Novel anti-fibrotic engineered macrophage therapy reduced liver fibrosis in preclinical models

新型抗纤维化工程巨噬细胞疗法在临床前模型中减少肝纤维化

Development candidate nomination expected in the first quarter of 2025

预计2025年第一季度提名发展候选人

PHILADELPHIA, May 8, 2024 /PRNewswire/ -- Carisma Therapeutics Inc. (Nasdaq: CARM) ('Carisma' or the 'Company'), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, today announced new data demonstrating preclinical proof of concept using engineered anti-fibrotic macrophages for the treatment of liver fibrosis.

费城，2024年5月8日/PRNewswire/--Carisma Therapeutics Inc.（纳斯达克：CARM）（“Carisma”或“公司”）是一家专注于发现和开发创新免疫疗法的临床阶段生物制药公司，今天宣布了新的数据，证明了使用工程化抗纤维化巨噬细胞治疗肝纤维化的临床前概念验证。

The data was presented in a poster session at the American Society of Gene and Cell Therapy (ASGCT) 2024 Annual Meeting on May 8, 2024, in Baltimore, MD..

该数据于2024年5月8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年年会上的海报会议上发布。。

'We are pleased to unveil preclinical proof of concept data for our liver fibrosis program, which highlight the potential of engineered macrophages to combat a prevalent disease that is associated with late-stage metabolic dysfunction-associated steatohepatitis (MASH) and represents a significant unmet need,' said Michael Klichinsky, PharmD, PhD, Co-founder and Chief Scientific Officer of Carisma.

Carisma联合创始人兼首席科学官Michael Klichinsky博士说：“我们很高兴为我们的肝纤维化项目发布临床前概念验证数据，该数据突出了工程化巨噬细胞对抗与晚期代谢功能障碍相关脂肪性肝炎（MASH）相关的流行疾病的潜力，并且代表了一个尚未满足的重大需求。”。

'The data, from two independent models, demonstrate that engineered macrophages trafficked to fibrotic tissues, expressed genetically encoded disease-modifying payloads, and significantly reduced fibrosis in the liver. Given these encouraging data, we look forward to further progressing the liver fibrosis program, which is our first expansion outside of oncology.'.

来自两个独立模型的数据表明，工程化巨噬细胞被贩运到纤维化组织，表达基因编码的疾病修饰有效载荷，并显着减少肝脏纤维化。鉴于这些令人鼓舞的数据，我们期待着进一步推进肝纤维化计划，这是我们在肿瘤学之外的首次扩展。”。

In the presentation titled 'Genetically Engineered Macrophage Cell Therapy Reverses Liver and Lung Fibrosis in Preclinical Models,' Carisma presented preclinical proof-of-concept data for engineered macrophage cell therapy in liver fibrosis. In liver models, the data showed that a single dose of macrophages co-expressing the anti-fibrotic factor relaxin and the anti-inflammatory cytokine IL10 significantly improved established fibrosis in a CCl4-induced liver fibrosis model, with a 116% reduction in fibrosis relative to untreated control.

在题为“基因工程巨噬细胞疗法在临床前模型中逆转肝和肺纤维化”的演讲中，Carisma介绍了肝纤维化中工程巨噬细胞疗法的临床前概念验证数据。在肝脏模型中，数据显示，共表达抗纤维化因子松弛素和抗炎细胞因子IL10的单剂量巨噬细胞显着改善了CCl4诱导的肝纤维化模型中已建立的纤维化，相对于未处理的对照，纤维化减少了116%。

Also, systemic administration of engineered macrophages co-expressing relaxin and IL10 significantly reduced liver fibrosis in a high fat diet MASH model, with a 45% reduction in fibrosis relative to untreated control. In both models, the relaxin-IL10 macrophage treatment also resulted in a greater reduction in liver fibrosis compared to non-engineered macrophages..

