Inovio Pharmaceuticals - Corporate Presentation

39
NASDAQ: INO Taking Immunotherapy to the Next Level IT’S ALL ABOUT THE T -CELLS J. Joseph Kim, Ph.D. President & CEO March 2017

Transcript of Inovio Pharmaceuticals - Corporate Presentation

Page 1: Inovio Pharmaceuticals - Corporate Presentation

NASDAQ: INO

Taking Immunotherapy

to the Next LevelI T ’ S A L L A B O U T T H E T - C E L L S

J. Joseph Kim, Ph.D.

President & CEO

March 2017

Page 2: Inovio Pharmaceuticals - Corporate Presentation

Forward Looking Statement

2

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

Inovio’s technology by potential corporate partners, capital market

conditions, timing of events, cash consumption, and other 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 year

ended December 31, 2016 and other regulatory filings from time to

time.

Page 3: Inovio Pharmaceuticals - Corporate Presentation

Leading the Development of DNA-based Immunotherapies

to Commercialization

3

Powerful platform,

multiple products

Efficacy in

phase II study

Phase III and

immuno-oncology

combo studies starting 1H17

Major partnership:

MedImmune/AstraZeneca

Our purposeDevelop

immunotherapies

and vaccines to

fight cancers and

infectious diseases

Page 4: Inovio Pharmaceuticals - Corporate Presentation

Executing “Inovio Vision 2020”

4

HPV-related pre-cancers

(VGX-3100)

Filed for marketing

approval

1

Immuno-Oncology

Filed for marketing

approval or in

pivotal study

2

Infectious diseases

Filed for marketing

approval or in

pivotal study

3

Page 5: Inovio Pharmaceuticals - Corporate Presentation

CELLECTRA

5PSP Device

• SynCon® antigen genetic code enables

precise targeting of cancer or pathogen

• Designed to break tolerance and

cover mutating strains

• Highly optimized SynCon plasmid +

novel CELLECTRA delivery generate

optimal antigen production IN THE

BODY

• Activates robust functional CD8+ killer

T cell and antibody responses

• Phase II efficacy

• Highly favorable safety profile in over

1300 subjects and 3800 immunizations

Immune Responses by Design

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SynCon

Immunotherapy

Optimized platform: SynCon® + CELLECTRA®

Page 6: Inovio Pharmaceuticals - Corporate Presentation

Inovio Vision 2020 Roadmap

6

1

Start PIII 1H17

Start PII 2017

VGX-3100, HPV-Related

Diseases

Filing for marketing approval by 2020

Cervical DysplasiaPhase II completed

Other HPV NeoplasiasPreparing INDs (VIN, AIN)

Page 7: Inovio Pharmaceuticals - Corporate Presentation

Fulfill Unmet Treatment Needs of HPV Related Diseases

High Grade Cervical Dysplasia (CIN 2/3)

• Current CIN excisional and ablative

procedures increase risk of pre-term births

from 5.6% to 10.7%;Kyrgiou et al meta-analysis published June 2016 in

British Medical Journal

• Existing procedures cannot eliminate HPV

outside treated area; recurrence risk post-

LEEP is 10-16%

• VGX-3100: potential first-line therapy; first

non-surgical treatment option

Vulvar & Anal Neoplasias

• No good existing treatments

• Surgery is disfiguring

7

EU: 15,000

US: 195,000

EU: 233,000

US: 13,400

EU: 2,514

CIN2/3

VIN

AIN

US: 23,000

Sources: Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J,

Bosch FX, de Sanjosé S, Castellsagué X. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human

Papillomavirus and Related Diseases in United States of America. Summary Report 2015-03-20., Henk et al J Low Genit Tract

Dis (2010), Insigna et al, Am J Obs Gyn (2004), Hartwig et al. Papillomavir. Res (2015), CDC, www.hpvcentre.net, WHO IARC

Annual Incidence

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Demonstrated Efficacy in Phase II Trial of VGX-3100

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Placebo-Controlled,

Randomized, Double Blind

• VGX-3100 SynCon® product

for HPV-related pre-cancers

• Targets HPV 16/18

subtypes, E6/E7 oncogenes

• 167 subjects

• 18-55 year old females

• High-grade cervical

dysplasia (CIN2/3)

• HPV 16 and/or

18 positive

• 3:1 randomization

• Dosing: week 0, 4, 12

Primary Endpoint

• Regression of CIN2/3

to CIN1 or normal

(week 36)

