MECOM

12月08日的《热心肠日报》，我们解读了 10 篇文献，关注：结直肠癌，肠干细胞，肿瘤演化，类器官，消化性溃疡，消化不良，口腔菌群，慢性疾病。 Cell：结肠干细胞的命运交响曲——致癌基因与微环境信号的共舞 Cell——[64.5] ① 对1107个结肠类器官的系统性单细胞分析揭示了受细胞内外信息（致癌突变和基质信号）调控的结肠干细胞（CSC）表型景观图谱；② 图谱两端分别是CLU+再生CSC（revCSC）和LRIG1+高增殖CSC（proCSC）；③ 成纤维细胞通过基质配体WNT3A和TGF-β1上调上皮YAP信号，使上皮细胞（EC）向revCSC极化；④ APC缺失和KRASG12D致癌突变及基质EGF/EREG则激活MAPK/PI3K信号，使EC向proCSC极化；⑤ APC缺失和KRASG12D共同阻断基质-上皮互作，将EC困在proCSC状态。 【主编评语】 癌细胞受细胞内在（致癌基因突变）和细胞外在（肿瘤微环境）信号的共同调控，但这些过程往往被分开研究，这些信号如何共同调控细胞命运仍待阐释。Cell最新发表的这项研究填补了这一空白。该研究通过scRNA-seq和高度复用的TOBis MC方法，对超过1000个结肠类器官培养物进行平行扰动分析，描绘了细胞内在/固有和外部信号共同调控的结肠干细胞（CSC）极化的连续表型景观图谱，并发现致癌基因突变和基质信号可竞争式地影响CSC表型特性，但致癌基因能通过阻断基质对细胞命运可塑性的调控，最终占据主导地位。（@mildbreeze） 【原文信息】 An oncogenic phenoscape of colonic stem cell polarization 2023-12-07, doi: 10.1016/j.cell.2023.11.004 Cell：患者类器官+单细胞分析，揭示大肠癌的化疗“保护伞” Cell——[64.5] ① 开发了一种高度复用的质谱平台以及Trellis方法，对＞2500个结直肠癌患者衍生类器官（PDO）和癌相关成纤维细胞（CAF）培养物进行单细胞水平的药物反应分析；② 即使对于抵抗化疗的PDO，药物对细胞周期阻断和DNA损伤的作用都较普遍，但药物诱导的凋亡则较少见且有患者特异性，与细胞的翻译后修饰信号有关；③ CAF能调节PDO可塑性，将增殖型结肠干细胞（proCSC）转变为慢周期的再生结肠干细胞（revCSC），从而在化疗中保护癌细胞。 【主编评语】 患者衍生类器官（PDO）可以建立个性化治疗反应模型；然而，目前的筛选技术无法揭示药物反应机制或肿瘤微环境细胞如何改变治疗效果。Cell发表的这项研究，利用一种名为Trellis的方法对超过2500个患者衍生类器官和癌症相关成纤维细胞（CAF）培养物进行单细胞分析，揭示了患者特异性药物反应，并发现CAF可改变PDO的结肠干细胞状态，从而使PDO抵抗化疗。这些发现为癌症治疗策略提供了新见解。（@mildbreeze） 【原文信息】 Trellis tree-based analysis reveals stromal regulation of patient-derived organoid drug responses 2023-12-07, doi: 10.1016/j.cell.2023.11.005 Cell：空间多组学解析大肠癌中的肿瘤-微环境共演化 Cell——[64.5] ① 对31例人结直肠癌（CRC）样本进行空间多组学分析，将瘤内不同区域作为癌症演化中的快照，绘制个体化的CRC进展轨迹谱系生物地理学图谱；② 肿瘤演化可归为3种主要模型，且可将局部肿瘤区域定位到涉及染色体不稳定性（CIN+）途径和高突变（HM）途径的癌症进展伪时间线上；③ 发现一种沿CIN+途径进展的免疫排斥（IEX）特征（DDR1、TGFBI、PAK4和DPEP1上调），呈现出细胞毒性免疫的抑制，可预测患者不良预后。 【主编评语】 结直肠癌（CRC）在从癌前病变向恶性发展的过程中表现出动态的细胞和基因异质性。Cell最新发表的这项研究，通过空间多组学分析，揭示了CRC肿瘤进展的个体化轨迹和克隆/微环境变化，特别是发现了与肿瘤进展相关的免疫排斥特征（涉及胞外基质调节因子），为患者分层和靶向治疗提供了重要信息。（@mildbreeze） 【原文信息】 Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors 2023-12-07, doi: 10.1016/j.cell.2023.11.006 Nature子刊：转座子诱变筛选解析炎症性CRC发生和进展分子机制 Nature Communications——[16.6] ① 结肠炎小鼠模型中进行转座子筛选，以解析炎症性结直肠癌（CRC）发生和进展的分子机制；② 鉴定出142个在炎症相关肿瘤中经常突变的基因，包括衰老和TGFβ-激活素信号基因；③ TNFα通过增强结肠上皮细胞的可塑性诱导干性和激活衰老信号传导，并作为选择性压力诱发炎症相关CRC中的衰老相关基因突变；④ Cdk4/6抑制剂对小鼠炎症相关CRC有效；⑤ 功能验证Arhgap5和Mecom是抑癌基因，为CRC治疗提供了可能的靶点。 【主编评语】 结直肠癌（CRC）是全球癌症相关死亡的第二大原因，其中慢性炎症促进其发生和进展。近日，发表在Nature Communications上的这篇文章，通过转座子诱变筛选鉴定出参与炎症相关CRC发展的基因和途径，并证明衰老途径失活在炎症微环境中CRC发生和进展中的重要性，有助于精准医学的进展。（@圆圈儿） 【原文信息】 Sleeping Beauty transposon mutagenesis identified genes and pathways involved in inflammation-associated colon tumor development 2023-10-16, doi: 10.1038/s41467-023-42228-z Cell子刊：消化性溃疡病促进胃癌机制 Cell Reports——[8.8] ① 胃癌（GC）特异性地经历解痉多肽表达化生（SPEM），然后是肠化生；② 转录辅激活因子YAP激活导致肠型GC患者生存率低且预后不良；③ YAP过表达诱导肿瘤前病变的发展如胃细胞萎缩、化生和过度增殖，而YAP缺失在Notch激活的胃腺瘤模型中可逆转肿瘤和化生的发展；④ YAP靶标组证明YAP与SPEM相关基因的活性染色质元件结合，这与其在化生和溃疡中表达激活相关；⑤ YAP信号在SPEM过程中被激活，即YAP是胃肿瘤和再生中SPEM的中央调节剂。 【主编评语】 胃癌是世界上最常见致命的癌症之一，由环境因素引起的消化性溃疡病会增加胃癌（GC）风险，然而这种关联机制尚不清楚。近日，山东大学郭海洋团队联合国外实验室在Cell Reports上发表文章，通过YAP靶组揭示在胃肿瘤前期进展和再生中SPEM的激活。（@圆圈儿） 【原文信息】 YAP targetome reveals activation of SPEM in gastric pre-neoplastic progression and regeneration 2023-11-30, doi: 10.1016/j.celrep.2023.113497 Nature子刊：胃肠细胞分化和激素调节会影响消化性溃疡？ Nature Genetics——[30.8] ① 对消化性溃疡疾病（PUD）进行大规模跨祖先荟萃分析，结合全基因组关联分析与日本和欧洲的研究（共52032例病例和905344例对照），发现25个新基因座在祖先间高度一致；② 对胃溃疡和十二指肠溃疡遗传结构表明两者间有相同风险位点，尽管遗传效应较小，但胃溃疡有更高异质性；③ 幽门螺杆菌（HP）分层分析识别到一个HP相关宿主遗传位点；④ 使用整体和单细胞转录组谱分析发现胃组织富含高表达基因的PUD遗传因素，特别在产生生长抑素的D细胞中。 【主编评语】 消化性溃疡主要指发生于胃和十二指肠的慢性溃疡，是一多发病、常见病。近日，日本东京大学研究人员在Nature Genetics发表最新研究，通过规模跨祖先荟萃分析和全基因组关联研究，发现胃肠细胞分化和激素调节在PUD病因学中至关重要，值得关注。（@九卿臣） 【原文信息】 East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease 2023-11-30, doi: 10.1038/s41588-023-01569-7 消化酶补充剂或有助于改善功能性消化不良 Biomedicine and Pharmacotherapy——[7.5] ① 纳入年龄18~59岁的120名受试者，每天服用2粒食品补充剂Poolzyme®Multi胶囊（含有200 mg广谱消化酶混合物），持续2个月；② 与安慰剂组相比，接受多酶混合物干预组功能性消化不良特异性指数（NDI-SF）1和NDI-SF 2-5均显著改善，而NDI-SF 6 无显著差异；③ 多酶混合物能改善生活和睡眠质量，降低疼痛严重程度；④ 在两个月的治疗期间，没有受试者报告与摄入食品补充剂相关的副作用或不良反应，包括没有过敏，耐受性良好。 【主编评语】 消化不良是一种由多种病理生理机制引起的复杂疾病，最常见形式是功能性消化不良，影响全世界约10~30%的人群，其特征不是胃肠道结构性或溃疡性病变，而是功能异常，并会随着时间的推移而恶化，功能性消化不良由于其高患病率以及症状的慢性和复发性而成为一个相当重要的临床问题。Biomedicine and Pharmacotherapy一项最新随机、安慰剂对照、双盲临床试验评估发现在正常饮食中补充从真菌发酵获得的多酶混合物可有效减少功能性消化不良症状并改善睡眠质量，并且耐受性良好。（@RZN） 【原文信息】 Efficacy of digestive enzyme supplementation in functional dyspepsia: A monocentric, randomized, double-blind, placebo-controlled, clinical trial 2023-11-14, doi: 10.1016/j.biopha.2023.115858 Nature子刊：口腔微生物组如何随着工业化进程发生变化？ Nature Microbiology——[28.3] ① 从生活在英国（约公元前2200年至1853年）的人身上采集235份古代牙石样本；② 鉴定出在英国共存数千年的多种口腔微生物群落，包括一个与甲烷杆菌相关的群落（一种厌氧古菌，在现代工业化社会的口腔微生物组并不常见）；③ 口腔卫生影响口腔微生物组的组成，而微生物功能反映过去饮食的差异；④ 甲烷杆菌相关的微生物群落与系统性疾病（例如骨膜炎和关节病变）的骨骼标志物有关，其显著变化与重大事件时间变化一致，包括黑死病的到来。 【主编评语】 近几十年来，慢性非传染性疾病的流行率急剧上升，特别是在工业化国家。有几项研究表明微生物组与这一趋势有关，但很少有研究考察工业化微生物组的进化史。Nature Microbiology近期发表的文章，采集并分析了生活在英国的古代牙石样本，发现工业化前的微生物群比以前认识到的更加多样化，或有助于我们理解工业化人群中慢性非传染性疾病的起源。（@章台柳） 【原文信息】 Ancient dental calculus reveals oral microbiome shifts associated with lifestyle and disease in Great Britain 2023-11-29, doi: 10.1038/s41564-023-01527-3 国内团队：门静脉循环中高浓度肠菌代谢产物影响西方疾病（社论） Journal of Allergy and Clinical Immunology——[14.2] ① 肠道菌群代谢物短链脂肪酸（SCFAs）在门静脉循环中以极高的浓度存在，特别是在结肠粘膜的小血管中；② 免疫细胞暴露于非常高浓度的SCFAs，然后通过G蛋白偶联受体或组蛋白去乙酰化酶发挥作用，影响细胞功能和代谢；③ 正常饲喂和低纤维饲喂的猪外周血中SCFAs的水平没有显著差异，但低纤维饮食的门静脉系统中的SCFAs水平显著降低；④ 缺乏SCFAs（如西式饮食）导致免疫细胞功能过度活跃，随后免疫细胞或移动到大脑、肺和肾等组织并介导疾病。 【主编评语】 肠道菌群紊乱可能西方生活方式疾病的致病基础。 由于肠道菌群通常局限于肠道，因此人们的注意力集中在可能通过血液运输的菌群代谢物的作用上。齐鲁工业大学药学院名誉院长查尔斯·麦凯教授团队在Journal of Allergy and Clinical Immunology发表最新社论，总结归纳了门静脉中高浓度的菌群代谢物（如短链脂肪酸）或是调节免疫细胞，影响西方生活方式疾病的潜在机制。（@RZN） 【原文信息】 High Metabolite Concentrations in Portal Venous Blood as a Possible Mechanism for Microbiota Effects on the Immune System, and Western Diseases 2023-11-20, doi: 10.1016/j.jaci.2023.10.029 国内团队Lancet子刊：西太平洋地区面临更严峻的慢性病负担挑战（综述） Lancet Regional Health-Western Pacific——[7.1] ① 系统阐述了西太区37个国家和地区慢性病负担和流行趋势、主要风险因素、新冠影响和防控策略等，为慢病防控提出建议旨在助力推动全球健康共同体建设；② 相比全球其他地区，西太区面临更严峻慢病负担挑战，宏观、群体、个体及系统性风险因素等共同影响着慢病防治；③ 新冠大流行导致慢病风险因素上升，包括不健康饮食增加、体育运动减少和睡眠障碍增加等；④ 数字健康技术在慢病管理方面取得积极效果，但将其推广至西太区基层，仍需持续努力。 【主编评语】 当前，慢性非传染性疾病防控已成为全球和西太区公共卫生领域的首要任务。慢性病是全球和西太区死亡和伤残主要原因。西太区慢性病死亡人数约占全球死亡人数的约四分之一。近日，西安交通大学王友发教授牵头，组织来自中国、韩国、澳大利亚、日本、越南等8个国家，世界卫生组织（WHO）、国际糖尿病联盟（IDF）等23家机构的35位专家学者共同合作完成。专辑共包含4篇文章，分别系统阐述了西太区37个国家和地区慢性病的疾病负担和流行趋势、主要风险因素、新冠疫情的影响、防控策略等，为西太区乃至全球慢性疾病防控提出建议，旨在助力推动全球健康共同体建设，值得精读。（@九卿臣） 【原文信息】 Dietary and other lifestyle factors and their influence on non-communicable diseases in the Western Pacific region 2023-12-01, doi: 10.1016/j.lanwpc.2023.100842 感谢本期日报的创作者：mildbreeze，圆圈儿，九卿臣，RZN，章台柳 点击阅读过去10天的日报： 12-07 | Nature重磅：用反向代谢组学方法，挖掘IBD中的微生物新分子 12-06 | 刘瑞欣、陈鹏等各取新突破，30分Cell子刊2文聚焦肠菌代谢与宿主健康 12-05 | 3篇Immunity重磅研究，聚焦肠道与免疫 12-04 | 菌群与癌症治疗，100分综述一文讲透 12-03 | 认知功能/情绪障碍/渐冻症，多文聚焦饮食与脑健康 12-02 | 战肠癌：聚焦筛查和治疗方法新进展 12-01 | 11月，最值得看的30篇肠道健康文献！ 11-30 | 《自然·综述》年度回顾：肠神经系统研究的三大进展 11-29 | 菌群寻宝：2篇Nature子刊深挖菌群中的抗菌肽 11-28 | 2篇高分研究，挖掘调节免疫的潜在益生菌

