rVSV-ZEBOV

New immunology data for INO-3107 supporting proposed mechanism of action presented at several recent conferences Data showed ability of INO-3107 to induce an antigen-specific cytotoxic T cell response against HPV-6 and HPV-11 and drive recruitment of T cells into airway tissues and papilloma Data showed INO-3107 induced expansion of new clonal T cells that infiltrate airway tissues and correspond with reduction of surgeries for RRP patients observed in Phase 1/2 trial Continued progress on preparing regulatory submissions for INO-3107 All non-device BLA modules on track for completion by end of 2024 BLA submission remains targeted for mid-2025 PLYMOUTH MEETING, Pa., Nov. 14, 2024 /PRNewswire/ -- INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced its financial results for the third quarter of 2024 and provided an update on recent company developments. "We continue to be focused on advancing INO-3107 and delivering a non-surgical option to RRP patients. Toward this goal, we expect to have all non-device modules for our BLA completed by year end, while in parallel we continue to implement the plan to resolve the previously announced manufacturing issue with the single-use array component of the device. With this progress, we continue to target the submission of our BLA in mid-2025," said Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer. "Our development of INO-3107 is supported by a growing body of research that collectively points to INO-3107's potential to be an important therapeutic option for all RRP patients regardless of the severity of their disease. We recently presented new immunology data highlighting the ability of INO-3107 to induce new populations of T cells that travel to the airway tissue and papilloma and correspond with clinical benefit. We've also presented our full safety and efficacy data, demonstrating that INO-3107 was shown to be well tolerated and have clinical benefit in the Phase 1/2 trial. Additionally, by the end of year, we anticipate announcing long-term clinical durability data. We continue to believe INO-3107 has the potential to become the preferred choice for the broadest number of RRP patients, healthcare providers and payors, if approved." Recent Business Highlights Lead Candidate, INO-3107 – Recurrent Respiratory Papillomatosis INOVIO's primary focus is driving toward the regulatory approval and commercialization of its lead product candidate, INO-3107. Recent progress includes advancing preparations for submitting the BLA, targeted for mid-2025, and announcing the following new data. New Immunology Data: INOVIO presented additional immunology data demonstrating the ability of INO-3107 to induce antigen-specific T cell responses against HPV-6 and HPV-11 and drive recruitment of those T cells into airway tissues and papilloma of RRP patients, which could potentially slow or eliminate papilloma regrowth. These data were presented at the American Association for Cancer Research (AACR) Special Conference and at the 36th International Papillomavirus Conference. In totality, this new data showed: Induction of T cell responses specific to HPV-6 and HPV-11, including