Summary of Sarepta Therapeutics (SRPT) Conference Call - July 18, 2025 Company Overview - **Company**: Sarepta Therapeutics (SRPT) - **Focus**: Gene therapy for Limb Girdle Muscular Dystrophy (LGMD) and related conditions Key Points Industry and Company Context - The call addressed recent developments in the LGMD program, particularly concerning the investigational candidate SRP-9004 for LGMD type 2D [3][4] - The company is transitioning focus from gene therapy to its siRNA platform due to risk-adjusted net present values (NPVs) and the need to manage expenses [4][10] Core Issues Discussed - A serious adverse event (fatality) occurred in a trial for SRP-9004, which was not deemed material to the overall discussions on the previous call [3][4] - The decision to discontinue other LGMD programs was based on risk-adjusted NPVs rather than safety events [10][18] - The company has paused dosing of Elevitus in non-ambulatory patients while developing a protocol for sirolimus as prophylactic immunosuppression [5][51] Safety and Regulatory Considerations - The event in question involved a 51-year-old non-ambulatory patient and was reported to the FDA, which has not changed its position regarding Elevitus [6][21][94] - The company maintains that the risk of acute liver failure (ALI) is a known risk associated with AAV-mediated therapies, particularly in non-ambulatory patients [52][83] - Approximately 30-40% of patients experience elevated liver enzymes, with a subset requiring hospitalization [47][88] Patient Population and Clinical Trials - Between 35 and 40 patients have been dosed across LGMD trials, with a roughly equal split between ambulatory and non-ambulatory patients [56] - The company has conducted three clinical trials for LGMD2E, with no fatalities reported in other gene therapy trials [32][41] Future Directions and Market Considerations - The company plans to continue pursuing the LGMD2E program (SRP-9003) despite the challenges, as it is an ultra-rare disease with significant unmet needs [60] - Discussions with the FDA regarding the use of sirolimus and its potential impact on the label for SRP-9003 are ongoing [41][51] Communication and Transparency - The company emphasizes its commitment to transparency with investors, patients, and physicians regarding safety signals and clinical trial results [18][100] - Ongoing communication with the physician community about the risks associated with Elevitus and LGMD therapies is prioritized [98] Additional Important Points - The company has a history of being transparent about safety signals and has communicated the risks of elevated liver enzymes to the physician community [18][98] - The manufacturing processes for different therapies (e.g., Elevitus vs. LGMD) are distinct, which may influence safety profiles [32][29] - The company is evaluating the potential need for additional data to support the Biologics License Application (BLA) for LGMD2E [41][68] This summary captures the essential points discussed during the conference call, focusing on the company's strategic direction, safety considerations, and ongoing communication efforts.

从CAR-T疗法（嵌合抗原受体T细胞免疫疗法）到RNA疗法（包括mRNA、siRNA、环状RNA等），上 海正在逐年积累起细胞与基因治疗（CGT）药物研发制造服务领域的能力。 "过往有很多基因编辑技术，需要将DNA双链完全切断，由于接好的双链可能有约有一半组织需要修 复，因此其效率偏低，且容易产生细胞凋亡和癌细胞扩增的风险。现在，我们原创的碱基编辑技术既不 切断双链，又能同时防止基因编辑做错误位点的编辑，从而实现更精准的治疗。" 日前，沪上科创企业正序生物就自主研发的碱基编辑技术与丹纳赫旗下的思拓凡在"细胞与基因治疗工 艺开发"这一领域达成合作，正序生物首席执行官牟晓盾在合作仪式后告诉第一财经。 牟晓盾称，公司已通过碱基编辑技术在全球范围内已治愈了近20例β-地中海贫血症和镰刀型细胞贫血患 者。谈及科学家团队与CXO（医药研发生产服务外包组织）的合作，牟晓盾表示，思拓凡有丰富的LNP （脂质纳米颗粒）与AAV载体库以及符合国际标准的GMP生产平台，"这使得企业能加速完成碱基编辑 技术下药物的体内递送系统，缩短药物的上市周期。" CGT领域的CXO服务方应如何真正为技术方增效降本？丹纳赫中国首席科学官方焯告诉记 ...

