LB-100

▎药明康德内容团队编辑 本期看点 1. 盐诱导激酶（SIK）抑制剂OMX-0407在1a期临床试验中使1名对多种化疗药物耐药的晚期实体瘤患者的肿瘤完全消失。 2. 治疗帕金森病的变构小分子疗法GT-02287的早期临床结果积极，它能够穿越血脑屏障并与靶标结合，同时展现良好的安全性与耐受性。 药明康德内容团队整理 OMX-0407：公布1a期临床试验数据 iOmx Therapeutics公司宣布，其潜在“first-in-class”的选择性SIK抑制剂OMX-0407的1a期临床试验已顺利完成，即将启动1b期临床试验。OMX-0407能够通过调控酪氨酸激酶信号直接干扰肿瘤细胞增殖。除了这种直接作用方式外，OMX-0407还能通过增强肿瘤坏死因子等死亡受体配体引发的肿瘤细胞凋亡，重塑肿瘤微环境。 初步数据显示，OMX-0407单药治疗是安全且耐受性良好的。OMX-0407对经过多次治疗的晚期实体瘤患者有抗癌活性。其中，一名对多种化疗药物耐药的患者达到了持久的完全缓解（CR），所有肿瘤病灶均消失。此外，生物标志物分析表明，循环血细胞中存在确凿的药理活性证据。 GT-02287：公布1期临床试验数据 Gain Therapeutics宣布其用于治疗帕金森病的在研变构小分子GT-02287在1期试验中获得积极结果。GT-02287是一种口服变构蛋白调节剂，具有可穿越血脑屏障的小分子量。该药物可恢复溶酶体蛋白酶葡萄糖脑苷脂酶（GCase）的功能，该酶由于GBA1基因突变（与帕金森病相关的最常见遗传异常）或其他与年龄相关的压力因素而发生错误折叠和受损。 在帕金森病的临床前模型中，GT-02287恢复了GCase酶功能，减少了聚集的α突触核蛋白、神经炎症和神经元死亡，提高了多巴胺水平，改善动物的运动功能和认知能力，可能具有减缓帕金森病进展的潜力。此外，GT-02287显著降低了血浆神经丝轻链（NfL）水平，这是一种神经退行性疾病的生物标志物。 此次公布的结果显示，GT-02287存在于受试者的脑脊液中，并与外周靶标相结合。在具良好安全性与耐受性的口服剂量下，该药物的血浆水平达到治疗性水平，并可抵达中枢神经系统并与靶标相结合，显示GT-02287是潜在的帕金森病疗法，无论患者是否具有GBA1突变。Gain Therapeutics预计在今年第四季度启动该疗法的1b期临床试验。 Exidavnemab：公布1期临床试验数据 BioArctic公司公布了其靶向聚集的α突触核蛋白的单克隆抗体exidavnemab的两项与艾伯维合作开展的1期研究的积极结果。该候选药物旨在治疗帕金森病等神经退行性疾病。结果显示，85名接受了exidavnemab静脉注射或皮下注射的受试者对治疗的总体耐受性良好。Exidavnemab的半衰期约30天，对聚集的α突触核蛋白具有高亲和力和选择性，这是其在大脑中保持高靶点结合力的关键。 OCU410ST：1/2期临床试验完成第三个队列的给药 Ocugen公司宣布，其针对Stargardt病开发的候选基因疗法OCU410ST的1/2期临床试验已完成第三个队列的给药。OCU410ST利用腺相关病毒（AAV）递送平台在视网膜递送RORA基因，可调节与Stargardt病相关的通路，例如脂褐素形成、氧化应激、炎症、细胞存活网络等。 FTX-101：IND申请获得FDA许可 Find Therapeutics公司宣布，美国FDA已经批准了FTX-101的IND申请，该公司计划在2024年第四季度启动FTX-101在健康志愿者中的1期临床研究。FTX-101是一种潜在“first-in-class”的髓鞘再生剂，旨在恢复慢性视神经病变患者的视力。FTX-101是一种经过合理设计的治疗肽，靶向Plexin A1和Neuropilin 1。Plexin A1和Neuropilin 1是大脑中存在的一种受体复合物，已被证明参与了少突胶质细胞前体细胞迁移和分化成髓鞘化少突胶质细胞的过程。临床前数据显示，FTX-101在脱髓鞘模型中具有很强的髓鞘修复活性。 ID110521156：IND申请获得韩国食品药品安全部许可 Yunovia公司宣布，韩国食品药品安全部（MFDS）已批准其口服的小分子GLP-1受体激动剂ID110521156用于治疗糖尿病和肥胖的IND申请，可启动1期多剂量递增（MAD）研究。ID110521156具有与GLP-1激素相同的作用，包括促进体内胰岛素的合成和分泌、降低血糖水平、调节胃肠道运动以及抑制食欲。作为一款小分子疗法，ID110521156与当前的标准治疗肽类注射剂相比，具有制造方便和使用简便等差异化特性。 Yunovia已于2024年7月完成了ID110521156的1期单剂量递增研究，包括食物效应研究。结果显示，ID110521156的耐受性良好，有望作为一种每日一次疗法。 MB097、MB310：获批在欧盟和英国启动1b期临床试验 Microbiotica公司宣布，其开发的两款活体生物治疗产品（LBP）MB097和MB310已获得监管部门的批准，可以在选定的欧盟国家和英国启动临床研究。MB097是一种每日一次的口服LBP，由九种细菌菌株组成，能够提供免疫检查点抑制剂（ICI）反应所需的微生物组信号，旨在提高ICI的疗效。临床前研究表明，MB097能够刺激免疫系统的核心途径，激活细胞毒性T淋巴细胞和自然杀伤细胞，使其能够杀死肿瘤细胞。此次开展的1b期研究将评估MB097联用PD-1抑制剂pembrolizumab治疗晚期黑色素瘤的安全性和疗效。 MB310是从健康供体中鉴定出的一个明确的微生物群落。临床前研究表明，MB310能够通过至少三种独立的机制发挥对溃疡性结肠炎的治疗作用，包括促进受损肠道上皮屏障的愈合，调节炎症和免疫调节细胞因子的平衡，以及诱导调节性T细胞反应。此次开展的1b期研究将评估MB310治疗溃疡性结肠炎的安全性和疗效。 ▲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] Ocugen Announces Completion of Dosing in Subjects with Stargardt Disease in High Dose Cohort of Phase 1/2 GARDian Clinical Trial of OCU410ST—A Modifier Gene Therapy. Retrieved August 30, 2024, from https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-completion-dosing-subjects-stargardt-disease [2] Study results from phase 1 studies with exidavnemab published in The Journal of Clinical Pharmacology. Retrieved August 30, 2024, from https://www.prnewswire.com/news-releases/study-results-from-phase-1-studies-with-exidavnemab-published-in-the-journal-of-clinical-pharmacology-302231302.html [3] Find Therapeutics Announces FDA Clearance of IND Application for a Phase 1 Study of FTX-101 for the Treatment of Chronic Optic Neuropathy. Retrieved August 30, 2024, from