PAS-004

▎药明康德内容团队编辑 本期看点 1. 嵌合抗原受体T（CAR-T）细胞疗法P-BCMA-ALLO1治疗复发/难治性多发性骨髓瘤患者的早期临床数据亮眼，优化淋巴细胞清除队列患者的总缓解率（ORR）达91%。 2. Metsera公司的超长效减肥疗法MET-097在临床1期试验中实现了显著且持久的减肥效果，受试者在接受治疗第36天后，体重下降达7.5%，并有望达到每月一次的给药频率。 3. 大环MEK抑制剂PAS-004在1期临床试验中使1名既往接受过多线治疗的3期结直肠癌患者获得长期疾病稳定。 药明康德内容团队整理 P-BCMA-ALLO1：公布1期临床试验的新数据 Poseida Therapeutics公司公布了其与罗氏（Roche）共同开发的同种异体B细胞成熟抗原（BCMA）靶向CAR-T疗法P-BCMA-ALLO1治疗复发/难治性多发性骨髓瘤患者的1期临床试验的新中期数据。截至2024年9月6日，72名患者被纳入意向治疗（ITT）人群，并在四个队列（S、A、B和C）中接受治疗，治疗包括不同的P-BCMA-ALLO1剂量和淋巴细胞清除方案组合。这些患者既往接受过三种或三种以上的治疗，包括蛋白酶体抑制剂、免疫调节药物和抗CD38单克隆抗体。 此次公布的结果显示，所有四个队列的ORR为54%，11%的患者获得了完全缓解（CR）或严格完全缓解（sCR），33%的患者获得了非常好的部分缓解或更佳（VGPR+）。值得一提的是，在优化淋巴清除组（队列C）中，患者的ORR为91%，此前未接受过BCMA靶向治疗患者的ORR达100%，既往接受过至少一种BCMA和/或GPRC5D靶向治疗方法的患者的ORR为86%。22%的患者达到CR或sCR，48%的患者实现了VGPR+。安全性方面，未发现剂量限制性毒性反应，细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）的发生率低，均为2级或2级以下，无移植物抗宿主病或帕金森病。 MET-097：公布1期临床试验数据 Metsera公司宣布，其超长效减肥疗法MET-097在临床1期试验中实现了显著且持久的减肥效果。MET-097是一款在研超长效皮下注射GLP-1受体激动剂。MET-097通过Metsera专有的HALO新型肽脂化平台所开发，具有超长的体内清除时间。 此次公布的结果显示，MET-097具有剂量线性药代动力学特征，具有380小时的半衰期，且在各受试者之间表现出一致性。受试者的体重相对于基线变化呈现剂量依赖性，接受1.2 mg剂量的受试者，在第36天（最后一次给药后的一周）时体重下降达7.5%，这一结果与现有获批和临床阶段GLP-1/GIP药物相当或更佳。在最后一次给药后四周（第57天），1.2 mg剂量组受试者的累计减重幅度达8.1%，显示药效持续性与观察到的380小时半衰期一致。安全性方面，患者的胃肠道不良事件与剂量相关，大多数为轻度且短暂。未观察到与治疗相关的严重不良事件，且无因治疗相关原因而中止研究药物的病例。 ISP-001：公布1期临床试验数据 Immusoft公司公布了其工程化B细胞疗法ISP-001用于治疗1型黏多糖贮积症（MPS I）的1期临床试验中首例患者的积极结果。MPS I是一种罕见且致命的儿童遗传病，会影响身体产生α-L-艾杜糖苷酸酶（IDUA，一种有助于分解细胞内长链糖的必需酶）的能力。糖链若无法分解会在细胞中积聚并造成渐进性损伤，这种积聚会发生在包括大脑的组织中。ISP-001细胞使用“睡美人”转座子系统（Sleeping Beauty transposon system）表达α-L-艾杜糖苷酶，从而改善MPS I症状。 分析显示，该名成年患者展现药效学和身体功能上的改善，并且在生活质量和日常生活活动上获得了显著的进步。患者与MPS I相关的疼痛也获得减轻。安全性方面，ISP-001的耐受性良好。截至2024年9月19日，尚未报告任何不良事件。ISP-001已获得FDA的孤儿药资格和MPS I的罕见儿科疾病认定。根据新闻稿，ISP-001是首个进入人体临床试验的工程化B细胞疗法。 PAS-004：公布1期临床试验的初步数据 Pasithea Therapeutics公司公布了其大环MEK抑制剂PAS-004治疗MAPK通路驱动的晚期实体肿瘤患者的1期临床研究中前两个队列的数据。与目前FDA批准的MEK抑制剂不同，PAS-004是大环化合物，环化可增强药物与靶受体的结合，被认为有望改善药代动力学和安全性。 该研究中的患者携带RAS、RAF或NF1突变，或有BRAF/MEK抑制剂治疗失败的经历。此次公布的结果显示，PAS-004的半衰期约为70小时，支持每日一次或更少频率的口服给药。该候选疗法还能够在稳态下实现恒定的靶点抑制，同时避免峰值血浆毒性。过往经验表明，结直肠癌患者接受MEK抑制剂单药治疗时的疗效有限，但观察到1例既往接受过4线治疗的BRAF K601E突变结直肠癌患者在接受PAS-004治疗后表现出长期稳定的疾病。目前，尚无针对BRAF K601E突变癌症的获批疗法。安全性方面，PAS-004的安全性和耐受性良好，没有与药物相关的剂量中断、减少或停药，迄今为止尚未观察到皮疹或皮肤毒性、胃肠道毒性或眼毒性。研究人员认为，PAS-004具有独特的MEK抑制谱，有望用于治疗NF1相关的丛状神经纤维瘤和皮肤神经纤维瘤、癌症和其他疾病。 ARO-INHBE：申请启动1/2a期临床试验 Arrowhead Pharmaceuticals公司宣布，已向新西兰的监管部门提交了启动RNAi疗法ARO-INHBE用于治疗肥胖症的1/2a期临床试验的申请。ARO-INHBE旨在降低INHBE基因在肝脏的表达并调节Activin E信号通路。INHBE是一个潜在的基因验证靶点，人类INHBE的功能丧失变异与较低的肥胖和代谢性疾病（如2型糖尿病）风险有关。Activin E在调节脂肪组织能量稳态的途径中起着配体的作用，利用ARO-INHBE干预这一途径有可能增加脂肪分解，减少脂肪过度生长和功能障碍、内脏脂肪过多和胰岛素抵抗。 IPH4502：IND申请获得FDA许可 Innate Pharma公司宣布，美国FDA已批准其抗体偶联药物（ADC）IPH4502用于治疗表达Nectin-4的晚期实体瘤的IND申请，该公司预计将在未来几个月内启动1期临床研究。IPH4502靶向Nectin-4，以拓扑异构酶I抑制剂exatecan为载荷。Nectin-4是一种细胞膜粘附蛋白，在多种实体瘤中过表达，包括尿路上皮癌、乳腺癌、食管癌、肺癌、卵巢癌和胰腺癌，在正常组织中的表达有限。在非临床模型中，IPH4502具有良好的耐受性，并在体外和体内显示出抗肿瘤活性。 VTP-1000：启动1期临床试验 Barinthus Biotherapeutics公司宣布启动其候选免疫疗法VTP-1000在成人乳糜泻患者中的首次人体1期试验。这项随机、安慰剂对照临床试验包括受控麸质挑战，将评估VTP-1000的安全性、耐受性、药代动力学和药效学。VTP-1000是一种在研注射用抗原特异性耐受免疫疗法，它利用该公司专有的SNAP-TI平台，将多种麸质肽抗原（来自小麦、大麦和黑麦蛋白）和免疫调节剂雷帕霉素包裹在纳米颗粒中同时递送至人体，以促进对麸质的免疫耐受。 ENA-001：IND申请获得FDA许可 Enalare Therapeutic公司宣布，其在研呼吸兴奋剂ENA-001的IND申请已获得美国FDA的批准，可针对与药物过量相关的呼吸抑制开展1期临床研究。该研究将包括Enalare的肌肉内制剂（IM）和静脉注射（IV）制剂。ENA-001具有新颖的作用机制，可通过颈动脉体内的外周化学感受器通路影响通气。