此外，在高脂饮食MASH模型中，共表达松弛素和IL10的工程化巨噬细胞的全身给药显着降低了肝纤维化，相对于未处理的对照，纤维化减少了45%。在这两种模型中，与非工程化巨噬细胞相比，松弛素-IL10巨噬细胞治疗也导致肝纤维化的减少更大。。

The presentation also included initial data for the use of engineered macrophages in pulmonary fibrosis. The data showed that a single dose of macrophages expressing a dominant negative TGFβ receptor, which nullified pro-fibrotic TGFβ signaling in the lung, prevented fibrosis in a bleomycin mouse model of pulmonary fibrosis, with a 90% reduction in fibrosis relative to untreated control..

该演讲还包括在肺纤维化中使用工程化巨噬细胞的初步数据。数据显示，表达显性负性TGFβ受体的单剂量巨噬细胞可使肺中的促纤维化TGFβ信号传导无效，可预防博来霉素小鼠肺纤维化模型中的纤维化，相对于未经治疗的对照，纤维化减少90%。。

Carisma expects to nominate a development candidate for its liver fibrosis program in the first quarter of 2025.

Carisma预计将在2025年第一季度为其肝纤维化项目提名一名发展候选人。

The poster presented at ASGCT 2024 is now available online in the 'Publications' section of Carisma's website at https://carismatx.com/technology/publications/

在ASGCT 2024上发布的海报现在可以在Carisma网站的“出版物”部分在线获得https://carismatx.com/technology/publications/

About Carisma

关于Carisma

Carisma Therapeutics Inc. is a clinical stage biopharmaceutical company focused on utilizing our proprietary macrophage and monocyte cell engineering platform to develop transformative immunotherapies to treat cancer and other serious diseases. We have created a comprehensive, differentiated proprietary cell therapy platform focused on engineered macrophages and monocytes, cells that play a crucial role in both the innate and adaptive immune response.

Carisma Therapeutics Inc.是一家临床阶段的生物制药公司，专注于利用我们专有的巨噬细胞和单核细胞工程平台开发用于治疗癌症和其他严重疾病的转化性免疫疗法。我们已经创建了一个全面的，分化的专有细胞治疗平台，专注于工程化巨噬细胞和单核细胞，这些细胞在先天性和适应性免疫反应中起着至关重要的作用。

Carisma is headquartered in Philadelphia, PA. For more information, please visit www.carismatx.com..

Carisma总部位于宾夕法尼亚州费城。有关更多信息，请访问www.carismatx.com。。

Cautionary Note on Forward-Looking StatementsStatements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute 'forward-looking statements' within the meaning of The Private Securities Litigation Reform Act of 1995.

前瞻性声明的警示说明本新闻稿中关于未来预期、计划和前景的声明，以及关于非历史事实事项的任何其他声明，可能构成1995年《私人证券诉讼改革法》所指的“前瞻性声明”。

These statements include, but are not limited to, statements relating to Carisma's business, strategy, future operations, cash runway, the advancement of Carisma's product candidates and product pipeline, and clinical development of Carisma's product candidates, including expectations regarding timing of initiation and results of clinical trials.

这些报表包括但不限于与Carisma的业务、战略、未来运营、现金跑道、Carisma候选产品和产品线的进展以及Carisma候选产品的临床开发有关的报表，包括关于启动时间和临床试验结果的预期。

The words 'anticipate,' 'believe,' 'contemplate,' 'continue,' 'could,' 'estimate,' 'expect,' 'goals,' 'intend,' 'may,' 'might,' 'outlook,' 'plan,' 'project,' 'potential,' 'predict,' 'target,' 'possible,' 'will,' 'would,' 'could,' 'should,' and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words..