Secondary Endpoint

• Regression of CIN2/3

to CIN1 or normal and

clearance of HPV

(week 36)

Page 9: Inovio Pharmaceuticals - Corporate Presentation

Robust Functional Antigen-Specific T Cells

Measured in Blood

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*Statistically significant; bars are 95% Cl

VGX-3100800

600

400

200

0

0 5 10 15 20 25 30 35 40

Placebo

Study Week

VG

X-3

100

Sp

ec

ific

T C

ells

1

Treatment at wks 0, 4, & 12

* * * *

• 167 subjects

• Published in The Lancet September 2015

• 1 Spot forming units/106 PBMCs above baseline

Page 10: Inovio Pharmaceuticals - Corporate Presentation

CD8+ T Cells Infiltrate Diseased Tissue, Clear HPV

Virus and Lesion

10

We

ek 0

IHC Staining: Lesion/HPV

We

ek 3

6

IHC Staining: CD8 +

Regression of CIN3 &

HPV to normal

Increase and persistent

presence of infiltrating CD8+

killer T cells

“Cold”

“Hot”

Page 11: Inovio Pharmaceuticals - Corporate Presentation

Phase II Achieves Primary and Secondary Endpoints

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• Efficacy correlates to immune responses

• PP and mITT p-values equal

• 167 subjects

• Paper published in The Lancet September 2015

• 1Strata-adjusted

Regression high grade

to low grade cervical

dysplasia or normal

Dysplasia regression

to low or normal AND

HPV clearance

Lesion

regression

to normal

VGX-3100 49.5% 40.2% 40.2%

Control 30.6% 14.3% 16.7%

Difference 18.9% 25.9% 23.5%

P-value1 p=0.017 p=0.001 p=0.006

Groups

Primary

Endpoint

Secondary

Endpoint

Primary –

Post Hoc

Page 12: Inovio Pharmaceuticals - Corporate Presentation

HPV Cervical Dysplasia Phase III

• Scaled biologic manufacturing to

commercial facility

• Completed CELLECTRA® commercial

delivery device design, manufacturing

process, production

• Phase III trial design similar to phase II

• < 400 total subjects

• Phase III trial package submitted. FDA

requested additional device-related

information; placed program on clinical hold

prior to initiation

• Aim to initiate phase III in 1H 2017

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Goal: Commercialize first medical alternative focused on

preserving women’s reproductive health; regress HPV-

caused lesions and eradicate virus itself

Page 13: Inovio Pharmaceuticals - Corporate Presentation

Inovio Vision 2020 Roadmap

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2Immuno-Oncology

One pivotal study or filing for marketing approval by 2020

IO combination trial start 1H17

Preliminary data 1H17

Start PI/II 1H17

INO-5150 Prostate CancerP1 enrollment completed

INO-5401 New Cancer TargetMulti-antigen immunotherapy + checkpoint inhibitor

INO-1400 hTERT9-cancer trial assessing immune responses

INO-3112 HPV CancerKiller T cells shown in phase I

Page 14: Inovio Pharmaceuticals - Corporate Presentation

Checkpoint

inhibitors

combined with

Inovio’s cancer

vaccines

Two studies

starting in 2017:

- INO-3112 with

MedImmune

- INO-5401

Checkpoint

combinations

Modestly higher

response rates

Toxicity up

DRAMATICALLY

Holy Grail of Immuno-Oncology:

Turning “Cold” Tumors to “Hot” Tumors

Need presence of robust, antigen-

specific, functional CD8+ killer

T cells to leverage the capabilities

of checkpoint inhibitors: KOLs

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Checkpoint

monotherapies

Few tumors responsive.

Successes: only

15-20%response ratesin most cancers

Page 15: Inovio Pharmaceuticals - Corporate Presentation

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Turning “Cold” Tumors to “Hot” Tumors

Before treatment

with INO-3112

After treatment

with INO-3112

Control: FoxP3 CD8

Page 16: Inovio Pharmaceuticals - Corporate Presentation

Inovio Vision 2020 Roadmap

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3Infectious Diseases

One pivotal study or filing for marketing approval by 2020

P1 data 2H17

Additional data

1H17

Immune response

data 1H17

Additional data

2017

Discuss

potential

regulatory

path 2017

CHRONIC INFECTIONS

INO-1800 HBV P1 enrolling

INO-4212 Ebola P1 expanded: 200 patients

EMERGING INFECTIONS

GLS-5300 MERS P1 fully enrolled

GLS-5700 Zika Two phase I studies

Page 17: Inovio Pharmaceuticals - Corporate Presentation

Post Challenge (Days)

