Adjuvanted Hepatitis B vaccine (Recombinant) (Dynavax)

Richard Lowenthal, Chief Executive Officer, Transitioning following More than a Decade of Leadership Since Co-Founding the Company Donn Casale, President, Appointed Chief Executive Officer and Director SAN DIEGO, July 07, 2026 (GLOBE NEWSWIRE) -- ARS Pharmaceuticals, Inc. (Nasdaq: SPRY), a biopharmaceutical company dedicated to empowering at-risk patients and their caregivers to better protect against allergic reactions that could lead to anaphylaxis, today announced a CEO succession, in which co-founder and CEO Richard Lowenthal will no longer serve as an employee and officer of the company effective July 6, 2026. The Board has appointed Donn Casale, currently President, as CEO and Director effective July 7, 2026. “Since co-founding ARS Pharma in 2015, Rich was integral to guiding the company from development to establishing neffy ® as a leading treatment for adults and children with Type 1 allergic reactions, including anaphylaxis, and we are grateful for his many contributions,” said Pratik Shah, chairman of the Board of Directors. “As we look ahead, Donn is a seasoned business leader with deep operational and financial acumen, and proven commercial track record, particularly in growing adoption and share in large, consumer-driven markets. We are confident that he has the right background and experience to drive the company through its next phase, growing the neffy franchise and positioning ARS Pharma for both near and long-term value-creation.” Mr. Casale brings more than 25 years of biopharmaceutical business and commercial leadership, with a track record of scaling innovative products in large, patient-driven healthcare markets. Prior to ARS Pharma, he served as Chief Commercial Officer at Dynavax Technologies, where he built the U.S. commercial infrastructure and helped scale the hepatitis B vaccine HEPLISAV-B® from launch to more than $300 million in annualized revenue and over 50% U.S. market share, positioning the company for Sanofi’s $2.2 billion acquisition. Before Dynavax, Mr. Casale held leadership positions in marketing and sales operations at Depomed, supporting the commercialization of GRALISE® and NUCYNTA®. Earlier in his career, he spent 14 years at Merck in progressive roles across sales, marketing, and corporate strategy, contributing to the successful launches of ZOSTAVAX®, GARDASIL®, ROTATEQ®, and PROQUAD®. “I am excited by the opportunity to lead ARS Pharma through its next evolution,” said Mr. Casale. “ neffy is a transformational product for patients, backed by a foundational intranasal technology platform, and I am confident in our ability to grow its impact in the years to come. I’m grateful for the foundation Rich and the Board have built, and I look