AFM-24

来源：药渡 撰文：Maskey    编辑：哦呼 欧洲杯激战正酣，各国球队为了荣誉和胜利而奋力拼搏。但如果换个角度，设想一下，若是让这些参加欧洲杯的国家在“最佳药物管道”这一特殊领域展开角逐，谁又将脱颖而出，问鼎桂冠呢？ 目前，世界各地的制药公司都在竞相开发最具创新性和最有效的常见人类疾病治疗方法。他们进行临床前研究和临床试验，希望他们的治疗方法能得到监管机构的批准。监管机构会为可能治疗严重疾病的新型试验药物授予突破性疗法认定和快速通道认定。近年来，越来越多的新型治疗方法（如细胞和基因疗法、单克隆抗体和抗体-药物偶联物）已获得监管机构的批准[1]。 因此，制药公司正在加大对这些创新疗法的开发投入。一些最大的制药公司位于欧洲，所有这些公司都在建立庞大的创新疗法药物管线。 图1.近年来美国食品药品监督管理局(FDA)批准的新分子实体（NME）和生物制剂的数量【1】 图2.获得批准的单克隆抗体百分比【2】    德国 拜耳是德国领先的制药公司之一。老年性黄斑变性药物阿柏西普、前列腺癌药物达罗他胺、抗凝药物利伐沙班和慢性肾病药物Finerenone是其产品组合中最有价值的药物。该公司正在开发33种新疗法，其中19种疗法正在进行1期临床试验，3种疗法正在进行2期临床试验[3]。该公司正在测试几种创新的重组腺相关病毒 (rAAV) 基因疗法，用于治疗亨廷顿氏病、帕金森氏病和庞贝氏病。 另一家德国制药公司勃林格殷格翰正在临床试验中测试40多种药物[4]。该公司已经开发出用于治疗多种疾病的小分子药物、T细胞接合剂和癌症疫苗。该公司的产品组合中包括有效的治疗药物，包括肺纤维化药物尼达尼布和抗糖尿病药物恩格列净。 默克集团是另一家德国制药公司，正在开发10多种用于治疗癌症、自身免疫性疾病和疟疾的药物[5]。其药物管线中一些有前景的在研药物包括小分子药物Enpatoran、抗体药物偶联物M9140和免疫检查点抑制剂avelumab。 BioNtech也是一家德国大型生物制药公司，与辉瑞公司成功开发了COVID-19疫苗BNT162b2(Comirnaty)。该公司还在对患有不同类型癌症（如结直肠癌和胰腺导管腺癌）的患者测试癌症疫苗Autogene Cevumeran[6]。BioNTech SE正在临床试验中测试30多种治疗方法，包括mRNA治疗、细胞疗法、基于蛋白质的疗法和小分子免疫调节剂。这些治疗方法旨在治疗癌症和传染病。其管道中最有前途的候选药物之一是单克隆抗体Gotistobart，正在非小细胞肺癌患者中进行测试。该公司开发的其他重要药物包括双特异性抗体Acasunlimab、BNT312/GEN1042和BNT327/PM8002。 德国规模较小的生物制药公司也在努力扩大其药物研发线。Ethris开发了一种新型吸入式mRNA治疗药物ETH47，用于治疗呼吸道病毒感染。海德堡制药公司研发线中的一种主要候选药物是用于治疗多发性骨髓瘤的抗体-药物偶联物HDP-101。Affimed开发了用于治疗非小细胞肺癌的双特异性先天细胞接合剂AFM24。Atai Life Sciences研发线中有几种用于治疗抑郁症和焦虑症的药物。    法国 法国最大的制药公司赛诺菲拥有庞大的药物管线，包括60多种临床阶段治疗药物[7]。该公司正在开发双特异性抗体、疫苗、单克隆抗体、NK细胞接合剂、酶替代疗法和基因疗法。其最畅销的药物是与Regeneron合作开发的单克隆抗体度匹鲁单抗。该药物已被批准用于多种适应症，例如特应性皮炎、嗜酸性食管炎和哮喘。其投资组合中的另一项重要资产是与阿斯利康合作开发的呼吸道合胞病毒 (RSV) 疫苗nirsevimab。其管线中的几种药物，如小分子药物SAR441566、单克隆抗体Amlitelimab和单克隆抗体Frexalimab，都有可能获得监管部门的批准并成为变革性的治疗方法。 法国还有几家不太知名的制药公司，包括Genfit、Abivax和Enterome，它们正在研发新的创新疗法。Genfit正在开发治疗胆管癌和高氨血症的新疗法。今年6月，FDA加速批准其药物Elafibranor，用于治疗原发性胆汁性胆管炎。Amolyt Pharma的药物管线包括治疗肢端肥大症和甲状旁腺功能减退症的药物。Enterome正在开发新的基于肽的免疫疗法，用于治疗惰性非霍奇金淋巴瘤和胶质母细胞瘤。Abivax已开发小分子药物obefazimod，用于治疗溃疡性结肠炎和克罗恩病。Antabio正在开发治疗铜绿假单胞菌感染和医院内感染的药物。Ipen的临床阶段管线中有10多种药物，包括治疗偏头痛、阿拉吉耶综合征、多发性骨髓瘤和胆道闭锁的药物[8]。    英国 英国-瑞典制药公司阿斯利康拥有最大的药物管线之一，拥有超过90种不同的临床阶段治疗药物[9]。该公司正在开发用于治疗癌症、呼吸系统疾病、代谢疾病、肾脏疾病和心血管疾病的新药。它拥有非常强大的肿瘤学产品组合，包括抗体药物偶联物trastuzumab deruxtecan和酪氨酸激酶抑制剂奥希替尼。该公司还通过购买和公司收购在其管线中增加了嵌合抗原受体T细胞(CAR-T)疗法、呼吸道合胞病毒疫苗和2型糖尿病药物。其与第一三共联合开发的抗体药物偶联物Datopotamab deruxtecan可能很快会在美国获得监管部门的批准。 葛兰素史克 (GSK) 已开发出60多种用于治疗艾滋病毒、癌症、传染病以及呼吸道和免疫疾病的药物。该公司最近开发的最成功的治疗方法之一是呼吸道合胞病毒疫苗Arexvy，该疫苗已获得FDA批准用于50岁以上的人群[10]。该公司在开发高效疫苗方面有着良好的记录，例如Gardasil、Arexvy和 Shingrix。今年，GSK收购了一家新兴生物制药公司Aiolos Bio，该公司开发了一种新型哮喘药物。 Verona Pharma开发了一种用于治疗慢性阻塞性肺病的药物Ensifentrine，今年可能会获得FDA的批准。Ellipses Pharma正在对2期临床试验中的四种药物进行评估[11]。该公司正在研发不同类别的药物，例如用于治疗癌症的双重抑制剂、纳米颗粒-药物偶联物和选择性雄激素受体调节剂 (SARM)。Evox Therapeutics正在临床前研究中开发外泌体递送的腺相关病毒(AAV) 基因疗法，用于治疗苯丙酮尿症和心血管疾病[12]。    瑞士 罗氏的研发管线中有70多种药物[13]。该公司开发的转化疗法之一是双特异性单克隆抗体Faricimab，用于治疗糖尿病性黄斑水肿和新生血管性年龄相关性黄斑变性。其他成功获得监管部门批准的重要治疗方法是抗体-药物偶联物polatuzumab vedotin-piiq双特异性单克隆抗体Emicizumab和双特异性抗体glofitamab-gxbm。其阿尔茨海默氏症药物gantenerumab在3期临床试验中未能显示出疗效。该公司已将小分子抑制剂camonsertib和双特异性抗体RG6286等抗癌药物从其管线中移除。罗氏正在优先考虑那些更有可能获得监管机构批准的治疗方法。 诺华是全球销售额最大的制药公司之一。其药物研发管线中有超过60种治疗方法[14]。其研发管线包括单克隆抗体、CAR-T疗法、基因疗法、小分子抑制剂、合成小干扰RNA (siRNA) 和其他治疗不同疾病的药物。