Bexicaserin

▎药明康德内容团队编辑 本期看点 1. 既能减重又能降低心血管风险的小分子疗法NT-0796在早期临床试验中表现积极。 2. T细胞受体（TCR）T细胞疗法SCG101在晚期乙型肝炎病毒（HBV）相关肝细胞癌（HCC）患者中展现出抗病毒和抗肿瘤双重活性，显著延长患者的生存期。 3. 白血病患者在接受造血干细胞移植后接受一剂INB-100治疗，100%可评估的患者于今年5月31日时仍然存活，并且维持完全缓解（CR）达到1年。 药明康德内容团队整理 NT-0796：公布1b/2a期临床试验数据 NodThera宣布其在炎症性肥胖受试者中进行的临床1b/2a期心血管风险研究取得了积极数据，该研究旨在评估其在研口服、可穿透血脑屏障的NLRP3炎性小体抑制剂NT-0796，对患者的炎症、心血管和代谢风险参数的影响。NLRP3炎症小体是一种经过高度验证的抗炎药物靶点。 分析显示，NT-0796可有效减少患者体内C反应蛋白（CRP）水平，并使患者的体重显著减少。此外，接受NT-0796治疗患者的其他促炎和心脏代谢生物标志物也有所减少，这是该研究的次要终点。与以往的试验一致，NT-0796总体上安全且耐受性良好，不良事件主要是轻度和短暂的，未观察到严重不良事件。NodThera目前正在为针对肥胖症，以及包括其他心脏代谢疾病和帕金森病在内的临床2期研究做准备。 SCG101：公布首次人体临床试验结果 星汉德生物（SCG Cell Therapy）宣布，其自主研发的HBV特异性TCR-T细胞疗法SCG101入选了2024年度欧洲肝脏研究协会年会（EASL Congress 2024）的焦点精选报告。SCG101是一种针对乙型肝炎病毒表面抗原（HBsAg）的特异性自体TCR-T细胞疗法。星汉德生物依托自主研发的独有GianT技术平台，筛选高亲力且高活性的天然TCR，可以有效靶向实体肿瘤中通过主要组织相容性复合体（MHC）表达的细胞内抗原。临床前和临床研究数据显示，SCG101具有肿瘤抑制和HBV cccDNA根除作用，可实现抗肿瘤和抗病毒功能。 此次公布的研究结果显示，SCG101在晚期HBV相关HCC患者中展现出抗病毒和抗肿瘤双重活性，显著延长了患者的生存期。至稿件截止日，客观缓解率（ORR）为33%，获得部分缓解（PR）的患者均维持缓解超过6个月，其中1例实现了靶病灶完全缓解（pCR），且持续缓解超过27个月。此外，患者的肿瘤应答与SCG101的抗病毒活性高度相关。4例血清HBsAg显著下降并维持在低水平的患者的肿瘤缩小，且无进展生存期和总生存期显著延长至5.9个月和19.0个月。 INB-100 IN8bio：公布1期临床试验的新数据 IN8bio公司公布了其在研现货型γδ T细胞疗法INB-100的最新1期临床试验结果。INB-100是一款来自健康供体的同种异体γδ T细胞，在体外经过扩增和激活后，被输注到白血病患者体内。在这项研究者发起的1期临床试验中，白血病患者在接受造血干细胞移植后，接受一剂INB-100的治疗。这些患者包括高风险和复发急性髓系白血病（AML）患者，他们此前已接受过多种疗法治疗，包括嵌合抗原受体（CAR）T细胞疗法。 截至2024年5月31日的数据，100%可评估的白血病患者仍然存活并且维持CR达到1年。此前发表的历史数据显示，高达50%的血液癌症患者在接受造血干细胞移植和减轻强度预处理（reduced intensity conditioning）的情况下会出现复发，并且在复发后不久去世。在这10名患者中，两名接受INB-100治疗的患者已经无癌三年半，另一名患者接近3年无癌。数据同时显示，接受单次治疗后的365天里，同种异体γδ T细胞能够长期持久地在体内扩增。新闻稿指出，这是首次同种异体细胞疗法表现出持续的扩增和持久性。安全性方面，INB-100没有出现剂量限制性毒性，未发现细胞因子释放综合征（CRS），神经毒性或免疫效应细胞相关神经毒性综合征（ICANS），未发现严重感染。 Delpacibart braxlosiran （AOC 1020）：公布1/2期临床试验的初步数据 Avidity Biosciences宣布其用于治疗面肩肱型肌营养不良症（FSHD）的在研抗体寡核苷酸偶联物（AOC）delpacibart braxlosiran（del-brax，AOC 1020）在临床1/2期试验FORTITUDE中的初步积极数据。FSHD是由于DUX4基因异常表达所引起。DUX4蛋白的异常表达导致肌肉细胞基因表达的变化，造成FSHD患者肌肉功能的终身、渐进性丧失。根据新闻稿，del-brax是首个旨在治疗FSHD根本原因的在研AOC疗法，由一种专有的转铁蛋白受体1（TfR1）靶向单克隆抗体，与靶向DUX4 mRNA的siRNA偶联所组成。 ▲Del-brax下调患者受DUX4调控的基因表达（图片来源：参考资料[2]） 此次公布的结果显示，FSHD患者接受该疗法后，其受DUX4调控的基因一致性地下调超过50%，并且患者的肌肉功能有改善的趋势。根据此积极结果，Avidity计划加速FORTITUDE研究中注册队列的启动。 Bexicaserin（LP352）：公布1b/2a期临床试验的新数据 Longboard Pharmaceuticals公司公布了PACIFIC研究的开放标签扩展（OLE）研究的积极数据。PACIFIC研究旨在评估其在研疗法bexicaserin（LP352）用于治疗与广泛发育性和癫痫性脑病相关癫痫发作的疗效与安全性。Bexicaserin是一款高选择性、口服、新型5-HT2C受体超激动剂，为潜在的“best-in-class”疗法。 所有41例完成PACIFIC研究的患者均选择参加OLE研究。结果显示，在OLE研究中接受bexicaserin治疗约6个月的可评估受试者（n=40）的中位可数运动性癫痫发作频率较进入PACIFIC研究时的基线水平降低56.1%。其中，在PACIFIC研究中被随机分配到接受bexicaserin治疗组的受试者（n=31）减少了54.9%，在PACIFIC研究中被随机分配到安慰剂组的受试者在OLE研究中过渡到bexicaserin治疗，这类患者（n=9）减少了57.3%。安全性方面，观察到的最常见的治疗伴发不良事件为上呼吸道感染、COVID-19、肺炎、鼻窦炎、癫痫发作和食欲下降。一名受试者因嗜睡而停药，一名受试者因撤回同意而停药。 JIN-A02：公布1/2期临床试验的新数据 J INTS BIO公司公布了其进行中的用于治疗非小细胞肺癌（NSCLC）的新型第4代口服EGFR酪氨酸激酶抑制剂（TKI）JIN-A02的1期临床研究的最新情况。JIN-A02具有高度的选择性，可有效对抗携带EGFR C797S双突变或三突变的NSCLC，并具有高脑渗透率和体内疗效。 截至目前，已有两名患者达到了确认的PR，还有3名患者达到了疾病稳定（SD）。此外，研究人员还在1例达到SD的患者中观察到脑转移灶缩小28.6%。安全性方面，未报告剂量限制性毒性，也没有发现皮疹、腹泻或心脏毒性这类通常与EGFR TKI的使用相关的副作用。 PCS6422：公布1b期临床试验的初步数据 Processa Pharmaceuticals公司公布了其下一代卡培他滨组合疗法（NGC-Cap）治疗III/IV期胃肠道癌症患者的1b期临床试验的初步结果。口服卡培他滨在体内代谢后会变成5-氟尿嘧啶（5-FU），进而代谢成两种分子，一种能主动杀死癌细胞，一种只会产生副作用。二氢嘧啶脱氢酶（DPD）在5-FU转化为引起副作用的分子方面起着重要作用。