forward to working alongside our team to increase access, accelerate adoption, and expand the reach of ARS Pharma, delivering on the promise that our treatments can have on patients worldwide.” About neffy ® neffy is a nasal spray used for emergency treatment of allergic reactions including anaphylaxis, in adults and children who weigh 33 lbs. or greater. INDICATION AND IMPORTANT SAFETY INFORMATION FOR neffy (epinephrine nasal spray) INDICATION neffy is indicated for emergency treatment of type I allergic reactions, including anaphylaxis, in adult and pediatric patients who weigh 33 lbs. or greater. IMPORTANT SAFETY INFORMATION neffy contains epinephrine, a medicine used to treat allergic emergencies (anaphylaxis). Anaphylaxis can be life-threatening, can happen in minutes, and can be caused by stinging and biting insects, allergy injections, foods, medicines, exercise, or other unknown causes. Always carry two neffy nasal sprays with you because you may not know when anaphylaxis may happen and because you may need a second dose of neffy if symptoms continue or come back. Each neffy contains a single dose of epinephrine. neffy is for use in the nose only. Use neffy right away, as soon as you notice symptoms of an allergic reaction. If symptoms continue or get worse after the first dose of neffy , a second dose is needed. If needed, administer a second dose using a new neffy in the same nostril starting 5 minutes after the first dose. Get emergency medical help for further treatment of the allergic emergency (anaphylaxis), if needed after using neffy . Tell your healthcare provider if you have underlying structural or anatomical nasal conditions, about all the medicines you take, and about all your medical conditions, especially if you have heart problems, kidney problems, low potassium in your blood, Parkinson's disease, thyroid problems, high blood pressure, diabetes, are pregnant or plan to become pregnant, or plan to breastfeed. Tell your healthcare provider if you take or use other nasal sprays or water pills (diuretics) or if you take medicines to treat depression, abnormal heart beats, Parkinson's disease, heart disease, thyroid disease, medicines used in labor, and medicines to treat allergies. neffy and other medications may affect each other, causing side effects. neffy may affect the way other medicines work, and other medicines may affect how neffy works. neffy may cause serious side effects. If you have certain medical conditions or take certain medicines, your condition may get worse, or you may have more or longer lasting side effects when you use neffy . Common side effects of neffy include: nasal discomfort, headache, throat irritation, chest and nasal congestion, feeling overly excited, nervous or anxious, nose