NasoVAX(Altimmune, Inc.)

近日，Altimmune在其年度财报中宣布将放弃该公司的乙肝药物HepTcell的开发。不过这一消息并未令公司股价下跌，原因在于该公司的核心减肥药物pemvidutide在去年11月展现出了较为优异的数据，更是迎头赶上了减肥药市场的火热，在其他跨界适应症中也展现出了较为优异的疗效。虽然减肥药方面的消息还算不错，但如果放到这家公司整体战略规划中来看，其实会发现这次被放弃的HepTcell的开发过程的行动力和Altimmune在这一过程的战略决策其实相当不靠谱。这或许就让人担心pemvidutide以后也会不会出现同样的问题。HepTcell的“龟速”开发HepTcell是一种基于合成肽的免疫治疗产品，由九种代表乙型肝炎病毒（HBV）保守序列的肽链组成，并与授权获得的IC31佐剂相结合。IC31是由Valneva SE生产的基于TLR9的佐剂，旨在增强免疫反应。HepTcell在2017年时，其实已经有I期临床的初步结果（2015-2018年），2019年报告的I期初步结果不是特别理想，单药疗效似乎微乎其微，安全性方面并无问题。这个时候的抉择可能是放弃这款药物，或者尝试其他开发方式。（下图一为I期临床，图2为II期临床开始时间）图1：HepTcell的I期临床图2：HepTcell的II期临床不过，这个决定直到2020年年末才做出……那时才准备继续开展HepTcell的II期临床。或许部分原因是因为2017年时Altimmune正在与PharmAthene公司合并的过程中……公司合并让这一项目束之高阁。（抑或是担忧临床终止开发会让公司市值缩水？）也或许是因为2019年年末，新冠大流行出现了，虽然官方发布的财报中并没有提及优先级关系，但这家公司似乎优先选择了开发新冠疫苗？这家公司本身有流感疫苗NasoVAX管线（腺病毒疫苗），但因为流感和新冠的症状类似，所以他们的想法同样的技术平台用作鼻腔给药能够在新冠病毒的初始攻击部位诱导免疫反应……因此以这种方式利用新冠的RBD结构域开发了AdCOVID管线，而治疗流感的NasoVAX管线就这样被雪藏了。而不幸的是，2021年6月份时AdCOVID被披露效果不尽如人意，遭到了该公司放弃。可以说这是经典的战略判断失误，赔了夫人又折兵。这样一来一回的折腾，最终这家公司还是笃定在乙肝药HepTcell和减肥药pemvidutide的开发上。不过随后HepTcell的临床招募也是相当缓慢……2020年年末开始临床招募，竟然到2023年4月才堪堪招募了80名患者……而随后就是最近的消息，HepTcell停止开发了……唯一希望的减肥药现在减肥药pemvidutide就成为了这家公司唯一的希望。不过这真的是希望吗？pemvidutide最开始是Altimmune通过收购Spitfire Pharma获得的（当时叫ALT-801），最开始这款药物似乎就没有开发减肥药的打算，第一项适应症确立的是NASH（非酒精性脂肪肝）后来在跟着司美格鲁肽等GLP-1类药物的减肥药适应症开发，这方面可以说是赛道的后来者，也可以说是跟风。而疗效方面，也有人持有反对意见。今年2月做空机构Kerrisdale在做空Altimmune的股票时认为，在减肥和跨界赛道中，pemvidutide在疗效方面竞争不过礼来的替尔泊肽和诺和诺德的司美格鲁肽。近期，财报中发布的pemvidutide的减重中74.5%的体重减轻来自脂肪组织倒是为pemvidutide给出了想对还不错的预期。但这里或许还是有个问题，是否能指望一家行动力不足，战略决策预判错误的公司在激烈赛道中胜出？参考来源：https://ir.altimmune.com/news-releases/news-release-details/altimmune-announces-positive-lean-mass-preservation-data

A statistically superior mucosal immune response providing a first line of defense against infection Six-month data demonstrates: A statistically superior mucosal immune response providing a first line of defense against infection; A durable serum immune response at six months compared to over 50% decline with Fluzone®; Continued clean safety profile. GAITHERSBURG, Md., Sept. 04, 2018 (GLOBE NEWSWIRE) -- Altimmune, Inc. (Nasdaq: ALT), a clinical-stage immunotherapeutics company, today announced additional positive data from a Phase 2a study of its NasoVAX intranasal influenza vaccine candidate. The Company previously announced positive results from the study in 60 healthy individuals, in which NasoVAX was well-tolerated at all doses, resulted in 100% seroprotection at the two highest dose levels and elicited influenza neutralizing antibodies similar to Fluzone® (a licensed injected influenza vaccine). NasoVAX also demonstrated the ability to elicit a significant T cell immune response as compared to Fluzone. Subjects were followed for an additional six months after vaccination to assess durability of the antibody response. These new NasoVAX data demonstrate (a) a durable, dose dependent protective immune response, (b) significant mucosal immune response one month after vaccination compared to both placebo and Fluzone, and (c) a clean safety profile. An influenza specific mucosal antibody (IgA) response was demonstrated at all dose levels of NasoVAX, with the highest responses in the highest dose groups, while Fluzone and placebo groups demonstrated no response. Mucosal antibodies can be found in tears, saliva and nasal mucous and are a first line of immune defense thereby preventing influenza infection at the site of entry in the respiratory tract. Serum antibody levels for NasoVAX were very stable through at least six months (the last time point tested), unlike Fluzone where antibody levels declined by over 50% during that time period. Flu season typically runs from October through March in the northern hemisphere according to the Centers for Disease Control (CDC), but most individuals are vaccinated very early in the Fall. The fact that NasoVAX induced antibodies that were very stable over the six month follow up period may indicate a higher likelihood of protection throughout the entire flu season. “The data are consistent with our expectations and we are quite pleased to see such impressive results. With strong seroprotection, clear dose-dependent results, unique T cell and mucosal immune responses and a clean safety profile, we are extremely encouraged by the data and look forward to initiating additional Phase 2 studies in 2019,” said William J. Enright, president and chief executive officer of Altimmune. “We have not seen the breadth of immune responses like these from other influenza vaccines, and we are excited to continue to advance development of this important product candidate.” Mr. Enright continued, “NasoVAX is egg-free and needle-free. We believe that an intranasally administered flu vaccine will be preferred by patients over traditional injected vaccines. Additionally, because NasoVax is grown in cell culture