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..

Biohaven报告了BHV-7000 1期研究的完整结果，该研究检查每日高达120 mg的剂量，证明BHV-7000在所有研究剂量下均具有良好的耐受性，没有与其他抗癫痫药物相关的典型中枢神经系统（CNS）不良反应（ASMs），如嗜睡和认知/情绪障碍。。

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.

在第一阶段脑电图（EEG）生物标志物研究中，BHV-7000证实了大脑中剂量依赖性的靶标参与，如通过所有大脑区域的EEG光谱功率的变化所测量的。

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)..

在美国癫痫学会年会上的其他海报展示将包括：BHV-7000临床前数据，局灶性癫痫患者的健康相关生活质量以及KCNQ2相关发育性和癫痫性脑病（KCNQ2-DEE）患者的功能障碍。。

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.

康涅狄格州纽黑文市，2023年12月1日/PRNewswire/-Biohaven Ltd.（纽约证券交易所：BHVN）今天宣布，它将在2023年美国癫痫学会（AES）年度会议上为BHV-7000提供扩展的EEG和安全性数据，于2023年12月1日至5日在佛罗里达州奥兰多举行。演讲内容包括BHV-7000 1期EEG生物标志物研究的结果以及1期单次递增剂量（SAD）/多次递增剂量（MAD）研究的其他BHV-7000安全性和耐受性数据。

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..

其他海报展示BHV-7000的临床前数据，局灶性癫痫患者健康相关生活质量（HRQoL）系统文献综述的结果，以及评估KCNQ2-DEE患者功能障碍的横断面调查结果。。

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.

Biohaven的医学总监兼癫痫临床负责人Jason Lerner评论说：“选择性Kv7激活剂是治疗癫痫最令人兴奋的新药靶点之一，BHV-7000在初步1期研究中显示出有利和不同的特征。日期。我们很高兴看到BHV-7000的安全性和耐受性良好，每日剂量高达120 mg，持续15天，没有通常与其他ASM相关的CNS不良反应，如嗜睡。

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.'.

结合临床前数据显示BHV-7000是一种缺乏GABAA激活的选择性Kv7.2/7.3通道开放剂，我们的1期EEG研究结果证实了目标参与，我们很高兴将BHV-7000推进癫痫患者的晚期发育。''。

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.'

Lerner博士补充说，“AES会议上强大的BHV-7000数据演示强调了Biohaven的进步，并致力于为癫痫患者开发新颖，有效且耐受性良好的疗法。”

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..

此外，系统的文献回顾和家长调查都说明了局灶性癫痫患者的健康相关生活质量问题的重要性，以及与家长相关的KCNQ2-DEE的发育表现，如沟通、饮食能力和运动障碍。。

Presentation Highlights:

演示文稿亮点：

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

海报2.510：新型选择性Kv7.2/7.3钾通道激活剂BHV-7000显示健康成人脑电图参数的剂量依赖性药效学效应

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.

在这项1期研究中，BHV-7000在健康成人大脑中的药效学活性通过EEG光谱功率的剂量依赖性增加得到证实。

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.

与之前报道的Kv7.2/7.3激活剂的EEG效应在δ频带中显示出最大的功率增加不同（Biondi等，2022），BHV-7000的最高光谱功率增加见于α，β和伽玛频段。

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.

虽然BHV-7000在所有频段都观察到了频谱功率的变化，但对较慢频率（即delta）的最小影响与BHV-7000第1阶段SAD/MAD研究中发现的中枢神经系统不良事件，特别是嗜睡的低发生率是一致的。

EEG delta activity is associated with somnolence, an undesirable CNS adverse event often seen with other ASMs.