2025年7月12日，为助力业内企业快速对接国际前沿技术标准，中国医药生物技术协会、大兴生物医药 基地联合主办了《肿瘤浸润淋巴细胞（TIL）制剂制备和质量控制指南》发布仪式暨肿瘤浸润淋巴细胞 关键技术培训班。中国医药生物技术协会秘书长赵北海，北京佑安医院副院长张永宏，大兴生物医药产 业基地公司副总经理李海涛，北京大学医学部免疫学系教授王月丹，四川大学遗传学教授、欧洲科学院 院士丁显平，中国人民解放军联勤保障部队北戴河康复疗养中心大校徐扬，北戴河医院院长宋长兴, 解 放军总医院和哈尔滨医科大学附属肿瘤医院等国内知名专家,以及北京循生免疫医学转化研究院院长张 秀军、上海君赛生物科技有限公司总监何周参加了此次会议。原卫生部部长曹泽毅发来视频致辞。 曹泽毅在致辞中表示TIL细胞疗法为不能耐受传统放化疗的晚期实体肿瘤患者提供了新的治疗途径，为 宫颈癌年轻患者保留子宫同时治愈提供了可能性。赵北海在致辞中表示中国医药生物技术协会将一如既 往发挥桥梁纽带作用，通过政策研究、学术交流、标准制定等工作，以指南发布、宣介和培训为契机， 为TIL技术及生物医药产业的高质量发展保驾护航。李海涛在致辞中承诺大兴生物医药基地将始终当 好" ...

Cultural Heritage and Development - Huizhou is recognized for its rich cultural heritage, with historical significance dating back over 1400 years, showcasing the integration of various cultural influences, particularly from the Song Dynasty poet Su Dongpo [2][3][4] - The city emphasizes the importance of cultural activities and education, with initiatives like the monthly science lectures and cultural events at the restored Fenghu Academy, which serves as a new cultural landmark [4][6] Economic Growth and Industrial Development - Huizhou has a coastline of 281.4 kilometers and a sea area of 4520 square kilometers, which has historically supported trade and maritime activities, contributing to its economic development [12] - The city has seen significant industrial growth, particularly in the petrochemical sector, with major projects from companies like Shell and ExxonMobil, indicating a strong confidence in the local industrial ecosystem [16][17] - In the past year, Huizhou's GDP surpassed 600 billion yuan, with the electronic information and petrochemical industries experiencing substantial growth rates of 13.6% and 17.9% respectively, aiming for the establishment of a trillion-level industrial cluster [17] Historical Significance and Red Culture - Huizhou played a crucial role during the anti-Japanese war, serving as a key transit point for rescuing cultural and political figures, which has contributed to its identity as a city with a strong revolutionary heritage [7][10] - The city is committed to preserving and promoting its revolutionary history, with initiatives to document and share stories of local heroes and significant events, reinforcing its cultural identity [10][11]

Core Viewpoint - Sarepta Therapeutics is experiencing a stock price increase following an update on the label expansion efforts for Elevidys, its gene therapy for Duchenne muscular dystrophy, despite the FDA's request for a black box warning regarding acute liver injury and failure [1][10]. Label Expansion and FDA Interaction - The FDA has requested a black box warning for Elevidys, which Sarepta agrees to, resolving material issues with the ambulant portion of the label [2][10]. - A Sarepta committee is reviewing cases of acute liver failure and is exploring enhanced immunosuppressive regimens for non-ambulant patients [3][4]. Financial Restructuring - Sarepta announced a strategic restructuring plan aimed at prioritizing programs and achieving approximately $400 million in annual cost reductions, with a workforce reduction of 36% impacting around 500 employees [5]. - The restructuring is projected to lower average annual non-GAAP R&D and SG&A expenses to between $800 million and $900 million starting in 2026 [5]. Financial Performance - Preliminary financial highlights for Q2 2025 show total net product revenue of $513 million, with Elevidys contributing $282 million [6]. - As of June 30, the company reported cash and investments of approximately $850 million [6]. Strategic Focus - The company is shifting its focus towards chronically administered therapies for neurodegenerative and pulmonary diseases, pausing several gene therapy programs for limb-girdle muscular dystrophy [7]. - Sarepta plans to submit a Biologics License Application for SRP-9003 for LGMD type 2E/R4 later this year [7]. Management Changes - In conjunction with the restructuring, Sarepta appointed Ian Estepan as President and Chief Operating Officer and Ryan Wong as CFO [9]. Analyst Insights - Analysts from William Blair suggest that the FDA's request for a black box warning indicates that complete removal of Elevidys from the market is unlikely, leading to increased investor confidence in the company's ability to manage long-term debts [10]. - There are expectations of short-term challenges for Elevidys as patients and doctors exhibit hesitation, with cautious investor sentiment until early results from the ENDEAVOR trial are available [10][11].

