Biological Mimetics, Inc' BIO IT COALITION UMBI Rockville, MD June 28, 2 007

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Biological Mimetics, Inc.BIO IT
COALITIONUMBIRockville, MD June 28, 2 007
Biological Mimetics, Inc.

• Peter L. Nara, M.Sc., D.V.M., Ph.D. Biological
  Mimetics, Inc.
• Frederick, MD. 21702

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BMI represents a new breed of biotechnology
company aimed at applying its technology to
improving and sustaining human and animal
healthcare (Food) for developed and developing
countries, and..quite possibly economic
stability by preventing epidemic and pandemic
disease, while providing an adequate return on
investment Global Responsibility           
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Small Pox Yellow Fever Poliomyelitis Measles Mumps
Rubella BCG/TB(?) Varicella Typhoid Adenovirus(?)

Hepatitis A Poliomyelitis Rabies Anthrax Cholera P
lague Pertussis JEV Influenza A, B(?)
Hepatitis B(?) Diptheria Tetanus H. influenzae
b Meningococcus Pneumococcus (?) Lyme Disease(?)
CLASS I PATHOGENS
HIV-1, Malaria, Tuberculosis, Chages,
Schistosomiasis, Leishmaniasis, African
Trypanosomiasis, Onchocerca volvulus, Rickettsia
africae, Anaplasmosis, Toxoplsmi
gondii, Cryptosporidiosis, Upper Respiratory
Viral bacterial diseases, Influenza A,B,C,
Human Rhinovirus -THE COMMON COLD!!!, Mycoplasma
pnenumonia, Dengue, SARS, Respiratory syncytial
virus, Para-influenza 1-4, Meta-pneumo virus,
Adenovirus, Non-typeable Haemophlius influenza
(otitis media of children), Streptococcus
pneumonia, Group A and B Strep, Diarrheal
diseases Norwalk, Astroviruses, Enteroviruses,
various toxigenic E.coli, Dengue, Lyme,
Hepatitis C,D,E,(?), Meningococcal disease,
Sexually transmitted Diseases Gonorrhea,
Treponema pallidium, Chlamydia, Trichomoniasis,
Herpes simplex, Human papilloma,virus (all
serotypes), Cancer, other diseases?
CLASS II PATHOGENS
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THE BIG PICTURE
WHO averages 200 outbreak investigations every
year, and around 50 will require an international
response. More than 30 new and highly infectious
diseases have been identified in the last 20
years. Furthermore, 20 known strains of diseases
such as tuberculosis and malaria have developed
resistance to antibiotics, while old diseases
have reappeared, such as cholera (in Angola, with
1,298 deaths), yellow fever (new cases recently
reported in Guinea, Sudan, Mali, and Senegal),
plague, dengue fever, meningitis, hemorrhagic
fever, and diphtheria.
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Company History

• Founded in Frederick, Maryland 1996 operational
  in 1997
• 2. Initial discovery and inventions were made at
  the National Cancer Institute
• 3. Capitalized with
• Starting investment from company co-founders
• Novel Technology Challenge Award from the State
  of Maryland Department of Business and Economic
  Development
• Private angel investors
• NIH/DOD Grants and Contracts
• Pharmaceutical Partnerships

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Corporate Profile

• Industry
• Biotechnology
• Management
• CEO Dr. Peter Nara
• CFO Dr. Ray Chauduri
• COO Dr. Greg TObin
• CMO Dr. George Lin
• Private Investor Consultant Geneviève Clavreul
• Number of Employees 5
• Law Firm
• Greber Associates P.C.
• Intellectual Property
• Steptoe Johnson LLP
• Knobe, Martens, Olsen and Bear

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Corporate Profile

• Accountant
• Don Coakley, C.P.A., M.S.T.
• Amount of Total Financing Sought
• 10 million staged
• Current Investors
• 60k in founder funding
• 60k in angel funding
• 50k Maryland Challenge Fund

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Corporate Profile

• Use of Funds
• Laboratory Staffing
• Administrative Staffing
• Preclinical/field trials for 4 animal health
  vaccines
• Preclinical, Phase 1 2 Clinical Trials for
  three human vaccines
• Intellectual Property, licensing, infringement
• Executive management