其产品组合中的重要资产是心力衰竭组合药物Sacubitril/valsartan、多发性硬化症药物 Ofatumumab、乳腺癌药物ribociclib和高脂血症药物inclisiran。其布鲁顿氏酪氨酸激酶(BTK)抑制剂remibrutinib很有可能被批准用于治疗慢性自发性荨麻疹。 ADC Therapeutics正在临床试验中测试大约3种治疗方法[14]。该公司开发了抗体药物偶联物loncastuximab tesirine-lpyl，该药物已获得FDA加速批准，用于治疗大B细胞淋巴瘤。Alentis Therapeutics的研发管线中有大约4种治疗方法，包括抗体药物偶联物和单克隆抗体[15]。 图3.销售额最高的制药公司和治疗方法【16】    丹麦 丹麦制药公司诺和诺德是欧洲最大的制药公司之一。诺和诺德的药物管线包括35多种药物，其中大多数药物正在对患有非酒精性脂肪性肝炎和糖尿病等慢性疾病的患者进行测试[17]。其最成功的药物是用于治疗肥胖症和糖尿病的索马鲁肽。诺和诺德开发了一种每周一次的糖尿病药物胰岛素Icodec，该药物已获准在欧洲使用。Genmab有10多种治疗方法正在临床试验中测试。它与辉瑞联合开发了抗体-药物偶联物tisotumab vedotin，该药物已获准用于治疗宫颈癌。其T细胞结合双特异性抗体epcoritamab也已获准用于治疗弥漫性大B细胞淋巴瘤。    比利时 比利时生物制药公司Union Chimique Belge (UCB)正在开发用于治疗系统性红斑狼疮和严重纤维肌痛综合征等神经和自身免疫性疾病的药物。其研发管线中有大约10种小分子药物和单克隆抗体[18]。其药物bimekizumab已在美国获批用于治疗斑块状银屑病。    荷兰 荷兰制药公司Argenx开发了抗体片段efgartigimod，该片段已获批用于治疗全身性重症肌无力。该公司正在对患有干燥综合征和特发性炎症性肌病的患者进行efgartigimod测试。该公司正在研发的另一种药物是单克隆抗体Empasiprubart，该药物已被开发用于治疗多灶性运动神经病。 总之，欧洲几家大型制药公司正在开发用于多种疾病的一流和一流药物。这些公司通过研究、收购和与其他公司的联合合作建立了强大的药物管线。在这些欧洲国家中，德国、英国、瑞士和法国都有成熟和新兴的生物制药公司，专注于开发创新疗法。大多数公司都开发出了有效的治疗方法，并已在许多国家获准使用。 编者按： 在这场假想的“最佳药物管道”欧洲杯中，每个国家都有机会展现自己的实力和风采，我们都期待看到其在“赛场”上展现出最佳的状态。未来我们应给予各国更多在医药研究上付出与收获的关注，以及他们为全人类的健康福祉所作出的杰出贡献。 参考文献（可上下滑动）： [1] Senior, M. (2023). Fresh from the biotech pipeline: fewer approvals, but biologics gain share. nature biotechnology, 41(2), 174. [2] Walsh, G., & Walsh, E. (2022). Biopharmaceutical benchmarks 2022. Nature Biotechnology, 40(12), 1722-1760. [3] Bayer (2024, 30 April ). Pharmaceuticals Pipeline Overview and Progress. https://www.bayer.com/sites/default/files/ph-rd-pipeline-2024-05-final-1.pdf [4] Boehringer Ingelheim (n.d.). Boehringer Ingelheim Human Pharma Clinical Pipeline. https://www.boehringer-ingelheim.com/bipdf/pipeline-february-2024 [5] Merck Group (n.d.). HEALTHCARE PIPELINE. https://www.merckgroup.com/en/research/healthcare-pipeline.html [6] BioNTech SE (2024, 7 April). Three-year Phase 1 Follow-Up Data for mRNA-based Individualized Immunotherapy Candidate Show Persistence of Immune Response and Delayed Tumor Recurrence in Some Patients with Resected Pancreatic Cancer. https://investors.biontech.de/news-releases/news-release-details/three-year-phase-1-follow-data-mrna-based-individualized [7] Sanofi (n.d.). Our Pipeline. https://www.sanofi.com/en/our-science/our-pipeline [8] Ipsen (n.d.). Pipeline. https://www.ipsen.com/pipeline/ [9] AstraZeneca (n.d.). Our pipeline. https://www.astrazeneca.com/our-therapy-areas/pipeline.html#cvrm [10] GSK. (2024, 7 June). US FDA approves expanded age indication for GSK’s Arexvy, the first respiratory syncytial virus (RSV) vaccine for adults aged 50-59 at increased risk. https://www.gsk.com/en-gb/media/press-releases/us-fda-approves-expanded-age-indication-for-gsk-s-arexvy-the-first-rsv-vaccine-for-adults-aged-50-59-at-increased-risk/#:~:text=GSK%20plc%20(LSE%2FNYSE%3A,who%20are%20at%20increased%20risk. [11] Ellipses Pharma (n.d.). PORTFOLIO. https://ellipses.life/portfolio/ [12] Evox Therapeutics (n.d.). Pipeline. https://www.evoxtherapeutics.com/pipeline/ [13] Johnston, I (2024, 24 April). Roche cuts drug pipeline in effort to revitalise business. Financial Times https://www.ft.com/content/d2dfc0c4-85e0-4cf5-b926-c10d630b2772 [14] ADC Therapeutics (n.d.). Our Pipeline. https://www.adctherapeutics.com/our-pipeline/ [15] Alentis Therapeutics (n.d.). Novel therapies for cancer and fibrosis. https://alentis.ch/pipeline/ [16] Verdin, P. (2024). Top companies and drugs by sales in 2023. Nature reviews. Drug Discovery. [17] Novo Nordisk (n.d.). R&D pipeline. https://www.novonordisk.com/science-and-technology/r-d-pipeline.html [18] UCB (n.d.). PIPELINE. https://www.ucb.com/our-science/pipeline *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！ 点击下方“药渡“，关注更多精彩内容 美国Arthrosi公司创新药AR882溶解痛风石，2期临床试验成果亮相2024欧洲风湿病学大会 全球First-in-class！迪哲医药戈利昔替尼重磅获批 2024年上半年FDA批准药物或新适应症（下） 点击蓝字 关注我们

Initial data from the LuminICE-203 study shows 85.7% overall response rate (ORR) (6 of 7 patients); 4 out of 7 patients with complete response (CR) AFM28 shows single agent efficacy with 2 CR/CRi and 3 stable disease (SD) in 6 patients treated at dose level of 300 mg weekly Acimtamig (AFM13) combination with AlloNK® (AB-101) natural killer (NK) cells: Recruitment in cohorts 1 and 2 completed. In the first 7 treatment refractory Hodgkin Lymphoma (HL) patients, an ORR of 85.7% observed, with 4 CRs and 2 partial responses (PRs) were observed by independent read. AFM24 combination with atezolizumab: In 17 EGFR wild-type (EGFRwt) non-small cell lung cancer (NSCLC) patients who failed chemotherapy and PD-1/PD-L1 treatment, 1CR, 3PRs and 8 SDs were observed. Disease control was 71%. 3 of the 4 responses were ongoing for more than 7 months and median progression free survival (mPFS) was 5.9 months. Initial efficacy data from the EGFR mutant (EGFRmut) NSCLC cohort showed objective responses in 4 out of 13 response-evaluable patients; 1 CR, 3 PRs and 6 SDs. Disease control was 77%. All responses confirmed by follow-up scans. AFM28 monotherapy phase 1 dose-escalation study: Completed enrollment of patients in the sixth and final cohort of the study without any unexpected safety signals or dose limiting toxicities. Of the 6 patients treated at dose level 6, a CR/CRi rate of 33% was reported (1 CR, 1 CRi and 3 SDs were observed). Cash runway into H2 2025: As of March 31, 2024, cash, cash equivalents and investments were €48.5 million. MANNHEIM, Germany, June 12, 2024 (GLOBE NEWSWIRE) -- Affimed N.V. (Nasdaq: AFMD) (“Affimed” or the “Company”), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, today reported financial results and provided an update on clinical and corporate progress for the quarter ended March 31, 2024. “We continue to make remarkable progress across our three clinical programs, AFM24, acimtamig, and AFM28,” said Dr. Andreas Harstrick, Chief Medical Officer, and acting Chief Executive Officer of Affimed. “The data that we are presenting today mark an important point for our company as we see clinical validation of our strategy to use the power of the innate immune system to fight cancer with all three assets. The initial data for the LuminICE-203 study, combining acimtamig and allogeneic NK cells (AlloNK®) are impressive with nearly 86% objective responses and more