当曾经的IT国际三巨头在中国的市场日渐收缩——IBM的PC和服务器业务相继易帜联想，惠普也将部 分业务出售给了紫光，唯有戴尔仍保持全业务线存在，在漫长的退潮中留下最后的身影。但这并非荣耀 剧的尾声，而是在时代浪潮下注定上演的转身。不可否认，受复杂的地缘关系和风起云涌的"国产替 代"浪潮冲击，戴尔的核心业务——无论是PC、服务器还是存储，国内市场份额已从傲视群雄的前三甚 至第一，退守至"Others"阵营；精简组织、持续裁员的现实，也为这片曾经的拓荒土地投下长长的暗 影。 笔者作为曾深耕戴尔体系十八载的见证者，愿意在喧嚣的传闻之外，讲述一些更具时间韧性的故事。 纵然业务布局因势而变，戴尔在中国市场锻造并淬炼出的那份独特销售基因与体系精神，早已超越物理 存在的范畴，化作可解析、可借鉴的底层商业逻辑。它不会"离开"，因为这套体系所验证的精密构建之 道，正持续成为销售组织能力升级的重要参考坐标。 将目光拉长至2000年到2025年这整整四分之一世纪，我们会发现一幅更为深邃的画卷。从2000年初戴尔 携直销利刃劈开中国市场，以其近乎偏执的体系化销售作战席卷千亿订单，到如今在不可逆趋势下的战 略调整与坚守，这本身就是一部 ...

创新药题材的崛起是政策、技术、资本三重驱动的结果，其发展历程可分为三个关键阶段，而当前市场 热度则源于多重利好的集中释放。 一、创新药题材的 "前世"：从仿制药主导到创新觉醒（2015 年前） 1. 政策桎梏与技术追赶 2015 年之前，中国医药产业以仿制药为主，药审周期长（平均需 3-5 年）、研发投入低（药企研 发费用率普遍不足 5%）。政策对创新药的支持有限，例如医保目录调整周期长达 4 年，创新药 上市后纳入医保的时间滞后，商业化进程缓慢。 恒瑞医药、百济神州等企业率先布局创新药研发。例如，恒瑞医药 2014 年推出首个国产 PD-1 抑 制剂卡瑞利珠单抗，开启免疫治疗国产化先河；百济神州的泽布替尼于 2019 年获 FDA 批准，成 为首个 "出海" 的中国原研药。 2025 年拟推出首版《商保创新药目录》，专门收录未纳入基本医保但临床价值突出的高价创新 药，通过医保数据赋能商业保险产品开发，拓展支付渠道。 2. 行业转型的催化剂 2015 年药审改革：国家药监局启动药品注册分类改革，将新药定义从 "未在国内上市销售的 药品" 调整为 "未在国内外上市销售的药品"，推动药企从仿制药向创新药转型。 2 ...