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Corporate HeadquartersFrederick, MD.
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Facility and Workforce

• Modern 2,600sq. ft. USDA BSL-2/3 certified
• laboratory
• 900sq.ft. administrative/conference space
• 5 employees- 3 senior scientists, and 1
• senior technician, hiring 1 post-doc.
• Established an extensive CRO network for all
  necessary research
• support activities-DNA sequencing, genomics,
  synthetic genes,
• protein sequencing, protein structure, high-end
  computing,
• animal studies- immunogenicity efficacy safety
  studies etc.
• 5. Contracted Lab Support part/full time
• B.S., M.Sc. technicians and Ph.D. scientists

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Patented and Licensed Platform Technology

• Dampening of an Immunodominant Epitope of an
  Antigen for Use in Plant, Animal and Human
  Compositions and Immunotherapy
• Inventors
• Peter L. Nara, Robert R. Garrity, and Jaap
  Goudsmit
• Issued
• December 17, 1996 (HIV-1)
• December 29, 1998 (all pathogens and cancer)
• NIH Worldwide Exclusive License
• April 17, 2002

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Collaborators and CROs

• Department of Defense-Division of Malaria and
  Retrovirology
• Henry M. Jackson Military Foundation for Medical
  Research
• Department of Defense-Walter Reed Army Institute
  of Infectious Diseases
• Defense Sciences Office (DSO)-The Defense
  Advanced Research Projects Agency (DARPA)
• U.S. Army Medical Research Institute of
  Infectious Diseases (USAMRRID-Ft. Detrick)
• USDA/ARS Plum Island Animal Disease Center and
  Homeland Security
• USDA/National Animal Disease and Diagnostic
  Centers, and Beltsville, MD. and Ames IA
• U. of Maryland Vaccine Center
• U. of Maryland Center for Marine Biotechnology
• U. of Maryland Center for Human Retrovirology
• U. of Maryland Biotechnology Institute-CARB II
• UCLA AIDS CARE Center, David Geffen School of
  Medicine
• U. of Pennsylvania Medical Center, Center for
  AIDS Research
• Iowa State University College of Veterinary
  Medicine
• The Ohio State University Ohio Agriculture
  Research and Development Center (OARDC)
• National Cancer Institute
• National Institute of Allergy and Infectious
  Diseases
• National Institutes of Health
• Armed Forces Institute of Pathology

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THE BUSINESS MODEL
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Business Development Strategy

• The Company is financing its early stage
  activities through two stages. The first stage of
  funding is intended to carry it through the
  remaining discovery and pre-clinical animal study
  phases.
• Stage I funding development with capital raised
  through private placements, mid-tier, large
  pharmaceutical alliances, licensing and
  government grants and contracts.
• Stage II funding is to cover early USDA/CV
  Biologics licensing (BPL)/ Field trials, Phase I,
  II, and III human clinical trials and
  manufacturing, marketing, and distribution of
  license vaccines.
• The Company will fund Stage II from either
  continued private placement, revenues from
  milestone payments, MA, or,, licensing
  arrangements, SBIR Phase II, royalties for
  vaccine sales or proceeds from a public offering.
  
• Exit Strategies. An initial public offering or
  acquisition event by a larger pharmaceutical
  company are potential earlier exits for
  investors.

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Competition

• Small and medium sized vaccine development
  companies likely provide more R D competition
  than the larger pharmaceutical companies.
• BMIs Immune Dampening and Refocusing technology
  has a unique and uncrowded niche, since it is one
  of the very few companies that is focusing on
  rational antigen design - fixing the antigen.
  Thus, these mid-tier companies can also be viewed
  as potential partners and not entirely as
  competition since it would be synergistic to meld
  BMIs antigen modifying expertise with the
  vaccine delivery expertise of these other
  companies.
• The strength of BMIs platform technology is that
  it is not beholden to any one delivery method.
• Academic institutions and research institutes are
  also active in the vaccine market but more so on
  the research and development side and not with
  product development and testing.
• Governmental agencies are also active
  participants in vaccine development. BMI has and
  continues to work with the U.S. military and the
  U.S. Defense Advanced Research Projects Agency
  (DARPA) in developing targeted vaccines of
  interest
• Many companies have focused on different vaccine
  sectors such as delivery modalities, immune
  enhancing and production issues, and adjuvants
  MedImmune, Chiron, AlphaVax, Iomai, Protein
  Sciences Corporation, and GenVec.
• Could benefit from a pipeline of new antigens
  such as BMI produces.

