Altimmune宣布从其2a期NasoVAX鼻内流感疫苗研究中获得阳性数据

StephenW

Altimmune Announces Positive Data From Its Phase 2a Study of NasoVAX Intranasal Influenza Vaccine and Provides an Update on Its Phase 1b Study of HepTcell Targeted Immunotherapy in Chronic Hepatitis B Infection

NasoVAX intranasal influenza vaccine demonstrated strong cellular immune response and 100% seroprotection

HepTcell vaccine was well tolerated but T-cell immunogenicity results were inconclusive

GAITHERSBURG, Md., March 27, 2018 (GLOBE NEWSWIRE) -- Altimmune, Inc. (Nasdaq:ALT), a clinical-stage immunotherapeutics company, today announced positive data from its Phase 2a study of NasoVAX intranasal influenza vaccine and provided an update on its Phase 1b study of HepTcell targeted immunotherapy in chronic hepatitis B infection. Results from the Phase 2a study of NasoVAX™ intranasal flu vaccine in 60 healthy individuals showed 100% seroprotection in the mid- and high-dose groups. Results from the Phase 1b study of HepTCell in hepatitis B infection showed that HepTcell was well tolerated at all doses tested, while the unblinded T-cell immunogenicity results were inconclusive.

“We strongly believe that NasoVAX could become an important alternative vaccine for the prevention of both seasonal flu epidemics and broader flu pandemics,” said William J. Enright, president and chief executive officer of Altimmune.  “The Phase 2a data are highly encouraging, especially since antibody responses like this -- with 100% seroprotection -- are unique and have not been achieved with any other needle-free vaccines, including FluMist®. In addition, the excellent tolerability attained, even at the highest dose, has us excited to complete development of the quadrivalent formulation with the intention to initiate a Phase 2 study in early 2019.”

Enright continued, “As for our HepTcell study, we are disappointed by the inconclusive results, but are continuing to evaluate the data.  Subjects will be followed for the full 6 months, as per the study protocol. We are evaluating our next steps and will provide an update as we better understand the results.”

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 (109vp, 1010vp and 1011vp). 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.

Data demonstrated 100% seroprotection for the middle and high dose groups of NasoVAX as compared to 95% seroprotection with Fluzone.  Mean antibody titers against influenza, as measured by the hemagglutinin inhibition and microneutralization assays increased up to 4.3-fold, 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 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 defending against influenza disease.  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.  Subjects will continue to be followed through six months after vaccination to assess durability of antibody response.  The company plans to submit the full data, which will also include mucosal antibody and serum antibody levels at other time points, for presentation at an appropriate scientific conference later this year.

About the Phase 1b HepTcell Trial
The Phase 1b study was a randomized, dose-escalation trial in 60 subjects with chronic HBV infection. Subjects enrolled in the trial were well controlled on currently licensed antiviral therapy and were randomized into one of three groups: high and low dose HepTcell peptides, with and without adjuvant (IC31), adjuvant alone, and placebo. All subjects received 3 injections 4 weeks apart and were followed for 4 weeks after the 3rd injection. Subjects will continue to be followed for 6 months after the 3rd injection, as per the study protocol.

The data showed that, overall, HepTcell was well tolerated. There was one unrelated SAE (infectious colitis).  Subjects were monitored carefully for evidence of liver flare, which was not observed in any of the subjects. Additionally, there were no autoimmune events noted. Results showed mild to moderate injection site reactions in < 20% of subjects in every group except the high dose with IC31 (36%). There were no severe injection site reactions.

Previous review of the blinded data by cohort indicated evidence of increased cellular immune responses in cohort 2 compared with cohort 1, both of which included control patients; however, in the unblinded analysis, the treated subjects were not appreciably different than placebo controls.

The company is continuing to evaluate the data and will provide further updates once it has completed its thorough review.

