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May 23, 2013
A human cell line that produces a
human antibody that neutralizes HIV
2
A human cell line that produces a human antibody that neutralizes HIV
BioClonetics has created a human cell line that produces a human antibody (designated as CLONE 3) that neutralizes HIV, the virus that causes AIDS.
As its primary mission, the Company is preparing for animal and human trials to ready its antibody for use in treating those with HIV/AIDS and for production of an AIDS vaccine.
Source: BioClonetics Immunotherapeutics,
3
Population GroupTotal Number
Infected1
Annual Infection Rate1
Annual Death Rate1
World 33 Million 2.7 Million 2 Million
Major Markets1 10.4 Million 720,000 556,000
North America and Western Europe
2.3 Million 155,000 111,000
Children (World wide) 3.1 Million 430,000 290,000
China 740,000 48,000 25,000
U.S. 1,700,000 56,000 18,000
The PROBLEM of the HIV/AIDS Pandemic
Source: (1) UNAIDS, World Health Organization; Avert.org; Center for Disease Control; Univ. Calif. San Francisco Medical Center; UNIAIDS China, 2009; Major markets include the countries North American, Western and Central Europe, Eastern Europe and Central Asia, South and Southeast Asia and Latin America.
The PROBLEM:Comparison of HIV and Cancer Affliction
Source: Estimates of UNAIDS; World Health Organization (WHO) 2009
Annual Occurrences of HIVIn children are greater than cancer
SubjectsHIV
Annual CancerAnnual
Children afflicted 430,000 160,000
Children who die 290,000 90,000
Individuals afflicted 3.1 Million 11 Million
Individuals who die 2.1 Million 7.4 Million
TOTAL Afflicted 33 Million 25 Million
4
5
The PROBLEM: Current chemotherapeutic ARVs are
unsafe, ineffective and expensive
No satisfactory or safe treatment is available; chemotherapeutic anti-retroviral (ARV) drugs are:• Highly toxic
• Cause liver and kidney failure,
• Cause increased cardiovascular disease (4 times as likely)
• Decrease bone density
• Cause severe vitamin deficiency
• Must be administered for life and do not provide a cure
• Create treatment resistant strains of the virus that cannot be treated and are fatal
ARV Treatment is expensive
• Current average annual costs (U.S.) per patient is $10,000 (drugs only)
• Life-time costs (U.S.) per patient (over an average treatment span of 24 years) is $240,000
Source: BioClonetics Immunotherapeutics,
Clone 3 provides a uncompromised SOLUTION
6
BioClonetics has produced a human monoclonal antibody, Clone 3, which neutralizes HIV
The antibody binds to a highly conserved four amino acid sequence KLIC (epitope) on the viral surface transmembrane outer protein envelope and kills the virus
Use of monoclonal antibodies against HIV is widely recognized as a promising approach to achieving effective therapy: NIH announcement May 2008: “New research program focused on generating broadly neutralizing antibodies”.
Source: BioClonetics Immunotherapeutics
HIV gp41 viral stalk
Clone 3
Technical Summary and Status
How Does Clone 3 Work?
For HIV to infect, it requires binding between the virus and the human CD4 cell at two target sites (a primary and secondary).
The Clone 3 interrupts the second binding site of the virus to the human CD4 cell and prevents infection by fusion.
Immunotherapy is safe and effective.
Administered in a finite period (12 months) rather than requiring life long use, as is the case with anti-retroviral therapies now used to treat HIV/AIDS.
The antibody is ready for testing in primates but must first be produced in the recombinant form for such tests and for human trials.
7Source: BioClonetics Immunotherapeutics
Proof of EFFICACY – First 3rd Party Evidence
The Clone 3 human antibody neutralized HIV in all clades and groups found around the globe. It has been tested at 5 research institutions against 45 strains of the virus:
1. University of California, San Francisco, CA, USA (Jay Levy, MD)
2. University of South Florida, Tampa, FL, USA (Kenneth Ugen, PhD)
3. Polymun Scientific, GmbH, Vienna, AUSTRIA, (Hermann Katinger, PhD)
4. Duke University, Durham, NC, USA (David Montefiori, PhD)
5. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, (Ruth Ruprecht, MD, PhD)
8Source: BioClonetics Immunotherapeutics
Proof of EFFICACY – 3rd Party Evidence
• Test in five (5) international research institutes have shown that Clone 3 antibody neutralizes (at IC90*) 41 of 45 (over 91%) of primary HIV isolates tested, from clades A, B, C, E, and F from around the globe. Clade C is the clade prevalent in China.
• By comparison, the clinical use of approved viral fusion-inhibitor Fuzeon, shows the post-therapy viral burden to be less than 50 copies of HIV in only an average of 33% of patients, and is known to be highly toxic and cannot eradicate the virus.