EEG delta活动与嗜睡有关，嗜睡是其他ASM常见的不良CNS不良事件。

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

海报3.265：评估BHV-7000（一种新型，选择性Kv7.2/7.3钾通道激活剂）在健康成人中的安全性和耐受性的首次人体1期研究

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

BHV-7000安全，耐受性良好，单剂量可达100毫克，多剂量可达120毫克，连续15天

No serious adverse events or severe treatment emergent adverse events were reported

没有严重不良事件或严重的治疗紧急不良事件的报告

Adverse events typically associated with other ASMs, such as somnolence and cognitive/mood disturbances, were not reported

不良事件通常与其他asm，如嗜睡和认知/情绪障碍，没有报告

Poster 2.249: Characterization of BHV-7000: A Novel Kv7.2/7.3 Activator for the Treatment of Seizures

海报2.249:BHV-7000的表征：用于治疗癫痫发作的新型Kv7.2/7.3激活剂

BHV-7000 is a potent activator of Kv7.2/7.3 channels, impacting both deactivation kinetics and voltage dependence of activation

BHV-7000是Kv7.2/7.3通道的有效激活剂，影响失活动力学和激活电压依赖性

BHV-7000 requires the Kv7.2 W236 residue for channel activity

BHV-7000需要Kv7.2 W236残基进行通道活动

No significant activation of the GABAA receptor with BHV-7000

BHV-7000对GABAA受体无明显激活作用

BHV-7000 is potent in the maximal electroshock seizure (MES) test without impact on neurobehavior or motor (rotorod) behavior

BHV-7000在最大电休克发作（MES）试验中是有效的，对神经行为或运动（转子）行为没有影响

Poster 1.487: Determinants of Health-Related Quality of Life of Patients with Focal Epilepsy: A Systematic Literature Review

海报1.487：局灶性癫痫患者健康相关生活质量的决定因素：系统文献综述

This systematic literature review identified multiple factors associated with lower HRQoL in patients with focal epilepsy

这篇系统的文献综述确定了局灶性癫痫患者HRQoL降低的多种因素

Depression and anxiety were among the most significant and frequent determinants of HRQoL change

抑郁和焦虑是HRQoL变化最重要和最常见的决定因素之一

Other relevant and frequent determinants of HRQoL change included cognition, ASM adverse events, seizure freedom, and employment

HRQoL变化的其他相关且频繁的决定因素包括认知，ASM不良事件，癫痫发作自由和就业

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

全面了解HRQoL的可修改决定因素与患者健康和福祉相关，可以为临床实践和观察/干预研究提供信息

Poster 2.451: Functional Impairments in Patients with KCNQ2-DEE: Associations Among Key Clinical Features

海报2.451:KCNQ2-DEE患者的功能障碍：关键临床特征之间的关联

Data obtained from a cross-sectional survey (2018-2020) of parents of children aged ≥2 years with KCNQ2-DEE was analyzed

分析了从KCNQ2-DEE≥2岁儿童父母的横断面调查（2018-2020）获得的数据

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

在KCNQ2-DEE患者中，存在一种损伤等级，其中沟通是最敏感的领域，经常与他人隔离地受到影响

Gross and fine motor skill impairments tend to be correlated

粗大和精细运动技能损伤往往是相关的

Hand use impairment is closely correlated with multiple other functional impairments

手部使用障碍与多种其他功能障碍密切相关

Full posters will be available on the Posters and Presentations page at: www.biohaven.com.

完整的海报将在海报和演示页面上提供：www.biohaven.com。

ReferenceBiondi A, et al. Sci Rep. 2022 Feb 4;12(1):1919.

参考文献Biondi A，et al.Sci Rep.2022 2月4日；12（1）：1919年。

About BHV-7000BHV-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).

关于BHV-7000BHV-7000，来自Biohaven Kv7平台的主要资产，是Kv7.2/Kv7.3的新型选择性激活剂，Kv7.2/Kv7.3是一种参与神经元信号传导和调节过度兴奋状态的关键离子通道，Biohaven正在开发用于治疗癫痫和情绪障碍。BHV-7000被合理地开发为异源Kv7.2/7.3钾通道的有效激活剂，钾通道是M电流（IKM）的分子底物。

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.

