Atezolizumab

In combination with atezolizumab or durvalumabStudy conducted under the CRADA agreement between NCI and Oryzon MADRID and CAMBRIDGE, Mass., April 15, 2025 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today that the first patient has been dosed in a Phase I/II trial of iadademstat, Oryzon’s potent and selective LSD1 inhibitor, in combination with immune checkpoint inhibitors (ICI) in first line small cell lung cancer (SCLC) patients with extensive disease, sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. This is the first clinical trial testing the combination of iadademstat with ICI. The trial (NCT06287775), titled “A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer”, will evaluate the safety, tolerability, dose finding and efficacy of iadademstat in combination with an ICI, either atezolizumab or durvalumab, in patients with extensive-stage SCLC who have initially received standard of care chemotherapy and immunotherapy. This Phase I/II clinical study is conducted and sponsored by the NCI, with Dr. Charles Rudin, from the Memorial Sloan Kettering Cancer Center (MSKCC) as the Principal Investigator. The trial will be conducted at a number of prestigious cancer centers in the US, including the MSKCC, the JHU Sidney Kimmel Comprehensive Cancer Center and many others. The trial plans to enroll 45-50 patients and will be carried out under a Cooperative Research and Development Agreement (CRADA) that Oryzon has in place with the NCI. Dr. Carlos Buesa, Oryzon’s CEO, stated: “We are very excited to have the first patient dosed in this study. The biology underlying iadademstat’s ability to make SCLC cells visible to the immune system and to boost significantly the number and the activation of cytotoxic CD8+ T cells is fascinating. Moreover, prior analyses of several Phase III trials in SCLC indicate that low LSD1 expression is a key factor in determining patients' likelihood of responding and surviving. If this trial confirms the preliminary findings reported by researchers at MSKCC and others, it would reinforce the rationale for this combination as a therapeutic option for this critically underserved patient population. In the event of positive results, the company could also initiate a complementary trial to generate additional data in support of a potential accelerated registration strategy.” About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About IadademstatIadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation & The Lancet Haematology, 2024, 11(7):e487-e498). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations, and in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study led by OHSU and in a trial sponsored by the U.S. National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI to collaborate on further clinical development of iadademstat in different types of hematologic and solid cancers. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is in a collaborative Phase II trial with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and in a Phase I/II randomized trial in 1L ED-SCLC in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center. Oryzon is further expanding the clinical development of iadademstat through additional investigator-initiated studies. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This document does not constitute an offer or invitation to purchase or subscribe shares in accordance with the provisions of Regulation (EU) 2017/1129 of the European Parliament and of the Council of 14 June 2017, and/or the restated text of the Securities Market Law, approved by Law 6/2023 of 17 March, and its implementing regulations. Nothing in this document constitutes investment advice. In addition, this document does not constitute an offer of purchase, sale or exchange, nor a request for an offer of purchase, sale or exchange of securities, nor a request for any vote or approval in any jurisdiction. The shares of Oryzon Genomics, S.A. may not be offered or sold in the United States of America except pursuant to an effective registration statement under the Securities Act of 1933 or pursuant to a valid exemption from registration.. Spain Oryzon IR & Media, Europe & US Patricia Cobo/Mario Cordera Emili Torrell Sandya von der Weid Atrevia Chief BD Officer LifeSci Advisors, LLC +34 91 564 07 25 +34 673 33 97 65 +34 93 515 1313 +41 78 680 05 38 pcobo@atrevia.com mcordera@atrevia.com etorrell@oryzon.com svonderweid@lifesciadvisors.com

在中国，胃癌胃癌堪称威胁民众健康的“罪魁祸首”之一，全球近半数新发与死亡病例在此发生。多数患者确诊时已至中晚期，治疗困境重重。 但值得欣慰的是，近年来，随着新型靶向药物、CAR-T 细胞疗法及癌症疫苗等创新抗癌技术相继问世，胃癌治疗格局正迎来突破性变革：晚期患者生存期显著延长，生命希望重燃。除已获批疗法外，更多前沿药物仍在加速研发，为无数患者铺就长生存之路。下面全球肿瘤医生网小编，就为大家盘点一下，在胃癌治疗领域成果卓越的几款癌症疫苗，以实例见证医学进步，助力病友们坚定抗癌信心！ 一、两款癌症疫苗重磅登场，点亮胃癌患者完全缓解新希望 （一）国研Neo-MoDC疫苗：助晚期胃癌患者病灶完全消失，持续缓解25个月创纪录 2022年6月，国际重磅期刊《Nature》子刊报道的一个“应用国研新抗原Neo-MoDC疫苗，治疗晚期胃癌的案例”，引起了学界震动。 一位IV期（Bormann III型）转移性胃癌患者，虽经历D2根治性远端胃切除术、FOLFOX方案治疗等，但仍出现腹膜与淋巴结转移。在临床已无合适他的治疗选择时，遂入组接受Neo-MoDC治疗，这是我国自主研发的一款个性化新抗原树突状细胞（DC）疫苗，通过激活人体免疫系统与T细胞，精准攻击癌细胞。 结果显示：该患者在接受Neo-MoDC+免疫检查点抑制剂（PD-1）联合治疗后， 肿瘤迅速缩小，最终病灶完全消失并持续长达25个月 （详见下图）。据悉， 这是全球首个通过新抗原DC疫苗联合PD-1疗法，实现晚期胃癌完全且持久缓解的临床案例 ，标志着DC疫苗治疗领域的重大突破！ ▼治疗期间目标肿瘤病变的代表性图像 ▲图源“npj”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 注：黄色箭头代表目标肿瘤病变；蓝色箭头代表肿瘤病变完全消退。 （二）新抗原mRNA cevumeran疫苗，助胃癌患者达完全缓解 Cevumeran（商品名：BNT122，研发代号：RO7198457）是一款个体化新抗原mRNA疫苗，可编码20余种肿瘤特异性新抗原。其核心优势在于通过分析患者肿瘤组织的体细胞突变数据，量身定制疫苗序列，精准激活机体对多种新抗原的T细胞应答，从而降低肿瘤复发风险并延长生存期。 《Nature Medicine》发表的1期GO39733临床研究（NCT03289962）揭示了cevumeran在晚期实体瘤中的突破性数据。 结果显示：在50µg单药治疗队列中，， 一位胃癌（Gastric cancer）患者的最佳总体反应（BOR）达到完全缓解（CR） （详见下图），为个体化新抗原疫苗的临床应用提供了关键实证。 ▼自基因cevumeran单药治疗对靶病变的影响 ▲图源“nature”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 三、小编寄语 癌症作为一种高度突变的复杂疾病，很难仅靠单一治疗手段，达到理想的治疗效果。目前比较理想的治疗手段是在权威医院（手术、放化疗等）传统治疗的基础上，结合患者病情、个体情况，突变靶点、经济状况等，辅助靶向药、免疫细胞治疗（如CAR-T、TCR-T、TIL细胞疗法、癌症疫苗）、质子治疗、电场疗法等新型治疗手段，以达到巩固传统治疗效果、降低肿瘤复发风险、提高患者生存质量、延长生存期等目的。 其中，癌症疫苗历经数十年的发展，逐渐从基础研究转向了临床研究阶段，近年来更是取得了突破性进展。NHS国家癌症临床主任Peter Johnson教授曾说过：“我们知道，即使手术成功，癌症有时也会复发。这可能与体内仍残留少量癌细胞有关，但使用针对这些残留癌细胞的癌症疫苗，或许可以阻止这种情况的发生”。 四、参考资料 [1]Guo Z,et al.Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer. NPJ Precis Oncol.2022 Jun 3;6(1):34. https://www.nature.com/articles/s41698-022-00279-3 [2]Lopez J,et al.Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial[J]. Nature Medicine, 2025: 1-13. https://www.nature.com/articles/s41591-024-03334-7 本文为全球肿瘤医生网原创，默认授权禁止转载。