Olaptesed Pegol

TME Pharma provides update on its activities TME Pharma enters the final evaluation phase of advanced discussions with two potential partners for a license agreement.Discussions and potential partnership are aimed at enabling the further development of the phase2-development of flagship product NOX-A12.NOX-A12 holds FDA and EU Orphan Drug and FDA Fast Track designations in glioblastoma, supported by recent peer-reviewed publication in Nature Communications.With estimated yearly peak sales potential (upon successful market approval and commercialization) of approximately $1 billion, NOX-A12 is a highly valuable flagship drug for treating brain cancer for which there is currently no known cure.TME Pharma has decided to focus its strategy for its second clinical asset strategy for NOX-E36 also on a licensing deal. Discussions regarding this are at a less advanced stage than those for NOX-A12.TME Pharma decided not to continue with the GRDC-project, but continues its efforts to bring alternative and additional business to the listed holding entity.TME Pharma reports a share transaction by the CEO, notified to the AFM in accordance with Article 19 MAR. Berlin, Germany, August 24, 2026, 8.00am CET – TME Pharma N.V. (Euronext Growth Paris: ALTME), a clinical-stage biotechnology company specializing in the development of novel therapies for brain cancer and eye diseases, today provides an update on its activities, including the strategic development options for its lead oncology asset, NOX-A12. Following comprehensive discussions and due diligence over recent months, TME Pharma has advanced conversations with two potential partners. The company is now approaching the decision-making stage to select the optimal partner and best path forward for the late-stage development and commercialization of NOX-A12. Strategic Decision Framework & Value CreationThe evaluation of these final strategic options extends beyond transactional valuation and financial terms. TME Pharma is strictly focused on structuring the continuation of the landmark GLORIA trial in a manner that creates the highest long-term value. Key strategic parameters currently under final review include: Trial Architecture & Regulatory Pathways: Maximization of the likelihood and confidence that the next step of clinical development will be funded and conducted by selecting a committed partner who is aligned with TME Pharma in the goal to perform the upcoming GLORIA study in a way that creates optimal additional value.Commercial potential: Structuring the research framework to ensure that NOX-A12 reaches its full peak revenue potential within the most favorable timeframe to maximize patent-protected revenues.Financial conditions: TME Pharma NV and its shareholders need to have a clear picture of a solid short-term future so that there is clarity regarding cash flow. Future potential value must be secured if the drug can be successfully brought to market. Robust Scientific Validation and Significant Peak Sales Potential for NOX-A12The strong clinical foundation of NOX-A12 in glioblastoma—an aggressive form of brain cancer with limited treatment options—is supported by compelling data from the GLORIA trial. The efficacy of the NOX-A12 "Triple Therapy" combination (NOX-A12, radiotherapy, and anti-VEGF / bevacizumab) was recently highlighted in a high-impact peer-reviewed publication in Nature Communications, demonstrating significantly improved overall survival (19,9 months against 9,5 months) compared to standard-of-care benchmark cohorts. Building on these findings, TME Pharma has a randomized, controlled Phase 2 trial protocol ready-to-go in Germany and approved in the US, secured Fast Track Designation from the U.S. FDA and Orphan Drug Designation (granted by both the U.S. FDA and the European Medicines Agency, EMA) for