PRESS RELEASE AB SCIENCE PRESENTS ITS FINANCIAL INFORMATION FOR THE FIRST HALF OF 2023 AND THE KEY EVENTS OF THE PERIOD Clinical development strategy based on two platforms: the late-stage masitinib platform and the new microtubule platform Masitinib platform: License search for masitinibStudies in amyotrophic lateral sclerosis (ALS), mastocytosis, MCAS and Covid-19 are ongoingOngoing EMA and Health Canada procedures for conditional authorisation of masitinib in ALSTimetable extension granted by EMA for examination of the masitinib marketing authorization application in ALSStrengthening of AB Science's intellectual property position in key indications, with protection guaranteed until 2037 in ALS, 2041 in multiple sclerosis and Alzheimer's disease, and 2042 in prostate cancer Microtubule platform: Encouraging preliminary efficacy results for low-dose AB8939 after three days of treatment with a bone marrow response in a patient with acute myeloid leukemiaNo decrease in neutrophils or platelets observed, which is unusual for a drug in this class Financial and operational information Operating loss of €8.9 million as of 30 June 2023, a decrease of 7.5% compared to the first half of 2022Cash position of €14.8 million as of 30 June 2022, plus the €11.1 million to be received of 2020, 2021 and 202 research tax creditReduction in AB Science's cost structure while preserving all key functions Paris, September 29, 2023, 7.45pm CET AB Science SA (Euronext - FR0010557264 - AB) today reports its revenues for the first half of 2023 and provides an update on its activities. CLINICAL DEVELOPMENT KEY EVENTS FOR THE FIRST HALF OF 2023 AND SINCE JUNE 30, 2023 Clinical development strategy based on two platforms: the late-stage masitinib platform and the new microtubule platform On 21 April 2023, AB Science announced its decision to focus its development strategy as follows: Allocation of current resources primarily to the development of masitinib for the treatment of amyotrophic lateral sclerosis and the development of the microtubule destabilizer agents (MDA) platform, with the clinical development of AB8939 in refractory acute myeloid leukemia and the initiation of regulatory preclinical development of a new oral molecule in the same microtubule class for sarcoma and solid tumors. AB Science wants to focus the majority of our clinical resources on the development of rare diseases with masitinib, on the development of the microtubule platform with AB8939 and future molecules of the same family due to the very encouraging first results. Acceleration of the process of seeking a license for masitinib. This acceleration is possible now that the confirmatory Phase 3 studies have been approved by the FDA in the United States and the major European agencies. To this end, the Company has retained the services of a leading investment bank. This license search is a priority in the Company's strategy, given the number of clinical studies already conducted and the maturity of the pipeline, and given the additional investments required to complete the clinical program, up to market authorizations. We want to highlight that the duration of this license search is not predictable and that the realization of a license is dependent on a number of factors and is not guaranteed. However, the milestones reached at this stage are essential factors that contribute to the feasibility of this strategy. As a result of the focus strategy, AB Science has decided to adapt its organization, which lead to a significant reduction in costs. AB Science has therefore implemented a redundancy plan. This strategic focus reinforces and sustains the existing agreement between certain shareholders of AB Science and Alain Moussy. Update on the European Medicines Agency’s (EMA) timetable for examination of the masitinib marketing authorization application in amyotrophic lateral sclerosis (ALS) AB Science provided an update on the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) timetable for examination of the masitinib marketing authorization application in amyotrophic lateral sclerosis (ALS). The timetable extension was requested by AB Science in order to address a question from the CHMP that arose following implementation of a guidance, updated on July 28, 2023, from the EMA. This guidance requested all marketing authorisation holders to review their manufacturing processes for all products containing chemically synthesised or biological active substances to identify and, if necessary, mitigate the risk of presence of nitrosamine impurities. Because performing this activity was not compatible with the conventional 30 days stop-clock, AB Science requested an extension of this stop-clock in order to complete a risk evaluation of the manufacturing process in terms of risk of formation of nitrosamines in active substance and finished product. An extension of clock-stop is not automatic. A request for extension together with a corresponding scientific justification must be submitted by the applicant and needs to be discussed in a CHMP plenary session. AB Science’s request was accepted during the September 11-14, 2023 CHMP session. Based on this updated timetable, the CHMP decision on masitinib marketing authorization in ALS is expected during the first quarter of 2024. Based on the current stage of investigations, AB Science is confident that the current manufacturing process of masitinib complies with this new EMA guidance. Strengthening of AB Science's intellectual property position in ALS AB Science announced that the patent office of Japan and the patient office of Canada have issued a Notice of Allowance (NOA) for a patent relating to methods of treating amyotrophic lateral sclerosis (ALS) with its lead compound masitinib. These new patents provide strong protection for masitinib in the treatment of ALS until 2037 and complete the IP coverage for ALS across all key geographic areas where masitinib could be marketed. First complete bone marrow response in an acute myeloid leukemia patient in its AB8939 Phase I/II clinical trial AB Science announced in March 2023 a case report from the initial stage of its Phase I/II study (AB18001) evaluating AB8939, a microtubule destabilizer, in patients with refractory and relapsed acute myeloid leukemia (AML). The AML patient in question was in failure to prior treatment with azacitidine and presented with a MECOM gene rearrangement, which is a biomarker