Phase 1 cross over biodistribution study of [203Pb]VMT01 for single photon emission computed tomography (SPECT) and [68Ga]VMT02 for positron emission tomography (PET) imaging of stage 4 melanoma

意义：黑色素瘤的发病率上升速度比任何其他癌症都快，转移性黑色素瘤通常 致命的对靶向治疗和免疫治疗的反应可能是显著的，但反应率低， 耐药性和不良副作用限制了这些患者的长期生活质量。总体答复率 所有的治疗仍然令人沮丧地接近50%，5年生存率<25%。临床前研究已经确定 靶向黑皮质素受体1（MC 1 R）的放射性标记肽作为潜在的治疗替代品。而 这种使用粒子发射器的方法在临床前很大程度上是无效的，以前的出版物和我们的 I期数据证明了Viewpoint的MC 1 R靶向VMT 01颗粒治疗在小鼠中的疗效 患有黑色素瘤。因此，VMT 01旨在满足重大未满足的医疗需求，以改善 这些患者的结局（最初指征为进展性4期转移性黑色素瘤）， 与FDA批准的黑素瘤药物组合的扩展适应症（例如，免疫疗法）。在这 修订后的II期SBIR项目，Viewpoint将完成1期首次人体临床试验，以确定 其伴随诊断的安全性。预计该公司将获得初步的 了解[68 Ga] VMT 02成像（PET）识别MC 1 R阳性肿瘤的有效性以及 [203 Pb] VMT 01成像（SPECT），用于进行个性化[212 Pb] VMT 01放射治疗的患者剂量测定。 类似I期里程碑包括：在小鼠中的疗效（治疗和成像）;铅的药理学/毒性 VMT 01;使用GMP套件自动化放射性药物生产; IP独家许可;临床联盟 与马约诊所和203 Pb供应与Lantheus医学成像; CRO用于统计/临床数据（完整软件， Inc.）;以及放射性药物合作伙伴（Hotshots Nuclear Medicine），负责[203 Pb] VMT 01的生产/分销。 股权投资：Viewpoint已获得65万美元的股权投资， 用于未来临床治疗试验的212 Pb发生器。该公司将完成以下目标，以实现其目标。 AIM 1.确保FDA“安全进行”指定，以进行[203 Pb] VMT 01的I期成像试验 [68Ga]VMT02，IND。 AIM 2.完成[203 Pb] VMT 01和[68 Ga] VMT 02成像的I期安全性和生物分布研究， 并证明了它们用于鉴定MC 1 R阳性肿瘤和进行 患者特异性剂量测定。 结果：我们希望证明[203 Pb] VMT 01和[68 Ga] VMT 02的临床安全性。我们进一步期待 初步了解[68 Ga] VMT 02 PET/CT识别MC 1 R+肿瘤的有效性， [203 Pb] VMT 01 SPECT/CT用于[212 Pb] VMT 01放射治疗的患者特异性剂量测定。因此，我们将 准备启动[212 Pb] VMT 01放射性粒子治疗转移性黑色素瘤的剂量学试验， 由第二B阶段SBIR研究和第三阶段股权投资资助。

SIGNIFICANCE: Melanoma incidence is rising faster than any other cancer and metastatic melanoma is typically fatal. Responses to targeted and immunotherapies can be remarkable, but low response rates, acquired resistance, and adverse side effects limit long-term quality of life for these patients. The overall response rate to all therapies remains dismally near 50% and the 5-year survival is <25%. Preclinical studies have identified radiolabeled peptides that target the melanocortin receptor 1 (MC1R) as a potential therapeutic alternative. While this approach using -particle emitters has been largely ineffective preclinically, previous publications and our Phase I data have demonstrated efficacy of Viewpoint’s MC1R-targeted VMT01 -particle therapy in mice bearing melanoma tumors. Thus, VMT01 is designed to meet the significant unmet medical need to improve outcomes for these patients (initial indication of progressive stage 4 metastatic melanoma), with potential for expanded indications in combination with FDA-approved melanoma drugs (e.g., immunotherapies). In this revised Phase II SBIR project, Viewpoint will complete a Phase 1 first-in-human clinical trial to determine the safety of its companion diagnostics. It is further expected that the company will have gained a preliminary understanding of the effectiveness of [68Ga]VMT02 imaging (PET) to identify MC1R positive tumors and the utility of [203Pb]VMT01 imaging (SPECT) for performing patient dosimetry for personalized [212Pb]VMT01 -therapy. PREDICATE PHASE I MILESTONES include: efficacy (therapy and imaging) in mice; pharm/tox of lead VMT01; automated radiopharmaceutical production with GMP kits; exclusive licenses to IP; clinical consortium with Mayo Clinic and 203Pb supply with Lantheus Medical Imaging; CRO for statistics/clinical data (Compleware, Inc.); and a radiopharmacy partner (Hotshots Nuclear Medicine) for manufacturing/distribution of [203Pb]VMT01. EQUITY INVESTMENTS: Viewpoint has secured $650,000 in equity investment to establish manufacturing of 212Pb generators for future clinical therapy trials. The company will complete the following Aims toward its goals. AIM 1. Secure FDA “safe to proceed” designation to conduct the Phase 1 imaging trial of [203Pb]VMT01 and [68Ga]VMT02 under IND. AIM 2. Complete a Phase 1 safety and biodistribution study of [203Pb]VMT01 and [68Ga]VMT02 imaging in human subjects and demonstrate their utility for identifying MC1R positive tumors and performing patient-specific dosimetry. OUTCOMES: We expect to demonstrate the clinical safety of [203Pb]VMT01 and [68Ga]VMT02. We further expect to develop preliminary understanding of the efficacy of [68Ga]VMT02 PET/CT to identify MC1R+ tumors and the utility of [203Pb]VMT01 SPECT/CT for patient-specific dosimetry for [212Pb]VMT01 -therapy. Thus, we will be prepared to initiate dosimetry-based trials of [212Pb]VMT01 -particle therapy for metastatic melanoma to be funded under Phase IIB SBIR studies and Phase III equity investments.