About NasoVAX
NasoVAX is a novel type of influenza vaccine that uses an adenoviral vector delivery vehicle and intranasal administration to deliver the vaccine to the respiratory tract where influenza infection occurs. Besides its easier intranasal delivery method, NasoVAX has many advantages over current vaccines. First, NasoVAX is a recombinant vaccine that is produced using cell culture, compared to traditional vaccines that use chicken eggs.  As described in the National Institute of Allergy and Infectious Disease (NIAID) Strategic Plan for a Universal Influenza Vaccine (www.NIAID.nih.gov), chicken eggs for vaccine production may allow for additional mutations during manufacture, which could compromise vaccine effectiveness. Additionally, NasoVAX is adjuvanted by its own adenoviral vector; no additional adjuvants are used. Adjuvants have been shown to enhance the immune response against an immunogen and provide dose-sparing benefits. Finally, NasoVAX stimulates cellular immunity, a T cell response, and a T cell mediated influenza vaccine may offer another pathway to achieve broad protection, making it an important part of a broad flu vaccine strategy.

About HepTcell
HepTcell is an immunotherapy product candidate directed against multiple hepatitis B virus (HBV) genotypes. HepTcell is a completely synthetic peptide composed of nine Densigen peptides that encode a high density of CD4+ and CD8+ T cell epitopes selected to broaden the HLA class reactivity of the product.

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 disease, including NasoVAX, a Phase 2 seasonal influenza vaccine candidate, and HepTcell, a Phase 1 immunotherapeutic candidate for the potential cure of chronic hepatitis B. The company also has two United States government funded, next-generation anthrax vaccine candidates that are intended to improve protection and safety while having favorable dosage and storage requirements compared to other anthrax vaccines. Additional information may be accessed at www.altimmune.com.

StephenW

Altimmune宣布从其2a期NasoVAX鼻内流感疫苗研究中获得阳性数据，并提供有关慢性乙型肝炎感染中HepT细胞靶向免疫治疗1b期研究的最新信息

NasoVAX鼻内流感疫苗表现出强大的细胞免疫应答和100％的血清保护作用

HepTcell疫苗耐受性良好，但T细胞免疫原性结果不确定

美国马里兰州盖瑟斯堡，2018年3月27日电 - 临床阶段免疫治疗公司Altimmune，Inc.（纳斯达克代码：ALT）今天公布了2a期NasoVAX鼻内流感疫苗研究的正面数据，并提供了更新在其针对慢性乙型肝炎感染的HepT细胞靶向免疫疗法的1b期研究中。来自60位健康个体的NasoVAX TM鼻内流感疫苗2a期研究的结果显示中剂量组和高剂量组中100％的血清保护作用。来自乙型肝炎感染HepTCell 1b期研究的结果表明，在所有测试剂量下HepT细胞都具有良好的耐受性，而非盲细胞T细胞免疫原性结果是不确定的。

“我们坚信，NasoVAX可能成为预防季节性流感疫情和更广泛的流感大流行的重要替代疫苗，”Altimmune总裁兼首席执行官William J. Enright表示。 “阶段2a的数据非常令人鼓舞，特别是因为像这样的抗体反应 - 具有100％的血清保护作用 - 是独一无二的，并且使用包括FluMist®在内的任何其他无针疫苗都无法实现。此外，即使在最高剂量下，达到极佳的耐受性也让我们兴奋地完成四价制剂的开发，并打算在2019年初启动第2阶段研究。“

恩莱特继续说：“至于我们的HepTcell研究，我们对未确定的结果感到失望，但仍在继续评估数据。根据研究方案，将对受试者进行完整的6个月随访。我们正在评估我们的下一步，并会在我们更好地理解结果时提供更新。“

关于2a期NasoVAX试验
随机2a期研究比较了在三个剂量范围内（109vp，1010vp和1011vp），在60名健康成人中，将单价NasoVAX疫苗与H1流感病毒株（A / California / 04/2009）进行鼻内安慰剂比较。在一项平行开放标签研究中，20名受试者的相似人群获得了持续注射流感疫苗Fluzone®。来自两项研究的血液样本都进行了测试，并且实验室对治疗分配不知情。