0 5 10 15 20 25 300

20

40

60

80

100

% S

urv

iva

l

ZIKV-prME (x1)

pVax1

n=10

2x106

X20

X20

X20

X40

X20

X20

iv

i ii

iii

pVax1 ZIKV-prME

v

vi

• ZIKV infection caused severe brain pathology in mice

• In contrast, vaccinated animals presented with normal histopathology in brain tissues

• Data supporting that protective antibodies induced by synthetic ZIKA-prME vaccine

could limit viral induced disease in the brain

GLS-5700 Zika Vaccine Protects from Death and Illness

Page 18: Inovio Pharmaceuticals - Corporate Presentation

Emerging Disease Vaccine Development Opportunities

Rapid response technology platform

desired by health authorities to

fight emerging infectious diseases

• Inovio technology demonstrates rapid design,

manufacturing, and clinical development of

new vaccines, e.g. Zika

• Financial drivers

• Grants, such as DARPA $45M Ebola

award, Gates $8.8M

• Priority review voucher potential

• Stockpiling contracts: scale manufacturing

• Commercial opportunity for some diseases

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DNA

Alternative Technologies

Design

DNA

Alternative Technologies

Manufacturing

Development Time Frames

Page 19: Inovio Pharmaceuticals - Corporate Presentation

Management & Financials

Page 20: Inovio Pharmaceuticals - Corporate Presentation

Peter Kies

CFO

• Ernst & Young

• Experience with

growth companies

Mark L. Bagarazzi, MD

CMO

• Clinical research

experience incl. Merck

• Led clinical/regulatory

for shingles and

rotavirus vaccines;

DNA vaccine expert

Management

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J. Joseph Kim, PhD

President & CEO

• Decades of

biotechnology/

pharma management

• Merck: hepatitis A

and B vaccines

manufacturing;

HIV vaccine (Ad5)

R&D

Niranjan Y. Sardesai, PhD;

COO

• Extensive biotech

management and

product development

experience

• Led diagnostics

development for

mesothelioma, bladder

cancer, and ovarian

cancer for Fujirebio

Diagnostics

Page 21: Inovio Pharmaceuticals - Corporate Presentation

Board of Directors

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Nancy Wysenski, MBA

• Former COO of Endo

Pharmaceuticals and

Vertex Pharmaceuticals

Simon X. Benito

• Former Senior Vice

President, Merck

Vaccine Division

Avtar Dhillon, MD

Chairman, BOD

• Seasoned venture

capitalist and biotech

entrepreneur

Morton Collins, PhD

• General Partner,

Battelle Ventures and

Innovations Valley

Partners

Angel Cabrera, PhD

• President, George

Mason University

J. Joseph Kim, PhD

• President & CEO,

Inovio

Adel Mahmoud, PhD

• Professor, Princeton Univ.

• Former President, Merck

Vaccines

• Responsible for Gardasil®,

Zostavax®, Proquad® and

Rotateq®

David B. Weiner, PhD

• Executive VP, The

Wistar Institute;

Director, Vaccine

Center

Page 22: Inovio Pharmaceuticals - Corporate Presentation

Scientific Advisory Board

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Anthony W. Ford-

Hutchinson, PhD

• Former SVP,

Vaccines R&D, Merck

• Oversaw development:

Singulair®, Januvia®,

Gardasil®,Zostavax®,

Proquad® and Rotateq®

Stanley A. Plotkin, MD

• Developed rubella and

rabies vaccines

• Oversaw Sanofi flu vaccine

• Emeritus Professor, Wistar

Institute

& University of

Pennsylvania

David B. Weiner, PhD

Chairman

• “Father of DNA

vaccines”

• Executive VP, The

Wistar Institute;

Director, Vaccine

Center

Page 23: Inovio Pharmaceuticals - Corporate Presentation

Financial Information

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1March 10, 2017 2December 31, 2016

3 Due from ApolloBio Corp: up to $50M in signing fee, milestone and equity investment, the latter two contingent upon lifting of clinical hold

Cash & short-term investments2 3 $104.8 M

0 MDebt2

Shares outstanding2 74.1 M

Recent share price1 $6.68

Market cap1 $494.9 M

Page 24: Inovio Pharmaceuticals - Corporate Presentation

Publish Zika phase I

immune response and

safety data

Report MERS phase I

immune response and

safety data (interim)