than 50% complete remissions in treatment refractory Hodgkin lymphoma patients. These data validate our approach of co-administration of ICE® molecules with allogeneic, off-the-shelf, cryopreserved NK cells. The results with AFM24 in combination with atezolizumab support our second strategy in which we leverage the combined forces of the innate and the adaptive immune system. We see objective responses in heavily pretreated NSCLC patients, both in the EGFRwt and EGFRmut subpopulations. The long duration of responses observed in the EGFRwt cohort, where 3 of 4 responses now continue for more than 7 months is very promising in these poor prognosis patients and demonstrate that this chemotherapy free approach is capable of providing long-lasting tumor control. Finally, for AFM28 we have established a pharmacodynamically and clinically active dose with a good safety profile. 5 of 6 patients in cohort 6 derived clinical benefit including two patients with an objective response. These results and the efficacy data observed with acimtamig plus allogeneic NK cells strongly support our strategic intention to develop AFM28 in combination with allogeneic NK cells for the treatment of refractory AML.” Program Updates Acimtamig (AFM13; CD30 / CD16A) Independent read data from the first 7 patients show an ORR of 85.7 % with 4 CRs and 2 PRs. All patients were heavily pretreated with a median of 4 lines of prior treatment including combination chemotherapy, brentuximab vedotin and checkpoint inhibitors; 71 % (5/7 patients) had also failed after prior autologous stem cell transplantation (ASCT). Treatment related adverse events were consistent with previous experience and were mainly mild to moderate IRR/CRS in nearly two thirds of the patients (4/7). One patient developed a short-lasting grade 3 CRS but was also diagnosed to have acute cytomegalovirus infection. All side effects were well manageable with standard of care treatment and there were no treatment discontinuations due to acimtamig or AlloNK® related adverse events. No cases of bleeding, immune effector cell-associated neurotoxicity syndrome or graft-versus-host disease were observed. Enrollment in cohorts 1 and 2 is completed; cohorts 3 and 4 are now open and enrolling. Continued updates from the study to be provided on upcoming earnings calls and scientific conferences. AFM24 (EGFR / CD16A) In the AFM24-102 trial (combination with atezolizumab): 4 confirmed responses (1CR, 4PR) and 8SD in 17 heavily pretreated EGFRwt NSCLC patients; mPFS of 5.9 months; 3 out of 4 responses ongoing for more than 7 months. All patients were pretreated with platinum-based chemotherapy and checkpoint inhibitors PD [L]-1. On May 29, the Company announced that it received FDA Fast Track designation for the combination treatment of AFM24 with atezolizumab for EGFRwt NSCLC patients. In 13 response-evaluable, heavily pretreated EGFRmut NSCLC patients, the combination of AFM24 with atezolizumab showed encouraging signals of clinical activity, including 1 CR, 3 PRs and 6 SDs. All responses are ongoing and have been confirmed