GMP vector for the HIV Functional Cure project was completed, and the automated GMP cell-processing protocol was locked. Successive pilot runs yielded confirming data regarding the ability to generate sufficient numbers of protected target cells for the cell therapy. AGT used a registered (non-IND) clinical trial to gather HIV-infected persons’ blood to test the cell manufacturing and final vector in order to produce the required data for the IND document to be submitted to the FDA, and to validate the treatment protocol before moving into clinical trials in 2018.
American Gene Technologies™ (AGT) had a successful pre-IND meeting with the FDA for AGT103, an HIV functional cure. This meeting launched the IND development process and the planned clinical trial in 2017. AGT filed patents for unique drug candidates that demonstrated high efficacy against the HIV virus in preliminary tests. AGT launched it Series D funding round to support the HIV clinical trials.
American Gene Technologies™ (AGT) continued to target its drug development efforts toward the projects with the clearest path to clinical studies. This work resulted in advanced genetic vector developments for HIV/AIDS, liver cancer and phenylketonuria (PKU). AGT also received an NIH grant for development of familial dysautonomia (FD) blindness therapeutic, initiated mouse studies on HCC with Dr. Dean Felsher at Stanford, and initiated its Phenylketonuria (PKU) project with University Pittsburgh Children’s Hospital. We retained Chief Scientific Officer David Pauza, a distinguished scientist with decades of experience in genetics, immunology and virology. We welcomed former Wisconsin Governor and U.S. Secretary of Health and Human Services Tommy Thompson as a senior advisor. We also successfully closed Series C financing.
American Gene Technologies™ (AGT) continued to deepen its expertise in HIV while also initiating two new drug development programs and established collaborations with leading scientists. These programs included: 1) Gene therapy treatment of Parkinson’s disease, in collaboration with Dr. Ted Dawson, Director of the Institute for Cell Engineering at the Johns Hopkins School of Medicine; and, 2) Gene therapy for treatment of Familial Dysautonomia (FD), with Dr. Frances Lefcort, Chair of the Department of Cell Biology & Neuroscience at Montana State University. AGT received funding from the Dysautonomia Foundation for developing an FD therapeutic, as well as from University of Wisconsin for development of the T1DM therapeutic. The company completed a Series B round of financing.
American Gene Technologies™ (AGT) completed in vitro studies validating the efficacy of its gene therapeutic for treating HIV/AIDS. The vector targets several HIV and host genes required for viral replication and infection. The therapeutic vector effectively inhibits HIV replication in CD4+ SupT1 cells by over 95% at an MOI of 3, while higher MOI resulted in over 99% inhibition. In addition, transduction of cells with the vector rendered them resistant to HIV infection, and had no effect on cell viability. Based on its therapeutic product line development, AGT completed a Series A Preferred venture capital funding in September 2013, allowing its expansion to new laboratory space as well as expansion of its Research and Development team.
American Gene Technologies™ (AGT) completed mouse studies of HCC (liver cancer). Significant tumor regression was observed in treatment groups and no apparent toxicity was found, while tumors in several control (un-treated) groups continued to grow. In addition to the HCC project, AGT was funded by NIH with two SBIR phase I projects to develop gene therapies for HIV/AIDS and hepatitis C virus (HCV) infection. Potent multiple-component lentiviral vectors with sophisticated safety features were successfully developed for treating HCV infection that drastically inhibited the replication of the HCV reporter strain by 99.7% in in vitro testing. AGT has tested more than 50 intermediate and related vectors/plasmids and a final construct with multiple potent anti-HIV RNA inhibitors has been refined for further testing.
After intensive engineering and tests of dozens of intermediate vectors, AGT successfully developed a lentiviral vector carrying multiple anti-tumor components that can potently inhibit the growth of hepatocellular carcinoma (HCC a.k.a. “liver cancer”). In vitro tests were performed on three HCC cell lines, representing different ethnic backgrounds and different cancer stages. The proliferation of all three HCC cell lines were inhibited by more than 90%. In the process, RNA interference technology was successfully introduced into AGT therapeutic vectors as an additional tool to correct human diseases on the cellular level.
AGT tested a revised AG1102 Pancreatic Cancer Therapeutic in vitro with promising results. In addition, design work was completed on the Company’s AG1103 Liver Cancer Therapeutic. Co-development/Licensing discussions for various indications were initiated with Chinese pharmaceutical companies.
In vivo testing of AGT AG1101 Prostate Cancer Therapeutic in mice yielded positive results. AGT scientists completed construction of a novel virus design targeting tumor suppressor genes in preparation for animal testing. Initial testing of AG1102 Pancreatic Cancer Therapeutic was completed. AGT formed its Scientific Advisory Board, with the commitment of leading scientists in the United States and Europe.
AGT scientists designed and tested novel high-expressing multi-gene lentiviral vectors in vitro. Design features included multiple cargo genes, tissue and intracellular targeting elements, and siRNA genes. Multiple variations were successfully cloned and tested.