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ADVANCES IN USING THE T-MAX PRECISION™ VACCINE PLATFORM AGAINST MAJOR VIRAL PATHOGENS

  1. Vaccine Technology Summit March 2023 Tom Tillett, CEO T-Max Precision™ T-Cell DNA Vaccines to Address Significant Unmet Needs in the Animal Health and Human Markets
  2. Next Generation Vaccines for One World. One Health. 21st Century Immunotherapeutics Animal Disease Equivalent Human Disease Equine Herpes Virus Herpes Simplex Virus Coronavirus COVID-19 MERS MERS Tuberculosis Tuberculosis Influenza (HPAI) Influenza MBF Therapeutics Proprietary Information
  3. Characteristics of an ideal vaccine* • Provides broad-spectrum protection against all isolates of the virus in all the affected species, preventing virus carriage and the possibility of shedding and transmission; • Stimulates the level of immunity necessary to drive effective and long-lasting immune responses; • Inexpensive to manufacture and simple to administer; • In the case of live attenuated vaccines, reversion to virulence has to be avoided; • Has a long shelf life and is heat stable; • Allows discrimination between infected and vaccinated animals; and • Provides strong levels of maternal immunity. * Based on the guidelines proposed by the Royal Society’s report on infectious diseases of livestock in 2002, UK MBF Therapeutics Proprietary Information
  4. SARS CoV-2 – The Great Pandemic Ø Greatest pandemic in the last century • Over 6.8M people died globally, 675M infected, still a major problem with 36K dying in the last month - JHU • New technologies (mRNA vaccines) have provided tremendous benefit and value • However significant improvements are still needed o Need to block transmission (both within the body and between people) o New variants continue to emerge requiring regular updated of vaccines o Antibody responses last only for months requiring repeat administration o People don’t want to endlessly get vaccinated o Cold storage is an issue in many places around the world MBF Therapeutics Proprietary Information
  5. African Swine Fever - The “Ebola Virus of Pigs” • Since 2018 ASF has been devastating pork production in Asia, spreading in parts of Europe o 100s millions of pigs have been impacted. Economic effects are in $Billions. • There are no safe and effective vaccines available after nearly 50 years and $000M of research • MLV vaccines have proven consistently problematic o Reversion to wild type o Chronicity issues – long terms effect of a live virus in pigs • Biosecurity is the only method currently working to control the disease MBF Therapeutics Proprietary Information
  6. High Pathogenic Avian Influenza • World Organization for Animal Health - “200 million birds have died due to disease or mass culling” • The most common way for the virus to enter a territory is through migratory wild birds spreading worldwide and persistent infection in resident bird populations • USDA APHIS – prohibits vaccination due to trade restrictions o MLV (modified live virus) are the only vaccines available today Many countries changing laws to allow vaccination with MLV vaccines despite trade issues • Spreading to multiple species of animals, sea lions, bears, cats, minks, etc. • New reports of zoonotic spread to humans in China, Ecuador and Cambodia • Gavi warns of H5N1 and H7N9 spillover to humans; is it the next pandemic? MBF Therapeutics Proprietary Information
  7. Porcine Reproductive and Respiratory Syndrome (PRRS) • USDA - “PRRS is probably the most important swine disease of the last half-century” o #1 disease problem in swine worldwide o The cost of the disease in the United States alone is estimated to be over $600 million annually. o The virus causes pneumonia in growing pigs, abortion in sows and loss of vigor • Gateway disease for other problems • Existing MLV vaccines have significant limitations o Killed virus (autogenous) vaccines have less efficacy o Several KOLs have stated, “nothing works” • Increasing problems with new variants o Some researchers link new variants to MLV vaccinations MBF Therapeutics Proprietary Information
  8. The Problem Ø Very little innovation in the animal health market Ø Origin of most vaccines is over 40 years old o MLV vaccines use a live virus that has been attenuated resulting in safety and chronicity issues and potential to mutate o Killed virus vaccines are safe, can be tailored to specific variants but don’t elicit a strong immune response Ø Challenge in finding better technology that is inexpensive to produce o Prices for swine vaccines are ~$1/dose, poultry vaccines are priced at $1-10/1,000 chicks o Secondary measures, biosecurity, elimination of infected animals, sanitation can be implemented by large producers but create significant problems for smaller producers