bleed, nose pain, sneezing, runny nose, dry nose or throat, tingling sensation, including in the nose, feeling tired, dizziness, nausea, and vomiting. Tell your healthcare provider if you have any side effects that bother you or that do not go away after using neffy . These are not all of the possible side effects of neffy . Call your healthcare provider for medical advice about side effects. To report side effects, contact ARS Pharmaceuticals Operations, Inc. at 1-877-MY-NEFFY (877-696-3339) or the FDA at 1-800-FDA-1088 or . Please see the full Prescribing Information and Patient Information for neffy . About Type I Allergic Reactions Including Anaphylaxis Type I allergic reactions are serious and potentially life-threatening events that can occur within minutes of exposure to an allergen and require immediate treatment with epinephrine, the only FDA-approved medication for these reactions. While epinephrine auto-injectors have been shown to be highly effective, there are well published limitations that result in many patients and caregivers delaying or not administering treatment in an emergency situation. These limitations include fear of the needle, lack of portability, needle-related safety concerns, lack of reliability, and complexity of the devices. There are approximately 40 million people in the United States who experience Type I allergic reactions. Of this group, over the last three years, approximately 20 million people have been diagnosed and treated for severe Type I allergic reactions that may lead to anaphylaxis, but (in 2023, for example) only 3.2 million filled their active epinephrine auto-injector prescription, and of those, only half consistently carry their prescribed auto-injector. Even if patients or caregivers carry an auto-injector, more than half either delay or do not administer the device when needed in an emergency. About ARS Pharmaceuticals, Inc. ARS Pharma is a biopharmaceutical company dedicated to empowering at-risk patients and their caregivers to better protect patients against allergic reactions that could lead to anaphylaxis. The Company is commercializing neffy ® (trade name EUR neffy ® in the EU and UK and 优敏速 ® in China), an epinephrine nasal spray indicated in the U.S. for emergency treatment of Type I allergic reactions, including anaphylaxis, in adult patients and pediatric patients who weigh 33 lbs. or greater, and in the EU for emergency treatment of allergic reactions (anaphylaxis) due to insect stings or bites, foods, medicinal products, and other allergens as well as idiopathic or exercise induced anaphylaxis in adults and children who weigh 15 kg or greater. For more information, visit . Forward-Looking Statements Statements in this press release that are not purely historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to: the belief that ARS Pharma is well-positioned to drive meaningful market share growth; expectations regarding prescription renewals and demand generally; ARS Pharma’s plans to increase access to, accelerate adoption of, and expand the reach of ARS Pharma and of neffy ; and other statements that are not historical fact. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “anticipate,” “believe,” “can,” “could,” “expect,” “if,” “may,” “on track,” “potential,” “plan,” “will,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon ARS Pharma’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation: risks associated with transitions of members of the senior management team; potential safety and other complications from neffy ; the ability to maintain regulatory approval for neffy in its currently approved indications; the scope, progress and expansion of developing and commercializing neffy ; the risk that personnel costs will be higher than anticipated; the scope, progress and expansion of developing our intranasal epinephrine technology; clinical trial results; the potential for governments and payors to delay, limit or deny coverage for neffy ; the size and growth of the market for neffy and the rate and degree of market acceptance thereof vis-à-vis intramuscular injectable products; ARS Pharma’s ability to protect its intellectual property position; and the impact of government laws, regulations and policies. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included under the caption 'Risk Factors' in ARS Pharma's Annual Report on Form 10-K for the year ended December 31, 2025, filed with the Securities and Exchange Commission ('SEC'), and as updated by the 'Risk Factors' in ARS Pharma's Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, filed with the SEC on May 15, 2026 . These documents can also be accessed on ARS Pharma’s website at by clicking on the link “ Financials & Filings ” under the “Investors & Media” tab. The forward-looking statements included in this press release are made only as of the date hereof. ARS Pharma assumes no obligation and does not intend to update these forward-looking statements, except as required by law. For more information, visit , and follow us on LinkedIn and X . Investor Contact: Monique Allaire, THRUST monique@thrustsc.com Media Contact: Nabeelah Khan nabeelahk@ars-pharma.com