此前，欧洲已经成功完成了5项使用ENA-001的IV制剂的1期研究，证明了其有效性和良好的耐受性。ENA-001新颖的作用机制和迄今为止的研究结果显示，该疗法有潜力改善多种致命疾病患者的生活，包括药物过量、术后呼吸抑制和早产儿呼吸暂停。 ▲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] Immusoft to Announce Positive Phase 1 Data for First Engineered B Cell Therapy in a Clinical Trial. Retrieved September 23, 2024 from https://www.prnewswire.com/news-releases/immusoft-to-announce-positive-phase-1-data-for-first-engineered-b-cell-therapy-in-a-clinical-trial-302255551.html [2] Arrowhead Pharmaceuticals Files for Regulatory Clearance to Initiate Phase 1/2a Study of ARO-INHBE for the Treatment of Obesity. Retrieved September 23, 2024 from https://ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-files-regulatory-clearance-initiate-3 [3] Innate Pharma Announces FDA Clearance of the IND for IPH4502, a Nectin-4 ADC to Be Developed in Solid Tumors. Retrieved September 23, 2024 from https://pipelinereview.com/innate-pharma-announces-fda-clearance-of-the-ind-for-iph4502-a-nectin-4-adc-to-be-developed-in-solid-tumors/ [4] Metsera Reports Highly Competitive Results from Ongoing Trial of Novel, Potential Once-Monthly Injectable GLP-1 Receptor Agonist MET-097. Retrieved September 24, 2024 from https://www.businesswire.com/news/home/20240924023447/en/Metsera-Reports-Highly-Competitive-Results-from-Ongoing-Trial-of-Novel-Potential-Once-Monthly-Injectable-GLP-1-Receptor-Agonist-MET-097 [5] Barinthus Bio Initiates Phase 1 Clinical Trial of VTP-1000 for the Treatment of Celiac Disease. Retrieved September 24, 2024 from https://investors.barinthusbio.com/news-releases/news-release-details/barinthus-bio-initiates-phase-1-clinical-trial-vtp-1000#:~:text=Investigational%20immunotherapy%20candidate,%20VTP-1000,%20seeks%20to [6] Pasithea Therapeutics Announces Positive Initial Safety, Tolerability, Pharmacokinetic (PK), and Preliminary Efficacy Data from its Phase 1 Clinical Trial of PAS-004 in Advanced Cancer. Retrieved September 27, 2024 from https://www.globenewswire.com/news-release/2024/09/26/2953686/0/en/Pasithea-Therapeutics-Announces-Positive-Initial-Safety-Tolerability-Pharmacokinetic-PK-and-Preliminary-Efficacy-Data-from-its-Phase-1-Clinical-Trial-of-PAS-004-in-Advanced-Cancer.html [7] Enalare Receives FDA Clearance to Initiate the First Phase 1 Clinical Study of ENA-001 to Be Conducted in the United States. Retrieved September 27, 2024 from https://www.newswire.com/news/enalare-receives-fda-clearance-to-initiate-the-first-phase-1-clinical-22429358 [8] KSQ Therapeutics Announces FDA Clearance of IND Application for KSQ-004EX, a CRISPR/Cas9 Engineered Tumor-Infiltrating Lymphocyte (eTIL®) Therapy. Retrieved September 27, 2024, from https://www.globenewswire.com/news-release/2024/09/24/2952011/0/en/KSQ-Therapeutics-Announces-FDA-Clearance-of-IND-Application-for-KSQ-004EX-a-CRISPR-Cas9-Engineered-Tumor-Infiltrating-Lymphocyte-eTIL-Therapy.html#:~:text=KSQ-004EX,%20an%20eTIL%20%C2%AE%20cell%20therapy [9] Minovia Therapeutics Announces FDA Clearance of IND Application for a Phase Ib Clinical Trial of MNV-201 in Low Risk Myelodysplastic Syndrome. Retrieved September 27, 2024, from https://www.globenewswire.com/news-release/2024/09/26/2954055/0/en/Minovia-Therapeutics-Announces-FDA-Clearance-of-IND-Application-for-a-Phase-Ib-Clinical-Trial-of-MNV-201-in-Low-Risk-Myelodysplastic-Syndrome.html [10] Assembly Biosciences Reports Positive Interim Phase 1a Results from Clinical Trial Evaluating Long-Acting Helicase-Primase Inhibitor Candidate ABI-5366. Retrieved September 27, 2024, from https://investor.assemblybio.com/news-releases/news-release-details/assembly-biosciences-reports-positive-interim-phase-1a-results [11] Alkermes to Present Positive Clinical Data From Phase 1b Study of ALKS 2680 in Patients With Narcolepsy Type 2 and Idiopathic Hypersomnia at Sleep Europe 2024. Retrieved September 27, 2024, from https://www.prnewswire.com/news-releases/alkermes-to-present-positive-clinical-data-from-phase-1b-study-of-alks-2680-in-patients-with-narcolepsy-type-2-and-idiopathic-hypersomnia-at-sleep-europe-2024-302254991.html [12] Carrick Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial of CT7439 (CDK12/13 Inhibitor). Retrieved September 27, 2024, from https://www.carricktherapeutics.com/news-media/press-releases/detail/25/carrick-therapeutics-announces-first-patient-dosed-in-phase [13] Georgiamune Announces First Participant Dosed in First-In-Class Phase 1 Healthy Volunteers Trial of GIM-407. Retrieved September 27, 2024, from https://www.globenewswire.com/news-release/2024/09/24/2952226/0/en/Georgiamune-Announces-First-Participant-Dosed-in-First-In-Class-Phase-1-Healthy-Volunteers-Trial-of-GIM-407.html#:~:text=The%20company%20has%20initiated%20three%20first-in-class [14] Poseida Therapeutics Reports Positive Interim Phase 1 Results for Allogeneic CAR-T Therapy P-BCMA-ALLO1 with High Overall Response Rates in Heavily Pretreated Relapsed/Refractory Multiple Myeloma Patients. Retrieved September 27, 2024, from https://www.prnewswire.com/news-releases/poseida-therapeutics-reports-positive-interim-phase-1-results-for-allogeneic-car-t-therapy-p-bcma-allo1-with-high-overall-response-rates-in-heavily-pretreated-relapsedrefractory-multiple-myeloma-patients-302261471.html 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

MIAMI, Sept. 26, 2024 (GLOBE NEWSWIRE) -- Pasithea Therapeutics Corp. (NASDAQ: KTTA) (“Pasithea” or the “Company”), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1) and other cancer indications, today announced that it has entered into definitive agreements for the issuance and sale of an aggregate of 1,219,513 shares of its common stock (or pre-funded warrants in lieu thereof), accompanying Series A warrants to purchase up to 1,219,513 shares of common stock and accompanying short-term Series B warrants to purchase up to 1,219,513 shares of common stock at a purchase price of $4.10 per share (or per pre-funded warrant in lieu thereof) and accompanying warrants in a private placement priced at-the-market under the rules of the Nasdaq Stock Market. The Series A and the short-term Series B warrants will have an exercise price of $3.85 per share and will be exercisable immediately upon issuance. The Series A warrants will expire five years from the issuance date and the short-term Series B warrants will expire 18 months from the issuance date. The closing of the offering is expected to occur on or about September 30, 2024, subject to the satisfaction of customary closing