by follow up scan. ORR and PFS data from the 25 patient EGFRmut NSCL cohort is expected in Q3 2024; data from the 40 patient EGFRwt cohort is expected in Q4 2024. AFM28 (CD123 / CD16A) Completed enrollment of the sixth and final cohort in the multi-center Phase 1 open-label, dose-escalation study (AFM28-101), of AFM28 monotherapy in CD123-positive r/r acute myeloid leukemia (AML). Of 6 patients treated at dose level 6 at 300mg, 1 patient showed a CR, 1 patient a CRi and 3 patients achieved SD, a CR/CRi rate of 33%. Of 6 patients treated at dose level 5 at 250 mg, 1 patient showed a CR, ongoing after 5 months; 5 patients achieved a SD as best response. No dose-limiting toxicities were reported in dose levels 5 and 6. Data from the study is expected to be presented at a future scientific conference. Further clinical development of AFM28 to be pursued in combination with an allogeneic, off-the-shelf NK cell product. Upcoming Milestones: Data readout from the 12 patients in cohorts 1 and 2 of the LuminICE-203 (AFM13 combination with AlloNK® cells) study in Q3 2024. ORR and PFS data from the 25 patients in the EGFRmut cohort of the AFM24-102 study in Q3 2024. ORR and PFS data from the 40 patients in the EGFRwt cohort of the AFM24-102 study in Q4 2024. First Quarter 2024 Financial Highlights Affimed’s consolidated financial statements are prepared in accordance with International Financial Reporting Standards (IFRS) as issued by the International Accounting Standard Board (IASB). The consolidated financial statements are presented in Euros (€), the Company’s functional and presentation currency. As of March 31, 2024, cash, cash equivalents and short-term investments totaled €48.5 million. Based on our current operating plan and assumptions, we anticipate that our cash, cash equivalents and short-term investments will support operations into H2 2025. Net cash used in operating activities for the quarter ended March 31, 2024 was €23.8 million compared to €33.2 million for the quarter ended March 31, 2023. The decline was mainly due to lower research and development expenditure. Total revenue for the quarter ended March 31, 2024, was €0.2 million compared with €4.5 million for the quarter ended March 31, 2023. Revenue in 2024 only related to a platform license provided to Genentech and 2023 predominantly related to the Roivant and Genentech research collaborations. Research and development expenses for the quarter ended March 31, 2024, were €15.4 million compared to €29.5 million in 2023. The decrease was primarily a result of lower expenses associated with the development of the AFM13 and AFM24 programs, due to a decrease in procurement of clinical trial material, clinical trial costs and manufacturing costs, decrease in head count due to the corporate restructuring which is compensated in quarter one by one-time costs, such as severance payments and impairment losses. General and administrative expenses for the quarter ended March 31, 2024, were €4.5 million compared to €6.9 million for the quarter ended March 31, 2023. The decrease was due to declines