NOX-A12 in glioblastoma. The Total Addressable Market for Glioblastoma is estimated at 2.5 billion. With estimated peak sales potential (upon successful market approval and commercialization) expected of approximately $1 billion, NOX-A12 represents a highly valuable flagship asset capable of transforming care in treatment-resistant solid tumors. Capitalizing on Favorable Biotech Market DynamicsTME Pharma has observed a clear improvement in market sentiment, characterized by increased demand from the sector for the acquisition and joint development of promising clinical-stage drugs. In addition, the stock markets are showing a positive trend, with renewed capital inflows into biotech companies. TME Pharma is well-positioned to capitalize on these favorable market conditions, supported by a strong asset portfolio and positive outlook. Furthermore, as announced on March 9, 2026, the company’s financial flexibility has been extended into the second quarter of 2027, providing the flexibility to find the optimal partner for NOX-A12. "Our discussions in the last months have yielded concrete strategic interest from two parties. As we enter the final evaluation phase, our priority is to select the partner and structuring strategy that maximizes both the commercial value of NOX-A12 and its clinical benefit for patients. We look forward to updating the market as soon as a decision has been made." Said Diede van den Ouden, CEO of TME Pharma NV NOX-E36The study announced in January has now been completed, and its objective to establish and validate a detection method for toxicology studies to support clinical ophthalmology development has been successfully achieved.In addition, TME Pharma continues to explore partnering opportunities for NOX-E36 and will update the market if and when there is a concrete development to report. GRDC and alternative activitiesOn November 5th 2025, TME Pharma announced that it had signed a LOI with a German Resource Development Company (‘GRDC’). TME Pharma has decided not to continue its collaboration with GRDC. As a publicly traded holding company, TME Pharma also intends to develop alternative business activities in addition to entering into licensing agreements for its lead biotech assets. The objective is to create additional value for shareholders and to generate cash flow from the Company’s own operations. TME Pharma will therefore continue its search for sound and future-proof companies and activities. It will inform the market when interesting opportunities arise and seek shareholder approval before making a final decision. Share transaction by the CEO TME Pharma today announces that it has received notification that Diede van den Ouden, Chief Executive Officer and a Person Discharging Managerial Responsibilities (“PDMR”), has sold 460,050 ordinary shares on Euronext Growth Paris on August 19, 2026 at an average price of EUR 0,1107 per share, pursuant to an irrevocable sell instruction with pre-set price limits and a volume cap, placed with his broker on May 20, 2026 and recorded by the broker’s compliance department. Following this transaction, Mr. Van den Ouden interests remain aligned with those of shareholders. Mr. van den Ouden holds 2,214,950 ordinary shares, approximately 6.8 million warrants (provided as part of two loan agreements by Mr. van den Ouden for a total amount of € 520,956 entered into in May 2025 and and August 2025) and 3.2 million options in the Company. The transaction has been notified to the AFM in accordance with Article 19 of the Market Abuse Regulation, and the overview of the CEO’s transactions in the Documentation section of the Company’s website has been updated accordingly. The orders were solely intended to diversify the risks across the entire portfolio. Currently, the broker still has 3 irrevocable sell