KCNQ2-related epileptic encephalopathy

Reported expanded safety results from BHV-7000 Phase 1 multiple ascending dose studies, including the once-daily extended-release formulation being evaluated in ongoing Phase 2 and 3 clinical studies, demonstrating excellent tolerability at all doses evaluated without central nervous system (CNS) adverse effects typically associated with other anti-seizure medications (ASMs), such as somnolence and cognitive/mood disturbances. Qualitative assessment of online social media platforms and forums provided a unique perspective of the unmet needs that people with epilepsy are vocalizing outside of the clinical setting, including the negative impact that ASM associated adverse events have on their quality of life. Additional nonclinical data presentations included characterization of BHV-7000 using optical electrophysiology as well as beneficial effects of BHV-7000 on pathogenic developmental epileptic encephalopathy-associated KCNQ2 variants NEW HAVEN, Conn., Dec. 6, 2024 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) announced today that it is presenting expanded safety data from BHV-7000 multiple-dose studies at the American Epilepsy Society (AES) 2024 Annual Meeting, taking place December 6-10, 2024, in Los Angeles, California. Additional poster presentations highlight BHV-7000 nonclinical data and unmet needs that persist for people living with epilepsy, including the negative impact of adverse effects associated with current ASMs. Jason Lerner, M.D., Medical Director and Epilepsy Clinical Lead at Biohaven, commented, "We are very excited to share the expanded safety results with the once-daily extended-release formulation being evaluated in ongoing Phase 2 and 3 clinical studies. We are encouraged to see BHV-7000 continue to demonstrate favorable safety and tolerability without dose-limiting toxicities or CNS adverse events commonly associated with other ASMs, such as somnolence. These results paired with previously demonstrated CNS target engagement in our Phase 1 EEG study and a nonclinical profile showing BHV-7000 is a selective Kv7.2/7.3 activator that dials out GABAA activation provide compelling rationale for why BHV-7000 offers a differentiated profile from other treatments currently available or in development." Dr. Lerner continued, "The evidence to date with BHV-7000 represents a potential paradigm shift in the treatment of epilepsy as many patients continue to be burdened by adverse events and do not achieve adequate seizure control with existing medications. As we continue advancing 5 ongoing pivotal Phase 2/3 trials with BHV-7000, including studies in focal epilepsy and idiopathic generalized epilepsy, Biohaven remains committed to developing novel, efficacious, and well-tolerated therapies for people living with epilepsy." In addition to 4 poster presentations at AES, Biohaven will be presenting 1 poster at the Partners Against Mortality (PAME) 2024 Conference in Los Angeles on Thursday, December 5th highlighting the patient-centric Phase 2/3 BHV-7000 study in idiopathic generalized epilepsy. American Epilepsy Society 2024 Annual Meeting Presentation Highlights: Poster 1.486: Phase 1 Multiple Ascending Dose Studies Demonstrate Safety and Tolerability of BHV-7000, a Novel Kv7 Potassium Channel Activator BHV-7000 is a selective Kv7.2/7.3 activator that was safe and well-tolerated at dose levels up to 120 mg daily for 15 days with no dose-limiting toxicities; 120 mg exceeds the doses being evaluated in ongoing Phase 2 and 3 clinical studies of up to 75 mg daily in focal epilepsy, idiopathic generalized epilepsy, bipolar mania, and major depressive disorder. There were low rates of CNS-related adverse events and no somnolence or cognitive/mood disturbances reported. Most AEs were mild and resolved spontaneously; and there were no serious adverse events or severe adverse events. New data with the BHV-7000 once-daily extended-release formulation demonstrated excellent tolerability. Poster 1.512: A Qualitative Assessment of the Epilepsy Patient Experience Through Social Media and Web-based Forums While seizure freedom remains the primary goal of epilepsy treatment, additional unmet needs of people living with epilepsy were assessed by investigating the patient experience directly through social media and online platforms where patients discuss epilepsy outside of a clinical setting. Patient perspectives