Independent Laboratory Test Results
Source: BioClonetics * IC90 - Inhibitory Concentration of Clone 3 mAb (<30 microgram/ml) that neutralizes 90% of HIV virions
Clades
Percent infections responding completely to Fuzeon treatment: average only 33%
Per
cen
t N
eutr
aliz
atio
n
Clone 3 mAb neutralized 91% (41/45) of all HIV clades tested
9
Proof of EFFICACY – 3rd Party Evidence
Clone 3 target site exists in 98% of all viral strains (clades and groups) of HIV around the globe and thus, Clone 3 can be broadly effective
Source: Los Alamos National Laboratories HIV Sequence Database; October 2010
The HIV target site data neutralized by Clone 3
2,229 HIV viruses identified in 60 countries representing all clinically-identified viruses
available to the National Laboratory at Los Alamos HIV viral sequence database repository
10
Clone 3 human antibody’s global geographic effectiveness including effectiveness against Clade B which is prevalent in North America
Source: BioClonetics Incorporated, Independent In Vivo Research Institute Studies, IAVI June 2009
Clone 3 Antibody is effective everywhere and has global application on all continents
(effective against all Clades)
Clone 3 Antibody is effective everywhere and has global application on all continents
(effective against all Clades)
HIV virus map by subtype (Clades)HIV virus map by subtype (Clades)
11
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International Studies Human Clinical Correlate TEST Results
A. P.A. Broliden et al. Infants who lacked anti-KLIC (Clone 3) antibodies had a rapid progression to symptomatic AIDS
B. Vanini et al. Decreasing concentration of anti-KLIC (Clone 3) antibodies directly correlated with HIV disease progression
C. Loomis-Price et al., High antibody reactivity to the peptide containing the immunogen epitope [KLIC] (Clone 3) is associated with slow progression to AIDS
D. Dietrich et al. Long-Term Non-Progressors (LTNPs) are individuals with the virus but having normal T‑cell counts, no opportunistic infections without ARVs) show the presence of anti-KLIC antibodies
E. Cano et al. Correlation between the presence of anti-linear peptide antibodies and the patient’s ability to endure the infection.
F. NIH conducted primate vaccine studies
Successfully vaccinated Rhesus macaque primates with a homologous immunogen that produces the Clone 3 neutralizing protective antibody
Proof of EFFICACY – More 3rd Party Evidence
The Company’s immunotherapeutic technologyprovides for a Therapy and Vaccine
• (A) Immunotherapy for those individuals who are HIV-infected
• (B) A prophylactic vaccine to prevent contraction of the virus. An effective immunogen, a vaccine, can be produced from the KLIC immunogen binding site on the virus.
Clone 3 Antibody
Clone 3 Antibody binds to gp41 viral stalk of HIV-1
(B) Clone 3 Active Vaccine
Immunizationfor all 6.7 billion un-infected
individuals
(A) Clone 3 Antibody Passive Immunotherapy
for all estimated 33 million HIV+ patients
Clone 3 Immunotherapeutic Technology Products
(B)(A)
HIV-1
Products
13
RecombinantAntibody
Source: BioClonetics Immunotherapeutics
14
2014 2014
Q1 Q2 Q3 Q4
Milestone 1: Production ofRecombinant Human Antibody; an FDA requirement for Primate Pre-clinical and Human Clinical Trials
Milestone 2: Primate Pre-clinical trials (Keeling Center for Comparative Medicine & Research – San Antonio, Texas USA or Zerun)
Proposed Recombinant Clone 3 Production and Animal Trials/FDA-EMEA IND Phase 1 meeting for Human Clinical Trial Study
Milestone 3: FDA-EMEA IND Phase I meetings for human clinical trial study initiation for Clone 3 passive immunotherapy and vaccine
Source: BioClonetics Immunotherapeutics
mAb Passive Immunotherapy
Commercial Recombinant
Antibody
Marketing and Sales Strategy:Clone 3 Patent Protection
15
First Company Patent
Vaccine
mAb Passive Immunotherapy
RecombinantAntibody
Pending Patent Protection - (1) Recombinant Antibody Production(2) Active Peptide Vaccine
Source: BioClonetics Immunotherapeutics
ParentAntibody
A
B
Business Model:Who are the HIV/AIDS market-space players?
