Bepirovirsen是一种具有三重作用机制的在研ASO疗法，旨在识别并破坏乙肝病毒的遗传成分(即RNA)， 从而可能使患者的免疫系统重新获得控制病毒感染的能力。 慢性乙型肝炎是全球范围内的一项重大健康挑战，影响着超过2.5亿人，并且已成为导致肝癌的主要原 因之一。目前，基于核苷(酸)类似物的标准治疗通常需要长期甚至终身用药，但其功能性治愈率仍然偏 低，通常仅约为1%。 GSK(GSK.US)今日宣布，其与Ionis Pharmaceuticals合作开发的在研反义寡核苷酸(ASO)疗法 bepirovirsen，在用于治疗慢性乙型肝炎(HBV)的两项关键性3期临床试验B-Well 1和B-Well 2中取得积极 结果。两项试验均达到主要终点。Bepirovirsen显示出具有统计学与临床意义的功能性治愈率。GSK计 划于2026年第一季度启动全球监管申报。 分析显示，B-Well试验达到了主要终点，且bepirovirsen显示出具有统计学意义并具有临床意义的功能性 治愈率。与单用标准治疗相比，bepirovirsen联合标准治疗显著提高了功能性治愈率。在所有终点中均达 到统计学显著性，包括基线HBsAg ...

Precision BioSciences (DTIL) Conference Call Summary Company Overview - **Company**: Precision BioSciences - **Focus**: Gene editing therapies, particularly for Duchenne muscular dystrophy (DMD) and chronic hepatitis B (HBV) Key Points from the Conference Call Industry and Market Context - **Duchenne Muscular Dystrophy (DMD)**: A genetic disorder leading to progressive muscle degeneration, with approximately 300,000 to 400,000 patients globally and 15,000 new cases in the U.S. annually [9] - **Current Treatment Landscape**: Existing therapies, including microdystrophins and exon skipping, have not achieved significant long-term muscle functional improvement [7][43] Core Program Updates - **PBGene DMD**: - A clinical-stage candidate aimed at providing durable muscle functional improvement for DMD patients, focusing on correcting mutations in the dystrophin gene [5][6] - The program is designed to address the highest unmet needs in DMD, with a unique mechanism that allows for the production of a near full-length dystrophin protein [20][31] - Preclinical data shows significant improvements in muscle force output in treated mice, maintaining improvements up to nine months post-treatment [22][23] Safety and Efficacy - **Safety Profile**: The use of lower doses of AAV (adeno-associated virus) is expected to enhance safety, reducing the risk associated with high doses [35][49] - **Durability of Treatment**: The ability to edit satellite cells is crucial for long-term muscle function improvement, with evidence of increased dystrophin protein expression over time [25][28][99] Regulatory Pathway - **FDA Interactions**: Precision BioSciences has had positive discussions with the FDA regarding their clinical trial design and biomarker linkage to functional improvement [59][102] - **Clinical Trial Timeline**: Targeting to file a CTA or IND by late 2025, with clinical trials expected to commence in 2026 [61][66] Financial and Operational Updates - **Resource Allocation**: The company is prioritizing its resources towards the HBV and DMD programs, pausing the PBGene 3243 mitochondrial DNA elimination program for fiscal reasons [62][64] - **Cash Runway**: The company has sufficient cash runway into the second half of 2026 to meet Phase 1 clinical requirements [68] Additional Insights - **Patient Perspective**: The potential for improved durability and better dystrophin expression is seen as a significant advancement over current therapies, which have struggled to demonstrate clinical efficacy [46][53] - **Commercial Considerations**: Screening for neutralizing antibodies will be critical, as many patients may have previously received AAV therapies, impacting eligibility for new treatments [80][83] Conclusion - Precision BioSciences is positioned to make significant advancements in the treatment of DMD and HBV, with promising preclinical data and a clear regulatory pathway. The focus on safety, efficacy, and patient needs underscores the company's commitment to addressing high unmet medical needs in these areas.