and unmet needs were identified across 3 areas: antiseizure medication-associated adverse events, mental health, and stigma. The 4 most frequently discussed ASM associated adverse events included: sleepiness, insomnia, mood changes, and cognitive effects; comments from patients captured the negative impact these adverse events have on their quality of life. People with epilepsy also reported a range of challenges with mental health, and the stigma associated with epilepsy pressured patients to remain silent about their struggles. Poster 1.534: Pharmacological Characterization of BHV-7000, a Novel and Selective Activator of Kv7 Channels, Using All-optical Electrophysiology The acute and chronic pharmacological effects of BHV-7000 on the excitability of primary rat cortical neurons were evaluated using the all-optical electrophysiology platform Optopatch (Quiver Biosciences), which measures neuronal activity with single-cell and single action potential resolution. Concentration-dependent dampening of neuronal excitability was observed, consistent with previous data with BHV-7000 in other experimental paradigms. Overall, BHV-7000 demonstrated potent in vitro effects to reduce neuronal activity impacting a diverse set of Optopatch functional features across the stimulus protocol, including spike timing and spike shape features in different stimulus periods, which indicates lower neuronal excitability near action potential threshold. Poster 1.431: BHV-7000 Is a Potent M-current Activator with Efficacy on Multiple Epilepsy-associated KCNQ2 Variants This in vitro study assessed the effects of BHV-7000 on 50 loss-of-function KCNQ2 variants. BHV-7000 rescued current density in all tested pathogenic KCNQ2 variants. Current density was restored to wild-type (WT) levels with BHV-7000 for most variants. These findings support the potential therapeutic value of BHV-7000 in KCNQ2-related epilepsy associated with a wide range of pathogenic KCNQ2 variants. Partners Against Mortality (PAME) 2024 Conference Highlights: PAME Poster 41: A Modern Design for a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BHV-7000 in Idiopathic Generalized Epilepsy (IGE) With Generalized Tonic–Clonic Seizures (SHINE) Epilepsy studies have traditionally been double-blind, placebo-controlled, change-from-baseline endpoint studies; in these studies, subjects receiving placebo for a fixed treatment duration remain at risk for continued seizures, injury, and Sudden Unexpected Death in Epilepsy (SUDEP). SHINE (NCT06425159) is an innovative, ongoing registrational study in IGE with the selective Kv7 activator BHV-7000 with an efficient, patient-centric design utilizing an FDA-endorsed time to event endpoint that decreases time on placebo, potentially reducing the risk of exposure to additional seizures, injury, and SUDEP. Full posters will be available on the Posters and Presentations page at: . About BHV-7000 BHV-7000 is a novel and selective activator of Kv7.2/Kv7.3, a key ion channel involved in neuronal signaling and in regulating the hyperexcitable state, that is being developed for the treatment of epilepsy and mood disorders. BHV-7000 was rationally developed as a potent activator of heteromeric Kv7.2/7.3 potassium channels, the molecular substrate that underlies the M-current (IKM). BHV-7000 is highly differentiated from ezogabine (known as retigabine in Europe), a Kv7 activator that was previously approved for adjunctive treatment of partial-onset seizures in adults. In comparison with ezogabine, BHV-7000 belongs to a significantly different structural class and differentiates from ezogabine in key properties, including pharmacology, plasma stability and stability to photooxidation. In addition, BHV-7000 does not exhibit GABAA receptor positive allosteric molecular activity as seen with ezogabine and similar compounds, which may contribute to the poor tolerability of ezogabine. This lack of GABAA receptor activity may translate to improved tolerability by reducing the typical dose dependent side effect profile often seen in patients receiving ezogabine and other anti-seizure medications. 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 nonclinical 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 (spinocerebellar ataxia); 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 . 