• Annual worldwide HIV/AIDS chemotherapeutic drug sales in 2008 were $10.7 Billion USD
- Annual sales are expected to climb to $15.1 Billion by 2017
- U.S. and European markets accounts for 60% of the gross annual revenues
• Marketed anti-retroviral (ARV) therapies
- NRTIs – Combivir by GlaxoSmithKline
- NNRTIs – Viramune by Boehringer
- PIs – Kaletra by Abbott
- FI – Fuzeon by Roche-Trimeris
Source: Datamonitor 2010, Cambridge Healthtech Institute
HIV/AIDS Chemotherapeutic Drug Revenues and Market Share
HIV Antiretroviral Market Share
Roche
Gilead
GlaxoSmithKline
generic drugs
Boehringer IngelheimGilead
Abbott
Bristol Myers Squibb
16
BioClonetics Immunotherapeutics Company Team Members
• Joseph Cotropia, MD–CSO and Founder–Physician (Internal Medicine),
Immunobiochemist–37 Years as a physician in private
practice, immunology research and discovery at BioClonetics
–FDA Fellow Research Scientist, senior reviewer of INDs at Center for Biologic Evaluation and Review (CBER)
–College Station, TX
• Charles Cotropia, JD–Vice-President/Counsel–39 years as an intellectual property
attorney–Dallas, TX
Source: BioClonetics Immunotherapeutics 17
• Tomasz Zastawny, DSc, PhD–Director Laboratory Operations–20 Years of expertise in Clinical Trials
Operations and Studies–Clinical Studies Operations Director for
Pro-pharmaceuticals–Senior Advising Consultant to large
pharmaceutical sector industry
• Paul D. Fellegy– Director Business Operations–25 Years of expertise in financial
services consulting, operations and management
–Senior consultant to Fidelity Investments, John Hancock, Putnam Investments, and State Street Global Advisors
• Tzvete Dentchev, MD–Director of Clinical Research–Senior Molecular Research Scientist
with 35 years of expertise –University of Pennsylvania (UPENN), PA
BioClonetics ImmunotherapeuticsScientific Advisory Team
• Dimiter Dentchev, MD, PhD–Chief, Clinical Pathology–Thomas Jefferson Hospital,
Philadelphia, PA–30 Years of Clinical Pathology Studies–BioClonetics Scientific Advisor
• Dalila M. Corry, MD–Professor of Clinical and General
Medicine–Chief, Division of Nephrology–University of California Los Angeles
(UCLA)–35 Years of human clinical trial studies–10 Years of HIV clinical trial studies
relating to HIV+ nephrology patients–David Geffen School of Medicine–BioClonetics Scientific Advisor
• Ellen S. Vitetta, PhD–Professor and Director, Cancer
Immunology Center, UT Southwestern Medical School Dallas, TX
–The Scheryle Simmons Patigian Distinguished Chair in Cancer Immunobiology
–Professor of Microbiology–35 Years of expertise in active vaccine
design and human clinical trial studies–BioClonetics Scientific Advisor
• Yvonne J. Bryson, MD–Professor of Pediatrics–Chief, Division of Pediatrics Infectious
Disease–University of California Los Angeles
(UCLA)–35 Years of pediatric clinical trial studies
in HIV/AIDS–David Geffen School of Medicine–BioClonetics Scientific Advisor
18
Source: BioClonetics Immunotherapeutics 19
BioClonetics ImmunotherapeuticsCollaborations
Name of Institution Institute or Department
Primary Contact Nature of Relationship
University of TexasSouthwestern Graduate Schoolof Biomedical SciencesDallas, TX
Center for Cancer Immunobiology
Ellen S. Vitetta, PhDDirector
Collaborative research and active peptide
vaccine design;Oral medications
formulation design
University of TexasMD Anderson Research CenterBastrop, TX
Michale E. Keeling Comparative Medicine and Research Center
Christian R. Abee, DVMDirector
Collaborative research and primate pre-clinical
Rhesus macaque neonatal studies
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Company Intellectual Property (IP)
Patent Number Owner Title
US Patent No. 6,083,504BioClonetics Immunotherapeutics
Human Monoclonal Antibodies Directed Against the Transmembrane Glycoprotein (GP41) of Human Immunodeficiency Virus-1 (HIV)
Status Owner Title
Filed BioClonetics Anti-HIV Small Molecular Peptides
Patent Applications Pending FilingRecombinant Human Monoclonal Antibodies Directed Against the Transmembrane Glycoprotein (GP41) of Human Immunodeficiency Virus-1 (HIV)
Sub-unit Vaccine against Human Immunodeficiency Virus-1 (HIV)
Patent Issued
Patent pending
Patent Applications Pending Filing
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CompanyIntellectual Property (IP)
Description
Clone 3 parent cell line is proprietary
Methodology and process for creating immortalized cells that produce stable human neutralizing monoclonal human antibodies are trade secrets
Proprietary IP
Company Near Term Objectives
• What the company will achieve in 12-18 months
1. Preparation of the commercial recombinant Clone 3 anti-HIV monoclonal antibody
2. Test the recombinant antibody in Rhesus macaques primates
3. Begin human trials
• What the company will achieve in 36 months
1. Prepare anti-HIV Vaccine based on Clone 3 anti-HIV monoclonal antibody
2. Pre-clinical studies and human studies leading to market application of an anti-HIV vaccine
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Clone 3 Antibody-based Immunotherapeutic Technologies Platform
SUMMARY
• Large unmet medical need
–ARV drugs can not eradicate virus from HIV-infected patients, nor provide a cure
–ARV drugs are not sufficiently effective, safe or protective
• Clone 3 antibody therapy will be safer, more effective and less expensive
–The technology provides a highly profitable, disruptive therapy that can supplant current ARV treatments now used by HIV patients
23