instructions from Mr. van den Ouden outstanding: 214,950 ordinary shares with a pre-set minimum price limit of €0.11, and two irrevocable sell instructions of 1.0 million ordinary shares each with pre-set minimum price limits of €0.14 and €0.17, respectively, capped at a maximum of 15% of the daily trading volume, and valid until the end op 2026. For more information, please contact:TME Pharma N.V.Diede van den Ouden, CEOir@tmepharma.comwww.tmepharma.com About TME Pharma TME Pharma is a clinical-stage biotechnology company specializing in the development of novel therapies for cancer and eye diseases. The Company’s lead compounds have been designed to act on the tumor microenvironment (TME) and the cancer immunity cycle by breaking tumor protection barriers against the immune system and blocking tumor repair. TME Pharma has currently 2 main assets for development: NOX-A12 (olaptesed pegol, an anti-CXCL12 L-RNA aptamer), which is being studied (GLORIA Phase 1/2 clinical trial) in newly-diagnosed brain cancer patients who will not benefit clinically from standard chemotherapy. The US FDA and the German BfArM have approved the design of a randomized Phase 2 trial in glioblastoma, and TME Pharma was awarded Fast Track Designation by the FDA for NOX-A12 in combination with radiotherapy and bevacizumab for use in the treatment of the aggressive adult brain cancer, glioblastoma. NOX-A12 in combination with radiotherapy had also previously received orphan drug designation (ODD) for glioblastoma in the United States and glioma in Europe. NOX-E36 (emapticap pegol, L-RNA aptamer inhibiting CCL2 and related chemokines), which is being evaluated in ophthalmic diseases with a high need for well-tolerated therapies with anti-fibrotic effect. The Company is currently seeking opportunities to secure the financial resources to unlock the value of NOX-A12 and NOX-E36. These steps include: Raising funds from alternative sourcesPursuing stable, cash-generating business opportunities to achieve positive operational cash flow for the CompanyLeveraging tax loss carry forwards Further information can be found at: www.tmepharma.com. About the GLORIA Study The GLORIA (NCT04121455) ‘ready to go’-study is TME Pharma’s dose-escalation, Phase 1/2 study of NOX-A12 in combination with radiotherapy in first-line partially resected or unresected glioblastoma (brain cancer) patients with unmethylated MGMT promoter (resistant to standard chemotherapy). About the OPTIMUS Study OPTIMUS (NCT04901741) is TME Pharma’s planned open-label two-arm Phase 2 study of NOX-A12 combined with pembrolizumab and nanoliposomal irinotecan/5-FU/leucovorin or gemcitabine/nab-paclitaxel in microsatellite-stable metastatic pancreatic cancer patients. Disclaimer Translations of any press release into languages other than English are intended solely as a convenience to the non-English-reading audience. The company has attempted to provide an accurate translation of the original text in English, but due to the nuances in translating into another language, slight differences may exist. This press release includes certain disclosures that contain "forward-looking statements.” Forward-looking statements are based on TME Pharma’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the risks inherent in oncology drug development, including clinical trials and the timing of and TME Pharma’s ability to obtain regulatory approvals for NOX-A12 as well as any other drug candidates. Forward-looking statements contained in this announcement are made as of this date, and TME Pharma undertakes no duty to update such information except as required under applicable law. Attachment ENG_TME Pharma provides update on its activities

