Papillomavirus-like Particles (VLP) as Broad Spectrum Human Papillomavirus (HPV) Vaccines

项目摘要 该SBIR快速通道项目的目标是进一步推动PathoVax的双价RGVax™的商业化 作为广谱人乳头瘤病毒（HPV）疫苗，靶向所有临床相关HPV。电流 HPV疫苗提供类型限制性保护，仅针对性传播的HPV， 意想不到的性病耻辱，直接影响吸收率。通过针对额外的HPV，特别是非性HPV， 引起肛门生殖器疱疹、皮肤疣和危及生命的喉 RGVax™提供了作为一般公共卫生疫苗销售的潜力。这提供了以下 有机会避开当前的社会耻辱，并有可能增加市场的吸收。这一独特优势 将吸引战略合作伙伴，PathoVax将与之合作，将RGVax™带入临床。PathoVax拥有 授权基于HPV病毒样颗粒（VLP）平台的基础原型技术， 360个拷贝的高度保守、稳定的HPV表位（RG 1）。动物疫苗接种研究利用这一点 原型已经证实了对27 HPV的广谱保护，这是对当前HPV的巨大改进。 HPV疫苗最多只能保护9种类型。鉴于广泛的保护，这一原型被授予NCI 防止资助，支持制造和IND使能研究。为了增加市场的机会 由于这一创新的成功，PathoVax开发了一种改进的二价RGVax™配方，作为最终产品。 商业产品，以满足FDA规定的抗体滴度标准，并提供全面的HPV- 疾病保护。在SBIR-Fast Track中，第一阶段的具体目标侧重于对我们最终确定的 制剂，以获得针对Gardasil-9®（HPV的现行护理标准）的竞争性分析数据 预防这将在用于验证当前Gardasil疫苗的相同动物模型中进行 默克公司拥有的特许经营权（目标1）。一旦我们证明了RGVax的优越性，我们将过渡到 第二阶段的具体目标是，PathoVax将在动物模型中证明RGVax的疗效数据， 模拟免疫抑制，从而开发关键的临床前数据，以支持PathoVax的临床策略 通过证明RGVax™能够预防器官移植受者（OTR）的皮肤HPV疾病， 上市批准的首个适应症（目标2）。此外，PathoVax将向FDA提供GMP 通过与疫苗合同合作生产二价RGVax™制剂的生产策略 制造商（CMO）开发生产和纯化工艺（目标3A），并证明这一点 该工艺生产的RGVax疫苗颗粒上级或等同于目前实验室生产的颗粒 颗粒（3B）。该数据包的及时开发对于我们即将进行的IND前FDA 讨论，向投资者团体筹集资金，并启动我们的IND启动计划，用于双价1b/2a期 临床试验

Project Summary The goal of this SBIR Fast-Track project is to further the commercialization of PathoVax’s bi-valent RGVax™ as a broad spectrum Human Papillomavirus (HPV) vaccine that targets all clinically relevant HPVs. Current HPV vaccines provide type-restricted protection that focuses only on sexually transmitted HPVs resulting in an unexpected STD stigma that directly affects uptake rates. By targeting additional HPVs especially non-sexual types that causes diseases such as recalcitrant anogenital, cutaneous warts, and life-threatening laryngeal papilloma’s, RGVax™ offers the potential to be marketed as a general public health vaccine. This provides the opportunity to sidestep current social stigma and potentially increase market uptake. This unique advantage will attract strategic partners that PathoVax will work with to bring RGVax™ into the clinic. PathoVax has licensed the underlying prototype technology based on a HPV virus-like particle (VLP) platform that displays 360 copies of the highly conserved, stable HPV epitope (RG1). Animal vaccination studies utilizing this prototype have confirmed broad-spectrum protection against 27 HPVs, a dramatic improvement over current HPV vaccine that only protects 9 types at best. Given the broad protection, this prototype was awarded an NCI PREVENT grant that supports manufacturing and IND enabling studies. To enhance the odds of market success for this innovation, PathoVax has developed an improved bi-valent RGVax™ formulation as the final commercial product to satisfy FDA-mandated antibody titer standards and provide comprehensive HPV- disease protection. In this SBIR-Fast Track, Phase 1 specific aims focuses on benchmarking our finalized formulation to obtain competitive profiling data against Gardasil-9®, the current standard of care for HPV prevention. This will be done in the same animal models used to validate the current Gardasil vaccine franchise owned by Merck (Aim 1). Once we have demonstrated RGVax’s superiority, we will transition into phase 2 specifics aims whereby PathoVax will demonstrate RGVax’s efficacy data in animal models that simulates immune-suppression, so as to develop pivotal preclinical data to support PathoVax’s clinical strategy by demonstrating RGVax™’s ability to prevent skin HPV disease in organ transplant recipients (OTRs) as a first indication for marketing approval (Aim 2). Additionally, PathoVax will provide the FDA with a GMP manufacturing strategy to produce the bi-valent RGVax™ formulation by working with a vaccine contract manufacturer (CMO) to develop a production and purification process (Aim 3A), and also demonstrate this process produces RGVax vaccine particles that are superior or equivalent to current laboratory produced particles (3B). The timely development of this data package is critical for both our upcoming pre-IND FDA discussion, fund raising to investor groups and initiating our IND-enabling program for a bi-valent phase 1b/2a clinical trial.