in head count, in legal and consulting expenses, insurance expenses and share-based payment expenses. Net finance income/costs for the quarter ended March 31, 2024 were €0.4 million income compared to €0.5 million costs for the quarter ended March 31, 2023. Net finance income/costs are largely due to foreign exchange gains/losses related to assets denominated in U.S. dollars as a result of currency fluctuations between the U.S. dollar and Euro during the year, interest on the Bootstrap loan and interest earned on the treasury bonds. Net loss for the quarter ended March 31, 2024, was €19.2 million, or €1.27 loss per common share compared with a net loss of €32.0 million, or €2.14 loss per common share, for the quarter ended March 31, 2023. The weighted number of common shares outstanding for the quarter ended March 31, 2024, was 15,129,952 shares. Additional information regarding these results will be included in the notes to the consolidated financial statements as of March 31, 2024, included in Affimed’s filings with the U.S. Securities and Exchange Commission (SEC). Note on International Financial Reporting Standards (IFRS) Affimed prepares and reports consolidated financial statements and financial information in accordance with IFRS as issued by the IASB. None of the financial statements were prepared in accordance with U.S. Generally Accepted Accounting Principles. Affimed maintains its books and records in Euro. Conference Call and Webcast Information Affimed will host a conference call and webcast on June 12, 2024, at 8:30 a.m. EDT / 14:30 CET to discuss first quarter 2024 financial results and corporate developments. The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the “Webcasts” section on the “Investors” page of the Affimed website at . To access the call by phone, please use link: , and you will be provided with dial-in details and a pin number. Note: To avoid delays, we encourage participants to dial into the conference call 15 minutes ahead of the scheduled start time. A replay of the webcast will be accessible at the same link for 30 days following the call. About Affimed N.V. Affimed (Nasdaq: AFMD) is a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer by actualizing the untapped potential of the innate immune system. The Company’s innate cell engagers (ICE®) enable a tumor-targeted approach to recognize and kill a range of hematologic and solid tumors. ICE® are generated on the Company’s proprietary ROCK® platform which predictably generates customized molecules that leverage the power of innate immune cells to destroy tumor cells. A number of ICE® molecules are in clinical development, being studied as mono- or combination therapy. Headquartered in Mannheim, Germany, Affimed is led by an experienced team of biotechnology and pharmaceutical leaders united by a bold vision to stop cancer from ever derailing patients’ lives. For more about the Company’s people, pipeline and partners, please visit: . Forward-Looking Statement This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions. Forward-looking statements appear