for resistance to standard chemotherapies that is associated with a high-risk of disease progression and inferior prognosis. One month after the first treatment cycle (i.e., three consecutive days of AB8939 treatment) there was a drastic reduction in bone marrow blast cells (i.e., leukemia cells), from a pretreatment level of 55% to 5% (i.e., a morphologic leukemia free state). Remarkably, this response was achieved at a very low dose of AB8939, corresponding to the second step of dose increment (out of 13 potential steps) in phase I. The patient also showed excellent tolerance to AB8939, having experienced no treatment-related toxicities. At the request of the investigator, AB Science has authorized further treatment cycles of AB8939 to this patient. One month after the second treatment cycle of three consecutive days at this dose, a good response has been maintained with bone marrow blasts being at 10% (corresponding to a 5-fold reduction relative to baseline). A third treatment cycle for this patient has been initiated. Considering the overall study to date, there have been no signs of moderate, severe or serious toxicity and approximately 50% of patients have requested further treatment cycles of AB8939 after the first cycle of treatment and a measurement at day 28. CONSOLIDATED FINANCIAL INFORMATION FOR THE FIRST HALF OF 2023 The operating loss as of June 30, 2023 was 8,850 K€, compared to a loss of 9,562 K€ as of June 30, 2022, i.e. a decrease in the operating loss of 712 K€ (7.5%). Operating income, exclusively made up of sales related to the operation of a veterinary medicine, amounted to 448 K€ as of June 30, 2023 compared to 629 K€ one year earlier, a decrease of 28.8%. This decrease is due to a product supply disruption between August 2022 and April 2023, due to a change in the synthesis process for Masivet active ingredient (masitinib), which required to submit a variation of Masivet marketing authorisation to the European Medicines Agency (EMA), which was approved in April 2023.Operating expenses amounted to 9,298 K€ as of June 30, 2023, compared to 10,192 K€ as of June 30, 2022, a decrease of 8.8%.Marketing expenses decreased by 13.8% from 253 K€ as of June 30, 2022 to 218 K€ as of June 30, 2023.Administrative expenses were stable compared with 30 June 2022 (down 2%).Research and development expenses decreased by 886 K€, i.e 10.9 %, from 8,099 K€ as of June 30, 2022 to 7,213 K€ as of June 30, 2023. This variation is mainly explained by: the increase in the research tax credit (633 K€),the decrease in the value of warrants issued as payment for research and development services, from 414 K€ as of 30 June 2022 to 160 K€ as of 30 June 2023. The financial income as of June 30, 2023 is a loss of 1,569 K€ compared to a gain of 2,424 K€ one year earlier. As of June 30, 2023, financial income (1,042 K€) corresponded mainly to the difference between the cancellation of the recognition of the ADPC debt following their cancellation for 3,692 K€ and the recognition of the new E shares, created to replace the ADPCs and with a value of 2,908 K€ as of 30 June 2023. This transaction generated net proceeds of 784 K€. Financial expenses (2,610 K€) mainly relate to the restatement of the bond loan contract (985 K€), interest on loans (947 K€) and the discounting of conditional advances (652 K€). These effects had no cash impact. The net loss as of June 30, 2023 amounts to 10,411 K€ compared to a loss of 7,141 K€ as of June 30, 2022. The following table summarizes the consolidated financial statements for the first half of 2023 prepared in accordance with IFRS, and comparative information with the first half of 2022: In thousands of euros, except for share data30/06/202330/06/2022Net turnover448 629 Cost of sales and marketing expenses(219) (158) Marketing expenses(218) (253) Administrative expenses(1,648) (1,682) Research and development expenses(7,213) (8,099) Operating income (8,850) (9,562) Financial income 1,0423,847 Financial expenses (2,610) (1,423) Financial income (1,569) 2,424 Net income (10,411)(7,141) Other comprehensive income for the period net of tax51174 Total comprehensive income for the period(10,360)(6,967) Basic earnings per share - in euros(0.22) (0.15) Diluted earnings per share - in euros(0.22) (0.15) In thousands of euros30/06/202331/12/2022Cash and cash equivalents14,7867,269Total Assets33,19823,841Equity(19,225)(35,670) Non-current liabilities1,209 393 Trade payables12,417 12,248 Current liabilities21,381 23,079 OTHER CORPORATE INFORMATION FOR THE FIRST HALF OF 2023 AND SINCE JUNE 30, 2023 Drawdown of the second tranche of €6 million under its financing agreement with the European Investment Bank AB Science announced in January 2023 that it has received payment of €6.0 million as the second tranche of a €15 million loan from the European Investment Bank (EIB). The second tranche has a maturity of five years and is therefore repayable in January 2028. It carries a capitalized annual interest rate of 7.0% and the issuance of 115,830 warrants, each giving the right to subscribe to one ordinary share of AB Science at 14.0 euros for 15 years. These warrants represent 0.22% of the current capital of the Company (if they were to be exercised in their entirety). Financial restructuring On 21 April 2023, AMY S.A.S and Alain Moussy (majority shareholders), AB Science and the minority shareholder entities (including in particular the convertible bondholders, the Tax Research Credit lenders and the APDC holders) signed an Agreement relating to: (i) the implementation of AB Science's new strategy, (ii) the financing of AB Science and (iii) the restructuring of AB Science's bond debt and Class C preference shares. These transactions were the subject of an agreement signed by the parties on 21 April 2023, the date on which all transactions were accounted for, and are detailed in section 12 of the notes to the consolidated financial statements as of 30 June 2023. Restructuring of convertible bonds issued in February 2022 and Class C preferred shares AB Science announced on 21 April 2023 the negotiation of a framework agreement under which the terms and conditions of the bond issue agreement (entered into with the holders of the US$8.5 million convertible bonds issued in February 2022 and to which 50,000 warrants were attached with an exercise price of 000 warrants with an exercise price of EUR 12.65) would be amended to provide, on 15 July 2023 and automatically, for the conversion of all the convertible bonds into ordinary shares of AB Science on the basis of a price per share of EUR 5.75 (i.e. the subscription price of the New Shares). The framework agreement has also been negotiated with the holders of Class C preferred shares (the “C Preferred”). It provides the C Preferred still in circulation to be repurchased by AB Science for one symbolic euro (and subsequently cancelled). 