Draft:American Gene Technologies

American Gene Technologies (AGT) is an American biotechnology company based in Rockville, Maryland.. . AGT was founded in 2007 after founder and CEO was introduced to viral vectors by NIH researcher Roscoe Brady MD, PhD and decided that he wanted to help continue Brady's research. The company focuses of gene therapy technologies, including but not limited to research into HIV, PKU, and immuno-oncology.

Roscoe Brady MD, PhD
NIH researcher and National Medal of Technology and Innovation recipient Roscoe Brady MD, PhD (1923-2016) is seen as the inspiration for the founding of AGT. Brady conducted research for over 50 years, starting with genetic lipid storage diseases and their metabolic defects, such as Tay-Sachs disease, Niemann-Pick disease, Fabry disease, and Gaucher disease.

Later in his career, as gene therapy began to gain momentum, Brady began to focus more on the applications of gene and enzyme replacement therapy, particularly for the diseases that he spent a majority of his career researching. This interest in gene therapy led to a meeting between Brady and Jeff Galvin, in which Brady explained the technology of viral vectors and their ability to deliver genetic material to the cells of patients in order to treat certain diseases. This meeting inspired Jeff Galvin to found American Gene Technologies, where Roscoe Brady served as Chief Scientific Advisor until his death in 2016.

Jeff Galvin
Jeff Galvin began his career in Silicon Valley, where he was a founder or executive of a variety of start-up tech companies, many of which were taken public or sold to other public companies. He then retired early to become an investor in high tech and real estate until an opportunity arose with the NIH and Roscoe Brady. After meeting Brady and learning about viral vectors and their potential in the field of medicine and gene therapy, Galvin decided he wanted to come out of retirement to found AGT in 2007 with the goal of using gene therapy to cure humanity's diseases. Galvin decided to found AGT in Rockville, Maryland, because of his belief in the area being an epicenter for cellular and gene therapy technology, leading to the area being referred to by some in the industry as DNA Valley

2007
Jeff Galvin founds American Gene Technologies in Rockville, Maryland.

2008
AGT researchers design and in vitro test multi-gene lentivirus vectors. Many versions were cloned and tested successfully.

2009
Formation of AGT's initial Scientific Advisory Board, including leading global scientists such as Fred Nyberg and John Rossi. AGT completes animal testing of AGT1101 for Prostate Cancer, yielding overall positive results. Initial testing of AGT1102 for Pancreatic Cancer is also completed.

2010
AGT scientists design a revised AGT1102 Pancreatic Cancer Therapeutic and complete in vitro testing with positive results. Initial design for the AGT1103 for Liver Cancer is completed. AGT begins licensing and co-development discussions with Chinese pharmaceutical companies.

2011
Successful development of a lentiviral vector with the capability to carry anti-tumor components that have the potential to limit or inhibit the growth and expansion of hepatocellular carcinoma (HCC) or liver cancer. Over 90% inhibition was seen in the three HCC lines that were tested on. These tests also successfully introduce RNA interference technologies into the AGT viral vectors, indicating their potential to be used in correcting human diseases at a cellular level.

2012
AGT receives NIH funding for two SBIR projects in order to develop gene therapies for Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). For these projects, AGT developed lentiviral vectors that inhibited the replication of HCV reporter strains in in vitro testing by over 99%. Testing was also completed for over 50 related and intermediate vectors and an anti-HIV RNA inhibitor final construct was improved to prepare for future testing.

2013
AGT secures Series A Preferred venture capital investment based on its success in therapeutic process line development. This capital was used to expand into a new laboratory space and expand its research and development team. Additional in vitro studies on the HIV gene therapy treatment are completed showing high rates of inhibition of HIV replication, with inhibition rates up to 99%.

2014
Initiation of two new programs in collaborations with other leading scientists including a gene therapy program to treat Familial Dysautonomia (FD) with the Chair of the Cell Biology Department and Neuroscience at Montana State, Dr. Frances Lefcort, and a gene therapy program to treat Parkinson's Disease with Dr. Ted Dawson, the cell engineering institute director at Johns Hopkins University. AGT also received investment from the Familial Dysautonomia Foundation to help with the development of a FD therapy. Series B financing was also secured.

2015
AGT secures Series C funding. Former U.S. Secretary of Health and Human Services Tommy Thompson is added as a senior advisor. AGT initiates three new projects including: Animal testing for an HCC therapeutic with Dr. Dean Felsher MD, PhD at Stanford University, an NIH grant for a FD blindness therapeutic, and a Phenylketonuria (PKU) project in collaboration with the University of Pittsburg Children's Hospital.

2016
AGT conducts a pre-IND (Investigational New Drug) meeting with the FDA for the product AGT103, which is their HIV gene therapy functional cure. Following this meeting, AGT started their IND development process and began to plan their clinical trials for AGT103. AGT also filed patents for HIV drugs that showed efficacy against the disease in preliminary trials.

2017
AGT collects blood from HIV-infected individuals for testing with the cell manufacturing and the final vector of AGT103. The data from these tests is used in the IND documentation to be submitted to the FDA as well as to validate the protocol of the treatment before clinical trials.

2018
AGT receives FDA Orphan Drug Designation for its gene therapy treatment for PKU. AGT receives five new patents for HIV and cancer assets from USPTO. The previous scientific advisor of AGT, Roger R. Redfield, MD, is appointed as Director of the Centers for Disease Control and Prevention (CDC). AGT also successfully secures Series D financing.