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 FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; 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 Relations [email protected] +1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] +1 (312) 961-2502 SOURCE Biohaven Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Biohaven's first-in-class Molecular Degrader of Extracellular Proteins (MoDE™) technology targeting IgG removal, BHV-1300, was selected for an oral presentation at AAN highlighting its novel mechanism of action and the latest preclinical data demonstrating rapid, robust, and selective target removal Biohaven announces it will present safety and IgG lowering data from its ongoing single ascending dose (SAD) study of BHV-1300 at the company's annual R&D day at the Yale Innovation Summit in New Haven, Connecticut on May 29, 2024 Safety, tolerability, and target engagement data showing the differentiated profile of BHV-7000 as a potential best-in-class Kv7 activator will be presented as both oral and poster presentations; the Phase 2/3 focal epilepsy program is now enrolling patients AAN Abstract of Distinction awarded to BHV-2100, which demonstrated potent reversal of pain in preclinical models and favorable initial safety and pharmacokinetic data in Phase 1 studies, highlighting the potential for TRPM3 antagonism as a novel nonopioid target to treat pain and migraine Oral and poster presentations of troriluzole as a novel glutamate modulating agent with favorable pharmacokinetics, safety, and outcomes data in the potential treatment of neurologic and neuropsychiatric disorders Biohaven announces the Data Monitoring Committee for its Phase 3 trial in obsessive-compulsive disorder convened in the second quarter to review the interim analysis and informed the Company that the study may continue Additional efficacy and safety data regarding troriluzole in spinocerebellar ataxia will also be presented in both oral and poster format Poster presentation of RESILIENT Phase 3 study design with taldefgrobep alfa in spinal muscular atrophy; study completed enrollment and topline results anticipated in the second half of 2024 Biohaven announces the FDA granted "rare pediatric disease" designation for taldefgrobep alfa thereby providing the potential to receive a priority review voucher (PRV) if ultimately approved for the indication of spinal muscular atrophy Other presentations and posters include development of the PARCOMS, a new outcome measure for Parkinson's disease clinical trials, application of machine learning in video assessment of gait, and data demonstrating a reduced risk for Parkinson's disease in patients taking anti-inflammatory agents Three oral presentations and 6 poster presentations from the Biohaven Clinical and Health Outcomes group describe the development and validation of novel scales and natural history studies in support of troriluzole and BHV-8000 development programs, the impact of immune-modulating therapy in Parkinson's disease, the burden of illness in focal epilepsy and KCNQ2-DEE (BHV-7000), and the application of AI machine learning technology to quantify patient mobility with troriluzole in spinocerebellar ataxia DENVER, CO and NEW HAVEN, Conn., April 13, 2024 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) announced today that 20 abstracts, including 8 oral presentations and 12 posters, will be featured this weekend starting April 13th at the 2024 American Academy of Neurology (AAN) Annual Meeting, taking place in Denver, Colorado. The presentations highlight Biohaven's leadership in neuroscience and extensive development programs evaluating novel therapies to treat neurological diseases, with abstracts covering programs that include Kv7 ion channel modulation, molecular degraders of extracellular protein (MoDEs), TRPM3 antagonism, TYK2/JAK1 inhibition, glutamate modulation, and myostatin inhibition. Irfan Qureshi, M.D., Chief Medical Officer of Biohaven, commented, "The research being presented at the AAN Annual Meeting emphasizes Biohaven's commitment to developing new therapeutic options across a range of neurological diseases. By targeting novel mechanisms of action, differentiated from currently available treatments and other therapies in development, and following innovative science, Biohaven continues to strive for better treatments for people living with neurological disorders. We are particularly honored that the AAN Science Committee selected our BHV-2100 (TRPM3) abstract as an AAN Abstract