Novel cardiotropic capsids transduce more than 90% of cardiomyocytes in non-human primates (NHPs) and detarget the liver and dorsal root ganglia (DRG); show safety and efficacy in a mouse model of cardiac dysfunction

新型向心衣壳在非人灵长类动物（NHPs）中转导超过90%的心肌细胞，并使肝脏和背根神经节（DRG）脱靶；在心脏功能障碍的小鼠模型中显示安全性和有效性

Novel BBB-penetrant capsid transduces more than 50% of neurons in NHPs across spinal cord, cortex, and deep-brain regions and detarget the liver and DRG; shows greater than 50% reduction of Ataxin-2, a gene believed to be involved in ALS

新型BBB渗透衣壳在脊髓，皮质和深部大脑区域转导NHP中超过50%的神经元，并使肝脏和DRG脱靶；显示Ataxin-2减少了50%以上，Ataxin-2是一种被认为与ALS有关的基因

WALTHAM, Mass., May 10, 2024 /PRNewswire/ -- Affinia Therapeutics ('Affinia'), an innovative gene therapy company with a proprietary platform for rationally designed adeno-associated virus (AAV) vectors and gene therapies for rare and prevalent devastating diseases, today announced the presentation of new preclinical data on its novel AAV capsids for genetic cardiomyopathies and diseases of the central nervous system (CNS) such as amyotrophic lateral sclerosis (ALS), as well as the Company's high-yield manufacturing process.

马萨诸塞州沃尔瑟姆，2024年5月10日/PRNewswire/-Affinia Therapeutics（“Affinia”）是一家创新的基因治疗公司，拥有一个专有平台，用于合理设计腺相关病毒（AAV）载体和罕见和流行的毁灭性疾病的基因治疗，今天宣布介绍其新型AAV衣壳的新临床前数据，用于遗传性心肌病和中枢神经系统疾病，如肌萎缩侧索硬化症（ALS），以及该公司的高产制造工艺。

This research will be presented in oral sessions today at the American Society of Gene and Cell Therapy (ASGCT) 2024 Annual Meeting, being held May 7-11, 2024 in Baltimore, MD and virtually..

这项研究将在今天于2024年5月7日至11日在马里兰州巴尔的摩举行的美国基因与细胞治疗学会（ASGCT）2024年年会上的口头会议上发表。。

Affinia has leveraged its proprietary platform to rationally design capsids with increased tropism to cardiac muscle, skeletal muscle, or CNS with more uniform tissue distribution than AAV9. This improved biodistribution is attained while detargeting the liver and dorsal root ganglia (DRG), both potential sites of toxicity.

Affinia利用其专有平台合理设计了对心肌，骨骼肌或中枢神经系统的趋向性增加的衣壳，其组织分布比AAV9更均匀。这种改进的生物分布是在去除肝脏和背根神经节（DRG）这两个潜在的毒性部位的同时实现的。

Affinia's novel capsids have favorable manufacturing yields and levels of preexisting population immunity. Preclinical efficacy and safety results with a cardiotropic vector encoding for the BAG3 protein provide proof-of-concept data to support the expansion to multiple cardiomyopathies. In addition, preclinical efficacy and safety results with a blood-brain barrier (BBB)-penetrant vector encoding for the knockdown of Ataxin-2 (Atxn2), a gene believed to be involved in sporadic ALS, provide proof of concept data to support the expansion to multiple CNS diseases..

Affinia的新型衣壳具有良好的制造产量和先前存在的群体免疫力水平。编码BAG3蛋白的向心载体的临床前疗效和安全性结果提供了概念验证数据，以支持扩展到多种心肌病。此外，编码Ataxin-2（Atxn2）（一种被认为与散发性ALS有关的基因）的血脑屏障（BBB）渗透载体的临床前疗效和安全性结果提供了概念验证数据，以支持扩展到多种中枢神经系统疾病。。

'Compared with AAV9, our next-generation bespoke capsids demonstrate superior cardiac transduction while detargeting the liver and DRG in single-clone NHP studies. Similarly, our BBB-penetrant capsid exhibits widespread distribution across the brain with more than 50% neurons transduced, while also detargeting the liver and DRG,' said Charles Albright, Ph.D., Affinia's Chief Scientific Officer.

'与AAV9相比，我们的下一代定制衣壳在单克隆NHP研究中表现出优越的心脏转导，同时使肝脏和DRG脱靶。同样，我们的BBB渗透衣壳在大脑中广泛分布，超过50%的神经元被转导，同时也使肝脏和DRG失去靶向性，”Affinia首席科学官查尔斯·奥尔布赖特博士说。

'The Affinia capsids are highly differentiated from conventional AAVs being used in cardiac and CNS programs currently in clinical trials, and we look forward to advancing programs with our capsids toward the clinic.'.

