A Novel PET Imaging based Companion Diagnostic

摘要 本申请是为了回应特别利益通知（NOSI）而提交的，该通知被确定为不- CA-20 - 012 高流失率--特别是在药物开发的后期--导致估计的20亿美元 将药物推向市场的成本。此外，许多进入市场的药物。包括反 血管生成学，仅使一部分患者受益。伴随诊断（CD），用于识别 可能对这些药物有反应的人都没有。这增加了医疗保健系统的显著成本， 对不太可能对特定疗法有反应的患者进行不必要的治疗。 我们的总体策略是开发VEGF-3S（一种VEGF拮抗剂）作为一种新的抗血管生成治疗诊断剂。 用于癌症治疗的药物，其中VEGF-3S将是治疗剂，[18 F] cVEGF-3S将是治疗剂。 相应的PET CD，以分层患者将受益于药物。我们相信我们的新方法 将具有显著的临床优势，使这些患者受益，因为选择的患者具有阳性[18F] cVEGF-3S PET肿瘤信号预期对VEGF-3S最有反应，使其成为一种高效的肿瘤抑制剂。 疗法这将有助于降低医疗保健系统的治疗成本。 我们目前资助的SBIR第一阶段可行性研究，以开发CD，[18 F] cVEGF-3S， VEGF-3S的后期临床前和临床开发已经迅速发展。为了加速 为了取得进展，我们将需要进行补充研究，以确定VEGF-3S的临床靶点。这将 帮助我们的项目定位，以获得更强大的第二阶段应用，并进一步激发私人战略投资者的兴趣 伙伴CD IND研究的临床研究设计需要确定临床目标，[18 F] cVEGF-3S。换句话说，在临床上确定哪种癌症是VEGF-3S治疗的理想选择， 第二阶段更有竞争力。这只能通过评估VEGF-3S在体内的功效来实现。 多种肿瘤模型。因此，我们建议在小鼠模型中测量VEGF-3S的体内功效 乳腺癌、结肠癌和肺癌。实现这一目标将为以下方面提供循证基础： 选择VEGF-3S的临床靶点。 配对我们完成的I期结果-这将建立[18 F] cVEGF-3S作为一种新的 PET成像为基础的CD-与VEGF-3S的临床靶点的选择将是定量的里程碑 进入IND使能研究的II期。这些综合结果将使我们在以下方面具有高度竞争力： 我们的第二阶段应用，并将加快SBIR产品的开发，以推动其向 商业化由于我们独特的产品将满足一个主要的未满足的医疗需求， 为病人提供个人化的治疗，我们相信这对我们的私营部门伙伴也会有吸引力。

Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT- CA-20-012. High attrition rates—particularly at the late stage of drug development—contribute to the estimated $2.0B cost of bringing a drug to the market. Furthermore, many of the drugs that reach the market. including anti- angiogenics, benefit only a subset of patients. Companion diagnostics (CDs) that identify patients who are likely to respond these drugs are not available. This adds significant costs to the healthcare system through the unnecessary treatment of patients that are not likely to respond to specific therapies. Our overall strategy is to develop VEGF-3S (a VEGF antagonist) as a novel anti-angiogenic theranostic agent for cancer therapy, where VEGF-3S will be the therapeutic and [18F] cVEGF-3S will be the corresponding PET CD to stratify patients that would benefit from the drug. We believe that our novel approach will have significant clinical advantages to benefit these patients because patients selected with positive [18F] cVEGF-3S PET tumor signals are expected to be most responsive to VEGF-3S, making it a highly efficient therapy. This will help reduce the cost to the healthcare system of treatment. Our currently funded SBIR Phase I feasibility studies to develop the CD, [18F] cVEGF-3S, to be used during the late preclinical and clinical development of VEGF-3S, have evolved rapidly. In order to accelerate our progress, we will need to conduct a supplementary study to determine clinical targets for VEGF-3S. This will help position our project for a stronger Phase II application and generate further interest from private strategic partners. A defined clinical target is necessary for the clinical study design for the IND studies of the CD, [18F] cVEGF-3S. In other words, identifying which cancer is ideal for VEGF-3S treatment in the clinic will make us more competitive for Phase II. That can only be achieved by evaluating the in vivo efficacy of VEGF-3S in multiple tumor models. Therefore, we propose here to measure in vivo efficacy of VEGF-3S in mouse models of breast, colon and lung cancer. Accomplishing this goal will provide the evidence-based foundation for selecting a clinical target for VEGF-3S. Pairing our completed Phase I results—which will establish the feasibility of [18F] cVEGF-3S as a novel PET imaging-based CD—with the selection of a clinical target for VEGF-3S will be the quantitative milestones to progress to Phase II for IND enabling studies. These combined results will make us highly competitive for our Phase II application and will accelerate the development of the SBIR product to advance it toward commercialization. Since our unique product will fulfill a major unmet medical need, allowing for more personalized treatment for patients, we believe that it will be attractive to our private sector partners as well.