https://www.prnewswire.com/news-releases/find-therapeutics-announces-fda-clearance-of-ind-application-for-a-phase-1-study-of-ftx-101-for-the-treatment-of-chronic-optic-neuropathy-302229869.html [4] Gain Therapeutics Announces Positive Topline Results from the Phase 1 Clinical Trial of GT-02287, a Novel GCase-Targeting Small Molecule Therapy for Parkinson’s Disease. Retrieved August 29, 2024, from https://www.gaintherapeutics.com/newsroom/press-releases/press-releases-2024/ainherapeuticsnnouncesositiveoplineesultsfromth20240829043502 [5] iOmx Therapeutics Initiates Phase Ib with OMX-0407. Retrieved August 30, 2024, from https://www.globenewswire.com/en/news-release/2024/08/22/2933999/0/en/iOmx-Therapeutics-Initiates-Phase-Ib-with-OMX-0407.html [6] AiViva Biopharma Completes Enrollment in a Phase 1 Clinical Trial of AIV007 for Age-Related Macular Degeneration and Diabetic Macular Edema. Retrieved August 30, 2024, from https://aiviva.com/2024/08/aiviva-biopharma-completes-enrollment-in-a-phase-1-clinical-trial-of-aiv007-for-age-related-macular-degeneration-and-diabetic-macular-edema/ [7] First Patient Dosed with LIXTE’s LB-100 in New Clinical Trial to Treat Colorectal Cancer, Collaborating with NKI, Supported by Major Pharma Company. Retrieved August 30, 2024, from https://ir.lixte.com/news-events/press-releases/detail/115/first-patient-dosed-with-lixtes-lb-100-in-new-clinical-trial-to-treat-colorectal-cancer-collaborating-with-nki-supported-by-major-pharma-company [8] ENA Respiratory Progresses Phase Ib Study of its Dry Powder Formulation of Intranasal Innate Immunomodulator INNA-051. Retrieved August 30, 2024, from https://www.globenewswire.com/news-release/2024/08/27/2935974/0/en/ENA-Respiratory-Progresses-Phase-Ib-Study-of-its-Dry-Powder-Formulation-of-Intranasal-Innate-Immunomodulator-INNA-051.html [9] Yunovia Announces IND Approval by the MFDS to Initiate Phase 1 MAD Study for the Small Molecule GLP-1 Agonist. Retrieved August 30, 2024, from https://www.prnewswire.com/news-releases/yunovia-announces-ind-approval-by-the-mfds-to-initiate-phase-1-mad-study-for-the-small-molecule-glp-1-agonist-302232393.html [10] Microbiotica’s Microbiome Medicines in Melanoma and Ulcerative Colitis Gain Regulatory Approvals in EU and UK for Phase 1b Studies. Retrieved August 30, 2024, from https://www.globenewswire.com/news-release/2024/08/27/2935969/0/en/Microbiotica-s-Microbiome-Medicines-in-Melanoma-and-Ulcerative-Colitis-Gain-Regulatory-Approvals-in-EU-and-UK-for-Phase-1b-Studies.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

-Collaboration with NKI and Funding Support for New Colorectal Cancer Clinical Trial by Major Pharma Company- -Distinguished Oncologist Jan Schellens Joins LIXTE as Chief Medical Officer- -Preclinical Data Published in Journal EMBO Reports Shows LB-100 as Potentially Enhancing the Benefit of Immunotherapy- -LIXTE to Present at Two Upcoming Investor Conferences- PASADENA, CA, Aug. 19, 2024 (GLOBE NEWSWIRE) -- LIXTE Biotechnology Holdings, Inc. (“LIXTE” or the “Company”) (Nasdaq: LIXT and LIXTW), a clinical-stage pharmaceutical company developing a new class of cancer therapy to enhance chemotherapy and immunotherapy, today provided an update on the Company’s recent activities. “We are encouraged by the growing interest shown by major pharmaceutical companies in our proprietary compound, LB-100, as demonstrated by their support in clinical trial collaborations,” said Bas van der Baan, LIXTE’s