EAAT2

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.

Biohaven and Vigeo Now Enrolling in GBM AGILE, Registrational Phase 2-3 Adaptive Platform Trial to Evaluate Interventions for Patients With Glioblastoma LARKSPUR, Calif.--(BUSINESS WIRE)-- Global Coalition for Adaptive Research (LARKSPUR, CA), Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN), and Vigeo Therapeutics -- The Global Coalition for Adaptive Research (GCAR) in collaboration with Biohaven and Vigeo Therapeutics, today announced the activation of Biohaven's troriluzole and Vigeo's VT1021 in GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment). GBM AGILE is a revolutionary patient-centered, adaptive platform trial for registration that tests multiple therapies for patients with newly-diagnosed and recurrent glioblastoma (GBM) – the deadliest form of brain cancer. This press release features multimedia. View the full release here: Biohaven's troriluzole and Vigeo's VT1021 are entering the GBM AGILE trial, which initially opened in July 2019 and has screened over 1200 patients to date. Troriluzole and VT1021 will enroll patients with newly-diagnosed and recurrent glioblastoma. Dr. Michael Lim, Chair of the Department of Neurosurgery at Stanford University and Dr. Michael Weller, Director Department of Neurology, University Hospital Zurich, Switzerland will serve as arm Principal Investigators for troriluzole’s evaluation in GBM AGILE. VT1021 will be led by arm Principal Investigators, Dr. Howard Colman, Professor, Huntsman Cancer Institute and Department of Neurosurgery, University of Utah, and Dr. Tom Mikkelsen, Medical Director, Precision Medicine Program & Clinical Trials Office, Henry Ford Health. “GBM AGILE is a ground-breaking trial that enables us to simultaneously and dynamically study the effects of multiple new drug candidates in an optimized learning environment. The trial’s nimble model allows us to more efficiently and rapidly identify effective therapies for GBM patients,” said Dr. Michael Lim, who also serves as a member of the GBM AGILE Arm Identification and Selection Committee. “We are excited to include troriluzole and VT1021 in GBM AGILE. These investigational drugs have the potential to support improved outcomes for GBM patients, who desperately need more effective treatment options.” GBM AGILE is an international, innovative platform trial designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization and a seamless phase 2/3 design. The trial, conceived by over 130 key opinion leaders, is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical partners to be evaluated simultaneously. With its innovative design and efficient operational infrastructure, data from GBM AGILE can be used as the foundation for a new drug application (NDA) and biologics license application (BLA) submissions and registrations to the FDA and other health authorities. The new interventions are opening first at Henry Ford Health Cancer in Detroit under Henry Ford site Principal Investigator Dr. Tom Mikkelsen and will subsequently open at more than 40 trial sites across the United States with additional global sites to follow. “Glioblastoma is a devasting disease with few effective treatment options and no cure. Currently the average survival rate is estimated to be only eight months,” noted Dr. Mikkelsen. “We are enthusiastic to be the first site to activate troriluzole and VT1021 in the GBM AGILE study. We are committed to finding our patients the best possible treatments.” Biohaven’s troriluzole is a novel, orally administered small molecule that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. Troriluzole is thought to restore glutamate homeostasis by enhancing glutamate cycling, decreasing presynaptic glutamate release, and augmenting the expression and function of excitatory amino acid transporters (i.e., EAAT2) located on glial cells that play a key role in clearing excess glutamate from the synapse. Troriluzole was selected for inclusion in GBM AGILE, based on compelling evidence showing deregulation of glutamate in glioblastoma. The therapeutic potential of troriluzole in glioblastoma and other oncology indications is supported by several recent clinical and translational research studies conducted with troriluzole and its active moiety. “The initiation of this pivotal trial of troriluzole for glioblastoma is an exciting milestone,” commented Dr. Vlad Coric, Chairman and Chief Executive Officer of Biohaven. “We are extremely proud to be joining the highly innovative GBM AGILE trial. We look forward to collaborating with the Principal Investigators, Drs. Lim and Weller, the team at GCAR, and the GBM AGILE trial sites in order to rapidly advance the development of troriluzole in combination with standard of