of Distinction, recognizing it as the top abstract in the pain category. Following the completion of Phase 1 studies in the first half of 2024, we look forward to initiating a Phase 2 study with BHV-2100 in migraine in the second half of the year and are excited by the potential for this novel nonopioid approach to treat pain." Vlad Coric M.D., Chief Executive Officer and Chairman of Biohaven, added, "Our leadership in neuroscience research is on full display at the AAN Annual Meeting with the breadth and depth of clinical, epidemiological, and preclinical programs highlighted in our scientific presentations. Central nervous system (CNS) disorders continue to represent one of the highest unmet medical needs facing our society and we must act urgently to bring better treatments to patients and improve clinical outcomes. We believe that the next generation of therapies for CNS disorders will include MoDEs for autoimmune disorders, ion channel modulation for epilepsy, migraine and other pain disorders, immune modulation for neurodegenerative disorders including Parkinson's and Alzheimer's diseases, myostatin targeting drugs for neuromuscular disorders and glutamate modulating agents for neuropsychiatric disorders. I am so proud of the team at Biohaven who are working tirelessly to alleviate the burden of these devastating disorders." The complete list of Biohaven's accepted abstract titles is below. Full abstracts can be viewed online at . Oral Presentations: Novel Bispecific Degrader BHV-1300 Achieves Rapid, Robust, and Selective IgG Reduction in Preclinical Models Including Nonhuman Primates BHV-2100, a First-in-class TRPM3 Antagonist for the Treatment of Pain (AAN Abstract of Distinction) Characterization of BHV-7000: A Novel Kv7.2/7.3 Activator for the Treatment of Seizures Association of Anti-inflammatory Therapy Use with the Incidence of Parkinson's Disease: A Person-Time Analysis Among Patients with Autoimmune Diseases Re-weighting MDS-UPDRS Motor Items for Optimal Sensitivity to Parkinson's Disease Progression in Untreated Patients Using Parkinson's Progression Markers Initiative Data Population Pharmacokinetic Modeling of Riluzole After Administration of a Next Generation Prodrug Troriluzole Next Generation Prodrug Troriluzole: Increased Bioavailability of Riluzole with No Food Effect in Healthy Subjects Matching-adjusted Indirect Comparison of Troriluzole Versus Untreated Natural History Cohort in Spinocerebellar Ataxia Poster Presentations: Phase 1 Study Evaluating the Safety and Tolerability of BHV-7000, a Novel, Selective Kv7.2/7.3 Potassium Channel Activator, in Healthy Adults Novel, Selective Kv7.2/7.3 Potassium Channel Activator, BHV-7000, Demonstrates Dose-dependent Pharmacodynamic Effects on EEG Parameters in Healthy Adults Determinants of Health-related Quality of Life of Patients with Focal Epilepsy: A Systematic Literature Review Functional Impairments in Patients with KCNQ2-DEE: Associations Among Key Clinical Features The Phase 3 RESILIENT Study: Taldefgrobep Alfa in Spinal Muscular Atrophy Re-weighting MDS-UPDRS Part II Items for Optimal Sensitivity to Parkinson's Disease Progression Using Parkinson's Progression Markers Initiative Natural History Data Safety, Tolerability, and Pharmacokinetics of Single and Multiple Rising Doses of a Next Generation Prodrug Troriluzole in Healthy Subjects Troriluzole Exhibits Favorable Hepatic Safety Profile Across a Diverse Range of Disorders No Clinically Relevant Effects of Hepatic Impairment on the Pharmacokinetics of a Next Generation Prodrug Troriluzole Automated Video-based Characterization of Movement Quality in a Phase III Clinical Trial of Troriluzole in Subjects with Spinocerebellar Ataxia Psychometric Validation of the Modified-functional Scale for the Assessment and Rating of Ataxia Development of a Novel Composite Measure (SCACOMS) to Assess Disease Progression in Spinocerebellar Ataxia Posters and presentations will be available on the Posters and Presentations page after the conference at . 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; and antibody recruiting, bispecific molecules and antibody drug conjugates for cancer. 