President and Chief Executive Officer. “Highlighting the Company’s recent progress is our new agreement with The Netherlands Cancer Institute, supported by F. Hoffmann- La Roche Ltd. (“Roche”), which is funding the clinical trial in metastatic colorectal cancer and providing atezolizumab (Tecentriq®, a PD-L1 inhibitor) through the imCORE network, an academic industry collaboration that aims at accelerating cancer immunotherapy research through institution sponsored studies. Already underway is a proof-of-concept trial, funded by GSK, of LB-100 plus GSK’s dostarlimab-gxly in ovarian clear cell cancer. “We are seeing encouraging results in the first phase of our clinical trial to determine appropriate dosing and toxicity for treating advanced soft tissue sarcomas with a combination of LB-100 and standard-of-care chemotherapy and expect to see the data from this first phase early in 2025. We are exploring alternative sites, including international locations, for our small cell lung cancer trial, following termination of that clinical trial at City of Hope due to limited patient accrual,” Mr. van der Baan added. Recent Company Highlights: Collaboration with the Netherlands Cancer Institute, supported by Roche, to conduct a new clinical trial (NCT06012734 in clinicaltrials.gov) in immune therapy for unresponsive (MSI Low) metastatic colorectal cancer. LIXTE is providing its lead compound, LB-100, and Roche will provide atezolizumab (Tecentriq®,a PD-L1 inhibitor). The clinical trial will test recent findings that indicate that LB-100 increases recognition of colorectal cancer cells by the immune system.Jan Schellens, M.D., Ph.D., joined LIXTE as Chief Medical Officer effective August 1, 2024. Dr. Schellens brings to the Company more than 25 years of clinical experience as a medical oncologist, pharmacologist and clinical pharmacologist, including more than two decades developing and bringing new drugs to market. Co-author of more 900 publications in peer-reviewed scientific journals, Dr. Schellens has held leadership positions at the Netherlands Cancer Institute in Amsterdam and the Dr. Daniel den Hoed Clinic-Erasmus University in Rotterdam. He was professor of clinical pharmacology at Utrecht University in the Netherlands, where he earned his M.D. degree, and he served as a board member and Chief Medical Officer of Byondis B.V. in Nijmegen, Netherlands. Dr. Schellens also earned a Ph.D. degree in Pharmaceutical Sciences from Leiden University in Leiden, Netherlands.New pre-clinical data in the journal EMBO Reports shows that LIXTE’s lead compound, LB-100, can turn immunologically “cold” tumors “hot,” potentially enhancing the benefit of immunotherapy. In a paper titled, “The Phosphatase Inhibitor LB-100 Creates Neoantigens in Colon Cancer Cells through Perturbation of mRNA Splicing,” the article reported that LIXTE’s collaborators from the Netherlands Cancer Institute have demonstrated that treatment of cancer cells with LB-100 disrupts the normal processing of the mRNA that encodes proteins, thereby generating neo-antigens that are presented to the host immune system. This new mechanism adds to several previous discoveries showing that LB-100 sensitizes cancer cells to immune checkpoint blockade.LIXTE will present at two upcoming investor conferences: the 2004 Summit Summer 2024 Virtual Conference, August 20, 2024, and the H.C. Wainwright 