DEVELOPMENT OF NOVEL ANTICANCER AGENT TO POTENTIATE SENSITIVITY TO ANTI-ESTROGEN THERAPY

我们的I期合同表明，抗gp88 （Progranulin）重组抗体AG1增强了基于抗雌激素（AE）的治疗抑制乳腺癌异种移植物肿瘤生长的功效。此外，我们已经证明AG1作为单一药物在肺癌异种移植中是有效的。值得注意的是：50%的雌激素阳性（ER+）乳腺癌患者对AE治疗不敏感，50%的肺癌患者即使在早期发现疾病也会死亡。因此，增强AE在ER阳性乳腺癌中的疗效可能为AE耐药患者提供治疗方案，改善早期肺癌的治疗选择可能减少死亡人数。这些生物学数据，连同我们为AG1开发的完整制造工艺和稳定性研究，支持将AG1推向最终的临床前研究。该PI正在以II期合同的形式请求支持，以便能够生产一批AG1，完成剂量研究，并在非人类灵长类动物中进行重复剂量的生命毒理学（先前进行的急性剂量），药代动力学和剂量评估，并向美国FDA提交IND，用于乳腺癌和肺癌适应症的首次人类安全性和有效性研究。

Our Phase I Contract demonstrated that AG1, an anti-GP88 (Progranulin) recombinant antibody potentiated the efficacy of anti-estrogen (AE) based therapy to inhibit tumor growth in breast cancer xenografts. Additionally we have demonstrated that AG1 is efficacious as a single agent in lung cancer xenografts. The significant: >50% of estrogen positive (ER+) breast cancer patients are, or become insensitive to AE therapy and ~50% lung cancer patients die even when disease is detected at an early stage. Thus potentiating efficacy of AE in ER+ breast cancer potentially offers a treatment solution for AE resistant patients and improving treatment options for early stage lung cancer may reduce the number of deaths. These biological data, together with the complete manufacturing process and stability studies that we have developed for AG1, supports moving AG1 into final pre-clinical studies. The PI is requesting support in form of a Phase II contract to enable the production of a batch of AG1, complete dosing studies, and perform repeat-dose in life toxicology (Acute dose previously performed), pharmacokinetics and dose assessment in non-human primates and file an IND with the US FDA for first in human safety and efficacy studies for indications of breast and lung cancer.