与Fluzone的95％血清保护相比，数据表明对于中等和高剂量的NasoVAX组100％血清保护作用。如通过血凝素抑制和微量中和测定所测量的，针对流感的平均抗体滴度增加至4.3倍，表明在该研究群体中诱导了高水平的免疫，即使之前对流感病毒株具有免疫性（A / California / 04 / 2009）。血清抗体反应也是强有力且剂量依赖性的。血清转化率和抗体反应的广度对于测试的最高NasoVAX剂量与Fluzone相当。此外，与Fluzone相比，最高剂量的NasoVAX诱导的流感细胞免疫水平高出近6倍，这是防御流感疾病的重要因素。所有剂量的NasoVAX耐受性良好，没有发热，严重不良事件（SAE）或中断的病例。局部和全身副作用的发生率没有随着剂量增加而增加，并且与安慰剂相比没有统计学差异。在接种疫苗后六个月内将继续跟踪受试者以评估抗体应答的耐久性。该公司计划在今年晚些时候的适当科学会议上提交完整的数据，其中还包括其他时间点的粘膜抗体和血清抗体水平。

关于1b期HepT细胞试验
1b期研究是对60名慢性HBV感染患者的随机，剂量递增试验。入选试验的受试者在目前获得许可的抗病毒治疗方面得到很好的控制，并被随机分为三组：高和低剂量HepT细胞肽，有和没有佐剂（IC31），仅有佐剂和安慰剂。所有受试者分别间隔4周接受3次注射，并在第3次注射后跟踪4周。按照研究方案，受试者在第三次注射后将继续跟踪6个月。

数据显示，总体而言，HepTcell耐受性良好。有一个无关的SAE（感染性结肠炎）。仔细监测受试者的肝脏闪光的证据，这在任何受试者中都未观察到。另外，没有注意到自身免疫事件。结果显示，除了高剂量IC31（36％）之外，每组中有少于20％的受试者的轻度至中度注射部位反应。没有严重的注射部位反应。
先前对队列盲数据的回顾表明队列2中的细胞免疫反应与队列1相比增加，两者都包括对照患者;然而，在非盲法分析中，治疗对象与安慰剂对照没有明显不同。

该公司将继续评估数据，并在完成彻底审查后提供进一步更新。

关于NasoVAX
NasoVAX是一种新型流感疫苗，它使用腺病毒载体递送载体和鼻内给药将疫苗递送至发生流感感染的呼吸道。除了更容易的鼻内给药方法外，NasoVAX与现有疫苗相比具有许多优点。首先，与使用鸡蛋的传统疫苗相比，NasoVAX是使用细胞培养物生产的重组疫苗。正如国家过敏和传染病研究所（NIAID）普及流感疫苗战略计划（www.NIAID.nih.gov）所述，用于疫苗生产的鸡蛋可能允许在生产过程中发生额外的突变，这可能会影响疫苗的有效性。此外，NasoVAX由其自身的腺病毒载体佐剂化;不使用额外的辅助剂。已显示佐剂增强针对免疫原的免疫应答并提供剂量节省的益处。最后，NasoVAX刺激细胞免疫，T细胞应答和T细胞介导的流感疫苗可能提供另一途径来实现广泛的保护，使其成为广泛流感疫苗策略的重要组成部分。

关于HepTcell
HepTcell是针对多种乙型肝炎病毒（HBV）基因型的免疫治疗产品候选者。 HepTcell是一种完全合成的肽，由9个Densigen肽组成，编码高密度的CD4 +和CD8 + T细胞表位，选择该表位以扩大产品的HLA类别反应性。

关于Altimmune
Altimmune是一家临床阶段免疫治疗公司，致力于开发产品以刺激预防和治疗疾病的强大而持久的免疫反应，包括第二阶段季节性流感疫苗候选人NasoVAX和第一阶段免疫治疗候选人HepTcell慢性乙型肝炎的潜在治愈方案。该公司还拥有两个美国政府资助的下一代炭疽疫苗候选药物，旨在提高保护和安全性，同时与其他炭疽疫苗相比具有良好的剂量和储存要求。更多信息可访问www.altimmune.com。