26th Annual Global Investor Conference, September 9-11, 2024. Both conferences will be virtual presentations. About LIXTE Biotechnology Holdings, Inc. LIXTE Biotechnology Holdings, Inc. is a clinical-stage pharmaceutical company focused on new targets for cancer drug development and developing and commercializing cancer therapies. LIXTE has demonstrated that its first-in-class lead clinical PP2A inhibitor, LB-100, is well-tolerated in cancer patients at doses associated with anti-cancer activity. Based on extensive published preclinical data (see www.lixte.com), LB-100 has the potential to significantly enhance chemotherapies and immunotherapies and improve outcomes for patients with cancer. LIXTE’s lead compound, LB-100, is part of a pioneering effort in an entirely new field of cancer biology – activation lethality – that is advancing a new treatment paradigm. LIXTE's new approach is covered by a comprehensive patent portfolio. Proof-of-concept clinical trials are currently in progress for colorectal, ovarian and sarcoma cancers. Additional information about LIXTE can be found at www.lixte.com. Forward-Looking Statement Disclaimer This announcement contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, and Section 21E of the Securities Exchange Act of 1934. For example, statements regarding the Company's financial position, business strategy and other plans and objectives for future operations, and assumptions and predictions about future activities, including the continuing development of proprietary compounds, the planning, funding, coordination and potential results of clinical trials, the patent and legal costs to protect and maintain the Company's intellectual property worldwide, and the Company’s ability to obtain and maintain compliance with Nasdaq’s continued listing requirements, are all forward-looking statements. These statements are generally accompanied by words such as "intend," anticipate," "believe," "estimate," "potential(ly)," "continue," "forecast," "predict," "plan," "may," "will," "could," "would," "should," "expect" or the negative of such terms or other comparable terminology. The Company believes that the assumptions and expectations reflected in such forward-looking statements are reasonable, based on information available to it on the date hereof, but the Company cannot provide assurances that these assumptions and expectations will prove to have been correct or that the Company will take any action that the Company may presently be planning. However, these forward-looking statements are inherently subject to known and unknown risks and uncertainties. Actual results or experience may differ materially from those expected or anticipated in the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, regulatory policies, available cash resources, research results, competition from other similar businesses, and market and general economic factors. Readers are urged to read the risk factors set forth in the Company’s filings with the United States Securities and Exchange Commission at https://www.sec.gov. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. For more information about LIXTE, Contact: info@lixte.com General Phone: (631) 830-7092; Investor Phone: (888) 289-5533 Or PondelWilkinson Inc. Investor Relations pwinvestor@pondel.comRoger Pondel: (310) 279-5965; Laurie Berman: (310) 279-5962