cytotoxic CD8+ T cells, which were still present at week 52, indicating an establishment of memory response Expansion of clonal T cell populations in peripheral blood, including induction of new clonal T cell populations that travelled to airway or papilloma tissue Induction of inflammatory responses in papilloma and airway tissue, including: - Interferon, cytokine and chemokine signaling - Adaptive and innate immune cell infiltration, with emphasis on T cells Cytotoxic signatures of infiltrated T cells in papilloma/airway tissue, providing direct evidence of increased overall T cell infiltration compared to pre-treatment T cell infiltration in airway tissues of clinical responders were predominantly new T cell clonal populations not detectable prior to INO-3107 treatment Clinical activity not impacted by immunosuppressive papilloma microenvironment Full Safety and Efficacy Data: INOVIO presented its full safety and efficacy data set for the Phase 1/2 trial in which INO-3107 was shown to be well tolerated and have clinical benefit. Of the 32 patients in the trial, 26 patients, or 81%, experienced a decrease in the number of surgical interventions in the year after treatment when compared to the year before treatment. These data were presented at both the International Society of Vaccines Conference and the Fall Voice Conference. In the trial, the overall clinical response (OCR) was 81%, with 26 of the 32 enrolled patients experiencing a decrease in the number of surgical interventions in the year after INO-3107 administration compared to the prior year, including 28% (9/32) that required no surgical intervention (i.e., complete response, or CR) during or after the dosing window. Further, 44% (14/32) of patients had a partial response (PR), measured by a reduction of at least 50%, but less than 100%, in the number of surgeries when compared to the prior year. The overall response rate (ORR) of patients (CR+PR) was therefore 72% (23/32). Other key data points presented include: INO-3107 was shown to be well tolerated and have clinical benefit - 41% (13/32) of patients reported a treatment-related Adverse Event (AE) - No treatment-related AEs greater than Grade 2 severity were reported - Most frequent treatment-related AE's reported were injection site pain (31%) and fatigue (9%) Modified Derkay-Pransky severity scores improved from baseline to the end of 52-week trial INO-3107 induced durable cellular responses and generated T cells against HPV-6 and HPV-11 Other Pipeline Updates INOVIO continued to advance plans for a Phase 3 trial of INO-3112 as a potential treatment for HPV-related oropharyngeal squamous cell carcinoma also known as throat cancer, through ongoing conversations with regulators in the European Union. This trial is anticipated to be conducted in North America and Europe. Previously, the FDA had indicated alignment with the proposed trial design, which was developed in conjunction with a trial steering committee. INOVIO continued to advance its plans for a Phase 2 trial of INO-4201 as a heterologous boost to the FDA licensed Ebola vaccine, Ervebo®. A meeting is scheduled with the FDA in the fourth quarter