conditions. H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering. The gross proceeds from the offering are expected to be approximately $5 million, prior to deducting placement agent’s fees and other offering expenses payable by the Company. Pasithea intends to use the net proceeds from the offering for working capital and other general corporate purposes. The securities described above are being offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”), and/or Regulation D promulgated thereunder and, along with the shares of common stock underlying the warrants, have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. Pursuant to a registration rights agreement with investors, the Company has agreed to file a resale registration statement covering the securities described above. This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. About Pasithea Therapeutics Corp. Pasithea is a biotechnology company focused on the discovery, research and development of innovative treatments for central nervous system (CNS) disorders and RASopathies. With an experienced team of experts in the fields of neuroscience, translational medicine, and drug development, Pasithea is developing new molecular entities for the treatment of neurological disorders, including Neurofibromatosis type 1 (NF1), Solid Tumors, and Amyotrophic Lateral Sclerosis (ALS). Forward Looking Statements This press release contains statements that constitute “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements regarding the ability of the Company to consummation of the private placement, the satisfaction of the closing conditions of the private placement and the use of proceeds therefrom, the Company’s ongoing Phase 1 clinical trial and the safety, tolerability, pharmacokinetic (PK) and preliminary efficacy of PAS-004, as well as all other statements, other than statements of historical fact, regarding the Company’s current views and assumptions with respect to future events regarding its business, as well as other statements with respect to the Company’s plans, assumptions, expectations, beliefs and objectives, the success of the Company’s current and future business strategies, product development, preclinical studies clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. Forward-looking statements are subject to numerous conditions, many of which are beyond the control of the Company. While the Company believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the Company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties, including risks that future clinical trial results may not match results observed to date, may be negative or ambiguous, or may not reach the level of statistical significance required for regulatory approval, as well as other factors set forth in the Company’s most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and other filings made with the U.S. Securities and Exchange Commission (SEC). Thus, actual results could be materially different. The Company undertakes no obligation to update these statements whether as a result of new information, future events or otherwise, after the date of this release, except as required by law. Pasithea Therapeutics Contact Patrick GaynesCorporate Communicationspgaynes@pasithea.com