“Affinia衣壳与目前临床试验中用于心脏和中枢神经系统项目的常规AAV高度不同，我们期待着将衣壳项目推向临床。”。

In an oral presentation today, Affinia will present clonal data in non-human primates (NHPs) for its novel, BBB-penetrant AAV capsid that has potential as a treatment for sporadic ALS. The capsid transduces more the 50% of neurons across spinal cord, cortical, and deep-brain regions. Dose-dependent increases in percent of neurons transduced, vector genome biodistribution, and transgene-mRNA expression were observed.

在今天的口头报告中，Affinia将介绍其新型BBB渗透性AAV衣壳在非人灵长类动物（NHP）中的克隆数据，该衣壳具有治疗散发性ALS的潜力。衣壳在脊髓，皮质和大脑深部区域转导更多的50%神经元。观察到转导的神经元百分比，载体基因组生物分布和转基因mRNA表达的剂量依赖性增加。

Biochemical and in-situ hybridization measurements of Atxn2 showed a reduction of greater than 50% in multiple CNS regions, the threshold required for potential therapeutic benefit. In spinal cord, the measurements were in cells relevant to ALS, the lower motor neurons. No adverse safety events were observed..

Atxn2的生化和原位杂交测量显示，多个中枢神经系统区域的减少幅度大于50%，这是潜在治疗益处所需的阈值。在脊髓中，测量是在与ALS（下运动神经元）相关的细胞中进行的。没有观察到不良安全事件。。

The oral presentation entitled, 'Reduction of Atxn2, a therapeutic target for sporadic ALS, in non-human primates using a novel, intravenously delivered AAV capsid,' will be presented by Giridhar Murlidharan, Ph.D., Senior Director, Head of Vector Translational Biology at Affinia, today, Friday, May 10, 2024 at 4:00-4:15 pm ET (Room 307-308; abstract 304)..

题为“使用新型静脉内递送的AAV衣壳在非人灵长类动物中减少散发性ALS的治疗靶点Atxn2”的口头报告将由Affinia载体转化生物学高级主任Giridhar Murlidharan博士于2024年5月10日（星期五）下午4:00-4:15（307-308室；摘要304）提交。。

A second oral presentation will feature Affinia's proprietary manufacturing process in HEK-293 suspension cells, yielding greater than 50% full capsids and greater than 1e15vg/L yield at harvest, with broad applicability across conventional and novel AAV capsids. These upstream performance measures translate to significant potential quality and cost advantages in the final product relative to current gene therapy manufacturing processes.

第二次口头演示将展示Affinia在HEK-293悬浮细胞中的专有制造工艺，在收获时产生超过50%的完整衣壳和超过1e15vg/L的产量，在常规和新型AAV衣壳中具有广泛的适用性。相对于当前的基因治疗制造工艺，这些上游性能指标转化为最终产品的潜在质量和成本优势。

The oral presentation entitled, 'A proprietary HEK293 AAV production system can achieve greater than 50% full capsids with greater than 1e15vg/L at harvest enabling scalable chromatography-based polishing with high yield and purity,' will be delivered by Matt Edwards, MBA, Senior Director, Head of Process Science at Affinia, today, Friday, May 10, 2024 at 4:00-4:15 pm ET (Ballroom 3; abstract 290)..

题为“专有HEK293 AAV生产系统在收获时可以实现超过50%的完整衣壳，超过1e15vg/L，从而实现基于色谱的可扩展抛光，具有高产量和纯度”的口头演讲将由Affinia高级主管兼过程科学主管Matt Edwards于2024年5月10日（星期五）下午4:00-4:15（宴会厅3；摘要290）发表。。

Affinia has also been invited to present on the rational design of cardiotropic capsids that detarget the liver and DRG. Sherry Cao, Ph.D., Senior Vice President, Computational Science will deliver the presentation entitled, 'Machine-learning guided rational design of cardiotropic capsids that detarget liver and DRG,' on Saturday, May 11, 2024 at 8:00 am ET in Room 339-342..

Affinia还被邀请介绍针对肝脏和DRG的向心衣壳的合理设计。计算科学高级副总裁Sherry Cao博士将于2024年5月11日（星期六）上午8:00在美国东部时间339-342室发表题为“机器学习指导的针对肝脏和DRG的向心衣壳的合理设计”的演讲。。

'Targeted delivery has long been a challenge, limiting the potential for gene therapy to unlock diseases and help patients,' said Laura Richman, MBA, D.V.M., Ph.D., D.A.C.V.P., Chief Development Officer of Affinia. 'Affinia capsids achieve high transduction efficiency in NHP cardiac and CNS regions while detargeting the liver and DRG potentially improving benefit-risk and differentiating our programs in the clinic.