PCS6422能够不可逆地抑制DPD。在相当剂量水平下，PCS6422单药在动物中既没有毒性也不具有活性。而当与卡培他滨或5-FU联合给药时，PCS6422降低了5-FU向仅引起副作用的分子的代谢，从而使更多的5-FU到达癌细胞。Processa Pharmaceuticals公司将PCS6422与低剂量的卡培他滨结合使用，组成了NGC-Cap。 此次公布的结果显示，在所有接受一剂PCS6422后再接受7天卡培他滨治疗的可评估患者中，12例可评估患者的疾病控制率为66.7%（8/12），包括2例PR和6例SD。这些患者的无进展生存期约为5-11个月。相比之下，在卡培他滨产品说明书中，301例接受卡培他滨单药治疗的转移性结直肠癌患者的总缓解率约为21%，患者发生进展的时间约为4.5个月。安全性方面，与卡培他滨单药治疗相比，在所有NGC-Cap剂量组中，5-FU的暴露量更高，副作用的发生情况相似或更少。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] NodThera’s NLRP3 Inhibitor NT-0796 Meets Primary Endpoint of Inflammation Reversal in Phase Ib/IIa Trial in Obese Subjects with Cardiovascular Risk. Retrieved June 14, 2024 from https://www.nodthera.com/news/nodtheras-nlrp3-inhibitor-nt-0796-meets-primary-endpoint-of-inflammation-reversal-in-phase-ib-iia-trial-in-obese-subjects-with-cardiovascular-risk/ [2] 重磅｜EASL 最新突破性数据：星汉德生物TCR-T细胞治疗晚期肝癌患者总生存期显著延长并伴随乙肝表面抗原清除，获选最佳精选报告. Retrieved June 14, 2024 from https://www.prnasia.com/story/450060-1.shtml [3] Avidity Announces Unprecedented AOC 1020 Data from Phase 1/2 FORTITUDE™ Trial Demonstrating Greater Than 50 Percent Reduction in DUX4 Regulated Genes and Trends of Functional Improvement in People Living with Facioscapulohumeral Muscular Dystrophy. Retrieved June 14, 2024 from https://www.prnewswire.com/news-releases/avidity-announces-unprecedented-aoc-1020-data-from-phase-12-fortitude-trial-demonstrating-greater-than-50-percent-reduction-in-dux4-regulated-genes-and-trends-of-functional-improvement-in-people-living-with-facioscapulohumeral-m-302170099.html [4] Avidity Biosciences Investor & Analyst Event Series – Vol. 9: Preliminary Data from Phase 1/2 FORTITUDE™ trial of AOC 1020 in people living with FSHD. Retrieved June 14, 2024 from https://aviditybiosciences.investorroom.com/events-and-presentations#:~:text=Avidity%20Biosciences%20Investor%20%26%20Analyst%20Event%20Series%20%E2%80%93%20Vol.%209%3A%20Preliminary%20Data%20from%20Phase%201/2%20FORTITUDE%E2%84%A2%20trial%20of%20AOC%201020%20in%20people%20living%20with%20FSHD [5] IN8bio Presents Positive Data Demonstrating Durable 1-year Complete Remission in 100% of Evaluable Patients in Phase 1 Trial of INB-100. Retrieved June 14, 2024, from https://www.globenewswire.com/news-release/2024/06/13/2898625/0/en/IN8bio-Presents-Positive-Data-Demonstrating-Durable-1-year-Complete-Remission-in-100-of-Evaluable-Patients-in-Phase-1-Trial-of-INB-100.html [6] Longboard Pharmaceuticals Announces Positive Interim Results from the Open-Label Extension (OLE) of the Phase 1b/2a PACIFIC Study Evaluating Bexicaserin in Participants with Developmental and Epileptic Encephalopathies (DEEs). Retrieved June 14, 2024, from [7] Processa Pharmaceuticals Announces Positive Efficacy Results from Preliminary Evaluation of Phase 1b Dose-escalating Trial with NGC-Cap in Gastrointestinal Cancer. Retrieved June 14, 2024, from https://www.globenewswire.com/news-release/2024/06/11/2896777/0/en/Processa-Pharmaceuticals-Announces-Positive-Efficacy-Results-from-Preliminary-Evaluation-of-Phase-1b-Dose-escalating-Trial-with-NGC-Cap-in-Gastrointestinal-Cancer.html [8] J INTS BIO, ASCO 2024 - JIN-A02 showed tumor reductions including brain metastasis in the