instead of in chicken eggs, we believe NasoVax will eliminate the risk of egg allergies with the potential to enable us to more quickly mass produce vaccine at scale and have potentially better matches to annual circulating strains. We believe NasoVAX to be a very differentiated and superior vaccine to those available on the market right now.” Earlier this year, the Company announced initial data from the Phase 2a trial, which demonstrated 100% seroprotection for the middle and high dose groups of NasoVAX as compared to 95% seroprotection with Fluzone. Mean serum antibody titers against influenza, as measured by the hemagglutinin inhibition and microneutralization assays increased up to 4.3-fold and 5.2-fold respectively, indicating that high levels of immunity were induced in this study population even with prior immunity to the influenza strain (A/California/04/2009). The serum neutralizing antibody responses were also robust and dose dependent. Seroconversion rates and breadth of antibody response were comparable to Fluzone for the highest NasoVAX dose tested. Additionally, compared to Fluzone, the highest dose of NasoVAX induced over nearly 6-fold higher levels of influenza cellular immunity, an important element in stopping the flu virus from spreading. Cellular immunity also has the potential to fight against mismatched strains. All doses of NasoVAX were well tolerated and there were no cases of fever, serious adverse events (SAEs) or discontinuations. Rates of local and systemic side effects did not increase with dose and were not statistically different than placebo. The company will present the full data-set from this NasoVAX Phase 2 trial at IDWeek, an international infectious disease conference, in San Francisco, California in October of this year. About the Phase 2a NasoVAX Trial The randomized Phase 2a study compared a monovalent NasoVAX vaccine against an H1 strain of influenza (A/California/04/2009) to intranasal placebo in 60 healthy adults across three dose ranges (10 9 virus particles (vp), 10 10 vp and 10 11 vp). In a parallel open label study, a similar population of 20 subjects were given Fluzone®, a licensed injectable influenza vaccine. Blood samples from both studies were tested and the lab was blinded to treatment assignment. About Altimmune Altimmune is a clinical-stage immunotherapeutics company focused on the development of products to stimulate robust and durable immune responses for the prevention and treatment of infectious disease. NasoVAX our influenza vaccine candidate has unique characteristics, stimulating multiple arms of the immune system that offer the potential to stop infection and the spread of flu, while being easier to administer through an intranasal spray. NasoShield is a next-generation anthrax vaccine candidate that is intended to improve protection and safety while having favorable dosage and storage requirements compared to other anthrax vaccines. Forward-Looking Statement Any statements made in this press release relating to future financial or business performance, conditions, plans, prospects, trends, or strategies and other financial and business matters, including without limitation, the prospects for commercializing or selling any product or drug candidates, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Altimmune, Inc. (the “Company”) may identify forward-looking statements. The Company cautions that these forward-looking statements are subject to numerous assumptions, risks, and uncertainties, which change over time. Important factors that may cause actual results to differ materially from the results discussed in the forward looking statements or historical experience include risks and uncertainties, including risks relating to: the terms of the Company’s Series B preferred stock offering and related warrants; our lack of financial resources and access to capital; realizing the benefits of the merger between Altimmune, Inc. and PharmAthene, Inc.; our ability to utilize the benefits of our tax assets and the results of a tax examination initiated by the IRS; clinical trials and the commercialization of proposed product candidates (such as marketing, regulatory, product liability, supply, competition, dependence on third parties and other risks); the regulatory approval process; dependence on intellectual property; the Company’s BARDA contract and other government programs, reimbursement and regulation. Further information on the factors and risks that could affect the Company’s business, financial conditions and results of operations are contained in the Company’s filings with the U.S. Securities and Exchange Commission, including under the heading “Risk Factors” in the Company’s annual reports on Form 10-K and quarterly reports on Form 10-Q filed with the SEC, which are available at .