昨天我们介绍了核酸适配体的基本概念——一种可以在体外筛选、化学合成的"化学抗体"。今天，我们抛开概念，聚焦数据：当适配体和抗体在实际应用中正面对决时，差距到底有多大？ 我们将从五个关键维度——蛋白质组覆盖率、体内稳定性极限、检测灵敏度、工业复用性和储运成本——用已经发表的真实实验数据，逐一拆解。一、蛋白质组学平台的"分歧"：同一批血清，两组结果 2026年发表在Nature Communications上的一项里程碑研究（Nicholas et al.），首次大规模头对头比较了适配体蛋白质组学平台和抗体蛋白质组学平台在真实人群样本中的表现。 研究设计和关键数字：1930名参与者 ，覆盖非洲裔和欧洲裔两个群体SomaScan 7k （适配体平台）：基于SOMAmer化学修饰适配体，同时测量~7000种蛋白质Olink Explore 3072 （抗体平台）：基于PEA（邻近延伸分析）技术，同时测量~3072种蛋白质重叠靶标：2157种蛋白质 核心发现：两个平台之间的中位Spearman相关系数仅为0.30，呈明显的双峰分布（一个峰在~0.15，另一个峰在~0.60）。 这不是说哪个平台"不准"。进一步分析表明，约25-30%的信号差异由蛋白质改变型变异（PAV）驱动——适配体和抗体倾向于识别同一蛋白质的不同构象或表位。 产业启示：适配体不是抗体的"低成本替代品"，而是提供了一种正交的蛋白质检测视角。对于生物标志物发现而言，同时使用两种平台可以获得比单一平台更完整的蛋白质组图谱。这也是Illumina在2025年斥资4.25亿美元收购SomaLogic的底层逻辑——不是买一个"更便宜的抗体平台"，而是买一个抗体无法覆盖的蛋白质组维度。二、体内稳定性：L-适配体把半衰期从分钟级拉到天级 抗体在体内可以稳定存在数天到数周，这是它最大的优势之一。未修饰的DNA适配体在血清中的半衰期通常只有30-120分钟——体内的核酸酶会迅速将其降解。 但有一类特殊的适配体，完全破解了这个难题：L-适配体（Spiegelmer）。 自然界所有的DNA和RNA都是D-构型（右旋），体内的所有核酸酶也只能识别D-构型的核酸。如果将核糖从D-构型翻转为L-构型（左旋），得到的镜像核酸分子将不被任何天然核酸酶识别——半衰期直接从分钟级跃升到天级。 修饰策略 血清半衰期 成本增幅 临床阶段 未修饰DNA 0.5-2小时 基准 仅体外应用 3'-inverted dT封端 ~8小时 +5% 研究级 2'-F修饰RNA >48小时 +30-50% 临床前 40kDa PEG化 延长9-12小时 +100% Macugen(FDA已批)L-适配体(Spiegelmer)>72小时 高(需L-靶标)Phase II临床 德国的NOXXON Pharma正在开发基于Spiegelmer技术的药物管线。其核心候选药物NOX-A12（靶向趋化因子CXCL12）正在脑肿瘤（胶质母细胞瘤）的临床试验中。由于Spiegelmer完全不受酶降解，它甚至可以考虑口服给药——这是传统抗体无法实现的给药途径。 当然，Spiegelmer也有其固有的技术壁垒：筛选过程中需要使用L-构型的靶标蛋白（因为镜像识别），这大大增加了靶标制备的难度和成本。但这种"终极稳定性"的潜力，使得它成为适配体药物领域最受关注的技术方向之一。三、检测灵敏度：SERS适配体传感器的aM级奇迹 在食品安全检测领域，灵敏度直接决定了技术能否落地。赭曲霉毒素A（OTA）是粮食中最常见的真菌毒素之一，国家标准规定的限量通常在μg/kg级（ppb级）。 传统抗体ELISA对OTA的检出限（LOD）通常在0.1-1 ng/mL（约0.25-2.5 nM）。而基于表面增强拉曼散射（SERS）的适配体传感器，对OTA的检出限达到了惊人的0.0078 aM（7.8×10⁻²¹ M）。 这个数字意味着什么？做一个直观的类比： 传统ELISA相当于在一个浴缸里检测OTA SERS适配体传感器相当于在3个标准奥运游泳池里检测OTA 达到这种灵敏度的技术原理是SERS的"热点效应"——金或银纳米颗粒表面的局域表面等离子体共振可以将拉曼散射信号放大约10⁶-10⁸倍。适配体作为识别元件，其尺寸仅约2 nm，可以精确嵌入这些"热点"区域，利用靶标结合引起的构象变化产生可检测的SERS信号偏移（Chemical Science, 2023）。 这个案例揭示了一个核心事实：适配体在某些检测体系中能实现抗体无法达到的灵敏度极限——原因不在于"亲和力更高"，而在于适配体的小尺寸和核酸本质使其可以集成到纳米光学结构中，而抗体（~15 nm）在这类体系中反而因为位阻效应成为瓶颈。四、工业复用性：一根适配体层析柱的200次循环 生物制药的下游纯化是一个百亿美元级别的市场。其中最关键的亲和层析步骤，长期被蛋白A填料垄断——利用蛋白A与抗体Fc区的特异性结合来纯化单克隆抗体。 蛋白A层析的痛点（Materials Today, 2025）：成本极高： $10,000+/L填料，占单抗生产成本的30-50%寿命有限： 通常50-100次循环后性能显著下降清洗苛刻： 低pH（2.5-3.5）洗脱，对层析柱和抗体均有损伤配基脱落： 蛋白A是蛋白本身，会在使用过程中浸出，需额外检测 基于DNA适配体的亲和层析柱，在上述四个维度上都展现了碾压级优势： 性能指标 蛋白A层析柱 适配体层析柱 填料成本/L $10,000+ $2,000-$3,500 重复使用次数 50-100次 >200次 清洗条件 低pH 2.5-3.5 0.5M NaOH (媲美CIP) 配基脱落风险 有（蛋白本质） 极低（核酸本质） 洗脱条件 酸性（损伤抗体） 中性或温和条件 适配体柱可以耐受0.5M NaOH的在线清洗（CIP），这在生物制药生产中意味着可以和整个生产线的其他层析步骤共用同一套CIP流程——既降低了操作复杂度，也减少了交叉污染风险。材料成本降低到1/3到1/5，循环次数翻倍以上，综合来看，单次纯化的成本可以降低5-10倍。五、储运成本："无需冷链"的经济账 最后一个维度，也是最容易被忽视的一个：储运成本。 抗体和基于抗体的诊断试剂（如胶体金试纸条、ELISA试剂盒）在储运过程中对温度敏感。典型要求： 抗体试剂：2-8°C冷链运输和储存 试纸条：4°C储存，有效期6-12个月 ELISA试剂盒：-20°C保存关键组分 适配体则完全不同。在干燥状态下，DNA适配体在常温下的稳定性可维持2年以上。即使用于侧流层析（LFIA）试纸条，适配体-金纳米颗粒偶联物在25°C、60%相对湿度的加速老化条件下，6个月后信号损失不超过15%（Sharma et al., Biotechnol Adv, 2017）。 这意味着什么？以食品安全快检为例： 一个县的食品安全检测点如果用抗体试纸条，需要配备冰箱和冷链物流，年维护成本可达数万元 换用适配体试纸条，试纸条本身成本降低（化学合成 vs 生物生产），冷链成本直接清零 在中国这样的发展中国家，基层食品安全的痛点不是"没有检测方法"，而是"有方法但用不起、存不住"。适配体在这个维度上的优势，远比实验室里的Kd值更有现实意义。结语：数据不会骗人，但产业需要时间 回到标题的问题：适配体凭什么被称为"下一代分子识别工具"？ 五个维度的数据给出了同一个答案：适配体不是"比抗体更好"，而是"能做抗体做不到的"。 抗体看蛋白质的一个视角，适配体看另一个——Nature Communications 2026已证明 抗体在体内活不过几小时的问题，L-适配体用镜像化学彻底解决 抗体ELISA做不到的单分子检测，SERS适配体做到了aM级别 抗体层析柱的清洗困境，适配体用NaOH轻松搞定 抗体试纸条离不开冷链，适配体常温放两年 但另一个数据同样值得冷静思考：适配体技术诞生至今35年，目前全球只有1款药物获批（Macugen，2004年），且已被抗体药物在商业上超越。产业化不是技术参数的简单累加，它需要GMP供应链、监管审批路径、临床验证数据，以及一个成熟的市场生态。 好在，这些条件正在加速形成。参考文献 Nicholas JC, Katz DH, Tahir UA, et al. Cross-ancestry comparison of aptamer and antibody proteomic measures. Nature Communications, 2026, 17: 1054. Sharma TK, Bruno JG, Dhiman A. ABCs of DNA aptamer and related assay development. Biotechnology Advances, 2017, 35(2): 275-301. Materials Today. Recent advances in aptamer discovery and applications. Materials Today, 2025, 88: Table 1. Chemical Science. Aptamer chemical biology: from SELEX to biosensors. Chemical Science, 2023: Table 1. Röthlisberger P, Hollenstein M. Aptamer chemistry. Advanced Drug Delivery Reviews, 2018, 134: 3-21.