ongoing first-in-human, dose-finding Phase 1 clinical study. Retrieved June 14, 2024, from https://www.prnewswire.com/news-releases/j-ints-bio-asco-2024--jin-a02-showed-tumor-reductions-including-brain-metastasis-in-the-ongoing-first-in-human-dose-finding-phase-1-clinical-study-302168022.html [9] Surrozen Presents Preliminary Results from Phase 1a Study of SZN-043 in Healthy Volunteers and Patients with a History of Liver Cirrhosis at the 2024 European Association for the Study of the Liver (EASL) in Milan. Retrieved June 14, 2024, from https://www.globenewswire.com/news-release/2024/06/10/2896001/0/en/Surrozen-Presents-Preliminary-Results-from-Phase-1a-Study-of-SZN-043-in-Healthy-Volunteers-and-Patients-with-a-History-of-Liver-Cirrhosis-at-the-2024-European-Association-for-the-S.html [10] Eilean Therapeutics Announces FDA Clearance of Investigational New Drug (IND) Application for Lomonitinib for the Treatment of Acute Myeloid Leukemia (AML). Retrieved June 14, 2024, from https://www.prnewswire.com/news-releases/eilean-therapeutics-announces-fda-clearance-of-investigational-new-drug-ind-application-for-lomonitinib-for-the-treatment-of-acute-myeloid-leukemia-aml-302167897.html [11] Ensem Therapeutics Announces Achievement of Milestone Following Entry of Small Molecule CDK2 Inhibitor into Clinical Trials for Solid Tumors. Retrieved June 14, 2024, from https://www.businesswire.com/news/home/20240612661711/en/ [12] Zumutor Biologics Announces Dosing of First Patient with ZM008, a First-in-Class Anti LLT1 Antibody. Retrieved June 14, 2024, from https://www.prnewswire.com/news-releases/zumutor-biologics-announces-dosing-of-first-patient-with-zm008-a-first-in-class-anti-llt1-antibody-302170537.html [13] KSQ Therapeutics Announces First Patient Dosed in Clinical Development Program for KSQ-001EX, a CRISPR/Cas9 Engineered Tumor Infiltrating Lymphocyte (eTIL®) Therapy. Retrieved June 14, 2024, from https://ksqtx.com/news-events/ksq-therapeutics-announces-first-patient-dosed-in-clinical-development-program-for-ksq-001ex-a-crispr-cas9-engineered-tumor-infiltrating-lymphocyte-etil-therapy/ [14] City of Hope CAR T Cell Therapy for Advanced Prostate Cancer Demonstrates Positive Results in Phase 1 Clinical Trial. Retrieved June 14, 2024, from https://www.businesswire.com/news/home/20240612751963/en [15] Assembly Biosciences Doses First Participant in Phase 1a/b Clinical Trial of Herpes Simplex Virus Helicase-Primase Inhibitor Candidate ABI-5366. Retrieved June 14, 2024, from https://investor.assemblybio.com/news-releases/news-release-details/assembly-biosciences-doses-first-participant-phase-1ab-clinical [16] VYNE Therapeutics Announces Dosing of First Participants in Phase 1a Trial of Novel BD2-Selective BET Inhibitor VYN202. Retrieved June 14, 2024, from https://vynetherapeutics.com/press-releases/vyne-therapeutics-announces-dosing-of-first-participants-in-phase-1a-trial-of-novel-bd2-selective-bet-inhibitor-vyn202/ 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

