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

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

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

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

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

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

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?

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

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

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

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

CaptaVax™ - Calcium Phosphate
Nanoparticle Delivery System
1
1
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

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

MBFT-304: 49-day Safety/Immunogenicity
Study in Weanling Pigs
13 plasmids expressing ASF proteins
ASF antigens

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

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

• 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

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

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

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

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

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 Confidential
Questions
Contact: Tom Tillett
ttillett@mbftherapeutics.com

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