BHV-7000与ezogabine（在欧洲称为retigabine）高度区别，ezogabine是一种Kv7激活剂，以前被批准用于成人部分发作性癫痫的辅助治疗。与ezogabine相比，BHV-7000属于显着不同的结构类别，并且在关键性质（包括药理学，血浆稳定性和光氧化稳定性）方面与ezogabine不同。

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..

此外，BHV-7000不像ezogabine和类似化合物那样表现出GABAA受体阳性的变构分子活性，这可能导致ezogabine的耐受性差。这种GABAA受体活性的缺乏可能为BHV-7000提供了一个广阔的治疗窗口，基于其他ASM临床试验中所见的剂量依赖性临床反应，应该转化为改善疗效，而没有在接受ezogabine和其他抗癫痫药物治疗的患者中常见的典型剂量依赖性副作用特征。。

About BiohavenBiohaven 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.

关于BiohavenBiohaven是一家全球临床阶段的生物制药公司，专注于发现，开发和商业化改变生命的疗法，以治疗广泛的罕见和常见疾病。Biohaven经验丰富的管理团队为偏头痛，抑郁症，双相情感障碍和精神分裂症等疾病的产品提供新药批准记录。

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.

该公司正在推进一系列疾病治疗方案，其中许多治疗方案有限或没有治疗选择，利用其成熟的药物开发能力和专有平台，包括Kv7离子通道调节癫痫和神经元过度兴奋，谷氨酸调节强迫症和脊髓小脑性共济失调，肌肉生长抑制素抑制神经肌肉疾病和代谢紊乱，脑渗透剂TYK2/JAK1抑制神经炎症性疾病。

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..

Biohaven的早期和晚期候选产品组合还包括针对神经性疼痛的TRPM3通道激活，CD-38抗体募集，多发性骨髓瘤的双特异性分子，抗体-药物偶联物（ADC）和靶向细胞外蛋白质降解的发现研究计划平台技术（模式™)可用于神经系统疾病，癌症和自身免疫性疾病。。

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.

前瞻性声明本新闻稿包括1995年“私人证券诉讼改革法”含义内的前瞻性声明。使用某些词语，包括“继续”，“计划”，“意愿”，“相信”，“可能”，“期望”，“预期”和类似的表达方式，旨在确定前瞻性陈述。

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.

投资者应警惕，任何前瞻性陈述，包括关于未来发展，时间安排和潜在营销批准以及开发候选人商业化的陈述，都不能保证未来的表现或结果，并涉及重大风险和不确定性。

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.

由于各种因素，实际结果，发展和事件可能与前瞻性声明中的实际结果，发展和事件有很大差异，包括：Biohaven计划和正在进行的临床试验的预期时间，开始和结果；计划与FDA互动和申请的时间；预期监管文件的时间和结果；遵守适用的美国。

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'.

法规要求；Biohaven候选产品的潜在商业化；Biohaven的产品候选人有可能成为一流的疗法；以及Biohaven候选产品的有效性和安全性。Biohaven向美国证券交易委员会提交的文件中描述了与前瞻性陈述相关的其他重要因素，包括“风险因素”和“管理层对财务状况和运营结果的讨论和分析”部分。

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, .

前瞻性声明自本新闻稿发布之日起作出，Biohaven不承担任何更新任何前瞻性声明的义务，无论是由于新信息。

MoDEs is a trademark of Biohaven Therapeutics Ltd.

MoDEs是Biohaven Therapeutics Ltd.的商标。

Investor Contact:Jennifer PorcelliVice President, Investor Relations[email protected]201-248-0741

投资者联系人：Jennifer PorcelliVice投资者关系总裁[电子邮件保护]201-248-0741

Media Contact:Mike BeyerSam Brown Inc.[email protected]312-961-2502

媒体联系人：Mike BeyerSam Brown Inc.[电子邮件保护]312-961-2502

SOURCE Biohaven Ltd.

SOURCE Biohaven Ltd。