  9. MBFT’s T-Max™ Platform • A novel antigen selection system selecting clinically relevant core antigens to produce cross-protective, “universal” vaccines • A portfolio of proprietary gene-based check point inhibitors and immunomodulators • Proprietary non-antibiotic plasmid system • USPTO allowed broad IP foundational claims supporting T-Max platform in both animals in humans, filed PTC A proprietary non-viral nanoparticle delivery system (CaptaVax™) that targets gene delivery • Exclusively in-licensed from SwRI Partnership business model Leadership Team • Tom Tillett – CEO • RheoGene • Rohm & Haas • Lorraine Keller – CSO • RheoGene • Immunotope, R&H • Ron Cravens – CMO • Novartis AH Vaccines • Amlan • Pfizer AH MBFT Assets MBF Therapeutics Proprietary Information
  10. 1 0 Outcome is experimental vaccine for next phase testing: • Formulation/dosing optimization • In depth mucosal and systemic immune analysis • Larger scale field study • Sow to pig passive immunity • Newborn pig preventive vaccination Step 1b Identify vaccine candidates by In vitro stimulation of T cells from blood samples from naturally infected animals Step 2 Safety/Immunogenicity vaccine study Formulate vaccine with pooled plasmids expressing viral antigens Vaccinate IN lymphoid tissues confirm immunogenicity of each vaccine antigen Step 1a Clone viral proteins individually into pMBFT plasmids Step 3 Challenge, measure viral titers in blood and organs, assess T cell responses to infection and for protection against disease T cells antibodies Precision Vaccine Design and Testing Process MBF Therapeutics Proprietary Information
  11. CaptaVax™ - Calcium Phosphate Nanoparticle Delivery System 1 1 MBF Therapeutics Proprietary Information SouthWest Research Institute (US 8,309,134) • Derivatized to enhance DNA binding and immune stimulation • Nonviral, biocompatible, degradable • Shape and size targeted for Antigen Presenting Cell uptake • Dissolve in acidic endosomes, release DNA into APC cytoplasm • Elicit T and B cell responses • Size range 10-999 nm • Can deliver DNA, RNA, proteins, small molecules, viruses • Can be readministered- ideal for all mucosal routes • Thermostable, no cold chain • Straightforward manufacturing, commodity reagents • Cost-effective for the livestock market
  12. Contrasting T-Max DNA vaccines with other DNA vaccines Feature T-Max PrecisionTM Vaccines Other DNA vaccines Antigen selection Natural antigens that elicit immune response in natural disease Predicted epitopes and protein subunits Targeted delivery of DNA I To Antigen Presenting Cells (APC) that result in direct translation to T-cells To the cell nucleus where mRNA is produced producing a systemic protein that indirectly elicits an immune response Targeted delivery of DNA II Mucosal tissue where APCs are concentrated and a barrier is created to block intra-body & inter-animal transmission Muscular tissue to elicit a systemic response that will NOT build a mucosal barrier to transmission Delivery System Non-viral CaptaVax that is designed to deliver DNA directly to APCs, can deliver bigger payload Normally virally vectored to get it into cells, or with a specialized delivery device MBF Therapeutics Proprietary Information
  13. MBFT-304: 49-day Safety/Immunogenicity Study in Weanling Pigs MBF Therapeutics Proprietary Information 13 plasmids expressing ASF proteins ASF antigens
  14. 1 4 Three week old weanling pigs were vaccinated intranasally with 13-plasmid pools of 35 µg/plasmid or 75 µg/plasmid of African Swine Fever Virus (ASFV) proteins formulated in CaPNP + Poly(I:C) on D0 and D14. There was no statistical difference in response to either dose. Peripheral blood mononuclear cells (PBMC) were collected on study D35 and D49. Stimulation with pooled ASF antigens increased the number CD3+CD8+IFNg+ T cells per 1000 CD3+CD8+ T cells measured by flow cytometry. Higher responses were observed to the more soluble protein pool 1. No responses to protein stimulation were observed in PBMC from control pigs vaccinated with CaPNP + Poly(I:C) (data not shown). CD8+ T Cell Responses to Intranasal DNA Vaccination of Weanling Pigs CD3+/CD8+ IFNg Expression in PBMC from piglets vaccinated IN with a 13-plasmid pool of African Swine Fever proteins MBF Therapeutics Proprietary Information
  15. Early Vaccine-Induced Immune Response to Vaccination: Gamma Delta T Cells are First Responders to Viral Infection Positive Control Negative Control Gamma Delta T cell expression of interferon gamma in Pig 5641 vaccinated with 75 µg DNA/plasmid/1 mg CaPNP/ Poly I:C. Q3 Red dots are negative for interferon gamma, Blue dots are positive for interferon gamma. Percentages are the fraction of gamma delta T cells expressing interferon gamma stimulated by positive and negative controls and Pools 1 and 2 of ASF antigens on Day 35. Q3 Negative control: Media only Positive control: PMA/ionomycin MBFT Propietary