in a number of places throughout this release and include statements regarding the Company’s intentions, beliefs, projections, outlook, analyses and current expectations concerning, among other things, the potential of AFM13, AFM24, AFM28 and the Company’s other product candidates, the value of its ROCK® platform, its ongoing and planned preclinical development and clinical trials, its collaborations and development of its products in combination with other therapies, the timing of and its ability to make regulatory filings and obtain and maintain regulatory approvals for its product candidates, its intellectual property position, its collaboration activities, its ability to develop commercial functions, clinical trial data, its results of operations, cash needs, financial condition, liquidity, prospects, future transactions, growth and strategies, the industry in which it operates, the macroeconomic trends that may affect the industry or the Company, such as the instability in the banking sector experienced in the first quarter of 2023, impacts of the COVID-19 pandemic, the benefits to Affimed of orphan drug designation, the impact on its business by political events, war, terrorism, business interruptions and other geopolitical events and uncertainties, such as the Russia-Ukraine conflict, the fact that the current clinical data of AFM13 in combination with NK cell therapy is based on AFM13 precomplexed with fresh allogeneic cord blood-derived NK cells from The University of Texas MD Anderson Cancer Center, as opposed to Artiva’s AB-101 and other uncertainties and factors described under the heading “Risk Factors” in Affimed’s filings with the SEC. Given these risks, uncertainties, and other factors, you should not place undue reliance on these forward-looking statements, and the Company assumes no obligation to update these forward-looking statements, even if new information becomes available in the future. Investor Relations Contact Alexander Fudukidis Director, Investor Relations E-Mail: a.fudukidis@affimed.com Tel.: +1 (917) 436-8102 Affimed N.V. Unaudited consolidated statements of comprehensive loss (in € thousand) For the three months ended March 31 2024 2023 Revenue 155 4,510 Other income – net 177 410 Research and development expenses (15,391 ) (29,531 ) General and administrative expenses (4,476 ) (6,850 ) Operating loss (19,535 ) (31,461 ) Finance income / (costs) – net 360 (519 ) Loss before tax (19,175 ) (31,980 ) Income taxes 0 (3 ) Loss for the period (19,175 ) (31,983 ) Total comprehensive loss (19,175 ) (31,983 ) Basic and diluted loss per share in € per share (undiluted = diluted) (1.27 ) (2.14 ) Weighted number of common shares outstanding 15,129,952 14,933,934 Affimed N.V. Consolidated statements of financial position (in € thousand) March 31, 2024 (unaudited) December 31, 2023 ASSETS Non-current assets Intangible assets 22 25 Leasehold improvements and equipment 2,404 4,905 Right-of-use assets 5,970 8,039 8,396 12,969 Current assets Cash and cash equivalents 14,348 38,529 Investments 34,158 33,518 Other financial assets 869 