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The Art Science of Deceptive Imprinting
Pablo Picasso 1881-1973
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THE ART- The original subjects-
Picasso sketch book Matador Bull
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THE ART of the SCIENCEDeceptive Imprinting
-The Players-
Picasso sketch book Matador Bull
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THE ART of the SCIENCEDeceptive Imprinting
-The Players-
The Host
Picasso sketch book Matador Bull
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THE ART of the SCIENCEDeceptive Imprinting
-The Players-
The Pathogen
The Host
Picasso sketch book Matador Bull
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THE ART of the SCIENCEDeceptive Imprinting
-The Players-
The Pathogen
The Host Immune system
The Decoy
Picasso sketch book Matador Bull
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Deceptive ImprintingAct I (the approach)
The Decoy
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Deceptive ImprintingAct II (the pass)
The Decoy
B and T cells
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Deceptive ImprintingAct III (the finale)
Misdirected Host immune system
The Decoy
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The Platform Technology

• IRT represents a one-of-a-kind conceptual and
  technical break-through solution for overcoming
  the two biggest unsolved roadblocks in vaccine
  development today (multiple strains-antigenic
  variation and non-protective immune responses)
• In short, the Technology works by both
  identifying the part of the microbe that acts
  like a decoy (Decotope) and then removes or
  dampens it, thus allowing for the development of
  a vaccine that now protects a person or animal
  year to year despite the pathogens continuously
  changing it genetic makeup

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Immune Refocusing Technology

• Therapeutic Antibodies

Identify Immunodominant Non-Protective Epitopes
Immune Dampen and Immune Refocus
Elicit and Identify Novel Immune Responses To
Targeted Regions
- Oligosaccharide

• Vaccine Candidates

Immunodominant Type Specific Non-Protective Antibo
dies
Broadly Reactive Protective and Therapeutic Antibo
dies
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Influenza Virus HAAntigenic Sites
B
HA1
A
D
E
C
HA2
Linda Stannard, Department of Medical
Microbiology, University of Cape Town
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Influenza Virus HAAntigenic Sites
B
HA1
A
D
E
C
HA2
Wilson (1981) Nature
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Influenza Virus HAReceptor Binding Region
Sialic Acid

• HA subunits depicted in red, orange, and yellow
• Cyan represents N-linked oligosaccharides
• Green represents sialic acid

Weis (1988) Nature
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Influenza Virus HAProtruding Loops (Sites A
and B)
Loop 155-164
Loop 140-146

• HA subunits depicted in red, orange, and yellow
• Cyan represents N-linked oligosaccharides
• Green represents sialic acid

Skehel and Wiley (2000) Annu. Rev. Biochem.
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10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
210
3.40