2019
AGT secures two patents in order to protect its cancer and HIV assets. AGT announces the launch of their Oncology Science Advisory Group (OSAG), which is used to help accelerate the research for a cancer cure. AGT is invited to the J.P. Morgan Healthcare Conference, which is the largest health care investment meeting in the industry. NIAID and AGT sign a Research Collaboration Agreement for a potential HIV cure.

2020
Headquarters is moved to a larger facility in Rockville, allowing for an expanded lab space. FDA clears AGT for Phase 1 Clinical Trials for their HIV cure program and the first patients are enrolled in the trial. AGT and NIAID publish their peer-reviewed paper on molecular therapy that illustrates positive preclinical data for the potential HIV cure. AGT also secures three more patents for their immuno-oncology asset.

2021
The first patient in the Phase 1 clinical trials is infused with AGT103-T. The Data Safety and Monitoring Board (DSMB) overseeing the Phase 1 clinical trials for AGT103 determines that the gene therapy had no serious adverse events and thus voted to allow the trials to continue at an increased rate with just quarterly DSMB meetings instead of meeting after each patient in the trial.

2022
Phase 1 trial results indicate that AGT103-T is not only compatible with humans but that the enhanced T-cells produced by the treatment are able to persist in the body and are ready to react to HIV. This data was published in the medical journal Frontiers. AGT then began withdrawing the Phase 1 trial patients from their antiretroviral drugs. The increased virus-specific T-cells from the treatment indicates possible improved immunity against HIV, which aligns with the goal of returning the natural immunity to HIV in patients.

2023
AGT launches its new HIV-focused division, Addimmune, to pursue an HIV cure using gene and cell therapies. This builds upon AGT's promising initial results. AGT will now focus on developing gene and cell therapies for other monogenic disorders.

Lentiviral Vectors
AGT is a global leader in the design, development, and use of lentiviral vectors. The vectors are designed for gene therapy processes, in which they are used to deliver genetic material to a variety of different cells in the body in order to treat a disease. AGT lentiviral vectors specifically are used for three main purposes: Down-regulate or completely shut down genes that are a part of disease pathology in specified cells, deliver genes to help replace genes that are either missing or mutated, and to kill a cell if completely necessary, such as for cancer treatment. AGT lentiviral vectors have the ability to be specialized to particular cell types as well as being controllable to only express their genes under specified circumstances. These vectors are also reusable between different diseases, which allows AGT to use them in potential cures and treatments for a variety of different diseases.

HIV
AGT's former leading product prior to the creation of Addimmune to focus on HIV, was their HIV cure candidate AGT103-T. AGT103-T is a cell therapy technique that delivers CD4 T cells that have been modified to protect against HIV infection to patients infected with HIV, since HIV depletes virus-specific CD4 T cells in the body. This allows the immune system to return closer to normal and thus better fight the virus and remove the need for the patient to take antiretroviral (ART) drugs. This technique also prevents HIV replication in reservoir cells.

AGT103-T is currently undergoing clinical trials and completed Phase 1 in 2023. Seven patients have been withdrawn from their ARTs, received AGT103-T, and have had no serious adverse effects. Addimmune hopes to finalize their DARWIN trial and gain approval for another trial later in 2023.

PKU
AGT's PKU program is a single-dose gene therapy technique in which a lentiviral vector carrying a functional phenylalanine hydroxylase (PAH) gene is injected into a patient's liver and blood stream. This gene therapy then enters the liver cells of the patients where the new PAH promotes the production of the PAH enzyme and the gene also blocks the production of the mutated PAH that causes the disease in the first place. This enables the metabolization of phenylalanine into tyrosine and thus returns the levels of phenylalanine in the patient back to normal, making the blood non-toxic. This product has shown promising preclinical data and AGT has been in contact with the FDA to hopefully move forward into clinical trials in the coming years.

Immuno-oncology
AGT's immuno-oncology project is the ImmunoTox program, which is a genetic medicine that is delivered to patients using AGT's third-generation lentiviral vectors. These lentiviral vectors are delivered to the tumor site to change the tumor cells' metabolism, slowing their growth, and causing them to over-produce the small molecule isopentenyl pyrophosphate (IPP) that causes gamma delta (үδ) T cells to become cytotoxic. These cells are highly specific to tumor cells and have a significant ability to distinguish cancer-infected tissue from normal tissue, allowing the treatment to not only target modified tumor cells, but all tumor cells in the area. The activated үδ T cells can also travel through the bloodstream to reach secondary tumors and kill off those cells as well. AGT has eight patents on the ImmunoTox program and is working towards clinical development and further testing of the technology in the coming years.

Recognitions

 * 2023 NABOE Award for World Changing Business.
 * 2019, 2021, and 2022 Maryland Tech Council Life Science Company of the Year Finalist.
 * Jeff Galvin won the 2022 Life Sciences Voice Top Industry Leaders Award.
 * 2022 BioBuzz Media Award for their "The Cure Chronicles" Series.
 * 2021 Moxie Award for Healthcare and Biotechnology.
 * 2021 NOVA Chamber Mid-Atlantic Innovators of the Year
 * 2020 BioBuzz Breakthrough Company of the Year