A Novel PET Imaging based Companion Diagnostic

基于 PET 成像的新型伴随诊断

• 批准号: 10362895
• 负责人: SUSANTA K SARKAR
• 金额: $ 9.75万
• 依托单位: CADENZAMED, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362895
• 关键词: Angiogenesis Inhibitors; Biodistribution; Breast Cancer Model; Breast Carcinoma; Cancer Patient; Clinic; Clinical; Clinical Research; Colon Carcinoma; Cysteine; Development; Disease; Drug Targeting; Endothelial Growth Factors Receptor; Engineering; FDA approved; Feasibility Studies; Female; Foundations; Funding; Generations; Goals; Grant; H1299; Healthcare Systems; Human; Label; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Medical; Modeling; Mus; N-terminal; Nude Mice; Organ; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phase; Play; Positioning Attribute; Positron-Emission Tomography; Private Sector; Privatization; Prognosis; Radiolabeled; Research Design; Role; Scheme; Signal Transduction; Site; Small Business Innovation Research Grant; Solid Neoplasm; System; Therapeutic; VEGFA gene; Vascular Endothelial Growth Factors; Woman; advanced disease; angiogenesis; anti-cancer therapeutic; base; cancer therapy; clinical development; commercialization; companion diagnostics; cost; drug development; efficacy study; evidence base; experimental study; improved; in vivo; individual patient; interest; lung Carcinoma; malignant breast neoplasm; mouse model; novel; novel strategies; patient stratification; patient subsets; personalized medicine; precision medicine; preclinical development; predictive marker; response; theranostics; tumor; unnecessary treatment

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.

抽象的 该申请是根据特殊利益通知（NOSI）提交的 CA-20-012。 高属性率（尤其是在药物开发的后期）归因于估计$ 2.0B 将药物带入市场的成本。此外，许多进入市场的药物。包括抗 血管生成，仅受益于一部分患者。识别患者的伴侣诊断（CD） 这些药物可能不可用。这通过 对不可能对特定疗法反应的患者进行不必要的治疗。 我们的总体策略是将VEGF-3（VEGF拮抗剂）发展为一种新型的抗血管生成疗法 癌症治疗的药物，vegf-3将是治疗，[18F] CVEGF-3将是 对应的PET CD将受益于该药物受益的患者分层。我们相信我们的新方法 由于选择阳性的患者[18F]，将具有显着的临床优势来使这些患者受益 CVEGF-3S PET肿瘤信号预计对VEGF-3的响应最快，使其效率很高 治疗。这将有助于降低医疗保健治疗系统的成本。 我们目前资助的SBIR I期可行性研究，以开发CD [18F] CVEGF-3S VEGF-3的晚期临床前和临床发展迅速发展。为了加速我们 进展，我们将需要进行一项补充研究，以确定VEGF-3的临床目标。这会 帮助将我们的项目定位为更强大的II期应用，并从私人战略中产生进一步的兴趣 合作伙伴。对于CD的IND研究的临床研究设计，定义的临床目标是[18F] CVEGF-3。换句话说，确定哪种癌症是诊所中VEGF-3S治疗的理想选择将使我们 对II期更具竞争力。这只能通过评估VEGF-3的体内效率来实现 多个肿瘤模型。因此，我们在这里提议测量小鼠模型中VEGF-3的体内效率 乳腺癌，结肠和肺癌。实现这一目标将为循证基础提供 为VEGF-3选择临床目标。 将我们完成的I阶段结果配对 - 这将确定[18F] CVEGF-3作为新颖的可行性 基于PET成像的CD-选择VEGF-3的临床目标将是定量里程碑 发展到II阶段进行IND促进研究。这些结合的结果将使我们在 我们的II期应用程序，并将加速SBIR产品的开发，以将其推进 商业化。由于我们独特的产品将满足主要的未满足的医疗需求，从而允许更多 为患者提供个性化治疗，我们认为这对我们的私营部门合作伙伴也将有吸引力。