  16. • Recombinant SARS CoV 2 proteome proteins tested for IFNgamma and perforin responses • PBMC were stimulated with four different protein pools representing the entire proteome • Strong IFN gamma and perforin responses to Groups 3 and 4 • Donor 9152200 (V/NC) responses may indicate immunity from earlier coronavirus infections • Further vaccine development will focus on Groups 3 and 4 Donor Status V/NC NV/C NV/C V: vaccinated, NV: Not Vaccinated C: Covid, NC: no Covid ELISpot Analysis of Human Donor PBMC MBF Therapeutics Proprietary Information
  17. Cove-001 Challenge Study in Mice – NSF Funded • Vaccinate C57Bl/6 mice IN with pooled plasmids representing complete SARS CoV2 proteome • Formulate in CaptaVax™ nanoparticles + Poly (I:C) • Challenge with a mouse-adapted SARS CoV strain • Study Readouts: Ø Lung, brain viral titers Ø Antiviral CD4+ and CD8+ T cells in spleens and lungs Ø Serum neutralization titer Ø Mucosal antiviral IgA titers MBF Therapeutics Proprietary Information
  18. MBFT Clinical data 2023 • COVE-001 SARS CoV-2 – Collaboration with Dr. Justin Richner, University of Illinois-Chicago o Final results from NSF funded study. • CSIRO – African Swine Fever - Dr. David Williams, CSIRO, o Objective: natural T cell antigen identification stimulating PBMC from infected pig with MBF-304 vaccine antigens o Outcome: Phase I - Identification of any natural T cell antigens, guiding design of next-gen experimental ASF vaccine. Phase II & III TBD • MBFT-305 PRRS o Objective: A challenge study to evaluate multiple antigens for safety and efficacy against PRRS through intranasal vaccination o Outcome: Successfully select 2 candidate vaccine (intranasal & intravaginal) for commercial development • MBFT-308 ILVT – Collaboration with Dr. Garcia University of Georgia o Objective: Expansion of the work proposed in the Egg & Poultry Assoc. Grant o Outcome: Successfully select a candidate vaccine for further development MBF Therapeutics Proprietary Information
  19. Grants – MBFT Continues to advance out T-Max platform • NIAID – Precision T cell vaccine for prevention of neonatal Herpes Simplex infection - Thomas Jefferson University • Egg Producers - DNA Immunization as a Safe and Economical Vaccination Strategy against ILTV - Dr. Maricarmen Garcia, UGA • NIAID - Protective T cell Vaccine for Mycobacterium tuberculosis - Dr. Fred Quinn, UGA • NIFA – Precision vaccination for protection from porcine reproductive and respiratory syndrome - Dr. Bob Rowland, UI 19 MBF Therapeutics Proprietary Information
  20. Experts Supporting Research and Clinical Development Swine Dr. Joe Conner- President/Founder Carthage Veterinary Service Dr. Bob Rowland- Head, Pathobiology U Illinois Veterinary School Dr. David Williams- Virologist, CSIRO, Geelong Australia Dr. Daniel Mead- Science Director, Animal Health Research Center University of Georgia Dr. Robert Jeff Hogan- Associate Professor Immunology University of Georgia Dr. Tobias Kaeser-Assistant Professor of Immunology at the Vetmeduni Vienna, Austria Dr. Ryan Saltzman Managing Veterinarian VRI LLC Ames Iowa Dr. Terry Coffey- former Chief Scientific Officer, Smithfield Foods Avian Dr. Maricarmen Garcia- Professor, Poultry Science, University of Georgia Dr. David Hurley- Emeritus Professor Immunology, University of Georgia SARS CoV2 Dr. Justin Richner- Asst. Professor Microbiology & Immunology University of Illinois Chicago Medical School R&D Dr. Malla Padidam- President, OneWorld Biotech Inc. Dr. Hong Dixon- Lead Scientist, Materials Science, SouthWest Research Institute
  21. Characteristics of an ideal vaccine* • Provides broad-spectrum protection against all isolates of the virus in all the affected species, preventing virus carriage and the possibility of shedding and transmission; • Stimulates the level of immunity necessary to drive effective and long-lasting immune responses; • Inexpensive to manufacture and simple to administer; • In the case of live attenuated vaccines, reversion to virulence has to be avoided; • Has a long shelf life and is heat stable; • Allows discrimination between infected and vaccinated animals; and • Provides strong levels of maternal immunity. MBFT – T-Max Precision™ DNA Vaccines • Uses multiple “natural” antigens from core conserved regions that generate cross-protective T-cell immunity in mucosal tissues that blocks virus transmission • Resident Memory T cell immunity provides a rapid, local response to new infections and long term protection • DNA vaccines are relatively inexpensive to produce and can be delivered needle-free • T-Max vaccines do not contain any live viruses insuring their safety • T-Max vaccines are stable at room temperature • T-Max vaccines are designed to be DIVA compliant • T-cell transfer thru colostrum well established, however we need to demonstrate this MBF Therapeutics Confidential * Based on the guidelines proposed by the Royal Society’s report on infectious diseases of livestock in 2002, UK MBF Therapeutics Proprietary Information
  22. MBF Therapeutics Confidential Questions Contact: Tom Tillett ttillett@mbftherapeutics.com
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