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 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 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 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 Relations [email protected] 201-248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] 312-961-2502 MoDE is a trademark of Biohaven Therapeutics Ltd. Biohaven AAN 2024 Oral & Poster Presentations: Functional Impairments in Patients with KCNQ2-DEE: Associations Among Key Clinical Features Sunday 4/14/24: 8:00-9:00 P1- Poster Session 1 Colorado Convention Center – Exhibit Hall B-E The Phase 3 RESILIENT Study: Taldefgrobep Alfa in Spinal Muscular Atrophy Sunday 4/14/24: 11:45 - 12:45 P2 - Poster Session 2 Colorado Convention Center - Exhibit Hall Association of Anti-inflammatory Therapy Use with the Incidence of Parkinson's Disease: A Person-Time Analysis Among Patients with Autoimmune Diseases Sunday 4/14/24: 1:00-3:00 (1:24-1:36) S2 – Movement Disorders: Epidemiology and Clinical Aspects Colorado Convention Center- Mile High 4CD Re-weighting MDS-UPDRS Motor Items for Optimal Sensitivity to Parkinson's Disease Progression in Untreated Patients Using Parkinson's Progression Markers Initiative Data Sunday 4/14/24: 1:00-3:00 (1:36-1:48) S2 – Movement Disorders: Epidemiology and Clinical Aspects Colorado Convention Center- Mile High 4CD Population Pharmacokinetic Modeling of Riluzole After Administration of a Next Generation Prodrug Troriluzole Sunday 4/14/24: 1:00 - 3:00 (2:12-2:24) S3 - General Neurology 1 Colorado Convention Center - Four Seasons 2/3 Next Generation Prodrug Troriluzole: Increased Bioavailability of Riluzole with No Food Effect in Healthy Subjects Sunday 4/14/24: 3:30 - 5:30 (4:30-4:42) S5 - ALS and CMT: New Therapeutic Approaches Colorado Convention Center - Four Seasons 1 BHV-2100, A First-In-Class TRPM3 Antagonist for the Treatment of Pain Monday 4/15/24: 11:15-12:15 (11:27-11:39) S13 – Pain Research Colorado Convention Center 605 Troriluzole Exhibits Favorable Hepatic Safety Profile Across a Diverse Range of Disorders Monday 4/15/24: 11:45 - 12:45 P4 - Poster Session 4 Colorado Convention Center - Exhibit Hall Safety, Tolerability, and Pharmacokinetics of Single and Multiple Rising Doses of a Next Generation Prodrug Troriluzole in Healthy Subjects Monday 4/15/24: 11:45 - 12:45 P4 - Poster Session 4 Colorado Convention Center - Exhibit Hall No Clinically Relevant Effects of Hepatic Impairment on the Pharmacokinetics of a Next Generation Prodrug Troriluzole Monday 4/15/24: 11:45 - 12:45 P4 - Poster Session Colorado Convention Center - Exhibit Hall Automated Video-based Characterization of Movement Quality in a Phase III Clinical Trial of Troriluzole in Subjects with Spinocerebellar Ataxia Tuesday 4/16/24: 8:00-9:00 P6- Poster Session 6 Colorado Convention Center – Exhibit Hall Psychometric Validation of the Modified-functional Scale for the Assessment and Rating of Ataxias Tuesday 4/16/24: 11:45-12:45 P7 – Poster Session 7 Colorado Convention Center – Exhibit Hall Development of a Novel Composite Measure (SCACOMS) to Assess Disease Progression in Spinocerebellar Ataxia Tuesday 4/16/24: 11:45-12:45 P7 - Poster Session 7 Colorado Convention Center – Exhibit Hall Phase 1 Study Evaluating the Safety and Tolerability of BHV-7000, a Novel, Selective Kv7.2/7.3 Potassium Channel Activator, in Healthy Adults Tuesday 4/16/24: 5:30 - 6:30 P8 - Poster Session 8 Colorado Convention Center - Exhibit Hall Novel, Selective Kv7.2/7.3 Potassium Channel Activator, BHV-7000, Demonstrates Dose-dependent Pharmacodynamic Effects on EEG Parameters in Healthy Adults Tuesday 4/16/24: 5:30 - 6:30 P8 - Poster Session 8 Colorado Convention Center - Exhibit Hall Determinants of Health-related Quality of Life of Patients with Focal Epilepsy: A Systematic Literature Review Wednesday 4/17/24: 8:00-9:00 P9- Poster Session 9 Colorado Convention Center – Exhibit Hall Characterization of BHV-7000: A Novel Kv7/2/7.3 Activator for the Treatment of Seizures Wednesday 4/17/24: 1:00-3:00 (2:00-2:12) S29- Epilepsy Diagnostics and Therapeutics Colorado Convention Center 605 Matching-adjusted Indirect Comparison of Troriluzole Versus Untreated Natural History Cohort in Spinocerebellar Ataxia Wednesday 4/17/24: 3:30-5:30 (5:06-5:18) S35 – Movement Disorders: Hyperkinetic Movement Disorders Colorado Convention Center – Four Seasons 4 Re-weighting MDS-UPDRS Part II Items for Optimal Sensitivity to Parkinson's Disease Progression Using Parkinson's Progression Markers Initiative Natural History Data Wednesday 4/17/24: 5:30-6:30 P11 – Poster Session 11 Colorado Convention Center – Exhibit Hall Novel Bispecific Degrader BHV-1300 Achieves Rapid, Robust, and Selective IgG Reduction in Preclinical Models Including Nonhuman Primates Thursday 4/18/24: 1:00 - 3:00 (1:36-1:48) S43 - General Neurology 2 Colorado Convention Center - 108/110/112 SOURCE Biohaven Ltd.