FORMULATION INSIGHT 寡核苷酸注射剂开发笔记 从处方设计到稳定性控制 导读 小核酸药物正在从罕见病、肝病等领域走向更广泛的慢病与精准治疗场景。对于寡核苷酸注射剂而言，真正的开发重点并不只是“配成水溶液”，而是围绕给药途径、API 理化性质、降解风险、包材相容性与储存条件，建立可解释、可控制、可申报的质量体系。 寡核苷酸注射剂看似处方简洁，但其质量控制的复杂性往往来自 API 结构、给药途径和长期稳定性的共同作用。 一、行业概况：小核酸药物进入发展快车道 小核酸药物是一类以核酸分子（DNA 或 RNA）为活性成分、通过调控基因表达发挥治疗作用的新型生物制剂。其作用靶点主要集中在转录或转录后水平，可对疾病相关基因实现更具针对性的调控。 从类型上看，小核酸药物主要包括反义核酸（ASO）、小干扰 RNA（siRNA）、微小 RNA（miRNA）、核酸适配体（Aptamer）以及转运 RNA（tRNA）碎片等。据统计，截至 2025 年，全球已有 26 款小核酸药物获批，近 170 个项目处于临床阶段，并逐步向慢病研发延伸。 凭借技术颠覆性、适应症拓展潜力以及中国企业的后发优势，小核酸药物已经成为生物医药领域的重要赛道。对于制剂开发而言，如何把活性寡核苷酸稳定、安全、可控地递送到目标给药场景，是从研发走向注册和商业化的关键环节。 二、制剂组成：简单处方背后的 QbD 思路 药品开发强调“质量源于设计”（QbD）。在处方开发前，首先需要充分理解 API 的理化性质，也就是开展系统的处方前研究。 对于小核酸药物而言，经过结构改造后的寡核苷酸通常具有更好的化学稳定性。许多市售产品采用相对简洁的水溶液处方，即可满足临床给药需求。 API 活性物质，市售浓度范围为2.1mg/mL-200mg/mL. 氯化钠 渗透压调节剂（适用于API浓度≤170mg/ml，高浓度API水溶液生理等渗不需要添加渗透压调节剂 磷酸盐缓冲液 pH缓冲 磷酸或盐酸+氢氧化钠 pH调节剂，6-8.7 注射用水 溶剂 表 1 市售小核酸产品常见处方 处方看似简单，但每个辅料选择都需要回到 API 性质、给药途径、渗透压耐受性、pH 稳定区间和长期储存表现中综合判断。 三、给药途径：质量属性要求需要按场景拆解 在了解 API 理化性质后，需要结合适应症、药理数据和临床使用方式确定给药途径。目前市售小核酸药物常见给药途径包括 IVT（眼内注射）、IV（静脉注射）、SC（皮下注射）、IT（鞘内注射）和 IM（肌内注射）。 研发早期建议重点评估 外观、鉴别、pH 值、渗透压、颗粒物、含量、纯度与杂质、可抽取体积、细菌内毒素和无菌性。 IM 常规给药剂量 2–5 mL 不同给药途径有差异的质量属性 内毒素ChP&USP：K = 5 EU/(kg·h) 代表药物及给药剂量 Heplisav-B：0.5 mL IVT 常规给药剂量 0.1 mL 不同给药途径有差异的质量属性 内毒素ChP&USP：一般不得超过 2.0 EU/剂。眼科冲洗产品限值一般不得超过 0.50 EU/mL。 不溶性微粒ChP&USP（每 1 mL 供试品）：  • ≥10 μm：不得过 50 粒  • ≥25 μm：不得过 5 粒  • ≥50 μm：不得过 2 粒 代表药物及给药剂量 Vitravene：0.05 mL  Macugen：0.09 mL IT 常规给药剂量 5–15 mL 不同给药途径有差异的质量属性 内毒素 ChP&USP：K = 0.2 EU/(kg·h) 不溶性微粒同 IV 途径 代表药物及给药剂量 Qalsody：15 mL Spinraza：5 mL IV 常规给药剂量 取决于体重，可达 200 mL 不同给药途径有差异的质量属性 内毒素ChP：K = 5 EU/(kg·h)；且标示装量 ≥100 mL 的注射液，限值一般不得超过 0.50 EU/mL。  不溶性微粒（ChP）  • 装量 ≥100 mL：每 1 mL 中 ≥10 μm ≤25 粒，≥25 μm ≤3 粒。  • 装量 100 mL（及无菌粉末等）：每个容器中 ≥10 μm ≤6000 粒，≥25 μm ≤600 粒。  不溶性微粒（USP）  • 装量 100 mL：每 1 mL 中 ≥10 μm ≤12 粒，≥25 μm ≤2 粒。  • 装量 100 mL：每个容器中 ≥10 μm ≤3000 粒，≥25 μm ≤300 粒。 代表药物及给药剂量 Amondys 45™：100–150 mL SC 常规给药剂量 0.5–1.5 mL 不同给药途径有差异的质量属性 内毒素ChP&USP：K = 5 EU/(kg·h) 不溶性微粒建议按照 IV 途径限度进行控制 代表药物及给药剂量 Givlaari  Oxlumo  Rivfloza™ 表 2 不同给药途径常规注射溶液的一般要求和代表药物 备注：药品细菌内毒素限值（L）一般按以下公式确定：L=K/M；式中L为供试品的细菌内毒素限值，一般以EU/ml、EU/mg或EU/U（活性单位）表示；K为人每千克体重或每平方米体表面积每小时最大可接受的内毒素剂量，以EU/（kg·h）表示；M为人用每千克体重或每平方米体表面积每小时的最大供试品剂量，以ml/（kg·h）、mg/（kg·h）、U/（kg·h）、ml/（m2·h）等表示，人均体重按60kg计算，注射时间若不足1小时，按1小时计算。 四、主要降解杂质：稳定性风险不只影响纯度 寡核苷酸的主要降解途径包括脱嘌呤、脱氨、脱硫和光解。这些降解路径不仅可能影响化学纯度，还可能释放游离嘌呤或产生元素硫，从而形成可见或亚可见颗粒物。 脱嘌呤 影响因素 pH、温度 主要产物 无碱基杂质、短链片段 应对策略 使用pH缓冲液如（磷酸盐缓冲系统1-10 mM）维持稳定 pH、冷藏保存（2-8°C）、；避光保护 脱氨作用 影响因素 pH、温度、氧化、光照 主要产物 嘧啶转化产物 应对策略 使用pH缓冲液如（磷酸盐缓冲系统1-10 mM）维持稳定 pH、冷藏保存（2-8°C）、；避光保护 脱硫作用 影响因素 pH、氧、光照 主要产物 P=O 杂质、单质硫 应对策略 使用pH缓冲液如（磷酸盐缓冲系统1-10 mM）维持稳定 pH、冷藏保存（2-8°C）、；避光保护 光解 影响因素 光照（尤其溶液状态） 主要产物 氧化产物、二聚体 应对策略 使用pH缓冲液如（磷酸盐缓冲系统1-10 mM）维持稳定 pH、冷藏保存（2-8°C）、；避光保护 表 3 寡核苷酸主要降解途径与控制策略 因此，稳定性研究不应只关注主峰含量变化，还应同时关注外观、颗粒物、杂质谱变化和潜在析出风险。 图1.常见的寡核苷酸降解途径[1] 五、主要工艺 目前市售的小核酸主要有两种类属性一种是常规溶液剂，一种是脂质纳米颗粒（LNP）制剂（ Onpattro®），其工艺可以概况为图2： 图2. 工艺流程图 A简单的小核酸溶液剂；B相对复杂处方的脂质复合物[1] 六、包材选择：兼顾相容性、避光与临床便利性 寡核苷酸注射剂的包材需要结合给药途径、药物与包材的相容性、是否需要避光以及临床使用便利性进行选择。市售小核酸产品常见包材包括西林瓶和预灌封组件。 容器 透明I型硼硅玻璃 胶塞/活塞 卤化丁基橡胶 + 含氟聚合物涂层 密封盖 铝制翻盖 表 4 市售小核酸产品常见包材材料 对于高浓度制剂或含特殊修饰基团的产品，还应关注吸附、浸出物、硅油、颗粒物以及预灌封系统中的滑动性能和剂量准确性。 七、储存条件与货架期：冷藏、避光和短期漂移需要提前设计 货架期需要根据稳定性数据确定。