Pharmacology & human Phase 1 safety & dose escalation studies using anti-GP88 in aggressive breast cancer

2017 年，美国预计将新增乳腺癌 (BC) 病例约 20 万例，相关死亡人数约 4 万例。 〜30,000 其中包括患有侵袭性三阴性 BC (TNBC) 或抗雌激素/芳香酶抑制剂耐药的患者 (AE/AI) BC，没有靶向治疗，依赖放疗和积极化疗。一个新的 需要开发使这些患者受益并延长预期寿命的方法。我们有 鉴定出 GP88，一种由癌细胞产生并刺激其生长和存活的糖蛋白 形成更具侵袭性的肿瘤。 GP88 存在于 BC 中，但不存在于正常乳腺组织中。有令人信服的 生物学和临床证据表明 GP88 可用于开发新型靶向治疗 伴随诊断可能会影响 TNBC 和 AE/AI BC 患者的治疗并提高其生存率。我们 开发了一种组织测试来识别表达 GP88 的肿瘤患者和抗 GP88 (AG1) 来阻断 GP88 对肿瘤组织的作用是 a) 抑制肿瘤生长和 b) 提高现有 BC 药物的功效。 我们拥有动物的安全性和有效性数据，并将在第一阶段开发小鼠的给药策略 作为第二阶段的一部分，进入人体研究。此外，还开发了一种血液测试来监测 患者在治疗期间。使用 AG1 作为疗法并结合两项伴随诊断测试，我们将进行一项 IA/B 期人体临床试验，以确定第二阶段根据 GMP 生产的 AG1 的安全性，并将 收集所有患者的肿瘤组织和血液以评估 GP88 表达（组织）和浓度（血液）。

In 2017, ~200,000 new cases of breast cancer (BC) and ~40,000 related deaths are expected in the US. ~30,000 of these are patients with aggressive triple negative BC (TNBC) or anti-estrogen/aromatase inhibitor resistant (AE/AI) BC that do not have targeted therapy and rely on radiotherapy and aggressive chemotherapy. A new approach that benefits these patients and provides increased life expectancy needs to be developed. We have identified GP88, a glycoprotein that is produced by cancer cells and stimulates their growth and survival leading to formation of more aggressive tumors. GP88 is found in BC but not in normal breast tissue. There is compelling biological and clinical evidence to suggest that GP88 can be used to develop novel targeted therapy with companion diagnostics that could impact treatment and improve survival of TNBC and AE/AI BC patients. We have developed a tissue test to identify patients with tumors expressing GP88 and an anti-GP88 (AG1) to block the action of GP88 on tumor tissues to a) inhibit tumor growth and b) increase the efficacy of current BC drugs. We have safety and efficacy data in animals and will in our Phase 1 develop a dosing strategy in mice before moving into human studies as part of the Phase 2. Additionally, a blood test has been developed to monitor patients while on treatment. Using AG1 as the therapy with two companion diagnostic tests, we will carry out a phase IA/B clinical trial in humans to determine safety of AG1 manufactured under GMP in the Phase 2 and will collect tumor tissue and blood on all patients to evaluate for GP88 expression (tissue) and concentration (blood).