Advance INO-5401

new cancer target

program

Publish Ebola clinical

data in peer-reviewed

manuscript

INO-3112

Initiate checkpoint

inhibitor combo study

VGX-3100 (CIN)

phase III study

initiation

Report INO-5150

(prostate) immune

response and safety

data (interim)

Upcoming Value Drivers and Milestones

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VGX-3100 (VIN)

phase II study

initiation

Page 25: Inovio Pharmaceuticals - Corporate Presentation

Investment Thesis: Inovio Positioned with Multiple

Transformational Steps as an Immunotherapy Leader

Taking immunotherapy to the next level

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Powerful technology

platform

Best-in-class data

Entering phase III

Validation: partners,

publishing, grants

INO:

NASDAQ

Page 26: Inovio Pharmaceuticals - Corporate Presentation

Appendix

Page 27: Inovio Pharmaceuticals - Corporate Presentation

Right Immune Targets,

Genetic Sequences &

Delivery Method

Immune Responses

Validated in Humans

T Cell Related

Efficacy in Humans

Late Stage Development

& Commercialization

2005-2009 2010-2013 2014-2016 2017-2020+

Inovio Refines and Validates DNA Immunotherapies

Inovio has built leading knowledge capital and IP

27

Breakthrough in

vivo generation of

immune responses

in large animals.

Integrated technology

platform achieves

robust immune

responses in humans.

Killer T cells

generated in the

body correlated to

efficacy.

Strong immune

responses across

multiple diseases.

Launching P3 and

combo cancer studies.

Pursuing efficacy data

in multiple studies.

Page 28: Inovio Pharmaceuticals - Corporate Presentation

Optimized DNA with Safe & Effective Delivery to Generate

Significant T Cells with Killing Activity

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Synthetic

Consensus

DNA

Protective universal antibodies

and killer T-cells produced by

immune system against a virus

or cancer self-antigen

Page 29: Inovio Pharmaceuticals - Corporate Presentation

Enhanced Cellular Delivery:

Key Enabler of DNA Immunotherapies

• DNA plasmids must get through

protective membrane into a cell

to work

• Best method to enhance cellular

uptake is electroporation

• SynCon® DNA plasmid and

CELLECTRA® delivery device

are phase III ready

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CELLECTRA® 5PSP Device

Page 30: Inovio Pharmaceuticals - Corporate Presentation

CELLECTRA® 5PSP Electroporation Delivery Device

30

Array

Drug

Page 31: Inovio Pharmaceuticals - Corporate Presentation

Natural Immune Activation in the Body

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T cells eliminate cells displaying

disease-specific antigen(s)

Immune system recognizes

“foreign” antigens; activates antigen-

specific T cells and antibodies

Effective, efficient,

safe in vivo T cell

and antibody

activation

Cellular machinery uses genetic code

to produce disease antigens

ANTIGENIC

PROTEINS

Deliver plasmids into human

cells using electroporation

Page 32: Inovio Pharmaceuticals - Corporate Presentation

0

1000

2000

3000

4000

5000

T Cell Responses By ELISpot Assay

1 x

10

-6 s

ple

en

ocy

tes

Immunized 3x with 15ug pNPresponses @2 wk post Imm

Display of GFP gene expression after

electroporation delivery into rabbit muscle

+EPE

P

Optim

ization

Design + Delivery = Improved Immune Responses

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Page 33: Inovio Pharmaceuticals - Corporate Presentation

† HVTN 080 (N = 48 total). Responses shown against global peptides post-third dose, based on evaluable responders.

‡ HVTN 070 (N = 120 total). Responses shown against global peptides post-third dose, based on evaluable responders.

Clinical Confirmation of Inovio Electroporation BenefitHIV Antigen Response

• CD4 and CD8 intracellular

cytokine staining (IFN-γ, IL-2)

response associated with IL-12

and EP administration (2 clinical

studies) with HIV gag, pol, env

antigens/plasmids

• Dosing at 0, 4, 12 weeks

• Performed by independent HVTN

Core Lab at University of

Washington in NIH-sponsored

trials

0

10

20

30

40

50

60

70

80

90

- IL-12 + IL-12 - IL-12 + IL-12

CD4+ Responders (%) CD8+ Responders (%)

