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Oncology Applications

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Two pivotal Phase III clinical trials in recurrent H&N cancer - Fast track designation, SPA ... Phase III pivotal trials for recurrent and new primary H&N cancers ... – PowerPoint PPT presentation

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Title: Oncology Applications


1
  • AMEX INO
  • Late Stage Development Company
  • Oncology Gene Delivery

Q3-2005 Avtar Dhillon, M.D. President and
CEO November 1, 2005
2
Forward Looking Statement
Our commentary and responses to your questions
may contain forward-looking statements, including
comments concerning clinical trials and product
development programs, evaluation of potential
opportunities, the level of corporate
expenditures, the assessment of Inovios
technology by potential corporate partners,
capital market conditions, timing of events, cash
consumption and other subjects. Information
concerning factors that could cause actual
results to differ materially from those set forth
in our Annual Report on Form 10-K for the
twelve-month period ended December 31, 2004, and
our Form 10-Q for the three-month period ended
June 30, 2005, and other regulatory filings.
3
Inovio Overview
  • Cancer Therapy (Solid Tumors)
  • Electrochemical tumor ablation eliminates the
    needs for surgical removal of tumors margins
  • Two pivotal Phase III clinical trials in
    recurrent HN cancer
  • - Fast track designation, SPA
  • European newly diagnosed and recurrent HN cancer
    pre-sales study - CE marked device
  • European newly diagnosed and recurrent skin
    cancer pre-sales study - Demonstrate efficacy
    pharmacoeconomic benefit
  • European sales launch with partner
  • Phase I pancreatic cancer trial (orphan
    designation)
  • Phase I breast cancer trial
  • Global marketing partnership discussions
  • DNA Vaccines / Gene Delivery
  • Phase I study in malignant melanoma with
    gene-based IL-2
  • Phase I study in malignant melanoma with
    gene-based IL-12
  • Phase I/II study in prostate cancer
  • Phase I cancer vaccine
  • Multiple commercial partnerships -
    Merck, Vical, RMR/Moffitt, University of
    Southampton

Late stage company with over 90m invested in
development technology validated by clinical
experience and industry partners
4
Therapeutic Platform Based on Electroporation
Electroporation
DC
Cell membrane during pulsing
Cell membrane after pulsing (Cell returns to
original state)
Cell membrane before pulsing
Electroporation applies brief electrical pulses,
inducing pores to open in the cell membrane and
dramatically increasing uptake of useful drugs,
genes DNA vaccines
A simple and effective system of delivering drugs
or genes into cells
5
Inovios Proprietary Medpulser System
Generator Capable of several thousand
treatments Generates square wave DC current
Applicator One per patient Usage restricted
by
smart-chip Sizeable gross margin
Revenue model sale of disposable, single
treatment applicators
6
Cancer Therapy Procedure Utilizing Selective
Electrochemical Tumor Ablation (SECTA)
Injection of Bleomycin
Pulsing the tumor withapplicator
Electroporation enables cellular uptake
Cell poration drug enters cells
Drug surrounds tumor cells
Cells reseal and die
Simple two-step procedure requiring minimal
training
7
Electrochemical Ablation of Basal Cell Cancer
BCC of the Earlobe
30 days post- treatment
Pre- treatment
Tumor cells turn black as they die
90 days post- treatment
120 days post- treatment
Wound healing itself
No further evidence of tumor
Surgery would have required cutting out a portion
of the ear
8
Cutaneous Cancer Therapy Clinical Data (H.Lee
Moffitt Cancer Center - USF)
Objective Response 56 of 56 (100) 84 of
85 (98.8) 1 of 1 (100) 4 of 4 (100) 145 of
146 (99.3)
Complete Response 51 of 56 (91.1) 75 of
85 (88.2) 0 of 1 (0) 4 of 4 (100) 130 of
146 (89.0)
Type Basal Cell Carcinoma Melanoma Squamous
Cell Carcinoma Kaposis Sarcoma Totals
of Patients 18 10 1 1 30
Complete response (CR) partial response
(PR) Heller et al., Cancer Vol. 83 (1), July 1,
1998
Complete response is similar to treatment by
surgery, without removal of healthy tissue
9
Electrochemical Tumor Ablation TherapyPre-clinic
al Clinical Experience
In vitro
In vivo
Tumor Type
Human
ovarian endometrial
prostate hepaticellular carcinoma Lewis lung
carcinoma non-small cell lung fibrosarcoma glioma
basal cell carcinoma melanoma Kaposis
sarcoma adenocarcinoma squamous cell
carcinoma oral, head and neck pancreatic liver
Electrochemical ablation is efficacious across
tumor types
10
Head Neck Cancer Clinical Data
Phase II, recurrent late stage HN tumors N.A.
and Europe
Bleo Only
Bleo Electroporation
Tumors Patients CR PR 37 25 0 3
Tumors Patients CR PR OR 20 17 30 25 55 31
25 19 39 58 18 12 28 28 56
N. America IN. America II Europe
69 54 26 32 57
Total
Market seeding, newly diagnosed HN tumors Europe
CR Complete response tumor shrinkage of
100 PR Partial response tumor shrinkage of
50 or more OR Objective response complete
partial responses NED No evidence of disease at
treatment site on histological
examination 4 weeks post-treatment ED Evidence
of disease
Tumors Patients NED ED 20 20 16 4
Europe
Complete response rate of 80
Excellent response rate in newly diagnosed HN
cancer patients
11
Electrochemical Ablation of SCC in Oral Cavity
Day of treatment - SCC on floor of mouth
Two weeks post-treatment - cancer cells are dying
Post-treatment - no evidence of cancer - no
structural damage
Destruction of healthy tissue is avoided with use
of electrochemical ablation
12
Electrochemical Ablation vs Surgery to Treat
Solid Tumors
Equivalent local tumor control Better
tissue preservation Better function
preservation Less cost
13
Two Pivotal Phase III Trials for SCCHN
Two open label, randomized trials comparing
electrochemical ablation to surgery in patients
with resectable tumors
Tumors anterior to the tonsillar pillar (200
patients)
SCCHN 2 pivotal studies
Tumors posterior to the tonsillar pillar (200
patients)
1o Endpoint superior preservation of function
(e.g. eating, swallowing, and talking) 2o
Endpoint local tumor control and survival that
are equivalent to surgery
Endpoints obtained under a Special Protocol
Assessment (SPA)
14
US Commercialization Strategy
SECTA treatment for HN cancers Phase III
pivotal trials for recurrent and new primary HN
cancers 124,000 annual incidences (Europe
and USA)
nearly 500,000 new cases worldwide SPA-review
ed Fast track designation Over 100
patients enrolled
15
US Commercialization Strategy
  • SECTA treatment of pancreas cancer
  • Over 32,000 cases will be diagnosed this year
    (U.S.)
  • Most patients are not candidates for surgery
  • Standard chemo-radiation outcomes are poor
  • Median survival 6-10 months
  • Phase I study in patients with non-resectable
    cancer
  • 1o Endpoint safety
  • 2o Endpoint pain control weight
    maintenance
  • Expect to conduct pivotal trials with a
    partner
  • Expect to complete enrollment in Q2 2006