Bexicaserin achieved an overall median seizure reduction of 56.1% in countable motor seizures over an approximate 6-month treatment period; participants randomized to the PACIFIC placebo group achieved a median seizure reduction of 57.3% Favorable safety and tolerability results observed 100% of participants who completed the PACIFIC Study entered the OLE End of Phase 2 Meeting scheduled for this summer LA JOLLA, Calif.--(BUSINESS WIRE)-- Longboard Pharmaceuticals, Inc. (Nasdaq: LBPH), a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases, today announced positive interim results from its ongoing 52-week open-label extension of the PACIFIC Study evaluating bexicaserin (LP352) in participants ages 12-65 years old with Developmental and Epileptic Encephalopathies. “We are thrilled to see a sustained, durable response in seizure reduction and a favorable safety and tolerability pro a broad range of DEE patients. Additionally, we saw compelling seizure reduction in the PACIFIC placebo patients who transitioned to bexicaserin in the OLE. These data provide further support to bexicaserin’s potential to offer a highly differentiated and best-in-class profile,” stated Dr. Randall Kaye, Longboard’s Chief Medical Officer. “Given the tremendous unmet need in patients living with DEEs, we are committed to rapidly advancing the development of bexicaserin. We expect to provide additional analyses of these participants as they progress in the OLE Study and transition to our Expanded Access Program,” Dr. Kaye continued. “With an End of Phase 2 meeting scheduled this summer, we remain on track to initiate our global Phase 3 program for bexicaserin later this year.” PACIFIC OLE Study Interim Analysis Results: The PACIFIC OLE Study is a 52-week Phase 2, open-label, long-term safety study of bexicaserin in participants with a range of DEEs, including Dravet syndrome (n=3), Lennox-Gastaut syndrome (n=20) and DEE Other (n=18), who completed the PACIFIC Study (n=41). The study objectives are to investigate the safety and tolerability of multiple doses of bexicaserin in participants with DEEs, and to analyze the effect of bexicaserin on the frequency of observed countable motor seizures and other seizure types. The interim analysis was conducted when participants reached the approximate 6-month point in the OLE Study. Summary of Efficacy Results: The median change in countable motor seizure frequency for participants in the OLE Study over an approximate 6-month treatment period was a decrease of 56.1% (n=40) from their baseline entering the PACIFIC Study. The median change in countable motor seizure frequency from baseline for: participants randomized to the bexicaserin-treated group in the PACIFIC Study was a decrease of 54.9% (n=31) participants randomized to the placebo group in the PACIFIC Study that transitioned to bexicaserin in the OLE was a decrease of 57.3% (n=9) Summary of Safety and Tolerability Results: Favorable safety and tolerability results were observed in this study. 