520,786 share warrants (each warrant entitling the holder to subscribe for one ordinary share of AB Science at par value for a period of 12 months) will be issued in substitution of the C Preferred. In addition, still in substitution of the C Preferred, it provides a new class of preferred shares to be created, benefiting from priority dividend rights (equal to 1.25% of the net sales of masitinib or of any licensing royalties, up to a limit of 9.0 million euros) and convertible into 750,000 ordinary shares of AB Science if the share price of AB Science exceeds a threshold of 30 euros for more than 90 consecutive days. Finally, it has been proposed to the shareholders to extend the term of certain lines of warrants already issued, to adapt to the evolution of AB Science’s strategy and of its clinical pipeline. These agreements were submitted approved by the General Meeting of AB Science held on 30 June 2023. Capital increase for an amount of 15 million euros AB Science announced on April 24, 2023 the success of its capital increase through the issuance of new ordinary shares with attached warrants, with a waiver of preferential subscription rights. The Capital Increase consisted of a private placement pursuant to Articles L. 225-136 of the French Commercial Code and L. 411-2 1° of the French Monetary and Financial Code and has been carried out with a waiver of preferential subscription rights, pursuant to the delegation of authority granted to the Board of Directors under the 20th resolution of the Combined General Shareholders’ Meeting of June 29, 2022. The Capital Increase has taken the form of the issuance of 2,608,686 actions new ordinary shares (the “New Shares”) to each of which are attached a share subscription warrant (the “Warrants”). The Capital Increase was made through a cash contribution of approximately EUR 11.5 million and by offsetting existing receivables, i.e. approximately EUR 3.0 million (receivables related to the pre-financing of the research tax credit for the 2020 financial year and maturing in 2023, as well as approximately EUR 500,000 in interest accrued to date on the convertible bonds issued in February 2022). Two warrants giving the right to subscribe to one ordinary share, all of the 2,608,686 New Shares and all of the 1,304,343 new shares that would be issued upon exercise of the warrants, i.e. a total of 3,913,029 shares in the Company, represent 7.36% of the Company's current share capital. The issue price of the New Shares has been set at 5.75 euros (0.01 euro par value and 5.74 euros issue premium) and the exercise price of the Warrants at 8.625 euros, representing a total fundraising of approximately EUR 15.0 million (taking into account the exercise of the warrants, the maximum amount of the Capital Increase could be increased by an amount of 26.3 million euros). The Warrants may be exercised from January 1st, 2025 to December 31, 2030. Renewal of the Programme d’Augmentation de Capital à Terme (PACT) concluded with Alpha Blue Ocean Alpha Blue Ocean is committed to subscribe, from April 28, 2023, to newly issued shares of AB Science (in tranches comprised of a number of shares between 500,000 and 1 million) over a period of 24 months, up to a maximum of 4.0 million shares in total (or 7.2% of the company’s share capital on the basis of the capital after the capital increase announced on 24 April 2023). Such subscriptions for new shares shall be carried out using the 28th resolution of the Shareholder’s Meeting of June 29, 2022 (as renewed or otherwise amended, if applicable). By way of example, based on the April 27, 2023 closing price of AB Science’s shares, i.e 6.27 euros, on Euronext Paris, it is estimated that AB Science could raise approximately 25 million euros through this equity financing facility. For each tranche, the issuance price of new shares of AB Science, subscribed by Alpha Blue Ocean, shall be equal to 100% of the volume-weighted average price of the shares of AB Science traded on Euronext Paris over the three trading days preceding a tranche drawdown request. For each tranche, and after the settlement-delivery of the new shares of AB Science following the relevant capital increase, 80% of the proceeds of the tranche shall be secured in an escrow account with a third-party escrow agent. The remaining balance shall be kept by AB Science. Following predefined trading rules for each tranche, Alpha Blue Ocean shall manage the orderly sale, on or off the market, of the AB Science shares subscribed to. 95% of the proceeds shall be distributed to AB Science on a monthly basis (minus a structuration fee), directly from Alpha Blue Ocean or by way of a release from the escrow account. AB Science has no obligations to draw down on the PACT and shall utilise this innovative financing solution only if necessary and if the market conditions are favourable to the interests of AB Science and its shareholders. For each drawdown, the number of shares issued with respect to this agreement and admitted to trading will be reported in an Euronext notice and in a specific communication on AB Science’s website. Investors are invited to take note of the risks associated with this transaction, potentially dilutive of 7.2% of the company’s share capital on the basis of the capital after the capital increase announced on 24 April 2023, which could create downward pressure on the AB Science share. Investors are also invited to be vigilant before taking the decision to invest in a company that carries out such operations, particularly when they are carried out successively. AB Science recalls that the present dilutive financing operation is not the first one it has put in place. Other events Other securities transactions During the first half of 2023, 2,739,516 share warrants were allocated, including 115,830 to the European Investment Bank as part of the financing agreement, 2,608,686 relating to the capital increase and 15,000 to the directors. Other information AB Science confirms its eligibility for PEA-PME (a share savings plan aimed at providing finance to SMEs) in accordance with decree no. 2014-283 of 4 March 2014 taken for the application of article 70 of law no. 2013-1278 of 29 December 2013 of finance for 2014 fixing the eligibility of companies for PEA-PME, i.e. less than 5,000 employees on the one hand, an annual turnover of less than 1,500 million euros or a total balance sheet of less than 2,000 million euros, on the other hand. About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment AB SCIENCE press release S1 2023 VEng VF