Biohaven reported full results from the BHV-7000 Phase 1 study examining doses up to 120 mg daily, demonstrating BHV-7000 was well-tolerated at all doses studied without the typical central nervous system (CNS) adverse effects associated with other anti-seizure medications (ASMs), such as somnolence and cognitive/mood disturbances. In a Phase 1 electroencephalogram (EEG) biomarker study, BHV-7000 demonstrated dose-dependent target engagement in the brain as measured by changes in EEG spectral power across all brain regions. Additional poster presentations at the American Epilepsy Society Annual Meeting will include: BHV-7000 preclinical data, health-related quality of life in patients with focal epilepsy, and functional impairments in patients with KCNQ2‐associated developmental and epileptic encephalopathy (KCNQ2-DEE). NEW HAVEN, Conn., Dec. 1, 2023 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) announced today that it is presenting expanded EEG and safety data for BHV-7000 at the 2023 American Epilepsy Society (AES) Annual Meeting, taking place December 1-5, 2023, in Orlando, Florida. The presentations include results from the BHV-7000 Phase 1 EEG biomarker study and additional BHV-7000 safety and tolerability data from Phase 1 single ascending dose (SAD) / multiple ascending dose (MAD) studies. Additional posters showcase BHV-7000's preclinical data, findings from a systematic literature review on health-related quality of life (HRQoL) in patients with focal epilepsy, and results from a cross-sectional survey assessing functional impairments in patients with KCNQ2-DEE. Jason Lerner, M.D., Medical Director and Epilepsy Clinical Lead at Biohaven, commented "Selective Kv7 activators are one of the most exciting new drug targets for the treatment of epilepsy, and BHV-7000 has shown a favorable and differentiated profile in preliminary Phase 1 studies to date. We are pleased to see favorable safety and tolerability with BHV-7000 dosed up to 120 mg daily for 15 days, without the CNS adverse effects typically associated with other ASMs, such as somnolence. Together with the preclinical data showing BHV-7000 is a selective Kv7.2/7.3 channel opener lacking GABAA activation and the results from our Phase 1 EEG study confirming target engagement, we are excited to advance BHV-7000 into late-stage development in epilepsy patients." Dr. Lerner added, "The robust BHV-7000 data presentations at the AES meeting underscore Biohaven's progress and commitment to developing novel, efficacious and well-tolerated therapies for people living with epilepsy." In addition, both the systematic literature review and parental survey illustrated the importance of Health-Related Quality of Life issues among patients with focal epilepsy and developmental manifestations of KCNQ2-DEE that are relevant to parents, such as communication, eating abilities, and motor impairments. Presentation Highlights: Poster 2.510: Novel, Selective Kv7.2/7.3 Potassium Channel Activator, BHV-7000, Demonstrates Dose-Dependent Pharmacodynamic Effects on EEG Parameters in Healthy Adults In this Phase 1 study, pharmacodynamic activity of BHV-7000 in the brain of healthy adults was demonstrated by dose-dependent increases in EEG spectral power. Unlike prior reports where EEG effects of a Kv7.2/7.3 activator showed the greatest power increase in the delta frequency band (Biondi et al. 2022), the highest spectral power increases with BHV-7000 were seen in alpha, beta, and gamma frequency bands. While changes in spectral power were observed across all frequency bands with BHV-7000, the minimal impact on slower frequencies (i.e., delta) is consistent with the low incidence of CNS adverse events, in particular somnolence, seen in the BHV-7000 Phase 1 SAD/MAD studies. EEG delta activity is associated with somnolence, an undesirable CNS adverse event often seen with other ASMs. Poster 3.265: A First in Human Phase 1 Study Evaluating the Safety and Tolerability of BHV-7000, a Novel, Selective Kv7.2/7.3 Potassium Channel Activator, in Healthy Adults BHV-7000 was safe and well-tolerated at single doses up to 100 mg and multiple doses up to 120 mg daily for 15 days No serious adverse