Affinia首席开发官、MBA、D.V.M.博士、D.a.C.V.P.劳拉·里克曼（LauraRichman）说，长期以来，靶向分娩一直是一个挑战，限制了基因治疗释放疾病和帮助患者的潜力Affinia衣壳在NHP心脏和中枢神经系统区域实现了高转导效率，同时使肝脏和DRG脱靶，从而潜在地提高了受益风险，并在临床上区分了我们的计划。

The data in a mouse model of cardiac dysfunction showing safety and improvement in cardiac function supports development of our cardiotropic capsids in cardiomyopathies. Likewise, the data in NHPs showing sufficient reduction of Atxn2 supports development of our BBB-penetrant capsid in sporadic ALS and has applicability to multiple other CNS diseases.'.

心脏功能障碍小鼠模型中的数据显示心脏功能的安全性和改善，支持了我们在心肌病中发展的向心衣壳。同样，NHPs中显示Atxn2充分减少的数据支持我们的BBB渗透衣壳在散发性ALS中的发展，并适用于多种其他中枢神经系统疾病。”。

In addition, members from Affinia's leadership team have been invited to chair the following sessions:

此外，已邀请Affinia领导团队的成员主持以下会议：

Scientific Symposium: 'Innovations in Cardiac Gene and Cell Therapy'

科学研讨会：“心脏基因和细胞疗法的创新”

Chair: Laura Richman, MBA, D.V.M., Ph.D., DACVP, Chief Development Officer

主席：Laura Richman，MBA，D.V.M.，博士，DACVP，首席开发官

Date/Time: Saturday, May 11, 2024, 8:00-9:45 am ET

日期/时间：2024年5月11日星期六，美国东部时间上午8:00-9:45

Location: Room 339-342

地点：339-342室

Scientific Symposium: 'Challenges to Immunological Responses to Therapeutic Interventions'

科学研讨会：“对治疗干预的免疫反应的挑战”

Co-chair: Roberto Calcedo, Ph.D., Vice President, Preclinical and Immunology

联合主席：Roberto Calcedo博士，临床前和免疫学副总裁

Date/Time: Saturday, May 11, 2024, 10:15 am-12:00 pm ET

日期/时间：美国东部时间2024年5月11日星期六上午10:15至下午12:00

Location: Room 339-342

地点：339-342室

Category of Abstracts: B5 – Neurologic Diseases Section 4

摘要类别：B5–神经系统疾病第4节

Chair: Lisa Stanek, Ph.D., Vice President, Translational Science

主席：Lisa Stanek博士，转化科学副总裁

Date/Time: Friday, May 10, 2024, 3:45-5:00 pm ET

日期/时间：美国东部时间2024年5月10日星期五下午3:45-5:00

Location: Room 307-308

地点：307-308室

Affinia also held two poster presentations. The first poster showcased data that confirm the safety and therapeutic efficacy of a novel cardiotropic AAV capsid in an animal model of cardiac dysfunction with a potential therapeutic application in genetic cardiomyopathies (abstract 605). The company also presented a poster on a screening platform for the discovery of novel, next-generation CNS tropic capsids, based on binding to cell receptors that facilitate BBB transcytosis and with potential applicability to non-AAV targeted delivery modalities (abstract 982).

Affinia还举行了两次海报展示。第一张海报展示了数据，这些数据证实了新型向心AAV衣壳在心脏功能障碍动物模型中的安全性和治疗效果，并在遗传性心肌病中具有潜在的治疗应用（摘要605）。该公司还在筛选平台上发布了一张海报，用于发现新一代中枢神经系统热带衣壳，该海报基于与促进BBB转胞吞作用的细胞受体的结合，并可能适用于非AAV靶向递送方式（摘要982）。

Abstracts can be found at https://annualmeeting.asgct.org/..

摘要可以在https://annualmeeting.asgct.org/..

About Affinia Therapeutics

关于Affinia Therapeutics

Affinia Therapeutics is pioneering a shift to a new class of rationally designed gene therapies that treat rare and prevalent diseases. Affinia Therapeutics' proprietary Affinia Rationally designed Therapeutics (ART) platform is intended to synergistically improve the efficacy, safety, and manufacturability of adeno-associated virus (AAV)-based gene therapies through the development of next-generation capsids, promoters, and manufacturing approaches.

Affinia Therapeutics率先转向一类新的合理设计的基因疗法，用于治疗罕见和流行的疾病。Affinia Therapeutics专有的Affinia合理设计治疗（ART）平台旨在通过开发下一代衣壳，启动子和制造方法，协同提高基于腺相关病毒（AAV）的基因疗法的功效，安全性和可制造性。