PRESS RELEASE AB SCIENCE PRESENTS ITS FINANCIAL INFORMATION AS OF DECEMBER 31, 2022 AND THE KEY EVENTS OF THE PERIOD Financial information and other corporate information Consolidated operating loss of €15.9 million as of 31 December 2022, compared with a loss of €13.8 million as of 31 December 2021, an increase of the operating loss of €2.1 million (15.4%)Cash position of €7.3 million as of 31 December 2022, plus a cash contribution of €11.5 million as part of the capital increase completed in April 2023, plus the €7.1 million of 2020 and 2021 research tax credit and €6.0 million for drawdown in January 2023 of the second tranche under the financing agreement with the European Investment Bank Capital increase for an amount of €15 million completed in April 2023, of which €11.5 million in cash and €3.5 million in debt compensationDrawdown of the two tranches (December 2022 and January 2023) under the financing agreement with the European Investment Bank for a total amount of €12 millionRenewal of the Programme d’Augmentation de Capital à Terme concluded by AB Science with Alpha Blue Ocean (Investors are invited to take note of the risks associated with this potentially dilutive transaction, which could create downward pressure on the AB Science share, as mentioned in sections 6.4.4 and 6.4.6 of the 2022 annual report). Clinical development Focus of the development strategy on amyotrophic lateral sclerosis with the masitinib platform and on the second microtubule platform and seeking licensing agreements for non-rare disease indications of masitinibFiling of a marketing authorization application for masitinib in the treatment of amyotrophic lateral sclerosis (ALS) in Canada, under the Notice of Compliance with Conditions (NOC/c) policy and response to the Notice of Deficiency (NOD)Filing of a conditional marketing authorization application to the European Medicines Agency (EMA) for masitinib in the treatment of amyotrophic lateral sclerosis (ALS) and response to the Day 120 assessment of the procedure in April 2023Approval of both confirmatory Phase 3 studies with masitinib in progressive forms of multiple sclerosis and Alzheimer's disease in Europe and in the USFirst complete bone marrow response in an acute myeloid leukemia patient in its AB8939 Phase I/II clinical trial Paris, 28 April 2023, 6.30pm CET AB Science SA (Euronext - FR0010557264 - AB) today reports its revenues for the year 2022 and provides an update on its activities. CLINICAL DEVELOPMENT KEY EVENTS DURING THE YEAR 2022 AND SINCE DECEMBER 31, 2022 Focus of the development strategy on amyotrophic lateral sclerosis with the masitinib platform and on the second microtubule platform and seeking licensing agreements for non-rare disease indications of masitinib On 21 April 2023, AB Science announced its decision to focus its development strategy as follows: Allocation of current resources primarily to the development of masitinib for the treatment of amyotrophic lateral sclerosis and the development of the microtubule destabilizer agents (MDA) platform, with the clinical development of AB8939 in refractory acute myeloid leukemia and the initiation of regulatory preclinical development of a new oral molecule in the same microtubule class for sarcoma and solid tumors. AB Science wants to focus the majority of our clinical resources on the development of rare diseases with masitinib, on the development of the microtubule platform with AB8939 and future molecules of the same family due to the very encouraging first results. Acceleration of the process of seeking a license for masitinib in non-rare disease indications, with priority given to progressive forms of multiple sclerosis and Alzheimer's disease. This acceleration is possible now that the confirmatory Phase 3 studies have been approved by the FDA in the United States and the major European agencies. To this end, the Company has retained the services of a leading investment bank. This license search is a priority in the Company's strategy, given the number of clinical studies already conducted and the maturity of the pipeline, and given the additional investments required to complete the clinical program, up to market authorizations. We want to highlight that the duration of this license search is not predictable and that the realization of a license is dependent on a number of factors and is not guaranteed. However, the milestones reached at this stage are essential factors that contribute to the feasibility of this strategy. As a result of the focus strategy, AB Science has decided to adapt its organization, which should lead to a significant reduction in costs. AB Science has therefore filed a redundancy plan to the authorities, aiming to cut a maximum of 41 jobs (out of a total of 100 employees). This strategic focus reinforces and sustains the existing agreement between certain shareholders of AB Science and Alain Moussy. Filing of a marketing authorization application for masitinib in the treatment of amyotrophic lateral sclerosis (ALS) in Canada, under the Notice of Compliance with Conditions (NOC/c) policy AB Science announced in February 2022 that Health Canada has granted authorization to file a New Drug Submission for masitinib in the treatment of amyotrophic lateral sclerosis (ALS) under the Notice of Compliance with Conditions (NOC/c) policy. AB Science subsequently announced on May 26, 2022 that Health Canada had issued a favorable opinion on the preliminary review of the dossier and that the review of the dossier had started. This assessment was made based on a pre-submission package sent by AB Science including, efficacy data of study AB10015, long-term survival data (75 months average follow-up from diagnosis) of study AB10015, and safety data. In December 2022, AB Science announced that it has received a Notice of Deficiency (“NOD”) from Health Canada. This NOD means that Health Canada has requested the provision of additional information related to masitinib New Drug Submission. Initially, AB Science had 90 days to respond to this NOD, but because EMA and Health Canada regulatory procedures were concurrent and in order to ensure the best quality of responses in both procedures, AB Science, in agreement with Health Canada, has extended the response period to Health Canada by 30 days. AB Science responded to this NOD. If granted, an NOC/c is authorization to market a drug with conditions. Such conditions will be discussed with Health Canada during the procedure. An estimated 3,000 Canadians are currently living with ALS. Each year approximately 1,000 Canadians die from ALS. A similar number of Canadians are diagnosed with ALS each year. Filing of a conditional marketing authorization application to the European Medicines Agency (EMA) for masitinib in the treatment of amyotrophic lateral sclerosis (ALS) AB Science announced in August 2022 that it has filed an application for conditional Marketing Authorization to the European Medicines Agency (EMA) for masitinib in the treatment of amyotrophic lateral sclerosis (ALS). The application is based on results from the phase 2/3 AB10015 study and its long-term survival follow-up. Study AB10015 was a randomized, double-blind, placebo-controlled trial over a 48-week treatment period, conducted with 394 ALS patients and evaluating Alsitek in combination with riluzole versus riluzole alone. This application has been validated by EMA and review by the Committee for Medicinal Products for Human Use (CHMP) has begun. The CHMP has a target of 210 active evaluation days to review the application. In April 2023, AB Science announced it has submitted its responses to the Day 120 assessment of the procedure. Approval of confirmatory Phase 3 study with masitinib in progressive forms of multiple sclerosis AB Science announced in January 2022 that it has been authorized by the French Medicine Agency, ANSM, to initiate a Phase III study (AB20009) evaluating masitinib in patients with Primary Progressive Multiple Sclerosis (PPMS) or non-active Secondary Progressive Multiple Sclerosis (nSPMS). This study has also been approved by several European agencies as well as by the US Food and Drug Administration (FDA). The study will enroll 800 patients from numerous study centers with Expanded Disability Status Scale (EDSS) score between 3.0 to 6.0 and absence of T1 Gadolinium-enhancing brain lesions as measured by magnetic resonance imaging (MRI). The primary objective of the study will be to evaluate the effect of masitinib on time to confirmed disability progression, with progression defined as 1-point worsening when EDSS baseline score ≤5.5, or 0.5 if baseline score >5.5 from randomization to week 96. This confirmatory study follows successful completion of a first Phase 2B/3 study (AB07002) in primary progressive (PPMS) and non-active secondary progressive (nSPMS) multiple sclerosis. This study met its primary analysis endpoint, demonstrating a statistically significant reduction in cumulative change on EDSS with masitinib 4.5 mg/kg/day (p=0.0256). Approval of confirmatory Phase 3 study with masitinib in Alzheimer's disease AB Science announced in October 2022 that the first authorizations have been received to initiate its phase 3 confirmatory study (AB21004) evaluating masitinib in patients with mild to moderate Alzheimer's Disease (AD) from the French Medicine Agency (ANSM) together with AEMPS (Spain agency) and EOF (Greece agency). This study has also been approved by the US Food and Drug Administration (FDA). Study AB21004 is a randomized, double-blind phase 3 study to evaluate the safety and efficacy of masitinib in patients with mild to moderate Alzheimer's disease, as an add-on therapy to standard of care, cholinesterase inhibitors and/or memantine. The study will enroll 600 patients with confirmed clinical diagnosis of mild and moderate Alzheimer's disease, corresponding to an Activities of Daily Living (ADCS-ADL) score of less than 73 and a Mini Mental State Examination (MMSE) score of between 14 to 25, inclusive. The objective of study AB21004 is to confirm treatment effect with masitinib 4.5 mg/kg/day as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate Alzheimer's disease. The primary endpoint of the study will be to evaluate the effect of masitinib on absolute change from baseline in ADCS-ADL score and in ADAS-Cog-11. This confirmatory study follows a first positive Phase 2B/3 study (AB09004) which showed that masitinib can generate a significant treatment effect relative to placebo in the primary endpoint of change from baseline in ADAS-Cog, an instrument that measures the effect on cognition and memory. First complete bone marrow response in an acute myeloid leukemia patient in its AB8939 Phase I/II clinical trial AB Science announced in March 2023 a case report from the initial stage of its Phase I/II study (AB18001) evaluating AB8939, a microtubule destabilizer, in patients with refractory and relapsed acute myeloid leukemia (AML). The AML patient in question was in failure to prior treatment with azacitidine and presented with a MECOM gene rearrangement, which is a biomarker for resistance to standard chemotherapies that is associated with a high-risk of disease progression and inferior prognosis. One month after the first treatment cycle (i.e., three consecutive days of AB8939 treatment) there was a drastic reduction in bone marrow blast cells (i.e., leukemia cells), from a pretreatment level of 55% to 5% (i.e., a morphologic leukemia free state). Remarkably, this response was achieved at a very low dose of AB8939, corresponding to the second step of dose increment (out of 13 potential steps) in phase I. The patient also showed excellent tolerance to AB8939, having experienced no treatment-related toxicities. At the request of the investigator, AB Science has authorized further treatment cycles of AB8939 to this patient. One month after the second treatment cycle of three consecutive days at this dose, a good response has been maintained with bone marrow blasts being at 10% (corresponding to a 5-fold reduction relative to baseline). A third treatment cycle for this patient has been initiated. Considering the overall study to date, there have been no signs of moderate, severe or serious toxicity and approximately 50% of patients have requested further treatment cycles of AB8939 after the first cycle of treatment and a measurement at day 28. CONSOLIDATED FINANCIAL INFORMATION FOR THE YEAR 2022 The operating result at 31 December 2022 was a loss of €15,937k, compared with a loss of €13,808k as of 31 December 2021, an increase in the operating loss of €2,129k (15.4%). Operating income, exclusively made up of revenues related to the operation of a drug in veterinary medicine, amounted to €958k as of 31 December 2022, compared to €1,607k a year earlier.Operating expenses amounted to €16,896k as of 31 December 2022, compared to €15,415k as of 31 December 2021, an increase of 9.6%.Marketing expenses were stable compared to 31 December 2021, rising from €493k at 31 December 2021 to €480k as of 31 December 2022.Administrative expenses decreased by 15% from €3,578k as of 31 December 2021 to €3,040k as of 31 December 2022.Research and development costs increased by €2,112k, or 18.8%, from €11,233k as of 31 December 2021 to €13,345k as of 31 December 2022. The gain of €2,326k at 31 December 2022 is mainly related to the recognition of the change in fair value between 31 December 2022 and 31 December 2021 of the preference shares resulting from the conversion of the bonds in December 2016 (class C), i.e. a financial gain of €2,557k with no impact on cash for the period. The consolidated net loss at 31 December 2022 is €13,615k compared to a loss of €14,463k as of 31 December 2021, a decrease of 5.9%. The following table summarizes the consolidated financial statements for the year 2022 prepared in accordance with IFRS, and comparative information with the year 2021: In thousands of euros, except for share data31/12/202231/12/2021Net turnover958 1 607 Cost of sales(31) (111) Marketing expenses(480) (493) Administrative expenses(3,040) (3,578) Research and development expenses(13,345) (11,233) Operating income (15,937) (13,808) Financial income 4,904887Financier expenses (2,578) (1,506) Financial income 2,326 (618) Net income (13,615) (14,463) Total comprehensive income for the period(13,356) (14,189) Basic earnings per share - in euros(0,29) (0,30) Diluted earnings per share - in euros(0,29) (0,30) In thousands of euros31/12/202231/12/2021Cash and cash equivalents7,269 8,721 Total Assets23,841 21,271 Equity(35,670)(23,198) Non-current liabilities36,43226,986 Trade payables12,24811,368 Current liabilities23,07917,482 OTHER CORPORATE INFORMATION FOR YEAR 2022 AND SINCE DECEMBER 31, 2022 Capital increase for an amount of 15 million euros AB Science announced on April 24, 2023 the success of its capital increase through the issuance of new ordinary shares with attached warrants, with a waiver of preferential subscription rights. The Capital Increase consisted of a private placement pursuant to Articles L. 225-136 of the French Commercial Code and L. 411-2 1° of the French Monetary and Financial Code and has been carried out with a waiver of preferential subscription rights, pursuant to the delegation of authority granted to the Board of Directors under the 20th resolution of the Combined General Shareholders’ Meeting of June 29, 2022. The Capital Increase has taken the form of the issuance of 2,608,686 actions new ordinary shares (the “New Shares”) to each of which are attached a share subscription warrant (the “Warrants”). The Capital Increase was made through a cash contribution of approximately EUR 11.5 million and by offsetting existing receivables, i.e. approximately EUR 3.0 million (receivables related to the pre-financing of the research tax credit for the 2020 financial year and maturing in 2023, as well as approximately EUR 500,000 in interest accrued to date on the convertible bonds issued in February 2022). Two warrants giving the right to subscribe to one ordinary share, all of the 2,608,686 New Shares and all of the 1,304,343 new shares that would be issued upon exercise of the warrants, i.e. a total of 3,913,029 shares in the Company, represent 7.36% of the Company's current share capital. The issue price of the New Shares has been set at 5.75 euros (0.01 euro par value and 5.74 euros issue premium) and the exercise price of the Warrants at 8.625 euros, representing a total fundraising of approximately EUR 15.0 million (taking into account the exercise of the warrants, the maximum amount of the Capital Increase could be increased by an amount of 26.3 million euros). The Warrants may be exercised from January 1st, 2025 to December 31, 2030. Drawdown of the first two tranches for a total amount of €12 million under its financing agreement with the European Investment Bank AB Science announced in December 2022 that it has received payment of €6.0 million as the first tranche of a €15 million loan from the European Investment Bank (EIB). AB Science announced in January 2023 that it has received payment of €6.0 million as the second tranche of the EIB loan. The agreement signed with the EIB provides a financing in two tranches of EUR 6.0 million and a third tranche of EUR 3.0 million, each subject to the fulfillment of certain conditions precedent, which have been satisfied for the first two tranches. Each tranche is accompanied by the issue of warrants, the number of which is calculated in relation to a reference price of 14 euros according to the following formula : Number of warrants = Amount of the tranche / (14 x m) with m = 3.4 for tranche 1 and 3.7 for tranche 2. The first tranche has a maturity of six years and is therefore repayable in December 2028. It carries a capitalized annual interest rate of 9.0% and the issuance of 126,050 warrants, each giving the right to subscribe to one ordinary share of AB Science at 8.61 euros for 15 years. These warrants represent 0.24% of the current capital of the Company (if they were to be exercised in their entirety). The second tranche, also of EUR 6.0 million, has a maturity of five years and is therefore repayable in January 2028. It carries a capitalized annual interest rate of 7.0% and the issuance of 115,830 warrants, each giving the right to subscribe to one ordinary share of AB Science at 14.0 euros for 15 years. These warrants represent 0.22% of the current capital of the Company (if they were to be exercised in their entirety). Renewal of the Programme d’Augmentation de Capital à Terme (PACT) concluded with Alpha Blue Ocean Alpha Blue Ocean is committed to subscribe, from the date of publication of the 2022 annual report, to newly issued shares of AB Science (in tranches comprised of a number of shares between 500,000 and 1 million) over a period of 24 months, up to a maximum of 4.0 million shares in total (or 7.2% of the company’s share capital on the basis of the capital after the capital increase announced on 24 April 2023). Such subscriptions for new shares shall be carried out using the 28th resolution of the Shareholder’s Meeting of June 29, 2022 (as renewed or otherwise amended, if applicable). By way of example, based on the April 27, 2023 closing price of AB Science’s shares, i.e 6.27 euros, on Euronext Paris, it is estimated that AB Science could raise approximately 25 million euros through this equity financing facility. For each tranche, the issuance price of new shares of AB Science, subscribed by