**MUST READ** Highlights for GeoVax Labs, Inc. (GOVX-OTC)GeoVax Labs, Inc. (“GeoVax” or the “Company”) is a clinical-stage biotechnology company creating human vaccines against infectious diseases and cancer using an innovative and patented Modified Vaccinia Ankara Virus Like Particle (MVA-VLP) platform technology. This technology supports production of non-infectious virus-like particles (VLPs) from the cells of the individual receiving the vaccine. The Company is currently focused on developing vaccines against human immunodeficiency virus (HIV), Zika virus (ZIKV), hemorrhagic fever (HF) viruses (Ebola, Sudan, Marburg, and Lassa), and malaria. The Company also has programs to develop a vaccine to treat chronic Hepatitis B virus (HBV) infection and to apply its MVA-VLP technology to cancer immunotherapy (immuno-oncology). GeoVax employs Modified Vaccinia Ankara (MVA) as a vector to express foreign antigens on VLPs generated in vivo within vaccinated patients. Its MVA-VLP is the fourth generation MVA vector, licensed from the National Institutes of Health (NIH), which is modified for insertion sites for high expression and transgene stability during manufacture. This platform has shown to be suitable for vaccination against a range of disease agents. The Company has multiple license and research collaboration agreements to advance its product candidates, including: (1) a Cooperative Research and Development Agreement (CRADA) with the NIH for MVAs used in the development of HF, Zika, HBV, malaria, and immuno-oncology vaccines; (2) a collaboration with the U.S. Centers for Disease Control and Prevention (CDC) for the development of a Zika vaccine; (3) a collaboration agreement with Georgia State University (GSU) for the advancement of the Company’s HBV therapeutic program; (4) a collaboration agreement with the Burnet Institute in Australia (www.burnet.edu.au) for the development of a malaria vaccine; (5) a research collaboration agreement with the University of Pittsburgh for the development of the Company’s immuno-oncology program; and (6) exclusive license from Emory University for HIV vaccines. Importantly, by working with collaborators on multiple vaccine candidates, GeoVax is able to manage risk by providing multiple paths on the road to selecting the best vaccine candidate.
HIV/AIDS Vaccine Program
The Company’s most advanced program is a preventive vaccine (GOVX-B11) for the clade B subtype of HIV, the most common form of HIV in the Americas, Western and Central Europe, Australia, and Japan. The preventive clade B HIV vaccine has successfully completed Phase 2a human clinical testing and in January 2017, GeoVax began the next human clinical trial (HVTN 114) on the path toward human efficacy trials. HVTN 114 is testing the ability of “late boosts” to increase the antibody responses elicited by GOVX-B11. These “late boosts” consist of the GeoVax MVA62B vaccine with or without a gp120 protein vaccine. HVTN 114 is being conducted by the HIV Vaccine Trials Network (HVTN)—the world’s largest publicly-funded international collaboration focused on developing vaccines to prevent HIV/AIDS (www.hvtn.org). with funding from the National Institute of Allergy and Infectious Diseases (NIAID). Information from this trial is expected to contribute to the design of future human clinical trials testing GOVX-B11 in the presence and absence of newer gp120 proteins, which are currently being cGMP (Current Good Manufacturing Practice) manufactured. During 2016, NIAID awarded GeoVax a Staged Vaccine Development contract of up to $7.8 million for production of the DNA vaccine component of GOVX-B11 in sufficient quantities for use in advanced clinical trials. Within the HIV category (in existence for roughly 35 years), there are no approved vaccines. GeoVax continues to move down the clinical pathway. The next goal is to reach an efficacy trial, which would be a Phase 2b trial (involving thousands of individuals). Current antiretroviral therapies (ARTs) do not eliminate HIV infection, where infected individuals must remain on ARTs for life.In March 2017, GeoVax began a collaboration with American Gene Technologies International Inc., (AGT) in which AGT plans to commence a Phase 1 human clinical trial testing the companies’ combined technologies to develop a functional cure for HIV infection. In an earlier Phase 1 clinical trial of the Company’s MVA-VLP HIV vaccine, GeoVax observed the ability of its vaccine to stimulate production of CD4+ T cells in HIV-positive individuals. The GeoVax vaccine will be used to stimulate virus-specific CD4+ T cells in vivo, which will then be harvested from the patient, genetically modified using AGT’s proprietary technology, and reinfused into the patient. The primary objectives of the trial (targeted to begin in 2017) are to assess the safety and efficacy of the combined therapy, with secondary objectives to assess the immune responses and levels of virus reservoirs as measures of efficacy.
Hemorrhagic Fever (HF) Vaccine Program
Initiated during 2014 in response to the Ebola epidemic in western Africa, GeoVax’s HF vaccine program is focused on developing a tetravalent vaccine (TV) designed to protect against all major HF viruses (Ebola, Sudan, Marburg, and Lassa) endemic in African countries. Each vaccine is also being developed as a monovalent vaccine. The Company’s initial preclinical studies in rodents and nonhuman primates for its first Ebola (EBOV) vaccine candidate (GEO-EM01) have shown 100% protection against a lethal dose of Ebola virus upon a single immunization. GeoVax is currently conducting challenge studies for its Lassa fever vaccine (GEO-LM01).