已获批的寡核苷酸药物中，多数产品需要在 2-8°C 下冷藏保存，货架期可覆盖 18-60 个月；部分 siRNA 产品可在 2-30°C 条件下室温或可控室温储存 36 个月。 多数产品要求避光，且通常禁止冷冻；部分冷藏产品允许短期温度漂移，例如从冷藏取出后可在特定温度范围内放置 14-42 天。 Macugen® 货架期 36个月 特殊说明 禁止冷冻或剧烈摇晃，防热避光 Kynamro® 货架期 30个月（西林瓶）/ 18个月（PFS） 特殊说明 避光 Exondys 51™ 货架期 18个月 特殊说明 禁止冷冻，避光 Spinraza® 货架期 48个月 特殊说明 禁止冷冻，避光 Tegsedi® 货架期 60个月 特殊说明 禁止冷冻，避光 Waylivra® 货架期 60个月 特殊说明 禁止冷冻，避光 Vyondys 53™ 货架期 24个月 特殊说明 禁止冷冻，避光 Viltepso® 货架期 18个月 特殊说明 禁止冷冻，避光 Amondys 45™ 货架期 24个月 特殊说明 禁止冷冻，避光 Qalsody™ 货架期 18个月 特殊说明 禁止冷冻，避光 Wainua™ 货架期 24个月 特殊说明 禁止冷冻，防热避光 Onpattro® 货架期 36个月 特殊说明 禁止冷冻 Rivfloza™ 货架期 36个月（西林瓶）/ 30个月（PFS） 特殊说明 禁止冷冻，防热避光 表 5 冷藏储存（2-8°C） Defitelio® 货架期 36个月 特殊说明 无 Leqvio® 货架期 36个月 特殊说明 禁止冷冻 表 6 室温储存（20-25°C） Vitravene™ 货架期 36个月（2-25℃） 特殊说明 避光 Oxlumo® 货架期 36个月（2-25℃） 特殊说明 避光 Oxlumo® 货架期 36个月（2-25℃） 特殊说明 禁止冷冻 Amvuttra® 货架期 36个月（2-30℃） 特殊说明 防热避光 表 7 可控室温储存 Macugen® 允许条件 ≤25°C（未拆封，原纸盒内） 最长允许时间 14天 Onpattro® 允许条件 ≤25°C（未拆封，原纸盒内） 最长允许时间 14天 Kynamro® 允许条件 ≤30°C（未拆封，原纸盒内） 最长允许时间 14天 Spinraza® 允许条件 ≤30°C（未拆封，原纸盒内） 最长允许时间 14天 Tegsedi® 允许条件 ≤30°C（未拆封，原纸盒内） 最长允许时间 42天(约6周) Waylivra® 允许条件 ≤30°C（未拆封，原纸盒内） 最长允许时间 42天(约6周) Wainua™ 允许条件 ≤30°C（未拆封，原纸盒内） 最长允许时间 42天(约6周) Qalsody™ 允许条件 ≤30°C（未拆封，原纸盒内） 最长允许时间 14天 Rivfloza™ 允许条件 15-30°C 最长允许时间 28天(4周) 表 8 允许的温度漂移（从冷藏取出后） Spinraza® 允许条件 除去外包装(内包装完好)后在8-25℃保存总时间≤30 小时 说明 原包装在8-30°C保存时间≤14天 Qalsody™ 允许条件 除去外包装(内包装完好)后在8-25℃保存总时间≤30 小时 说明 原包装在8-30°C保存时间≤14天 表 9 开瓶/稀释后的使用中稳定性 这些信息提示我们，储存条件并不是注册后才确定的标签内容，而应在早期处方和工艺设计阶段就被纳入风险评估。对于 LNP 制剂和高浓度制剂，还需要额外关注粒径、包封状态、黏度和外观变化。 从处方前研究到货架期设定，核心逻辑始终是 QbD：识别关键质量属性，找到影响因素，并在工艺与控制策略中前置管理。 八、结语：从 API 到 DP 的一站式开发逻辑 当前大多数已获商业批准的寡核苷酸原料药多为单链反义寡核苷酸或双链小干扰RNA，其中多数结构为硫代磷酸酯/磷酸二酯骨架加脱氧核糖或核糖加碱基（部分碱基会经过化学修饰），而其主要降解途径包括脱嘌呤、脱氨和脱硫，这些途径产生的降解产物不仅会影响化学纯度，还可能向药物溶液中释放游离嘌呤、硫单质或其他不溶性杂质而产生沉淀形成可见或亚可见的颗粒物；同时，小核酸修饰还会添加一些靶向结构如GalNAc，或者延长药效的基团如PEG，这些基团的引入不仅会改变小核酸的溶解度和稳定性，而且对高浓度产品的粘度也有冲击。故制剂端的处方开发要充分考量这些因素，基于质量源于设计原理（QbD）提前对其进行考察，以避免处方确认后出现产品澄清度、可见异物超限，或产品长期稳定性不满足预期要求的现象。 诺泰制剂产线 杭州诺泰诺和生物医药科技有限公司提供临床前研究生产至商业化生产一站式服务，支持寡核苷酸产品在处方筛选、工艺开发、质量属性评估、稳定性研究和 IND 至 NDA 申报阶段的方案定制。服务范围覆盖多种非肠道给药途径的溶液剂与脂质体/LNP 制剂开发。 制剂端配备3类主流非肠道给药生产线，包括西林瓶生产线3条、卡式瓶生产线2条、预灌封生产线2条，可适配多种规格的内包材，生产批量覆盖1L至500L，能够满足小核酸产品在non-GMP阶段（如毒理批、工程批、表征批）及GMP阶段（如临床批、工艺验证、商业化生产）的多样化需求。此外，针对批量小于100L的小核酸产品，为有效减少产品损失并降低共线污染风险，诺泰生物产线可根据项目需求适配一次性生产系统，与药液接触生产组件均可定制为项目专用组件。 （更多产品与服务，请咨询 info@apextide.com） 撰稿：诺泰诺和制剂研发部          推荐阅读       寡核苷酸治疗药物结构特点、化学修饰及功能简述 快速理解 ASO / siRNA 药物设计逻辑。 查看全文 → 寡核苷酸上市药物及 FIH试验研究 解析寡核苷酸 FIH 试验难点，汇总全球上市核酸药物临床开发方案 查看全文 → 寡核苷酸药物高级结构与聚集体的系统评估与表征策略(一） 解析寡核苷酸高级结构与聚集体成因，梳理 CMC 风险及系统评估控制思路 查看全文 → 参考资料 [1] Vinjamuri B P, Pan J, Peng P. A review on commercial oligonucleotide drug products[J]. Journal of Pharmaceutical Sciences, 2024, 113(7): 1749-1768. 关于诺泰诺和 诺泰诺和（Apextide），诺泰生物（股票代码688076）旗下子公司，位于杭州下沙，聚焦于高难度寡核苷酸及多肽CDMO项目，提供临床前研究生产至商业化生产一站式服务。 （www.apextide.com）