100% of PACIFIC Study completers elected to enroll in the OLE with 95.1% (39 out of 41) remaining in the ongoing open-label study. One participant discontinued due to the adverse event (AE) of lethargy and one participant discontinued by withdrawal of consent. The most common treatment emergent AEs in the overall group (n=41) occurring in >5% of patients were upper respiratory tract infections, COVID-19, pneumonia, sinusitis, seizures, and decreased appetite. ABOUT THE PACIFIC STUDY AND THE OLE STUDY The PACIFIC Study is a Phase 1b/2a double-blind, placebo-controlled clinical trial to assess the safety, tolerability, efficacy and pharmacokinetics of bexicaserin (LP352) in 52 participants between the ages of 12 and 65 years old with DEEs at 34 sites across the United States and Australia. Following a 5-week screening period and baseline evaluations, study participants initiated a dose titration over a 15-day period and subsequently continued on the highest tolerated dose throughout the maintenance period of 60 days. Following the maintenance period, participants were then titrated down, and eligible participants were given the opportunity to enroll in a 52-week open-label extension study. ABOUT LONGBOARD PHARMACEUTICALS Longboard Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases. Longboard is working to advance a portfolio of centrally acting product candidates designed to be highly selective for specific G protein-coupled receptors (GPCRs). Longboard’s small molecule product candidates are based on more than 20 years of GPCR research. Longboard plans to advance bexicaserin (LP352), an oral, centrally acting 5-hydroxytryptamine 2C (5-HT2C) receptor superagonist, with no observed impact on 5-HT2B and 5-HT2A receptor subtypes, into a global Phase 3 program. Longboard recently reported positive topline data from a Phase 1b/2a clinical trial (the PACIFIC Study) evaluating bexicaserin in participants ages 12 to 65 years old with Developmental and Epileptic Encephalopathies (DEEs), including Lennox-Gastaut syndrome, Dravet syndrome and other DEEs. Longboard is also evaluating LP659, an oral, centrally acting, sphingosine-1-phosphate (S1P) receptor subtypes 1 and 5 modulator, which is in development for the potential treatment of rare neuroinflammatory conditions. Longboard is conducting a Phase 1 single-ascending dose (SAD) clinical trial for LP659 in healthy volunteers, with topline data expected in the second quarter of 2024. FORWARD-LOOKING STATEMENTS Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. In some cases, you can identify forward-looking statements by words such as “focus”, “potential”, “expect”, “committed to”, “scheduled”, “remain on track”, “working to”, “designed to”, “plans”, “will”, or the negative, plural or other tenses of these words, references to future dates or time periods, or other comparable language, and they may include, without limitation, statements about the following: Longboard’s clinical and preclinical product candidates and programs, including their potential (including for bexicaserin to be differentiated and to have a best-in-class pro advancement, timing of initiating clinical trials (including a global Phase 3 program for bexicaserin), timing of topline data from clinical trials (including the Phase 1 SAD data for LP659), , the end of Phase 2 meeting, the ability of patients to progress in the OLE Study and transition to an expanded access program, and their design and characteristics; Longboard’s ability to develop product