CROSSING BARRIERS AND DEFEATING DEGENERATION MAY 2025 ©2025 Denali Therapeutics Inc. DISCLAIMERS Forward-Looking Statements. This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements do not relate strictly to historical or current facts and they may be accompanied by such words as "anticipate," "believe," "could," "estimate," "expected," "forecast," "intend," "may," "plan," "potential," "possible," "futu ...

2025 年 6 月 5 日，加州大学欧文分校的研究人员在 Cell 子刊 Cell Stem Cell 上发表了题为： Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins 的研究论文。 该研究利用 CRISPR 基因编辑修饰的 人类诱导多能干细胞来源的小胶质细胞 （iMG） ，实现了 中枢神经系统 （SNS） 范围内的疾病修正蛋白递送，并验证了 撰文丨王聪 编辑丨王多鱼 排版丨水成文 血脑屏障 （Blood-Brain Barrier，BBB）， 是指脑毛细血管壁与神经胶质细胞形成的血浆与脑细胞之间的屏障，和由脉络丛形成的血浆和脑脊液之间的屏障，仅 允许特定类型的分子从血流进入大脑神经元和其他周围细胞。 血脑屏障的存在，对于阻止有害物质由血液进入大脑具有重要意义，但这也同时阻止了绝大部分小分子和大分子药物 （例如多肽，蛋白质和核酸） 的转移，严重 限制了中枢神经系统疾病 （例如神经退行性疾病、脑肿瘤，脑部感染和中风等） 的治疗。 尽管该领域近年来取得了一些进展，但我们仍然迫切需要能够跨越血脑屏 ...

Core Insights - Denali Therapeutics has completed the Biologics License Application (BLA) submission for tividenofusp alfa, marking a significant milestone in its development as a late-stage commercial organization focused on treating Hunter syndrome [2][3] - The company is preparing for the commercial launch of tividenofusp alfa, expected in late 2025 or early 2026, which would be the first FDA-approved enzyme replacement therapy designed to cross the blood-brain barrier [2][3] - Denali's clinical pipeline includes ongoing programs for Sanfilippo syndrome Type A and frontotemporal dementia, with collaborations with the FDA and Takeda, respectively [4][5] Financial Performance - For Q1 2025, Denali reported a net loss of $133.0 million, an increase from a net loss of $101.8 million in Q1 2024 [10] - Research and development expenses rose to $116.2 million in Q1 2025 from $107.0 million in Q1 2024, primarily due to increased spending on clinical and preclinical programs [11] - General and administrative expenses increased to $29.4 million in Q1 2025 from $25.2 million in Q1 2024, driven by activities related to the BLA submission for tividenofusp alfa [14] Clinical Program Updates - The BLA submission for tividenofusp alfa is based on data from a Phase 1/2 study involving 47 participants, with the FDA's review process now initiated [3] - Denali is conducting a global Phase 2/3 COMPASS study to support regulatory approvals for tividenofusp alfa [3] - The company is also advancing DNL126 for Sanfilippo syndrome Type A, with ongoing discussions with the FDA for an accelerated development path [4] Corporate Developments - Denali has launched a clinical biomanufacturing facility in Salt Lake City, enhancing its manufacturing capabilities and supply chain control [9] - The company is actively participating in several upcoming investor conferences to engage with stakeholders and present its developments [13]