel IgG degrader, BHV-1300, on track for submission in 2023. TYK2/JAK1 Inhibition in Immune-Mediated Brain Disorders: Began dosing with BHV-8000 (an oral, brain-penetrant, dual TYK2/JAK1 inhibitor) in a ­­­Phase 1 study in normal healthy volunteers. Taldefgrobep Alfa: In Spinal Muscular Atrophy: Enrollment of approximately 225 patients in global Phase 3 trial now anticipated to complete in 2023. In Metabolic Disorders: Planned Phase 2 trial initiation in 2H2023. Vlad Coric M.D., CEO and Chairman of Biohaven, commented, "Today's R&D Day review of our robust pipeline highlights Biohaven's continued dedication to advance novel therapeutics for brain disorders and builds upon our team's successes with the prior approvals of Nurtec® ODT and Zavzpret™ that have changed the treatment paradigm in migraine." "The NDA we submitted for troriluzole for SCA3 represents approximately seven years of effort by the Biohaven team to bring forward a potentially new treatment for this ultra-rare disease. Advancing a new investigational drug for a rare disease that has no current therapy is a multi-year process that is the culmination of not only our own internal efforts but also close coordination with patient advocacy groups including the National Ataxia Foundation (NAF), leading academic researchers and regulatory agencies. Rare brain diseases are particularly challenging to research given relatively small populations of patients to run / participate in clinical trials, the need to rely on real-world data and often a lack of standardized ratings scales or biomarkers. We could not have advanced the SCA program this far without the leadership from the National Ataxia Foundation that has supported basic science research as well as the development of natural history cohorts in SCA that serve as an external control for longitudinal studies. The Biohaven clinical trials in SCA were a first of its kind in this area and utilized a newly developed rating scale (the functional SARA or f-SARA) that was developed in close consultation with the FDA using standard regulatory pathways to elucidate this new scale. We look forward to interactions with the US FDA, EMA and other regulatory agencies across the globe as our submissions advance in the review process," Dr. Coric added. "We are pleased that our decades-long investment in ataxia research and understanding of disease progression has accelerated treatment development for SCA," said Andrew Rosen, Executive Director of the National Ataxia Foundation. "Thank you to all NAF members who participated in these important trials." Bruce Car PhD, Biohaven's CSO, stated, "Given the lack of efficacious therapies for many brain disorders, we must urgently evaluate new mechanisms and approaches to change the treatment paradigm in this therapeutic area. Our R&D Day today demonstrates the commitment that we have given to this effort with exciting new approaches ranging from our submission of a glutamate modulator in SCA to immune modulation using small molecule degraders to ion channels targeting agents for epilepsy and mood disorders, as well as a biologic treatment to enhance muscle growth in SMA. Our scientific and clinical team is poised to file multiple new INDs from our deep pipeline and complete late-stage clinical trials in the next couple of years. It is an exciting time at Biohaven for our passionate employees, patients and investors as we advance these novel investigational drugs in our pipeline." The Research & Development Day presentations will be made available following the conclusion of the program on . About Biohaven Biohaven is a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies for people with debilitating diseases, including rare disorders. Biohaven's experienced management team brings with it a track record of delivering new drug approvals for products for diseases such as migraine, depression, bipolar disorder and schizophrenia. The company is advancing a pipeline of therapies for diseases with little or no treatment options, leveraging its proven drug development capabilities and proprietary platforms, including Kv7 ion channel modulation for epilepsy and neuronal hyperexcitability, glutamate modulation for obsessive-compulsive disorder and spinocerebellar ataxia, myostatin inhibition for neuromuscular diseases, and brain-penetrant TYK2/JAK1 inhibition for immune-mediated brain disorders. Biohaven's portfolio of early- and late-stage product candidates also includes discovery research programs focused on TRPM3 channel activation for neuropathic pain, CD-38 antibody recruiting, bispecific molecules for multiple myeloma, antibody drug conjugates (ADCs), and targeted extracellular protein degrader platform technology (MoDE™) with potential application in neurological disorders, cancer, and autoimmune diseases. For more information, visit . Forward-looking Statements This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the Food and Drug Administration; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; the potential for Biohaven's product candidates to be first in class therapies; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this new release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. MoDEs is a trademark of Biohaven Therapeutics Ltd. Investor Contact: Jennifer Porcelli Vice President, Investor Relations [email protected] +1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] +1 (312) 961-2502 SOURCE Biohaven Ltd.