care therapies as a novel treatment for people suffering from glioblastoma, which is amongst the most recalcitrant and lethal of all cancers.” Vigeo’s VT1021, is a first-in-class dual modulating compound that blocks the CD47 immune checkpoint and activates the apoptotic and macrophage reprogramming activity of CD36. The result of the dual modulating activity is the induction of apoptosis in tumor and endothelial cells, as well as an increase in both CTL:Treg and M1:M2 macrophage ratio. The biological/therapeutic activity of VT1021 is mediated by the stimulation of thrombospondin-1 (Tsp-1). Through these dual-modulating effects VT1021 reprograms the tumor microenvironment from one that is immune suppressive, or “cold,” to immune enhanced (or sensitized), or “hot,” that are more susceptible to attack from the immune system. With its novel mechanism of action and clinical data from a Phase 2 expansion study in recurrent GBM patients, VT1021 is undergoing further studies to determine its effect in treating the disease, given that CD36 and CD47 are found to be highly expressed in tumor cells compared to normal brain tissue. Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors. “VT1021 has seen remarkable patient response, with a great safety profile, in our earlier clinical trials. We are excited that VT1021 is included as part of this global, multi-site effort to treat such a devastating disease,” said Jim Mahoney, Chief Executive Officer, Vigeo Therapeutics. “The opportunity to work with these distinguished Principal Investigators and to test our drug in both newly diagnosed and recurrent GBM patient populations are key factors in our decision to join AGILE.” About Global Coalition for Adaptive Research (GCAR) The Global Coalition for Adaptive Research (GCAR) is a 501(c)(3) nonprofit organization uniting physicians, clinical researchers, advocacy and philanthropic organizations, biopharma, health authorities, and other key stakeholders in healthcare to expedite the discovery and development of treatments for patients with rare and deadly diseases by serving as Sponsor of innovative and complex trials including master protocols and platform trials. GCAR is the sponsor of GBM AGILE, an adaptive platform trial for patients with GBM – the most common and deadliest of malignant primary brain tumors. Key strategic partners for the GBM AGILE trial effort include the National Brain Tumor Society, National Foundation for Cancer Research, Asian Fund for Cancer Research, and Cure Brain Cancer Foundation, four nonprofit organizations that are working together to provide philanthropic support as well as assistance in communicating with patients and families and inviting all others to join in supporting this innovating approach to brain tumor treatment development. To learn more about GCAR, visit gcaresearch.org About Biohaven Biohaven is a global commercial-stage biopharmaceutical company with a portfolio of innovative, best-in-class therapies to improve the lives of patients with debilitating neurological and neuropsychiatric diseases, including rare disorders. Biohaven's Neuroinnovation™ portfolio includes FDA-approved NURTEC® ODT (rimegepant) for the acute and preventive treatment of migraine (EMA-approved as VYDURA® for the acute treatment of migraine with or without aura, and prophylaxis of episodic migraine in adults who have at least four migraine attacks per month) and a broad pipeline of late-stage product candidates across five distinct mechanistic platforms: CGRP receptor antagonism for the acute and preventive treatment of migraine and other CGRP-mediated diseases; glutamate modulation for obsessive-compulsive disorder and spinocerebellar ataxia; myeloperoxidase (MPO) inhibition for amyotrophic lateral sclerosis; Kv7 ion channel activators for focal epilepsy and neuronal hyperexcitability, and myostatin inhibition for neuromuscular diseases. More information about Biohaven is available at . NURTEC, NURTEC ODT and VYDURA are registered trademarks of Biohaven Pharmaceutical Ireland DAC. Neuroinnovation and NOJECTION are trademarks of Biohaven Pharmaceutical Holding Company Ltd. About Vigeo Therapeutics Based in Cambridge, MA, Vigeo Therapeutics is a clinical-stage immuno-oncology company pioneering novel cancer therapies. The company is building a first-in-class drug development pipeline being led by VT1021, its dual-modulating compound that blocks the CD47 immune checkpoint and reprograms CD36 mediated activities. Single-agent VT1021 has been investigated in a Phase 1/2 clinical trial in patients with glioblastoma, pancreatic cancer and other solid tumors, and is currently progressing to late-stage clinical development. For more information visit vigeotherapeutics.com or follow us on LinkedIn and Twitter.