of 2024 to discuss the proposed Phase 2 trial design. Patients continue to be dosed in the GBM-001 trial with INO-5401. Regeneron and Inovio have discussed that an appropriate next step would be a controlled Phase 2 trial. Third Quarter 2024 Financial Results Cash, Cash Equivalents and Short-term Investments: As of September 30, 2024, cash, cash equivalents and short-term investments were $84.8 million compared to $145.3 million as of December 31, 2023. Research and Development (R&D) Expenses: R&D expenses for the three months ended September 30, 2024, were $18.7 million compared to $15.5 million for the same period in 2023. The increase in R&D expenses was primarily the result of overall higher drug manufacturing costs and higher engineering professional and outside services related to device development, offset by lower employee and consultant compensation, including non-cash stock-based compensation, among other variances. General and Administrative (G&A) Expenses: G&A expenses were $8.6 million for the three months ended September 30, 2024 compared to $9.9 million for the same period in 2023. The decrease in G&A expenses was primarily related to a decrease in employee compensation, including non-cash employee and consultant stock-based compensation, and a decrease in legal expenses, among other variances. Total Operating Expenses: Total operating expenses were $27.3 million for the three months ended September 30, 2024, compared to $35.9 million for the same period in 2023. During the three months ended September 30, 2023, the company recognized a non-cash goodwill impairment charge of $10.5 million. Net Loss: Net loss for the three months ended September 30, 2024 was $25.2 million, or $0.89 per basic and diluted share, compared to net loss of $33.9 million, or $1.52 per basic and diluted share, for the three months ended September 30, 2023. Shares Outstanding: As of September 30, 2024, INOVIO had 26.1 million common shares outstanding, 2.1 million pre-funded warrants outstanding, and 29.9 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting, and conversion, as applicable, of its outstanding pre-funded warrants, options, restricted stock units and convertible preferred stock. INOVIO's balance sheet and statement of operations are provided below. Additional information is included in INOVIO's quarterly report on Form 10-Q for the quarter ended September 30, 2024, which can be accessed at: . Cash Guidance INOVIO estimates its cash runway to extend into the third quarter of 2025. This projection includes an operational net cash burn estimate of approximately $24 million for the fourth quarter of 2024. These cash runway projections do not include any further capital-raising activities that INOVIO may undertake. Conference Call / Webcast Information INOVIO's management will host a live conference call and webcast with slides at 4:30 p.m. ET today to discuss INOVIO's financial results and provide a general business update. The live webcast and replay may be accessed by visiting INOVIO's website at . About INOVIO's DNA Medicines Platform INOVIO's DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO's proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software the body's cells can download to produce specific proteins to target and fight disease. INOVIO's proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body's cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms. About INOVIO INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit . Contact: Media: Jennie Willson (267) 429-8567 [email protected] Investors: Thomas Hong (267) 440-4298 [email protected] Forward-Looking Statements This press release contains certain forward-looking statements relating to our business, including our plans to develop and commercialize DNA medicines and our expectations regarding our research and development programs, including the planned initiation and conduct of clinical trials and the availability and timing of data from those trials, the planned submission of a BLA in mid-2025, expectations regarding INO-3107's potential to be an important therapeutic option for RRP patients and the preferred choice of RRP patients, healthcare providers and payors, as well as plans for discussions with regulatory authorities, the planned commercial launch of INO-3107 if regulatory approval is obtained, and expectations with respect to our cash resources into the third quarter of 2025 and expected cash burn for the fourth quarter of 2024. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that the results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law. SOURCE INOVIO Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

摘要:2019冠状病毒病（COVID-19）大流行的出现使我们意识到迅速开发治疗方法和拯救生命的重要性。这场针对这种新型冠状病毒的疫苗研发竞赛在大流行出现之初就开始了。时间是唯一的限制因素。从1796年针对天花的第一种疫苗到最新的COVID-19疫苗，已有多种疫苗减轻了疾病的负担，以及相关的死亡率和发病率。多年来，我们在生物体分离、细胞培养、全基因组测序和重组核技术方面取得了许多新的进展。这些技术极大地促进了疫苗的开发。每种疫苗都有自己的开发故事，通过学习疫苗开发中的突破，我们可以获得很多智慧。 1.背景 尽管接种实践始于500多年前，但“疫苗”这个词是在18世纪由爱德华·詹纳首次描述的。它源自拉丁语“Vacca”，意为牛。1796年，詹纳将挤奶女工手上的牛痘病灶接种给一个八岁的男孩，最终赋予了对天花的免疫力。80年后，路易·巴斯德在开发针对人类的狂犬病活减毒疫苗方面发挥了重要作用，取得了巨大成功。在19世纪，我们见证了通过科赫发现的众多微生物而发展起来的病原体理论。到了20世纪中叶，在引入减毒毒素（类毒素）之后，第一代疫苗得以开发。通过这一发展，人们得以制造出白喉和破伤风疫苗。在1930年代，实验室技术的重大进步使得病毒能够在鸡胚的卵黄囊膜上培养。这促成了流感和黄热病疫苗的开发。15年后，细胞培养的进化促成了脊髓灰质炎疫苗的创造，这标志着疫苗的黄金时代的开始。在这一时期，一系列重要的疫苗如麻疹、腮腺炎、风疹和水痘疫苗被开发出来。重组DNA和全基因组测序技术的引入是疫苗开发的里程碑。它为研究人员提供了开发针对以前不可能的病原体的新疫苗的工具。我们的目标是涵盖上个世纪开发的大多数疫苗的时间线和发展（图1）。 图1：疫苗历史时间线 COVID-19，2019冠状病毒病；FDA，美国食品药品监督管理局；HPV，人乳头瘤病毒 2.综述 2.1.天花 天花是最古老的已知传染病之一。它造成了数亿人死亡。关于这种疾病的最早书面记录可以追溯到4世纪的中国。一些研究表明，在埃及木乃伊上发现了类似天花的皮疹，表明它可能至少可以追溯到3000年前。1980年，世界卫生组织（WHO）宣布天花成为全球首个因积极的免疫努力而被根除的疾病。 最早的关于接种的文献记录是在16世纪的中国和印度。这是通过鼻腔或皮肤途径接种天花脓液或痂皮实现的。在全球天花爆发期间，早期的接种试验于1721年在英国和马萨诸塞殖民地进行。此外，还有来自奥斯曼帝国和北非的接种报告。尽管接种的起源并不确定，无论是起源于亚洲还是非洲，接种的做法最早是由爱德华·詹纳在1796年引入的。他观察到患有牛痘病灶的挤奶女工对天花感染有免疫力。然后他让一个小男孩接触到挤奶女工的病灶，并观察到这个男孩获得了对天花的免疫力。他将这种做法扩展到更多的孩子，并记录了类似的结果。从那时起，人们一直在不断努力开发更安全的疫苗技术。 目前，FDA批准了三种主要的天花疫苗。Dryvax®是20世纪早期根除天花的主要组合之一。它的生产始于19世纪的Wyeth实验室，并在1982年全球根除目标实现后暂停。Dryvax®一直储备到2008年，直到被ACAM2000取代，ACAM2000是第二代疫苗，更安全，但与Dryvax®具有相同的效力概况。最新的天花疫苗是MVA-BN。它于2013年在欧洲和加拿大获得批准，2019年在美国获得批准。与Dryvax®和ACAM2000相比，MVA-BN在患有特应性皮炎和免疫缺陷的患者中有更好的安全性概况。尽管天花已被根除，但卫生感染控制实践咨询委员会和免疫实践咨询委员会推荐在某些高风险群体中采取疫情前措施。 2.2.人乳头瘤病毒 人乳头瘤病毒（HPV）是宫颈癌的最常见原因，也是全球女性第四常见的癌症。HPV最初是在1983年的宫颈癌活检中检测到的。二十年后，关于第一种HPV疫苗临床试验的最早出版物发布。第一种HPV疫苗于2006年获得FDA批准。针对HPV的普遍疫苗接种计划已导致宫颈癌的发病率和死亡率显著降低。 