events or severe treatment emergent adverse events were reported Adverse events typically associated with other ASMs, such as somnolence and cognitive/mood disturbances, were not reported Poster 2.249: Characterization of BHV-7000: A Novel Kv7.2/7.3 Activator for the Treatment of Seizures BHV-7000 is a potent activator of Kv7.2/7.3 channels, impacting both deactivation kinetics and voltage dependence of activation BHV-7000 requires the Kv7.2 W236 residue for channel activity No significant activation of the GABAA receptor with BHV-7000 BHV-7000 is potent in the maximal electroshock seizure (MES) test without impact on neurobehavior or motor (rotorod) behavior Poster 1.487: Determinants of Health-Related Quality of Life of Patients with Focal Epilepsy: A Systematic Literature Review This systematic literature review identified multiple factors associated with lower HRQoL in patients with focal epilepsy Depression and anxiety were among the most significant and frequent determinants of HRQoL change Other relevant and frequent determinants of HRQoL change included cognition, ASM adverse events, seizure freedom, and employment A comprehensive understanding of the modifiable determinants of HRQoL is relevant to patient health and well-being and can inform clinical practice and observational/interventional studies Poster 2.451: Functional Impairments in Patients with KCNQ2-DEE: Associations Among Key Clinical Features Data obtained from a cross-sectional survey (2018-2020) of parents of children aged ≥2 years with KCNQ2-DEE was analyzed Among individuals with KCNQ2-DEE, there is a hierarchy of impairments wherein communication is the most sensitive domain and is often affected in isolation from others Gross and fine motor skill impairments tend to be correlated Hand use impairment is closely correlated with multiple other functional impairments Full posters will be available on the Posters and Presentations page at: . Reference Biondi A, et al. Sci Rep. 2022 Feb 4;12(1):1919. About BHV-7000 BHV-7000, the lead asset from Biohaven's Kv7 platform, is a novel and selective activator of Kv7.2/Kv7.3, a key ion channel involved in neuronal signaling and in regulating the hyperexcitable state, that Biohaven is developing for the treatment of epilepsy and mood disorders. BHV-7000 was rationally developed as a potent activator of heteromeric Kv7.2/7.3 potassium channels, the molecular substrate that underlies the M-current (IKM). BHV-7000 is highly differentiated from ezogabine (known as retigabine in Europe), a Kv7 activator that was previously approved for adjunctive treatment of partial-onset seizures in adults. In comparison with ezogabine, BHV-7000 belongs to a significantly different structural class and differentiates from ezogabine in key properties, including pharmacology, plasma stability and stability to photooxidation. In addition, BHV-7000 does not exhibit GABAA receptor positive allosteric molecular activity as seen with ezogabine and similar compounds, which may contribute to the poor tolerability of ezogabine. This lack of GABAA receptor activity potentially gives BHV-7000 a wide therapeutic window which, based on dose-dependent clinical responses seen in other ASM clinical trials, should translate to improved efficacy without the typical dose dependent side effect profile often seen in patients receiving ezogabine and other anti-seizure medications. About Biohaven Biohaven is a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases. 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 and schizophrenia. The company is advancing a pipeline of therapies for diseases, many of which have limited 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 metabolic disorders, and brain-penetrant TYK2/JAK1 inhibition for neuroinflammatory 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 degradation platform technology (MoDE™) with potential application in neurological disorders, cancer, and autoimmune diseases. 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 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 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 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. MoDEs is a trademark of Biohaven Therapeutics Ltd. Investor Contact: Jennifer Porcelli Vice President, Investor Relations [email protected] 201-248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] 312-961-2502 SOURCE Biohaven Ltd.