Core Viewpoint - The research led by Tsinghua University focuses on a novel strategy for enhancing plant immunity against pathogens, addressing the growing threats to global food security and environmental sustainability posed by plant diseases [1][4]. Group 1: Research Innovation - The study introduces a simple and efficient method for designing artificial plant disease resistance genes by utilizing protein engineering [1]. - A fusion protein is expressed in plants, combining a pathogen protease recognition cleavage site (PCS) with an active plant NLR immune receptor (aNLR) [4]. - The aNLR remains inactive until cleaved by the pathogen's protease, which triggers a strong immune response in the plant [4]. Group 2: Experimental Validation - The engineered NLR receptor has been shown to confer broad-spectrum and complete resistance to various potyviruses in model plants like Nicotiana benthamiana and economically important crops such as soybeans [6]. - This approach demonstrates the potential for a single engineered receptor to provide extensive protection against multiple viral threats [6]. Group 3: Broader Implications - The strategy is promising for developing universal plant disease resistance, as various pathogens across different kingdoms encode proteases [7]. - This could lead to enhanced resistance against a wide range of pathogens, including viruses, bacteria, fungi, and nematodes [7].

Summary of the Conference Call Company and Industry Overview - The conference call involved Qiu Le Seed Industry, a company operating in the seed industry, which is a strategic and foundational sector for national food security and agricultural development [1][3][4]. Key Financial Performance - In 2024, Qiu Le Seed Industry achieved a revenue of 391 million yuan and a net profit of 50.44 million yuan [1]. Strategic Planning and Innovation - The company plans to increase investment in breeding corn, wheat, and peanuts, focusing on high-yield and resilient varieties to meet diverse market demands [2]. - Qiu Le Seed Industry aims to explore advanced biotechnologies such as transgenic and gene editing to enhance its product offerings [2][10]. Market Expansion and Sales Strategy - The company intends to deepen its presence in markets like Huang'an and expand into Northeast, Northwest, and Southwest regions, optimizing its development layout and enhancing brand recognition [2]. - Qiu Le Seed Industry is exploring order-based agriculture to improve product coverage and sales channels [2]. Mergers and Acquisitions - The company is actively seeking mergers with other seed companies that share similar values and have strong R&D capabilities to enhance its competitive edge [2]. Industry Context and Challenges - The seed industry is currently undergoing a rapid development phase, with many companies restructuring or repositioning themselves due to market changes [6]. - Historical adjustment cycles in the industry have been noted, with significant changes occurring approximately every ten years [6]. Product Development and Collaborations - Qiu Le Seed Industry has introduced several new corn varieties, including Qiu Le 368, which is among the top ten promoted varieties in the country [8]. - Collaborations with various research institutions and universities are ongoing to develop new products, including transgenic varieties that are nearing market introduction [10]. Commitment to National Strategy - The company emphasizes its alignment with national agricultural strategies, aiming to ensure food security and promote the revitalization of the seed industry [3][5]. Conclusion and Investor Engagement - The conference concluded with an invitation for investor questions, indicating a commitment to transparency and engagement with stakeholders [11].

张同作介绍，这是国内外首个基于多物种、大规模宏基因组分析构建的鹿科动物肠道微生物资源 库，为微生物资源利用以及濒危物种保护提供了坚实的数据基础。 张同作介绍，通过系统发育和共进化分析发现，肠道微生物与宿主在长期演化过程中形成了稳定的 互利关系。更为关键的是，通过比较宏基因组分析，研究人员发现高原鹿科动物的肠道微生物在能量代 谢与碳水化合物活性酶通路上具有显著的适应性增强，其相关功能基因的相对丰度显著高于平原鹿类。 （原载于《科技日报》 2025-07-16 第06版） 记者7月14日从中国科学院西北高原生物研究所获悉，该所动物生态与资源保护研究团队首次构建 了涵盖多个物种的鹿科动物肠道宏基因组图谱，建立了当前最为系统、全面的鹿科动物肠道微生物组数 据库。相关研究成果日前发表于学术期刊《BMC生物学》。 青藏高原具有极端低氧、低温以及营养匮乏等特殊环境条件，对野生动物的生存构成了严峻挑战。 肠道微生物作为宿主适应外部环境的重要"隐形器官"，在能量代谢、营养吸收、免疫调节等方面发挥着 关键作用。 中国科学院西北高原生物研究所动物生态与资源保护研究团队研究员张同作介绍，研究团队采集了 青藏高原地区多种鹿科动物的粪便 ...