Antigenic Index - Jameson-Wolf
0


Flexible Regions - Karplus-Schulz
F

6



Surface Probability Plot - Emini
1

0

4.5


Hydrophilicity Plot - Kyte-Doolittle
0


-4.5
VP 1GH
-
Loop








119 126
128

135



145

152 159

FMDV Strains










FMDV
-
01

YTAPHR
V
L
A
T

VYNG
ECR
Y
N RNAVP
---
-
NL
RGD
LQV
L
A
Q
K
V
A
RT
----
LP


Type O

YTAPHR
V
L
A
T

VYNG
SSK
Y
G DTSTN
----
NV
RGD
LQV
L
A
Q
K
AERT
----
LP

SAT
-
1

BOT

YTAPHR
L
L
S
T

VYNG
ECE
Y
-
KTAVTA
----
I
RGD
RAV
L
A
A
K
Y
A
-
DTRHT
LP

SAT
-
2

MOZ

YTAPHR
L
L
S
T

VYNG
ECE
Y
-
KTAVTA
----
I
RGD
RAV
L
A
A
K
Y
A
-
DTRHT
LP

Type A22

YTAPHR
V
L
A
T

VYNG
TGK
Y
S AGGMG
-
---
R
-

RGD
LEP
L
A
AR V
A
AQ
----
LP


Type C

YTAPHR
V
L
A
T

GYTGTTT
Y
-

----
TA
---
ST
RGD
LAH
L
TAT R
A
GH
----
LP

Figure 2.
Immunochemical profile of the VP1GH
-
loop capsid protein of FMDV (A) and sequence
alignments of the GH
-
loop of various serotypes of FMDV. Brown denotes
gt97
, blue gt80
conserved and green,gt 60 conserved. Dashes and
black amino acid letters indicate positions of
high variability, substitutions, insertions or
deletions.

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Human Rhinovirus ICAM-1 Receptor Binding Canyon
ICAM-1 Binding Canyon
VP1
VP2
VP3
immunodominant strain-specific epitopes to be
targeted for immunodampening NIm Sites IA, IB,
II, and III
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EPITOPE MAP
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Additional contacts
EPITOPE MAP
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Additional contacts
Missing contacts
EPITOPE MAP
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BMI Targeted Vaccine Products

• During the past 10 years the company has brought
  4 veterinary and 3 human vaccine candidates
  through proof-of-concept studies to the
  preclinical development stages.
• The Veterinary vaccines include
• (1) Coccidia for the poultry industry-a potential
  for a 350 million dollar a year worldwide market
  and growing
• Recombinant immune refocused 24K protein
• Delivered as DNA, viral vector combination in ovo
• Stage-final antigen optimization, dosing studies
  and field trial efficacy studies

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BMI Targeted Vaccine Products

• (2) Infectious Pancreatic Necrosis Virus (IPNV)
  for the aquaculture business (sea and freshwater
  raised major fish species (salmon, halibut,
  trout, cod etc.)- approximately a 50 million
  dollar a year market and growing at 10 per year
• Immune refocused VP2 e-coli recombinant protein
• Delivered as DNA or whole-killed virus
• Stage early delivery optimization, dosing
  studies, safety and field trial efficacy studies

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BMI Targeted Vaccine Products

• (3) Foot and Mouth Disease Virus (FMDV)-a major
  virus of all domestic and wild- hoofed stock food
  animals in the world and a proof-of-concept for
  the closely related human cold virus. The FMDV
  market globally is estimated to be 250 million
  dollars annually and growing. It is important to
  note in addition, that FMDV is considered by U.S.
  Homeland Security to be the most important
  agro-bioterrorism agent in the world
• Recombinant immune refocused viral capsid
• Delivered in adenovirus vector
• Stage early antigen optimization, dosing
  studies, field trial efficacy studies
• Provides proof-of-concept studies for developing
  a vaccine against the Common Cold Virus

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BMI Targeted Vaccine Products

• (4) Porcine Respiratory Reproductive Disease
  Virus (PRRS)-the most important viral disease of
  the swine industry globally, estimated markets
  size of approximately 250-300 million dollars
  per year and growing at 5 year
• Immune refocused attenuated PRRS virus
• Stage early antigen optimization, immunogenicity
  studies, dosing studies, experimental efficacy
  studies, field trial efficacy studies

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BMI Targeted Vaccines-(cont.)

• (5) Human Immunodeficiency Virus (HIV-1) vaccine
  for AIDS, estimated to be a 700 million to 1
  billion dollar market worldwide and one of the
  major existing global threats to economic
  stability worldwide
• Recombinant immune refocused subunit protein
• Delivered in licensed adjuvant
• Stage later antigen optimization, preclinical
  immunogenicity, safety studies, phase 1 2 human
  trials
• (6) Influenza, estimated to be a market size of
  approximately 3 billion dollars per year and the
  looming threat of a worldwide Avian pandemic
• Recombinant immune refocused baculovirus subunit
  protein
• Delivered in licensed adjuvant
• Stage later antigen optimization, preclinical
  immunogenicity, safety studies, phase 1 2 human
  trials

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BMI Targeted Vaccines-(cont.)