“预期”、“相信”、“沉思”、“继续”、“可能”、“估计”、“期望”、“目标”、“打算”、“可能”、“可能”、“展望”、“计划”、“项目”、“潜力”、“预测”、“目标”、“可能”、“意志”、“将会”、“可能”、“应该”等类似的表达都是为了识别前瞻性陈述，尽管并非所有前瞻性陈述都包含这些识别词。。

Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, (i) Carisma's ability to obtain, maintain and protect its intellectual property rights related to its product candidates; (ii) Carisma's ability to advance the development of its product candidates under the timelines it anticipates in planned and future clinical trials and with its current financial and human resources; (iii) Carisma's ability to replicate in later clinical trials positive results found in preclinical studies and early-stage clinical trials of its product candidates; (iv) Carisma's ability to realize the anticipated benefits of its research and development programs, strategic partnerships, research and licensing programs and academic and other collaborations; (v) regulatory requirements or developments and Carisma's ability to obtain and maintain necessary approvals from the U.S.

任何前瞻性声明都是基于管理层目前对未来事件的预期，并受到许多风险和不确定性的影响，这些风险和不确定性可能导致实际结果与此类前瞻性声明中规定或暗示的结果产生重大不利差异。这些风险和不确定性包括但不限于：（i）Carisma获得、维护和保护与其候选产品相关的知识产权的能力；（ii）Carisma有能力根据其在计划和未来临床试验中预期的时间表以及目前的财务和人力资源推进其候选产品的开发；（iii）Carisma在后期临床试验中复制其候选产品的临床前研究和早期临床试验中发现的阳性结果的能力；（iv）Carisma实现其研发计划、战略伙伴关系、研究和许可计划以及学术和其他合作的预期收益的能力；（v） 监管要求或发展，以及Carisma从美国获得和维持必要批准的能力。

Food and Drug Administration and other regulatory authorities related to its product candidates; (vi) changes to clinical trial designs and regulatory pathways; (vii) risks associated with Carisma's ability to manage expenses; (viii) changes in capital resource requirements; (ix) risks related to the inability of Carisma to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; and (x) legislative, regulatory, political and economic developments..

食品和药物管理局及其候选产品相关的其他监管机构；（vi）临床试验设计和监管途径的变化；（vii）与Carisma管理费用的能力相关的风险；八资本资源需求的变化；（ix）与Carisma无法获得足够的额外资本以继续推进其候选产品及其临床前计划有关的风险；（x）立法、监管、政治和经济发展。。

For a discussion of these risks and uncertainties, and other important factors, any of which could cause Carisma's actual results to differ from those contained in the forward-looking statements, see the 'Risk Factors' set forth in the Company's Annual Report on Form 10-K for the year ended December 31, 2023, as well as discussions of potential risks, uncertainties, and other important factors in Carisma's other recent filings with the Securities and Exchange Commission.

有关这些风险和不确定性以及其他可能导致Carisma的实际结果与前瞻性报表中所含结果不同的重要因素的讨论，请参阅公司截至2023年12月31日的10-K年度报告中列出的“风险因素”，以及Carisma最近向证券交易委员会提交的其他文件中对潜在风险、不确定性和其他重要因素的讨论。

Any forward-looking statements that are made in this press release speak as of the date of this press release. Carisma undertakes no obligation to revise the forward-looking statements or to update them to reflect events or circumstances occurring after the date of this press release, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws..

本新闻稿中的任何前瞻性声明均自本新闻稿发布之日起生效。Carisma没有义务修改前瞻性声明或更新前瞻性声明以反映本新闻稿发布日期后发生的事件或情况，无论是由于新信息、未来发展还是其他原因，除非联邦证券法要求。。

Investors:Shveta DigheHead of Investor Relationsinvestors@carismatx.com

投资者：Shveta Dighe投资者负责人Relationsinvestors@carismatx.com

Media Contact:Julia Stern(763) 350-5223jstern@realchemistry.com

媒体联系人：Julia Stern（763）350-5223jstern@realchemistry.com

SOURCE Carisma Therapeutics Inc.

来源Carisma Therapeutics Inc。