2.3.埃博拉病毒 1976年在西非首次记录了埃博拉病毒病的流行后，发生了多次短期爆发性疫情，严重程度不一。2014年发生的最致命和最近的一次爆发，病死率高达85%。这导致世界卫生组织在2014年8月宣布该流行病为国际公共卫生紧急情况。在此之前，已经进行了多项非人类试验，以开发针对埃博拉病毒家族的疫苗。2015年，开始了一场创造安全有效疫苗的竞赛，并且建立了许多人临床试验来测试多种疫苗候选物。为了快速进行安全性和免疫原性测试，使用了一种表达扎伊尔埃博拉病毒（ZEBOV）糖蛋白的复制型重组水泡性口炎病毒（rVSV）基疫苗。以Ervebo®的品牌名，它在2019年11月获得了欧洲药品管理局（EMA）的授权，并在2019年12月获得了FDA的授权。第二种疫苗是两剂异源Ad26.ZEBOV和MVA-BN-Filo埃博拉疫苗方案，这是两种不同的疫苗，相隔约56天给予。它在2020年7月被EMA批准用于医疗用途。尽管许多疫苗仍在试验中，但这些是唯一获批针对埃博拉病毒家族的疫苗。 2.4.轮状病毒 轮状病毒于1973年首次被发现，被发现是儿童急性胃肠炎的主要病原体。自1981年以来，已经进行了几项I-III期临床试验，以开发针对轮状病毒的安全疫苗。第一个获得FDA批准的疫苗品牌名为Rotashield®，于1998年获得许可，但由于与肠套叠的证实关联，在不到一年的时间里被撤回。又过了八年，直到一种更安全的轮状病毒疫苗才获得许可。2006年，RotaTeq®（RV5：五价）被引入美国的普及疫苗接种计划。然后，Rotarix®（RV1：单价）在2008年获得了FDA的许可。在美国进行的多项病例对照研究的元分析，比较了不同轮状病毒疫苗类型的有效性，没有显示出统计学上的显著差异。 2.5.甲型肝炎病毒 甲型肝炎病毒于1973年在美国首次被检测到。花了三十年时间开发出一种安全有效的疫苗。第一个针对甲型肝炎的疫苗名为Havrix®，于1992年获得许可。随后是疫苗Vaqta®，于1993年获得许可。这些是美国唯一获批的针对甲型肝炎病毒的疫苗。 2.6.流感嗜血杆菌 流感嗜血杆菌于1892年首次被描述。最初，它被错误地认为是流感大流行的病原体，直到1933年揭示了其病毒病因。它负责一系列局部和侵袭性传染病。它被分类为有胶囊和无胶囊变体。有胶囊的被根据胶囊抗原亚分为a-f六个血清型。最有毒和侵袭性的血清型是b型菌株（Hib）。针对Hib开发的第一种疫苗是在20世纪70年代初在芬兰。它由胶囊多糖胶囊多聚核糖核糖磷酸盐（PRP）组成。纯多糖疫苗于1985年在美国首次获得许可，并推荐给超过18个月的人使用。研究表明，由于免疫系统的不成熟，PRP疫苗在18个月以下的年龄段没有效果。它一直使用到1988年，当时显示结合疫苗在诱导婴儿免疫反应方面更好，这被认为是侵袭性Hib感染的高峰年龄。PRP附着在蛋白结合物如破伤风和白喉类毒素上是开发结合疫苗的第一步。目前，获批的产品是与其他疫苗产品的组合，如乙肝和百白破疫苗。 2.7.流感 流感大流行的确切时间尚不清楚。最早的类似流感的疾病由希波克拉底在公元前400年的“流行病学”中提到，然而，并非所有研究人员认为这实际上是流感。第一个肯定符合当前流感描述的大流行是在1580年记录的。从那时起，世界各地发生了多次流感大流行。其中最具破坏性的大流行是1918年的“西班牙流感”，导致数千万人的死亡。直到1931年从感染患者的鼻分泌物中分离出流感病毒，人们错误地认为大流行有细菌病因。20世纪30年代中期进行了首次开发疫苗的试验。1938年，成功进行了一次实验，开发了一种单价灭活疫苗，以保护美国军队免受甲型流感病毒的侵害。该疫苗于1945年在美国获得公共使用许可。不久之后发现了一种新菌株“乙型流感”，几年后，第一种双价疫苗获得许可供公共使用。 抗原的移位和漂移以及病毒成分的持续变化使得有必要建立一个监测循环流感菌株的监测系统。第一次监测是由世界卫生组织在1952年创建的。发现新菌株和不同大流行中不同类型的血凝素和神经氨酸酶抗原导致在20世纪70年代引入了三价疫苗。随后，四价疫苗于2012年获得FDA许可。细胞培养技术、重组DNA和全基因组测序的进步使科学家能够迅速应对不断演变的流感大流行，如1997年的“禽流感”和2009年的“猪流感”，在几个月内创造出安全有效的疫苗。当前的研究重点包括开发能够应对当前和不断演变菌株的通用疫苗。 2.8.COVID-19 2019年12月，中国武汉首次报告了COVID-19病例。一群原因不明的呼吸道感染患者被证明是由一种名为SARS-CoV-2的新型冠状病毒引起的。这种病毒属于冠状病毒科，其中还包括严重急性呼吸综合征冠状病毒-1（SARS-CoV-1）和中东呼吸综合征冠状病毒（MERS-CoV）。2020年3月11日，世界卫生组织（WHO）宣布COVID-19为大流行病。发热、肌肉痛、咳嗽、呼吸困难和类似流感的症状是COVID-19最常见的症状，主要影响呼吸系统。从无症状感染到呼吸衰竭、多器官功能障碍和死亡，COVID-19具有广泛的临床表现。除了呼吸系统外，COVID-19还与其他身体系统的危害有关。尽管与SARS-CoV和MERS-CoV相比，SARS-CoV-2的死亡率较低，但其传播性和扩散性远高于SARS-CoV-1和MERS。2020年初，开发有效安全疫苗的竞赛开始了。很快，全球有200多个候选疫苗处于临床前和临床开发阶段。少数疫苗进入了临床三期试验，到2020年12月，由辉瑞和BioNTech合作开发的第一种COVID-19疫苗获得了批准。COVID-19疫苗的开发被认为是疫苗科学史上最快速的之一。由于疾病的有限传播和需求减少，SARS-CoV-1和MERS疫苗候选物没有超过I期，但它们帮助理解了身体对冠状病毒的反应。2020年12月31日，WHO为辉瑞COVID-19疫苗（mRNA疫苗）发布了紧急使用清单（EUL）。2021年2月15日，WHO为阿斯利康/牛津COVID-19疫苗（腺病毒载体疫苗）发布了EUL。2021年3月12日，WHO为强生COVID-19疫苗（腺病毒载体疫苗）发布了EUL。目前，这些是由EUL发布的唯一疫苗。另一种由Moderna生产的mRNA疫苗于2020年12月18日获得FDA许可，并于2021年1月6日获得EMA许可。虽然其他疫苗如中国国药、科兴、诺瓦瓦克斯和卫星疫苗等正在其他国家分发，但它们并未包含在撰写本文时由WHO发布的紧急使用清单中。不同类型的疫苗、它们的给药途径以及它们的作用机制在表1中进行了总结。 表1：不同类型疫苗的总结。 COVID-19疫苗许可日期基于WHO建议提供。IM，肌肉内注射；HPV，人乳头瘤病毒 3.结论 疫苗在减轻传染病负担方面发挥了至关重要的作用。这一切都始于500年前中国人和印度人的最初接种努力。这种做法的旅程穿越了奥斯曼和非洲，最终传入欧洲和北美。当爱德华·詹纳的理念为疫苗接种奠定了基础时，他希望自己的努力最终能导致天花的根除。从那时起，这是一段充满挑战和失败的漫长旅程，但他的希望最终在1980年世界卫生大会宣布世界摆脱这种疾病时得以实现。疫苗开发的知识体系不断增长，实验室技术的进步挽救了数百万生命。此外，COVID-19疫苗的空前成功为证明疫苗有效性的证据库增添了另一种武器。每种疫苗都有其独特的发展历史，研究它可能提供我们在将来大流行中可能需要的智慧。因此，我们希望利用这个机会分享我们对历史上各种疫苗发展深入调查的结果。 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。