851 Trade and other receivables 6,038 5,327 Inventories 0 463 Other assets and prepaid expenses 6,044 5,500 Assets held for sale 700 0 62,157 84,188 TOTAL ASSETS 70,553 97,157 EQUITY AND LIABILITIES Equity Issued capital 1,523 1,500 Capital reserves 595,674 593,666 Fair value reserves (1,231 ) (1,231 ) Accumulated deficit (555,303 ) (536,128 ) Total equity 40,663 57,807 Non-current liabilities Borrowings 4,966 6,319 Contract liabilities 309 464 Lease liabilities 4,300 6,660 Total non-current liabilities 9,575 13,443 Current liabilities Trade and other payables 12,891 18,916 Borrowings 5,833 5,833 Lease liabilities 972 539 Contract liabilities 619 619 Total current liabilities 20,315 25,907 TOTAL EQUITY AND LIABILITIES 70,553 97,157 Affimed N.V. Unaudited consolidated statements of cash flows (in € thousand) For the three months ended March 31 2024 2023 Cash flow from operating activities Loss for the period (19,175 ) (31,983 ) Adjustments for the period: - Income taxes 0 3 - Depreciation and amortization 2,090 289 - Net loss on disposal of leasehold improvements and equipment 46 0 - loss from write-down of inventories 456 0 - Share-based payments 789 4,158 - Finance income / (costs) – net (360 ) 519 (16,154 ) (27,014 ) Change in trade and other receivables (700 ) 655 Change in inventories 7 (39 ) Change in other assets and prepaid expenses (269 ) (2,781 ) Change in trade, other payables, provisions and contract liabilities (6,460 ) (4,235 ) (23,576 ) (33,414 ) Interest received 104 520 Paid interest (346 ) (347 ) Paid income tax 0 (3 ) Net cash used in operating activities (23,818 ) (33,244 ) Cash flow from investing activities Purchase of leasehold improvements and equipment, including upfront payments for right-of-use assets (1 ) (8 ) Net cash used for investing activities (1 ) (8 ) Cash flow from financing activities Proceeds from issue of common shares, including exercise of share-based payment awards 1,270 0 Transaction costs related to issue of common shares (24 ) 0 Repayment of lease liabilities (205 ) (124 ) Repayment of borrowings (1,458 ) (510 ) Net cash used for financing activities (417 ) (634 ) Exchange-rate related changes of cash and cash equivalents 55 (552 ) Net changes to cash and cash equivalents (24,236 ) (33,886 ) Cash and cash equivalents at the beginning of the period 38,529 190,286 Cash and cash equivalents at the end of the period 14,348 155,848 Affimed N.V. Unaudited consolidated statements of changes in equity for the year (in € thousand) Issued capital Capital reserves Fair Value reserves Accumulated deficit Total equity Balance as of January 1, 2023 1,493 582,843 (1,231 ) (430,190 ) 152,915 Equity-settled share-based payment awards 4,158 4,158 Loss for the period (31,983 ) (31,983 ) Balance as of March 31, 2023 1,493 587,001 (1,231 ) (462,173 ) 125,090 Balance as of January 1, 2024 1,500 593,666 (1,231 ) (536,128 ) 57,807 Issue of common shares 23 1,219 1,242 Equity-settled share-based payment awards 789 789 Loss for the period (19,175 ) (19,175 ) Balance as of March 31, 2024 1,523 595,674 (1,231 ) (555,303 ) 40,663