% R

es

po

nd

ers

33

+ EP

- EP

Spyros A. Kalams, et al., The Journal of Infectious Diseases 2013;208:818–29

Responses to three doses of vaccine

delivered with EP are greater than

responses to four doses of vaccine

delivered IM

P= 0.0003

P < 0.0001

Page 34: Inovio Pharmaceuticals - Corporate Presentation

First Partnership to Initiate Immuno-Oncology Strategy

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ProductsINO-3112 HPV-driven cancer immunotherapy

+ 2 new R&D products

Upfront

Payment$27.5 million

Development

CostsAll development costs

Milestone

Payments$700 million

RoyaltiesUp to double digit tiered royalties on INO-3112 +

royalties for additional cancer vaccine products

AstraZeneca/MedImmune(deal signed August 2015)

MedImmune intends to study INO-3112 in combination with

selected immuno-oncology molecules within its pipeline

Page 35: Inovio Pharmaceuticals - Corporate Presentation

Perforin

Gra

nu

lys

in

Gra

nzym

e A

Gra

nzym

e B

• Lytic phenotype: patient PBMCs stimulated 120 hours in vitro with antigen. No co-

stimulation; no cytokine added at any time.

• Activation markers: CD38, CD69, CD137

• Lytic proteins: perforin, granzyme A, granzyme B, granulysin

INO-3112 Drives Antigen Specific CD8+ T Cells with Lytic

Phenotype in Patient with HPV16/18 Head & Neck Cancer

35

Page 36: Inovio Pharmaceuticals - Corporate Presentation

HPV 16/18

Specific CD8+

T Cell

Activation

HPV 16/18

Specific CD8+

T Cell

Activation and

Expression of

Lytic Proteins

8 of 9 patients show

CD8+ responses

to INO-3112

Induction of CD8+ Activation, Lytic Protein Synthesis, and Humoral Immune

Responses to HPV 16 and 18 in INO-3112 Treated HNSCC Patient

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0 .0

0 .2

0 .4

0 .6

0 .8

1 .0

IN O -3 1 1 2

% C

D8

/CD

38

& C

D6

9 &

CD

13

7

B e fo r e

IN O -3 1 1 2

A fte r

IN O -3 1 1 2

Representative

patientBefore

INO-3112

After

INO-3112Before

INO-3112After

INO-3112

Page 37: Inovio Pharmaceuticals - Corporate Presentation

dMAb™ Products: Multiple Immune Mechanisms & Products

Inovio’s DNA-based monoclonal antibody products target:

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Cancers Infectious Diseases

• Influenza A

• Influenza B

• Pseudomonas

• MRSA/Staph

• Ebola

• MERS

• Dengue

• CHIKV

• Other infectious

diseases

• Checkpoint Inhibitors

(CI)

• PD-1

• PD-L1

• 4 additional CIs

• Herceptin

• Anti-Tregs

• Other anti-cancer

pathways

DARPA funded programs

Page 38: Inovio Pharmaceuticals - Corporate Presentation

Promising Preclinical dMAb Data

DARPA awards $57M to advance dMAb application and develop products for Ebola,

influenza and antibiotic resistant bacteria

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0%

20%

40%

60%

80%

100%

Tu

mo

r C

lea

ran

ce

(%

)

Cancer dMAbProstate cancer model in mice

(Unpublished data)

dMAb (7 of 10) Control (0 of 10)

70%

0%0%

20%

40%

60%

80%

100%

Pro

tec

tio

n in

Ch

all

en

ge w

ith

Den

gu

e

Vir

us

(%

)

Dengue dMAb(Nature Scientific Reports 2015)

dMAb (10 of 10) Control (0 of 10)

100%

0%

Page 39: Inovio Pharmaceuticals - Corporate Presentation

Antigen-Generating/T Cell Activating SynCon® Products

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Product Name Indication Preclinical Phase I Phase II

VGX-3100

INO-5150

INO-1400

Phase III

INO-3112

hTERT (antigen) Therapeutic

Prostate Cancer Therapeutic

HPV-Related Cancers Therapeutic

Cervical Dysplasia Therapeutic

INO-1800 Hepatitis B Therapeutic

EbolaINO-4212

Preventive

PENNVAX®-GP HIVPreventive/

Therapeutic

INO-8000 Hepatitis C Therapeutic

Preventive

EXTERNALLY FUNDED

Infectious Disease

Programs

INTERNALLY

FUNDED

Cancer Programs

EXTERNALLY

FUNDED

Cancer Programs

GLS-5300 MERS Preventive

INO-5401 Cancer Target Therapeutic

Zika PreventiveGLS-5700