16
US Commercialization Strategy
  • SECTA treatment for breast cancer
  • 184,000 cases will be diagnosed this year
    (U.S.)
  • Most frequently diagnosed cancer in U.S.
    women
  • Second leading cause of death in U.S. women
  • In 10-20 of patients receiving a partial
    mastectomy, the cancer recurs along the area of
    the previous incision
  • Phase I study in patients with recurrent
    breast cancer
  • 1o endpoint safety
  • 2o endpoint tumor response
  • Expect to conduct pivotal studies with
    partner
  • Expect to complete enrollment by Q2 2006

17
Breast Cancer Skin Metastases Post-Mastectomy
  • Initially treated with chemotherapy followed by
    mastectomy and radiotherapy
  • Subsquently developed skin metastases that were
    treated with SECTA
  • Lesions disappeared completely
  • Only pigmentation and fibrosis in biopsy

Before
After
18
European Commercialization Strategy
  • CE certified market-ready device (HN and
    cutaneous)
  • Two pre-marketing studies
  • Head and neck cancer
  • Skin cancers


  • Efficacy and pharmacoeconomic studies ?
    reimbursement and partnership
  • Additional indications could be rapidly developed
    by partner
  • Therapy benefits meet reimbursement adoption
    requirements
  • Fast procedure operating room cost savings ?
    payer preference
  • Less invasive minimal tissue damage ? patient
    preference
  • Ease of use minimal training ? physician
    preference
  • Little upfront investment ? institutional
    acceptance

Electrochemical ablation characteristics favor
rapid adoption
19
Present Technologies for DNA Delivery
Vector Issues
Economics
Efficacy
MutationsImmune responseInfection
symptoms Toxicity No vector No vector
Viral Lipids Naked DNA (EP enhanced)


Electroporation enhanced gene expression is
effective, low cost and avoids the side effects
associated with viral lipid vectors
20
Expression of SEAP in Pig Muscle
Serum levels of SEAP following expression in pig
muscle
N/6/200 V/cm/60ms
No pulse
L
M
Expression is enhanced nearly 100 times by a less
than one second of electroporation pulsing
21
DNA Vaccination
The promise rapid vaccination (including cost
effective, mass immunization) The challenge
achieving therapeutic immune responses
Potential solution electroporation (EP) to
enable DNA-based immunization Pre-clinical
studies demonstrate that EP induces rapid,
strong, durable immunity
22
Collaborations
  • Multiple first-in-man clinical trials
  • - Electroporation-mediated gene delivery
  • - Enables strong immunological responses to
    DNA vaccines
  • All clinical programs funded by partners

23
Intellectual Property Overview
60 US and 140 corresponding foreign patents, plus
numerous pending patents in the US and abroad
covering a broad range of applications
24
Inovios Product Pipeline 10 Clinical Trials
Oncology Pipeline United States
In Progress
Completed
Oncology Pipeline Europe
In Progress
Completed
DNA Vaccine / Gene Delivery Pipeline
Completed
In Progress
25
Near-Term Milestones
  • Cancer Therapy
  • Phase III recurrent HN cancer trials (fast
    track, SPA) - Increase enrollment (over 100
    patient enrolled)
  • European newly diagnosed and recurrent HN cancer
    pre-sales study - Pharmacoeconomic comparison
    to surgery
  • European newly diagnosed and recurrent skin
    cancer pre-sales study - Pharmacoeconomic
    comparison to surgery
  • Adoption of technology by European physicians
  • Complete enrollment in Phase I non-resectable
    pancreatic cancer trial
  • Complete enrollment in Phase I recurrent breast
    cancer trial
  • Pursue oncology partnership(s)

DNA Vaccines / Gene Delivery Additional
commercial partnerships Data from H. Lee
Moffitt Cancer Center Phase I melanoma
study Data from Vical Phase I melanoma
study Data from Southampton Phase I prostate
cancer study Data from Phase I cancer vaccine
trial
Major data flow and partnership opportunities
26
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