candidates and deliver medicines; and Longboard’s focus and work. For such statements, Longboard claims the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Longboard’s expectations. Factors that could cause actual results to differ materially from those stated or implied by Longboard’s forward-looking statements include, but are not limited to, the following: risk that topline or interim data may not accurately reflect the complete results of a particular study or trial, and that final data may differ materially from topline or interim data; PACIFIC Study participants' diagnoses are as of time of screening and are subject to change; risks related to Longboard’s limited operating history, financial position and need for additional capital; Longboard’s need for additional managerial and financial resources to advance all of its programs, and you and others may not agree with the manner Longboard allocates its resources; risks related to the development and commercialization of Longboard’s product candidates; Longboard’s product candidates are in the early to middle phases of a lengthy research and development process, the timing, manner and outcome of research, development and regulatory review is uncertain, and Longboard’s product candidates may not advance in research or development or be approved for marketing; results of clinical trials and other studies are subject to different interpretations and may not be predictive of future results; enrolling participants in Longboard’s ongoing and intended clinical trials is competitive and challenging; risks related to unexpected or unfavorable new data; nonclinical and clinical data is voluminous and detailed, and regulatory agencies may interpret or weigh the importance of data differently and reach different conclusions than Longboard or others, request additional information, have additional recommendations or change their guidance or requirements before or after approval; macroeconomic events and their impact on Longboard's clinical trials and operations, the operations of Longboard's suppliers, partners, collaborators, and licensees, and capital markets; risks related to relying on licenses or collaborative arrangements; other risks related to Longboard’s dependence on third parties; competition; product liability or other litigation or disagreements with others; government and third-party payor actions, including relating to reimbursement and pricing; risks related to regulatory compliance; and risks related to Longboard’s and third parties’ intellectual property rights. Additional factors that could cause actual results to differ materially from those stated or implied by Longboard’s forward-looking statements are disclosed in Longboard’s filings with the Securities and Exchange Commission (SEC). These forward-looking statements represent Longboard’s judgment as of the time of this release. Longboard disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law. View source version on businesswire.com: Contacts CORPORATE CONTACT: Megan E. Knight VP, Head of Investor Relations IR@longboardpharma.com 858.789.9283 Source: Longboard Pharmaceuticals, Inc. View this news release online at: