IsoTis SA

Mr. van den Berg is an industry veteran with proven track record in building high-performance teams and delivering on strategic and financial transactions ZURICH--(BUSINESS WIRE)-- Memo Therapeutics AG (“MTx”), a late-stage biotech company developing best-in-class therapeutic antibodies, announced today the appointment of Erik van den Berg as Chief Executive Officer (CEO). This press release features multimedia. View the full release here: Erik van den Berg, CEO of Memo Therapeutics AG (Photo: Business Wire) Mr. van den Berg joins MTx with over 25 years’ industry experience and proven track record in leading and growing companies. During his career, Mr. van den Berg has successfully completed over 20 transactions and partnerships, including a $600 million alliance with Pfizer, $290 million partnership with Kyowa Kirin and $500M in equity and debt financings for biotechnology companies from seed through IPO. He succeeds Dr. Karsten Fischer, who stepped down to pursue other opportunities. “As Memo continues to make progress to address unmet medical needs of patients, Erik is the perfect person to lead the company through late-stage clinical development and towards potential commercialization of our lead program, AntiBKV. On behalf of the Board and entire team, I’d like to welcome Erik to MTx and look forward to our future endeavors,” said Elias Papatheodorou, Chairman of MTx’s Board of Directors. “I’d also like to thank Dr. Karsten Fischer who served as our CEO for the past 5 years for his dedication and leadership in taking our technological approach into the clinic with multiple antibody candidates.” Mr. van den Berg was CEO of AM-Pharma for over 12 years and remains on its Board. He is also Chairman of Step Pharma, TargED Therapeutics, co-founder and previous (executive) Chairman of Lava Therapeutics and co-founder and previous (executive) Chairman of Heatmatrix Group (sold to BosNieuwkerk). Previously, Mr. van den Berg also held business development roles at Organon and IsoTis (sold to Integra Lifesciences). Mr. van den Berg holds a master’s degree in chemistry from the University of Utrecht and an MBA from Manchester Business School. “Memo has already made great strides in its development of novel antibody candidates. As CEO, I look forward to continuing this momentum and build on the great progress made recently with AntiBKV in the clinic and its Fast Track designation from the FDA, as well as the recent successful Series C fundraising,” said Mr. van den Berg. About Memo Therapeutics AG Memo Therapeutics AG (“MTx”) is a late-stage biotech company developing best-in-class therapeutic antibodies to transform the lives of patients with virus infections and cancer. MTx’s lead program, AntiBKV, is a highly effective and safe neutralizing antibody to treat BK virus infection in kidney transplant recipients. This infection can lead to loss of kidney function, as well as organ failure and rejection. MTx’s pipeline consists of additional candidate therapeutic antibodies focusing on infectious diseases, such as cytomegalovirus (“CMV”), immuno-oncology targets as well as a partnership with Ono Pharmaceutical. MTx is a private company located in Schlieren / Zurich, Switzerland. View source version on businesswire.com: Contacts Memo Therapeutics AG info@memo-therapeutics.com Halsin Partners Mike Sinclair +44 (0) 7968 022075 msinclair@halsin.com Source: Memo Therapeutics AG Smart Multimedia Gallery Photo Erik van den Berg, CEO of Memo Therapeutics AG (Photo: Business Wire) Logo View this news release and multimedia online at:

世界肝炎日特别活动：动物实验能否被取代？| 药效与安全性-肝病新药研发非临床评价的关键要素（图片来源：电影海报）正文共： 10887字 30图预计阅读时间： 28分钟近日，环码生物宣布与辉瑞达成研发合作协议，双方将共同探索环形RNA疗法的潜力。本次合作将充分发挥环码生物独有的环形RNA技术平台，结合辉瑞在制药行业的广泛专长及经验，双方携手深化对环形RNA技术的理解，共同促进环形RNA技术转化为药物候选分子。同月，百奥赛图宣布与专注抗体药物偶联物（ADC）开发的Pheon Therapeutics（Pheon）达成一项抗体授权协议，该公司正在针对各种难治性肿瘤开发下一代ADC。根据协议条款，Pheon将推进基于一个由百奥赛图专有RenMice®平台得到的抗体分子产品的开发及商业化。百奥赛图将获得首付款，潜在开发和商业化的里程碑付款，以及基于产品的个位数净销售额分成。新协议的达成扩充了Pheon的ADC产品线，旨在开发同类首创和同类最优ADC药物，以满足肿瘤领域未满足的重大临床需求。纵览2023年上半年，共有8家国内企业完成技术授权License-out，仅晶泰科技与礼来披露交易金额（2.5亿美元），其中和铂医药及其子公司诺纳生物产生的技术授权最多（3笔）。接下来，我们将对交易内容进行阐述，并对各国内企业的技术平台进行详细的解读。一环码生物环码生物是一家专注于环形RNA核酸药物开发的创新型生物科技公司，利用自主研发的环形RNA技术平台，专注于开发治疗性药物和疫苗来解决未被满足的医疗需求。（一）技术平台1、核酸技术平台：拥有自主研发的专利，该专利技术基于II型内含子自剪接核酶的活性可在体外环化任意RNA，该技术具有无序列残留、环化产物均一、环化效率高、反应条件温和等特点，适合于工业化放大。环形RNA在其形态方面具有天然优势，因不易被体内的RNA降解系统识别，使其在体内较mRNA更稳定，发挥药效的时间窗口更长。同时，环形RNA的免疫原性很低，因而无需使用修饰碱基，即可提高药物耐受剂量。环形RNA的翻译起始不同于mRNA系统，不需要5’帽结构和3’多聚腺苷酸尾。它可以通过特定的翻译起始元件以组织或细胞特异性的方式启动翻译，使得药物表达具有更好的特异性，减少副作用。2、序列设计平台：环形RNA的翻译起始不同于mRNA，利用特定的翻译起始元件通过帽非依赖性的方式启动翻译。通常这些翻译起始元件的活性弱于mRNA的5’帽结构，但其具有一定的细胞和组织特异性。环码生物建立了一套基于环形RNA的高通量筛选系统可以高效筛选翻译起始元件，目前已完成数百万条序列的筛选并获得了大量翻译起始元件。在此基础上，利用计算生物学的方法建立了针对环形RNA的序列设计优化平台，该平台可以设计优化翻译起始元件及编码区序列从而实现环形RNA的高效翻译。（二）研发管线目前，公司已披露在研药物10余种，均处于临床前的在研阶段。二百奥赛图百奥赛图是一家创新技术驱动新药研发的国际性生物技术公司，基于其自主研发并拥有完全独立知识产权的全人抗体RenMice®平台（RenMab®、RenLite®和RenNano®小鼠），将单抗、双抗和纳米抗体开发技术平台、动物体内药效筛选平台、强大的临床开发能力有机整合在一起，形成了独具特色、涵盖药物研发全流程的新药研发能力。截至2023年5月31日，百奥赛图已签署了46项药物合作开发/授权/转让协议并与包括多家MNC在内的20家企业达成RenMice®平台授权。2022 年9 月1 日，百奥赛图登陆港交所IPO，募集资金5.49 亿港元；2023 年6 月20 日，公司科创板IPO 获受理，拟募资18.93 亿元。（一）公司平台基于SUPCE技术，采取大片段原位替换策略，替换人源抗体基因序列，保留小鼠Fc区域序列，保证全人抗体的产生和免疫系统发育正常，RenMice平台具有丰富多样性、高亲和力和强特异性抗体的产生能力，在抗体药物开发过程中更具优势。1） 全人抗体RenMab®小鼠RenMab®小鼠中，编码重链和κ轻链的小鼠抗体可变区基因被原位替换为人相应的基因，保留完整的鼠源的恒定区以及重要调控元件，同时敲除鼠源λ链基因。RenMab®小鼠的人源化抗体基因替换长度和完整性显著优于同类已有模型。与正常小鼠相比，RenMab®小鼠的免疫系统发育并无异常。由于其具有更为丰富的抗体基因多样性，RenMab®小鼠在抗体药物开发过程中具有更高的潜力，可以得到更多的强特异性、高亲和性、丰富多样性的抗体药物。2）全人抗体RenLite®小鼠在RenLite®小鼠中，重链可变区基因被原位替换为人的相应基因，同时轻链可变区基因被替换为单一人轻链可变区基因。固定轻链并不影响抗体在小鼠体内完成亲和力成熟，RenLite®小鼠同野生型小鼠一样，可生成具有高亲和力、特异性和多样性的候选抗体分子，以供下游抗体药物筛选。同时RenLite®小鼠生成的共轻链抗体可大幅提高后续组装双抗等复杂药物分子的效率。3)全人纳米抗体RenNano®小鼠纳米抗体分子量小、渗透性好，可穿越血脑屏障、浸润肿瘤，到达普通抗体所无法到达的区域；同时，由于其CDR3区较普通抗体更长，所以能触及GPCR等困难靶点的隐秘表位，对于破解难治疾病具有重要意义。RenNano®小鼠是百奥赛图在其全人抗体小鼠RenMab®的基础上，进一步对抗体恒定区进行改造生成的，可以直接产生全人仅重链抗体（HCAb）。与世界上为数不多的其它纳米抗体模型相比，百奥赛图的RenNano®小鼠携带有原位置换的完整的人类抗体重链可变区基因，其产生的全人单链抗体序列无需再经过体外人源化改造便可用于药物开发，节省了大量的时间和费用，也降低了后续开发的风险。基于小鼠的快速繁殖能力以及成熟的鼠单抗制备技术，与羊驼等其它单链抗体动物相比，RenNano®小鼠可以用来进行规模化高通量全人HCAb的开发。用多种不同抗原免疫RenNano®小鼠后，可获得CDR3序列多样、识别表位丰富的HCAb抗体。这些抗体结合抗原不依赖轻链，并且具有nM级别的高亲和力。实验表明，RenNano®来源的抗体在体外、体内具有良好的生物学功能。生成的纳米抗体结构简单、无需配对，适合模块化组装，易于构建双/多抗、CAR-T等。（二）公司管线百奥赛图致力于开发出满足患者需求的创新型抗体药物，聚焦肿瘤、自身免疫、代谢及抗感染等多个疾病领域，充分利用独特的创新药物开发优势，现已拥有包含单克隆抗体、双特异性抗体、ADC药物等在内的十多个研发管线。YH003：是一款靶向CD40的人源化IgG2激动型抗体，通过特异性结合CD40受体，促进抗原提呈细胞的活化，正向调控抗肿瘤T细胞的效应活性。临床前抗体筛选阶段，公司充分利用百奥赛图自主研发的CD40人源化小鼠上的肿瘤模型，能够快速在小鼠体内筛选到完全抑制肿瘤生长，同时又没有肝毒性等副作用的单克隆抗体。YH001：是一款重组人源化CTLA-4 IgG1单克隆抗体，基于动物syngeneic肿瘤模型进行筛选获得。通过提高机体自身针对肿瘤细胞的免疫应答，强化肿瘤微环境中调节性T细胞的去除，从而达到治疗多种肿瘤的目的。YH002：是一款重组人源化激动型OX40 IgG1单克隆抗体，具有高抗肿瘤活性。YH002模拟OX40L的功能与OX40结合，其独特的抗原结合表位使其成为出色的免疫激活抗体，亦兼备良好的安全性。YH004：是一款安全性良好的重组人源化激动型4-1BB IgG1单克隆抗体。有效激活CD8+T细胞的同时，对于高表达4-1BB的Treg细胞具有良好的ADCC清除作用。三晶泰科技2023年5月，晶泰科技宣布与礼来（“Eli Lilly”）签署一项 AI 小分子新药发现合作，预付款及里程碑总收益可达 2.5 亿美元。根据协议规定，礼来将支付最高可达 2.5 亿美元的预付款及里程碑费用，针对某个未披露的创新靶点，由晶泰科技利用其特有的小分子药物发现平台 ID4Inno™ 研发首创新药，填补未满足的临床用药需求。（一）公司介绍晶泰科技是一家世界前沿的以人工智能（AI）和机器人驱动创新的科技公司。2014年创立于美国麻省理工学院（MIT），致力于实现生命科学和新材料领域的数字化和智能化革新。公司基于量子物理、人工智能、云计算及大规模实验机器人集群等前沿技术与能力，为全球生物医药、化工、新能源、新材料等产业提供创新技术、服务及产品。（二）技术平台公司致力于以智能化自动化创新小分子药物发现的 ID4Inno™ 和致力于下一代创新抗体药物发现的 XupremAb™ 两大特色技术平台，助力创新药物研发企业实现特色竞争力布局，为病患带来更大临床获益。1、ID4Inno™智能化自动化创新小分子药物发现平台 ID4Inno™ 系统部署了人工智能药物发现平台 ID4Idea™ 和高精度计算化学 ID4Gibbs™。ID4Idea™ 平台：集成了晶泰科技自有的规模庞大的 AI 模型体系，构建了药物发现不同场景的数字化流程和智能化算法，完成定向分子设计、高通量评估、以及辅助合成、测试等步骤；同时，在分子设计阶段引入多目标优化，在筛选阶段同时评估活性、可合成性、成药性，降低沉没成本。ID4Gibbs™ 平台：基于量子力学、分子力学以及统计力学等物理原理，构建了针对挑战研发场景的高精度结合模式预测 ( XPose ) 以及高精度、高通量的亲和力评估 ( XFEP ) 流程，从靶点序列到结合亲和力综合评估药物-靶标相互作用，有力支持了活性、选择性、以及突变耐药性的优化。在这两大平台的支持下，ID4Inno™ 系统为针对 First-in-Class, Best-in-Class 以及 Fast Follow-on 等不同研发目标和场景提供强大的技术保证。2、 XupremAb™ AI 驱动的下一代抗体发现平台XupremAb™ 将 AI 和经典的抗体发现技术有机融合，于药物发现的多个环节如苗头抗体发现、亲和力成熟及超级人源化等工程化改造以及抗体可开发性评估与优化，赋能创新抗体药物及新形式的发现和构建。3、X-Degrader™ 智能化计算平台 X-Degrader 为 PROTAC 及分子胶类药物发现实现设计、合成、测试的全流程服务。（三）在研管线XBD-101：候选分子具有高选择性，高活性，对多个临床耐药突变敏感，展现出良好的临床前有效性和安全性等优点，是现有竞品中覆盖突变最多及药效最优的新一代抑制剂。该项目已获得美国FDA临床批件，国内IND申报中。XBD-202：候选分子具有新颖的作用方式，较好的成药性和动物体内有效性等优点，目前该项目正在进行IND enabling阶段。XBD-207：设计合成多类新颖骨架分子，其中一类实现了生物利用度从40%到90%的提升，并且在银屑病等药效模型中展现了卓异的效果，这也是该靶点在自免领域中应用的首次验证。XBD-105：已获得成药性佳的临床前候选化合物（PCC）。可与标准疗法（化疗）联用，也可联用PD-1/L1用于消化道肿瘤治疗。XBD-201：First-in-class 项目，获得多个成药性良好的临床前候选化合物，计划开展CMC研究，目前该项目正在美国进行IND申报。四映恩生物2023年5月，映恩生物宣布与Adcendo扩大合作。根据协议，Adcendo有机会提名两个新的ADC靶点，新的靶点将使用映恩生物的linker-payload平台进行评估，旨在产生具有卓越安全性、在肿瘤中可持续递送和释放有效载荷以及对抗原低表达和阴性细胞的有效旁观者杀伤的ADC。经过评估后，Adcendo可选择使用Duality的下一代ADC技术平台。该协议是基于今年1月，映恩生物授予Adcendo其独创的DITAC平台的技术许可，用于Adcendo治疗间叶组织肿瘤的uPARAP ADC项目基础上的拓展。（一）公司介绍映恩生物（“DualityBio”）是一家临床阶段的创新生物药公司，专注于为癌症和自身免疫性疾病患者研发新一代ADC治疗药物。目前，公司正在继续研发其新型蛋白质工程和ADC技术，以开发下一代“超级ADC”分子，包括不同有效载荷类别、双特异性ADC和双有效载荷ADC。（二）技术平台公司团队在注重差异化的基础上，开发了包含DITAC, DIMAC和DISAC在内的多个具有独立知识产权的ADC技术平台。这些技术平台包含一系列专有的连接子有效载荷库（linker payload libraries），可应用于包括肿瘤学和自身免疫性疾病在内的多个领域。这些连接子载荷和偶联药物是根据所需的物理化学特性、生物活性和DMPK特性合理设计和选择的，以便于能够达到最佳的安全性和有效性。这些平台可以很容易地扩展到各种靶向分子，包括抗体、蛋白质、肽和小分子，为开发潜在的同类最佳和/或同类第一的候选药物提供快速有效的方法，以满足未满足的医疗需求。1、DITAC（Duality Immune Toxin Antibody Conjugate）技术平台DITAC作为免疫毒素ADC技术平台，相比于目前国际领先的ADC技术平台，具有肿瘤靶向性药物释放更精准、疗效更好以及治疗窗口更宽等显著优势。基于该平台开发的新一代ADC产品具有多重优势：有望大幅提升药物的治疗窗口，对抗原表达水平较低的肿瘤适应症仍有较好的治疗效果。具有优越的系统稳定性，减少游离毒素的脱落率，同时毒素脱落时也能够实现快速的全身清除，从而有望大幅提高安全性。具备持续的肿瘤选择性药物释放、高效的旁观者杀伤效应、有效载荷可快速的扩散至肿瘤微环境等特点，从而提升药品疗效。2、DIMAC(Duality Immune Modulating Antibody Conjugate)技术平台DIMAC是映恩生物针对自身免疫疾病的ADC技术平台，该平台开发的药物具有较长的响应持久性、高靶点选择性、覆盖更广泛的适应症、更好的优效性及更少的不良反应等优势。在2022年多个行业大会上，映恩生物也介绍了其新一代DIMAC免疫调节型ADC的开发思路：在有效载荷设计方面，首先，由于ADC药物精准靶向的特点，要求有效载荷的活性要强于传统的激素类小分子；其次，由于ADC药物给药频次低的特点，要求有效载荷具备长效的作用特点，在糖皮质激素受体上的作用时间要长于传统的激素类小分子；最后，为了最大限度地减少激素类药物对于全身其他脏器的副作用，要求有效载荷具备在人体内被快速清除的机制。在靶点和抗体选择方面，要求靶点本身对于自身免疫疾病的发病和发展具有驱动作用，而抗体在具备高度的靶点选择性的同时，同时需要具备对靶点功能的调节作用和对自身免疫疾病的治疗效果。此外映恩生物还开发了基于免疫刺激抗体偶联物DISAC平台，有望在肿瘤环境中恢复和增强机体免疫反应。（三）公司管线截至目前，映恩生物在临床和临床前阶段布局了9个创新药物，其中包括四个国际多中心（MRCT）临床阶段项目。映恩生物研发管线汇总DB-1303：一种人源化抗HER2 IgG单克隆抗体，2023年4月，DB-1303和DB-1313（未公开靶点）一起以16.7亿美元授权给BioNtech。根据1/2a期临床数据显示，23名患者（44.2%，23/52）根据RECIST 1.1有客观部分肿瘤反应；所有患者中，DCR为88.5%（46/52）；对于HER2+BC和HER2-low BC患者，DCR分别为96.2%（25/26）和84.6%（11/13）。DB-1305：通过酶促切割的四肽接头将抗Trop-2抗体与新型拓扑异构酶I抑制剂P1021偶联而成的靶向ADC。在体外，DB-1305选择性地结合Trop-2阳性细胞并被内吞，呈现浓度依赖性细胞毒性。在体内，DB-1305在乳腺癌（MDA-MB-468）、结肠癌（COLO205）和肺癌（DMS-53）的小鼠模型中显示出强大的抗肿瘤活性，相对于DS-1062疗效显著提高。DB-1310：是一款靶向HER3 ADC药物，临床前研究中显示，DB-1310表现出优于patritumab的肿瘤抑制效果和安全性；并且在与EGFR小分子抑制剂联合治疗中表现出优秀的协调治疗效果。五诺纳生物/和铂医药2023年5月，诺纳生物宣布与OPKO Health子公司ModeX Therapeutics达成合作协议，利用诺纳生物具有全球专利的全人源小鼠平台技术支持ModeX在多特异性抗体领域的持续开拓，开发创新疗法。ModeX将有权使用诺纳生物全人源小鼠平台Harbour Mice，以加速ModeX MSTAR平台的单克隆抗体发现，大幅提高临床前开发效率。2023年4月，诺纳生物宣布与ExeVir Bio公司达成合作协议，综合利用双方的专长和资源，共同探索传染病领域，加速开发创新疗法，以填补未满足医疗需求。2023年2月，诺纳生物宣布已与ADC药物开发商Mythic Therapeutics达成合作协议。通过此次合作，诺纳生物将向Mythic提供具有全球专利的HCAb转基因小鼠平台技术使用权及抗体发现服务，并结合Mythic的抗体工程技术，以开发针对多种癌症的下一代ADC疗法。（一）公司介绍诺纳生物是一家致力于尖端技术创新的全球性生物技术公司，并提供从“创意到创新”(“I到ITM”)的整体解决方案，涵盖靶标验证、抗体发现到临床前研究。公司运用整合创新的抗体技术平台及全球领先的科学家团队，向客户提供涵盖抗原制备、动物免疫、单B细胞筛选、抗体开发与工程、成药性评估和药理评估的一站式抗体发现解决方案。诺纳生物拥有Harbour Mice®全人源抗体转基因小鼠平台、HBICE免疫细胞衔接器双抗平台，能够提供一站式抗体即抗体的发现服务。由于有着完整的技术开发路径、广泛的专利布局和知识产权壁垒，Harbour Mice®平台吸引了多家大型生物制药企业的注意，达成技术授权或共同开发的海外合作方包括礼来、Dragonfly、Moderna、AbCellera、科伦博泰等。（二）技术平台Harbour Mice是全人源单克隆抗体平台以及高效产生新型抗体类治疗药物的平台，可生成经典双轻链、双重链(H2L2)形式及仅重链(HCAb)形式的全人源单克隆抗体。HCAb 平台是全球第一个产生并应用于治疗性抗体发现的 HCAb 转基因小鼠平台。由于其仅含两条“重链”抗体，不含轻链，因此其大小约为常规IgG的一半，因此肿瘤穿透性更好。同时，HCAb具有与IgG 抗体类似的药代动力学特性和Fc介导的效应功能，不需要额外的人源化或抗体工程改造。不含轻链的优势也最大限度地减少了轻链错配和异二聚的问题。普通抗体与HCAbs结构比较此外，该平台还可以开发多种分子结构形式的单域抗体、双特异性和多特异性抗体、抗体药物偶联物、CAR-T或其他VH单域衍生产品。相较于传统方式产生的全人源化抗体，省去了冗长的抗体人源化过程，为筛选候选药物分子提供了足够的灵活性和多样性。由于技术难度较高，全球范围内成熟的重链抗体平台微乎其微，除和铂医药外还包括：赛诺菲ablynx（48亿美金收购的骆驼重链）、安进Teneobio（25亿美金收购的大鼠重链）。（三）公司管线通过自研+多元化合作，和铂医药快速拓展其新药研发管线，目前已经建立了强大的研发管线，覆盖单抗、双抗、ADC等多种抗体药物形式。从免疫通路的角度，覆盖了直接杀伤型、T细胞募集型、T/NK细胞激活型、NK细胞募集型、解除肿瘤微环境免疫抑制性等等。Porustobart（HBM4003）：是抗CTLA-4全人源单克隆重链抗体（HCAb），通过增强抗体依赖的细胞毒性作用(ADCC)活性，对肿瘤微环境中高表达CTLA-4的Treg细胞具有极高的特异性剔除。上半年，和铂于2023 AACR和2023 ASCO上分别公布了porustobart联合特瑞普利单抗治疗晚期高级别神经内分泌肿瘤的Ib期临床试验结果，显示：（1）Porustobart联合特瑞普利单抗治疗晚期高级别神经内分泌肿瘤显示出良好的抗肿瘤活性；在两种剂量组之间未观察到疗效上的显著差异。（2）Porustobart联合特瑞普利单抗显示出可接受的安全性；（3）Porustobart联合特瑞普利单抗显示出独特PK/PD特征。HBM7008（CLN-418）：是一款针对B7H4x4-1BB的双特异性抗体，也是目前全球针对这两个靶点的唯一双抗，目前正处于I期临床开发阶段。临床前研究结果显示，在B7H4阳性的同基因模型中，HBM7008 1 mg/kg剂量可完全使肿瘤消退；在小鼠肿瘤模型中，观察到完全缓解（CR）。六英矽智能2023年3月，英矽智能（Insilico Medicine）宣布与诺和诺德达成合作。诺和诺德将在英矽智能人工智能靶点发现引擎PandaOmics的帮助下，结合其自身药物发现和研究的专长，针对肝纤维化识别潜在的新颖靶点，并对其展开验证。（一）公司介绍英矽智能是一家由生成式人工智能驱动的药物研发公司，通过下一代人工智能系统连接生物学、化学和临床试验分析，利用深度生成模型、强化学习、转换模型等现代机器学习技术，构建强大且高效的人工智能药物研发平台，识别全新靶点并生成具有特定属性分子结构的候选药物。英矽智能聚焦癌症、纤维化、免疫、中枢神经系统疾病、衰老相关疾病等未被满足医疗需求领域，推进并加速创新药物研发。2023 年6 月27 日，英矽智能在港交所申请IPO。（二）技术平台英矽智能开发了多种以生成对抗网络（GAN）驱动药物发现的方法和功能，并将这些算法整合到一体化、高度集成、端到端药物研发平台Pharma.AI。该平台覆盖生物学、生成化学和临床研究等多个领域，包括可商业化的靶点发现引擎PandaOmics，分子生成和设计引擎Chemistry42和临床试验结果预测引擎inClinico。1、PandaOmics 是人工智能驱动的生物靶点发现平台，利用先进的深度学习模型和人工智能算法，基于组学数据、文本数据、科研基金数据和行业权威观点的综合评分来预测与特定疾病相关的靶点基因。PandaOmics目前正被广泛运用于学术研究和药物开发中。PandaOmics平台的算法还可以根据新颖性、置信度、商业性、成药性、安全性和其他影响靶点选择的关键因素对靶点蛋白进行排序。2、Chemistry42平台集成多种前沿算法模型，包括生成自编码器、生成式对抗网络、基于流的生成模型、进化算法、语言模型等。Chemistry42界面设计友好、工作流程直观等优点，只需简单三步，即可得到可用的先导化合物类似分子。无论是对老药新用项目还是潜在的新疗法，Chemistry42都可以对化合物进行设计、排序和评分，从数百万种候选化合物中找到数百种具有所需特性的化合物。3、inClinico（临床试验结果预测平台）其功能主要是预测临床II期-III期的成功率，并设计临床试验方案，让试验成功的概率更大。（三）公司管线依托生成式人工智能驱动的自有药物研发平台，英矽智能迅速搭建涵盖约30条创新疗法管线的多元化疗法组合，其中3条管线已推进到临床阶段。ISM3091：是一款口服的选择性USP1抑制剂，在针对具有HRD突变的广泛肿瘤谱系中显现出潜在疗效。体外数据显示，该化合物在BRCA基因突变的肿瘤细胞中具有强效抗增殖活性和优异的选择性。ISM3312：是一款抗新冠口服3CL蛋白酶抑制剂，其优势在于：1）广谱性强，对各种新冠病毒变异和耐药毒有良好效果，并且对其他病毒也有效；2）采用全新的共价不可逆机制，可在低剂量下起效，且单药有效，不用与其他药物联用；3）合成简单，成本低廉，可及性高。ISM018_055：用于罕见病特发性肺纤维化(IPF)治疗的全球首创AI药物，已完成中国和新西兰的I期临床试验，并于2023年1月获FDA孤儿药认定（ODD）。七三迭纪2023年3月，三迭纪医药与勃林格殷格翰签署合作协议，此次合作旨在探索3D打印技术在加速新化学分子（NCE）药物剂型开发中的应用。本次合作由勃林格殷格翰中国药物开发部中心牵头，双方将围绕新药物分子进行快速制剂研发。三迭纪通过MED 3D打印技术进行药物制剂的结构设计，开发多种原型制剂，探索新化合物分子的剂量设计和释放行为，以期提升新药研发速率与成功率。（一）公司介绍三迭纪成立于2015年7月，是3D打印药物领域的引领者。公司致力于建设全新的3D打印药物技术平台，形成了从药物剂型设计、数字化开发，到连续化生产全链条的专有技术。三迭纪是中国唯一的3D打印药物专业公司，唯一入选美国FDA新兴技术项目的中国药企。公司定位为3D打印药物技术平台型公司，具有自主研发产品和合作开发产品并行的商业模式。（二）技术平台公司独创的熔融挤出沉积3D打印技术的主要特点有：技术原创：自建制药专用3D打印机及规模化产线，系统研究药用高分子材料，设计三维结构新型制剂；全新工艺：全新增材制药（3D打印）工艺，从原辅料到成品片一站式成型；应用价值：为制药长链条提供端到端的技术解决方案，包括药物产品设计、产品开发、产品生产和产品供应。（三）公司管线公司拥有丰富的3D打印产品管线，首款产品T19、第二款和第三款产品T20和T21均已获得美国FDA的IND批准，同时T19已获得中国NMPA的IND批准。T19：根据时辰治疗学原理，针对类风湿性关节炎症状的昼夜节律进行设计。患者睡前服用T19，血液中的药物浓度在疼痛、关节僵硬及功能障碍等疾病症状最严重的早晨达峰，并维持其日间血药浓度，从而取得最佳的药物治疗效果。T20：是三迭纪自主研发的全球T系列产品中的第二款，T20在美国FDA的注册申报路径是505(b)(2)，原研药为全球最畅销的抗凝血药物，从2018年起连续四年是全球小分子药物销售冠军，临床疗效包括降低非瓣膜病性房颤患者的卒中和全身性栓塞风险、预防和治疗深静脉血栓（DVT）和肺栓塞（PE）等。T21：是一款治疗溃疡性结肠炎的原研药物，通过结肠靶向递送技术，将药物精准递送到病灶，达到局部给药、局部起效的作用。T21产品采用了创新的剂型设计实现了结肠靶向的递送，它通过精准的结肠释药，降低全身血药浓度暴露量，从而减少药物的副作用，提升了安全性。【备注】原文题目：洞察|中国技术平台型Biotech--用底层专利造就的基石，叩响技术出海的"大门"封面图/摘要图来源：电影海报精彩推荐百济神州PD-1有望欧盟上市，在美获批还会远吗？谁的PD-1能率先出海？据研究，这能提升20%新药开发成功率和50%患者招募率，以患者为中心的临床试验获益明显小核酸巨头Alnylam之《长安三万里》——创始CEO讲述19年征程背后的神奇故事（终篇）谢雨礼博士：药物递送——生物医药未来的“卡脖子”技术点击阅读原文，与药时代一起快乐学习！

Discovery collaboration underway with Center for Cellular Immunotherapies Lab at University of Pennsylvania to Study Combinations of Novel Viral Immunotherapy and CAR-T Cell Therapy Candidates in Solid Tumor ModelsUpcoming clinical data presentations at SITC and SNO Annual MeetingsVirtual R&D Day on December 6, 2022, with Candel leadership and renowned oncology experts NEEDHAM, Mass., Nov. 10, 2022 (GLOBE NEWSWIRE) -- Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on helping patients fight cancer with viral immunotherapies, today reported financial results for the third quarter ended September 30, 2022 and provided a corporate update. “Candel made important progress across multiple facets of the organization this quarter,” said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. “We have bolstered the Company’s capabilities and future potential with the appointment of three new board members and two new leadership executives, an orphan drug designation from the European Commission for CAN-2409 in glioma, and most recently a discovery partnership with the University of Pennsylvania’s Center for Cellular Immunotherapies, led by Dr. Carl June, the Richard W. Vague Professor for Immunotherapy, to study the combination of our enLIGHTEN™ Discovery Platform and their CAR-T cells in solid tumors. We will close the year with new clinical results coming from our pipeline being presented at R&D Day and we look ahead with confidence to deliver our world-class viral immunotherapy candidates to patients battling cancer.” Jason A. Amello, Chief Financial Officer, added, “The third quarter of 2022 was marked by significant momentum as the Company broadened its viral immunotherapy footprint and continued to execute across all of its programs in an efficient and cost-effective manner.” Third Quarter 2022 and Recent Highlights In August, the Company enhanced its Board of Directors with the appointments of three new Board members. (View Release) Joseph Papa, Chief Executive Officer of Bausch + Lomb CorporationGary Nabel, MD, PhD, Chief Innovation Officer of OPKO and Chief Executive Officer, ModeX Therapeutics, Inc., an OPKO Health companyRenee Gaeta, Chief Financial Officer of Eko Devices In September, the Company strengthened its executive leadership team with appointments of Jason A. Amello as Chief Financial Officer and Garrett Nichols, MD, MS, as Chief Medical Officer. (View Release)Separately in September, the Company submitted the protocol for a phase 3 clinical trial evaluating CAN-2409 in patients living with high-grade glioma (HGG) to a central institutional review board.Also in September, the European Medicines Agency (EMA) issued a positive opinion for orphan drug designation for CAN-2409 in glioma. (View Release)In October, the European Commission adopted the EMA’s decision to grant CAN-2409 orphan drug designation for the treatment of glioma. Also in October, the Company formed a partnership with Neil Sheppard, DPhil, Director of the T Cell Engineering Lab at the University of Pennsylvania’s Center for Cellular Immunotherapies, led by Carl. H June, MD, the Richard W. Vague Professor of Immunotherapy, to study combinations of novel viral immunotherapy and CAR-T cell therapy candidates in solid tumors. (View Release)In early November, Dr. Tak participated in separate fireside chats with Credit Suisse and BMO Capital Markets. (View Webcasts) Key Upcoming Milestones and Events 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (View Release) On November 11, Anne R. Diers, PhD, Director of Early Research at Candel, will lead an in-person poster session on pre-clinical CAN-2409 data.Also on November 11, Patrick Y. Wen, MD, Principal Investigator from Dana-Farber Cancer Institute, will present new data in an in-person oral session on CAN-2409 in combination with nivolumab and standard of care from the Company’s phase 1b clinical trial in newly diagnosed HGG. On November 16, Dr. Tak will take part in an in-person fireside chat at Jefferies London Healthcare Conference. (Register Here)27th Annual Meeting of the Society for Neuro-Oncology (SNO) (View Release) On November 18, new clinical data from the Company’s phase 1 trial of CAN-3110 in recurrent HGG will be presented in an in-person oral session by Alexander Ling, PhD, a Postdoctoral Research Fellow from Brigham and Women’s Hospital. On December 6, the Company will hold its virtual R&D Day with leadership and