• (7) Non-typeable haemophluis influenza (NTHI),
  the major bacterial cause of childhood ear and
  upper respiratory infections worldwide-a market
  estimated to be 300 -700 million dollars
• Immune refocused outer membrane fimbrie proteins
  or recombinant whole bacteria
• More antigen engineering required
• Delivered in licensed adjuvant
• Stage early antigen optimization, preclinical
  immunogenicity, safety studies, phase 1 2 human
  trials

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Vaccine Timeline Estimated Times to regulatory
filing
HIV-1/AIDS NTHI Influenza PRRS IPNV FMDV COCCIDIA
12
9
7
5
3
5
5
0 2 4 6
8 10 12
Years
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PROMISING NEW VACCINE TARGETS-impacting human
health worldwide-

• AIDS
• Malaria
• Chages, Schistosomiasis, Leishmania, African
  Trypanosomiasis sleeping sickness
• Tuberculosis
• Upper Respiratory Viral bacterial diseases
• Influenza A,B,C
• Human Rhinovirus -THE COMMON COLD!!!
• SARS
• Respiratory syncytial virus
• Para-influenza 1-4
• Adenovirus
• Non-typeable Haemophlius influenza (otitis media
  of children)
• Streptococcus pneumonia, pyogens
• Diarrheal diseases
• Norwalk, astroviruses, enteroviruses
• E.coli
• Dengue
• Lyme
• Hepatitis B C

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PROMISING NEW VACCINE TARGETS Veterinary
Pathogens
Companion Animal
Aquaculture
Avian
Cattle / Swine

• Influenza
• Parainfluenza
• BRSV
• FMDV
• TGE/PCRV
• BVD
• PRRS
• Step suis
• H. parasuis
• Actin. suis
• P. multocida
• ETEC
• Bovine TB
• Coccidia
• marginale
• Leptospirosis

FIP CCV Equine influenza Equine Rhino Strep
equi Canine leishmania
Influenza IBDV IBV Adenovirus P.
multocida ETEC Clostridia Coccidia
IPNV ISA
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Four neutralization Immunogens (NIm) sites have
been resolved by cross-neutralization tests.
Sites are labeled NIm IA, IB, II, and III. The
symbols approximate the size of the area. IB is a
smaller area than IA. 5
/ \ IA(VP1) Q83,K85,D138,S139
/ IA\ IB(VP1)D91,E95
/ \ / \
II(VP2)E136,S158,A159,E161,V162
/ IB \ (VP1)E210 / /
\ / / \ III(VP3)N72,R75,
E78,G203 / / \
(VP1)K287 /______ / \
/ \ \ / II \
\ / \ III \ The major
antigenic site is on the BC
3/________________\_________\3 loop in VP1 and
VP3 but in the EF loop 2 in
VP2.
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Type Specific Neutralizing MAb Binding Pattern
Differs from ICAM-1 Binding

• Fab17/12
• strong neutralization
• little aggregation
• bivalent binding
• Fab1
• poor neutralization
• more aggregation
• monovalent binding

ICAM-1 binding
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EPITOPE MAP
48
Additional contacts
EPITOPE MAP
49
Additional contacts
Missing contacts
EPITOPE MAP
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Acknowledgments/Collaborators

• Department of Defense-Division of Retrovirology
• Dr.s Debbie Birx, Merlin Robb Vickie Polonis
• Walter Reed Army Institute
• Dr. Rip Ballou
• Dr. Jeff Lyon
• Dr. Tony Holder
• USDA/ARS Plum Island
• Late Dr. Fred Brown
• Dr. Marvin Grubman
• Children's Hospital Ohio State
• Dr. Lauren Bakaletz
• Cambrex Inc.
• Ms. Kathleen Sterling
• Biological Mimetics Inc.
• Dr. Gregory Tobin