Zika Virus (ZIKV) Vaccine Program
GeoVax is also collaborating with the CDC to develop a preventive vaccine against the Zika virus (ZIKV). Zika disease is an emerging, rapidly-spreading mosquito-borne infectious disease that has been linked to an increase in microcephaly in infants (a condition in which a baby’s head is significantly smaller than expected, often due to abnormal brain development) and Guillain-Barré syndrome in adults (a condition in which the immune system attacks the nerves). A highly rigorous preclinical challenge model has been developed and has demonstrated impressive results for the Company’s Zika vaccine, protecting 100% of outbred immunocompetent mice infected with a lethal dose of ZIKV delivered directly to the brain. The vaccine also generated strong humoral and T cell responses against ZIKV. The Company’s Zika vaccine (GEO-ZM02) is based on the NS1 (non-structural-1) protein of Zika, which is not associated with Antibody Dependent Enhancement (ADE) of infection—a safety concern for all other Zika vaccines under development. An NS1-based vaccine, GeoVax’s candidate also has the potential to block transmission of ZIKV from humans to its mosquito vectors, as was shown with antibodies generated against NS1 proteins of DEN2 and ZIKV. Based on these results, GeoVax is advancing into non-human primates (NHP), GMP manufacture, and Phase 1 human trials.
Cancer Immunotherapy Vaccine Program
GeoVax is employing its MVA-VLP platform to express abnormal hypoglycosylated forms of the cell surface-associated Mucin 1 (MUC1) protein, linked to a range of cancers, including breast, colon, ovarian, prostate, pancreatic, and lung. The Company’s approach is to use standard-of-care (SOC) treatments, vaccinations, and immune checkpoint inhibitors (ICIs) to harness patient’s immune system to fight their cancer. GeoVax has a research collaboration with a leading expert in cancer immunotherapy at the University of Pittsburgh to help select vaccine candidates. The Company is also collaborating with ViaMune, Inc. of Athens, Georgia, with preliminary testing demonstrating that the MVA-VLP-MUC1 vaccine in combination with ViaMune’s synthetic MUC1 vaccine has meaningfully reduced tumor burden in a transgenic (Tg) human MUC1 therapeutic mouse model.
Hepatitis B Virus (HBV) Vaccine Program
Approximately 240 million people are chronically infected with HBV, of which 780,000 die each year despite the availability of an effective prophylactic vaccine since 1982. Currently, a variety of therapeutic vaccine candidates are being evaluated in clinical trials though none have induced the strong IgG1, IgG3, and CD4+ and CD8+ T cell responses necessary for complete viral clearance. Clinical data from GeoVax’s HIV vaccine trials have demonstrated that its MVA-VLP HIV vaccine elicited strong IgG1, IgG3, and CD4+/CD8+T cell responses. The Company has constructed vaccine candidates containing multiple protective antigens from the HBV genotype D (causing more severe disease), which are currently being tested in mice in its collaborator’s laboratories at Georgia State University (GSU) and Shenzen Graduate School of Peking University.
Malaria Vaccine Program
Malaria causes 214 million infections and 438,000 deaths every year worldwide. Despite decades of research, tested vaccine candidates have yet to be successful at inducing substantial protection (e.g. >50%). The majority of these vaccines have been based on truncated proteins or VLP proteins targeting a limited number of antigens derived from only one stage of the malaria life cycle. GeoVax’s MVA-VLP multi-antigen malaria vaccine candidates are designed to induce a Th1-biased immune response with durable functional antibodies (IgG1 and IgG3) and CD4+ and CD8+ T cell responses—all attributes of an ideal malaria vaccine. The Company is developing this vaccine with the Burnet Institute to prevent both malaria infection as well as its transmission by targeting antigens derived from multiple stages of the parasites’ life cycle. GeoVax has completed construction of multiple vaccine candidates, which are expected to be tested at Burnet Institute in July 2017.
Intellectual Property
GeoVax is the licensee of 10 issued and two patent applications in the U.S. and 12 issued and 4 patent applications in non-U.S. jurisdictions. GeoVax’s patent portfolio includes applications directed to DNA- and MVA-based HIV vaccines, their genetic inserts expressing multiple HIV protein components, composition, structure, claim of immunization against multiple subtypes of HIV, routes of administration, safety, and other related factors and methods of therapeutic and prophylactic use, including administration. GeoVax has patents pending for HF, Zika, HBV, malaria, and immuno-oncology vaccines.
Leadership
GeoVax recently appointed Farshad Guirakhoo, Ph.D., as its new chief scientific officer (CSO) to succeed Harriet Robinson, Ph.D., who remains as CSO Emeritus and director of the Company’s HIV vaccine program and who is very well known in the HIV community. Guirakhoo was named one of the ‘50 Most Influential People in Vaccines’ in Vaccine Nation’s 2014 list. In January 2017, GeoVax announced the formation of a Scientific Advisory Board composed of world-class scientists, including Thomas Monath, MD; Stanley Plotkin, MD; Barney Graham, MD, Ph.D.; Scott Weaver, Ph.D.; and Olivera Finn, Ph.D. This group of experts is focused on helping the Company advance its various development programs.
Government Support
The Company’s vaccine development activities are financially supported by the U.S. Government in the form of research grants, in-kind support in terms of animal experiments, and indirect support for human clinical trials. GeoVax’s HIV program receives substantial federal support (>$50 million to date from the NIH).