renowned oncology experts to present an in-depth overview of the Company’s viral immunotherapy platforms and clinical pipeline including additional data from its phase 2 clinical trial of CAN-2409 in combination with anti-PD-1 or PD-L1 agents in patients with stage III/IV non-small cell lung cancer. Financial Results for the Quarter Ended September 30, 2022 Research and Development Service Revenue, related party: Research and Development Service Revenue, related party, for the third quarters ended September 30, 2022 and 2021 was $31,000. Research and Development Expenses: Research and development expenses were $5.4 million for the quarter ended September 30, 2022 compared to $5.3 million for the comparable period in 2021. The increase was primarily due to personnel-related costs for additional headcount, as well as operating expenses related to the conduct of five ongoing clinical studies. Research and development expenses includes non-cash stock compensation expense of $343,000 and $1.5 million for the third quarter of 2022 and 2021, respectively. General and Administrative Expenses: General and administrative expenses were $3.5 million for the third quarter of 2022 compared to $2.8 million for the third quarter of 2021. The increase was primarily due to higher recruiting costs, personnel-related costs, and professional and consulting fees associated with operating as a public company. General and administrative expenses includes non-cash stock compensation expense of $400,000 and $390,000 for the third quarter of 2022 and 2021, respectively. Net Loss: Net loss for the third quarter of 2022 was $8.7 million compared to $16.2 million for the comparable period of 2021. The net loss for the third quarter of 2022 includes non-operating interest, dividend and investment expense of $176,000 and a non-cash credit of $369,000 for the change in the fair value of the Company’s warrant liability. The net loss for the third quarter of 2021 includes net non-operating income of $117,000 and a non-cash charge of $8.3 million for the change in the fair value of the Company’s warrant liability. Cash Position: Cash and cash equivalents as of September 30, 2022 were $77.2 million compared to $82.6 million as of December 31, 2021, and reflects the receipt of $20.0 million from the term loan with Silicon Valley Bank in February 2022. Based on current plans and assumptions, the Company expects that its existing cash and cash equivalents will be sufficient to fund its current operating plan into the first quarter of 2024. Candel Therapeutics, Inc. Consolidated Statements of Operations (in thousands, except share and per share amounts)(amounts are unaudited) THREE MONTHS ENDEDSEPTEMBER 30, NINE MONTHS ENDEDSEPTEMBER 30, 2022 2021 2022 2021 Research and development service revenue, related party $31 $31 $94 $94 Operating expenses: Research and development 5,376 5,265 15,815 11,324 General and administrative 3,536 2,795 10,900 6,756 Total operating expenses 8,912 8,060 26,715 18,080 Loss from operations (8,881) (8,029) (26,621) (17,986)Other income (expense): Grant income — 131 — 927 Interest, dividend and investment income (expense), net (176) (14) (716) (42)Change in fair value of warrant liability 369 (8,250) 13,626 (20,619)Total other income (expense), net 193 (8,133) 12,910 (19,734)Net loss $(8,688) $(16,162) $(13,711) $(37,720)Net loss per share, basic and diluted $(0.30) $(0.69) $(0.48) $(2.42)Weighted-average common shares outstanding, basic and diluted 28,891,909 23,325,716 28,798,284 15,579,267 Candel Therapeutics, Inc. Consolidated Balance Sheet Data (in thousands)(amounts are unaudited) SEPTEMBER 30,2022 DECEMBER 31,2021Cash and cash equivalents $77,183 $82,642 Working capital (1) 73,172 79,583 Total assets 85,007 89,205 Warrant liability 4,626 18,252 Total other liabilities 28,254 6,816 Accumulated deficit (94,006) (80,295)Total stockholders equity $52,127 $64,137 (1) Working capital is calculated as current assets less current liabilities About Candel Therapeutics Candel is a clinical stage biopharmaceutical company focused on helping patients fight cancer with viral immunotherapies that elicit a systemic anti-tumor immune response. Candel’s engineered viruses are designed to induce immunogenic cell death through direct viral-mediated cytotoxicity in cancer cells, thus releasing tumor neo-antigens while creating a pro-inflammatory microenvironment at the site of injection. Candel has established two clinical stage viral immunotherapy platforms based on novel, genetically modified adenovirus and herpes simplex virus (HSV) gene constructs, respectively. CAN-2409 is the lead product candidate from the adenovirus platform and CAN-3110 is the lead product candidate from the HSV platform. The enLIGHTEN™ Discovery Platform is the first systematic, iterative HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors. For more information about Candel, visit www.candeltx.com. Forward-Looking Statements This press release includes certain disclosures that contain “forward-looking statements,” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the timing and advancement of development programs, including key data readout milestones and indications; expectations regarding the therapeutic benefit of its programs; and expectations regarding cash runway and expenditures. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of development programs; expectations regarding the therapeutic benefit of the Company’s programs; the Company’s ability to efficiently discover and develop product candidates; the Company’s ability to obtain and maintain regulatory approval of product candidates; the Company’s ability to maintain its intellectual property; the implementation of the Company’s business model, and strategic plans for the Company’s business and product candidates, and other risks identified in the Company’s SEC filings, including the Company’s most recent Quarterly Report on Form 10-Q filed with the SEC, and subsequent filings with the SEC. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent the Company’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Media ContactCassidy McClainAccount DirectorEvoke CanaleCassidy.McClain@evokegroup.com(619) 694-6291 Investor ContactSylvia WheelerPrincipalWheelhouse Life Science Advisorsswheeler@wheelhouselsa.com