Alpha Blue Ocean, shall be equal to 100% of the volume-weighted average price of the shares of AB Science traded on Euronext Paris over the three trading days preceding a tranche drawdown request. For each tranche, and after the settlement-delivery of the new shares of AB Science following the relevant capital increase, 80% of the proceeds of the tranche shall be secured in an escrow account with a third-party escrow agent. The remaining balance shall be kept by AB Science. Following predefined trading rules for each tranche, Alpha Blue Ocean shall manage the orderly sale, on or off the market, of the AB Science shares subscribed to. 95% of the proceeds shall be distributed to AB Science on a monthly basis (minus a structuration fee), directly from Alpha Blue Ocean or by way of a release from the escrow account. AB Science has no obligations to draw down on the PACT and shall utilise this innovative financing solution only if necessary and if the market conditions are favourable to the interests of AB Science and its shareholders. For each drawdown, the number of shares issued with respect to this agreement and admitted to trading will be reported in an Euronext notice and in a specific communication on AB Science’s website. Investors are invited to take note of the risks associated with this transaction, potentially dilutive of 7.2% of the company’s share capital on the basis of the capital after the capital increase announced on 24 April 2023, which could create downward pressure on the AB Science share, as mentioned in sections 6.4.4 and 6.4.6 of the 2022 annual report. Investors are also invited to be vigilant before taking the decision to invest in a company that carries out such operations, particularly when they are carried out successively. AB Science recalls that the present dilutive financing operation is not the first one it has put in place. Restructuring of convertible bonds issued in February 2022 and Class C preferred shares AB Science announced on 21 April 2023 the negotiation of a framework agreement under which the terms and conditions of the bond issue agreement (entered into with the holders of the US$8.5 million convertible bonds issued in February 2022 and to which 50,000 warrants were attached with an exercise price of 000 warrants with an exercise price of EUR 12.65) would be amended to provide, on 15 July 2023 and automatically, for the conversion of all the convertible bonds into ordinary shares of AB Science on the basis of a price per share of EUR 5.75 (i.e. the subscription price of the New Shares). A framework agreement has also been negotiated with the holders of Class C preferred shares (the “C Preferred”). The C Preferred still in circulation would be repurchased by AB Science for one symbolic euro (and subsequently cancelled). 520,786 share warrants (each warrant entitling the holder to subscribe for one ordinary share of AB Science at par value for a period of 12 months) will be issued in substitution of the C Preferred. In addition, still in substitution of the C Preferred, a new class of preferred shares would be created, benefiting from priority dividend rights (equal to 1.25% of the net sales of masitinib or of any licensing royalties, up to a limit of 9.0 million euros) and convertible into 750,000 ordinary shares of AB Science if the share price of AB Science exceeds a threshold of 30 euros for more than 90 consecutive days. These agreements will be submitted to AB Science shareholders for approval at the next annual general shareholders meeting, Alain Moussy having declared that he was in favour of the planned restructuring. Finally, it will be proposed to the shareholders to extend the term of certain lines of warrants already issued, to adapt to the evolution of AB Science’s strategy and of its clinical pipeline. Decision of the Enforcement Committee of the French market regulator (AMF) following the investigation relating to the financial information and the market for AB Science shares, opened in September 2017 On March 24, 2022, the AMF Enforcement Committee ruled that there was no privileged information, neither at the time of the two capital increases carried out by AB Science on March 24 and 27, 2017, nor at the time Alain Moussy sold a part of his shares on March 31, 2017. The AMF Enforcement Committee therefore completely exonerated Alain Moussy, prosecuted for insider trading, and found that AB Science had not failed to comply with its disclosure obligations at the time of these capital increases in March 2017. The AMF Enforcement Committee nevertheless considered that AB Science should have communicated as early as April 7, 2017 the high probability of a negative opinion from the European Medicine Agency (EMA) on the marketing authorization application for masitinib for the treatment of mastocytosis and ordered AB Science to pay the sum of one million euros. In application of its internal procedures, AB Science had nevertheless put in place a deferral of privileged information from this date of April 7, 2017, considering that the delay in communication was in the interest of the Company and in line with industry practices of not communicating before the final vote of the CHMP, or else withdrawing the registration dossier, which AB Science had no intention to do. Given this difference in assessment concerning a technical point relating to one of the criteria for the deferred communication of privileged information, as well as the amount of penalty, AB Science has decided to appeal to the Paris Court of Appeal. The President of AMF also appealed against the Enforcement Committee's decision. It concerns in particular the exoneration of Alain Moussy. Other events Autres opérations sur les valeurs mobilières During the year 2022, the following were granted: 183,040 share warrants, of which 50,000 were granted to a historical investor, 126,050 to the European Investment Bank as part of the financing agreement and 6,990 to directors5,000 stock-options to an employee PEA-PME eligibility AB Science confirms its eligibility for PEA-PME (a share savings plan aimed at providing finance to SMEs) in accordance with decree no. 2014-283 of 4 March 2014 taken for the application of article 70 of law no. 2013-1278 of 29 December 2013 of finance for 2014 fixing the eligibility of companies for PEA-PME, i.e. less than 5,000 employees on the one hand, an annual turnover of less than 1.5 billion euros or a balance sheet total of less than 2 billion euros, on the other hand. About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment AB SCIENCE Resultats 2022 VENG VF