Corporate Overviewcontent.equisolve.net/genvec/media/cf148f344865a9ffc78789c610f0… · Corporate Overview 3 Discovery Preclinical Phase 1 Phase 2 Phase 3 Approved Hearing Loss [Novartis]

Developing a pipeline of innovative therapeutics and vaccines that deliver on the promise of gene-based medicine

Corporate Overview December 2015

Statements herein relating to future financial or business performance, conditions or strategies and other financial and business matters, including expectations regarding future revenues and operating expenses, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. GenVec cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks and uncertainties, including the failure by GenVec to secure and maintain relationships with collaborators; risks relating to clinical trials; risks relating to the commercialization, if any, of GenVec’s proposed product candidates (such as marketing, regulatory, patent, product liability, supply, competition and other risks); dependence on the efforts of third parties; dependence on intellectual property; and risks that we may lack the financial resources and access to capital to fund our operations. Further information on the factors and risks that could affect GenVec’s business, financial conditions and results of operations are contained in GenVec’s filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. The forward-looking statements speak only as of the date of this presentation, and GenVec assumes no duty to update forward-looking statements.

Safe Harbor Statement

1 December 2015 Corporate Overview

Pioneering biotechnology company focused on leveraging its proprietary AdenoVerse™ gene delivery platform to develop a pipeline of cutting-edge therapeutics and vaccines

Clinical stage hearing loss program partnered with Novartis

GenVec therapeutics and vaccines safely administered to over 3,000 clinical study subjects

AdenoVerse™ platform provides multiple opportunities for product development and licensing, and is supported by strong IP

Investment Highlights

2 Corporate Overview December 2015

GenVec Pipeline

3 Corporate Overview

Preclinical Phase 1 Phase 2 Phase 3 Approved Discovery

Hearing Loss [Novartis]

Respiratory Syncytial Virus, RSV

Herpes Simplex Virus 2, HSV-2

Malaria [LMIV, NMRC]

Enterovirus-D68, EV-D68

Neural Stem Cell (NSC) Therapeutics [TheraBiologics]

Foot & Mouth Disease in Cattle [DHS, USDA; Commercial license – Merial, a Sanofi co.]

Vaccines Therapeutics Key: [ Product Partner(s) ]

December 2015

Hearing loss is a multi-billion dollar market opportunity

Disabling conditions with high and increasing prevalence worldwide

An estimated 1 in 6 adult Americans suffer from hearing loss

90% of hearing loss is sensorineural

No current pharmaceutical treatment options

Hearing and Balance Program The Opportunity


How We Hear


Causes of Sensory Cell Loss

• Age Related

• Infection

• Drug Induced

• Sound Trauma

The Problem Loss of Sensory Cells


Sensory Cells

December 2015

Deliver the Atonal gene to the supporting cells using an

adenovector

Produce Atonal protein in supporting cells

Trigger conversion of supporting cells into sensory cells

The Solution Generate New Sensory Cells

Sensory cell

Supporting cell


Regeneration of Sensory Cells

Data taken from Izumikawa et al. study, Nature Medicine, 2005, 11(3): 271-276

Damaged and Untreated Damaged and Treated


Restoration of Hearing

Data taken from Izumikawa et al. study, Nature Medicine, 2005, 11(3): 271-276


Sensory Cell Count

0

500

1,000

1,500

2,000

2,500

Control Damaged Damaged &

Treated

Schlecker et al. Gene Therapy, 2011, 18: 884-890

Regeneration of Sensory Cells


Restoration of Balance

Mice improved swim test scores 8 weeks after Atonal gene delivered

(Untreated) (Treated)

Baker et al. 2009. Adv. Otorhinolaryngol. 66: 52-63


Sensory Cell Innervation Regenerated Sensory Cells Attract Neuronal Outgrowths


Control

Damaged Damaged & Treated

Sensory Cells (red)

Neurons (green)

Schlecker et al. Gene Therapy, 2011, 18: 884-890

December 2015

Novartis responsible for worldwide development and commercialization

Up to $206.6 million in milestone payments ($5.6 million realized to date)

Royalties on sales

GenVec qualified by Novartis to support program

Novartis Collaboration Overview


Clinical Candidate (CGF166)

Vector Schematic

E1 region replaced with transgene

expression cassette

E4 region replaced

with spacer

Adenovirus Serotype 5

GFAP promoter

E3 region deleted

Hath1 SV40 polyA

Ad5.GFAP.Hath1 CGF166

E1 E3 E4 E2

CGF166 leverages GenVec’s AdenoVerse™ Platform:

• Vector backbone safely administered to over 3,000 subjects

• E1, E3, E4-deleted adenovirus serotype 5 (Ad5) vector

• Replication-incompetent, non-integrating vector

• Engineered to deliver the human atonal transgene expressed under the control of a cell specific promoter to restrict expression to inner ear supporting cells


CGF166 Preclinical Testing Sensory Cell Regeneration Data


CGF166 Preclinical Testing Hearing Functional Restoration

AB

R T

hre

sho

ld R

eco

very

(d

B)

AB

R T

hre

sho

ld R

eco

very

(d

B)

Frequency: 32 kHz Injured + Ad5.GFAP.Math1 Injured + CGF166 (HATH 1)

5.5 x 106 5.5 x 107 5.5 x 108 5.5 x 106 5.5 x 107 5.5 x 108

0

5

10

15

20

25

*

*

Mean ± SEM; *P<0.05, n = ~15

0

5

10

15

20

25

*

Frequency: 32 kHz


Post Ad5.CMV.GFP – green marker shows transduced supporting cells, no sensory hair cells evident

Post CGF166 - red Anti-myosin VIIa hair cell marker shows regenerated sensory hair cells in human tissue

CGF166 Preclinical Testing

Neomycin + Ad5.CMV.GFP

1 x 107 vp/µl

Neomycin + CGF166

1 x 107 vp/µl

Untreated

Untreated tissue - human inner ear, schwannoma patient

Sensory Cell Regeneration in Human Tissue


Clinical Plan Overview

Trial Design

Multicenter trial of 26 to 45 patients with severe to profound hearing loss

• Single, 3-patient cohort

• Dose: 20 µl Part A: Safety

• 2-5 cohorts of 3 patients each

• Dose volume between 30 µl and 90 µl

Part B: Dose

Volume Escalation

• Single cohort of 20 patients at dose determined by Part B

• Option to resize Part C: Efficacy


Primary Endpoints

• Change from baseline in pure tone audiometry measured at frequencies between 0.5 and 16 kHz

Secondary Endpoints

• Speech recognition

• Balance function measurements

Exploratory Endpoints

• Jacobson Dizziness Handicap Inventory

• Hearing Handicap Inventory for Adults

• Tinnitus Reaction Questionnaire

Clinical Endpoints


The minimum criteria for efficacy are an “inversion” of established criteria for ototoxicity

A 10 dB change is considered meaningful

dB Level Noise Source

10 Normal breathing

20 Rustling leaves

30 Quiet conversation

50 Normal conversation

60 Loud television

80 Noisy office

100 Loud car horn

120 Jet plane take-off (100 feet)

130 Threshold of pain

Change in dB Level

Impact

1 dB Generally not perceptible

3 dB Just barely perceptible

5 dB Clearly noticeable

10 dB Twice or ½ as loud

20 dB Four times or ¼ as loud

Efficacy Criteria


Key Inclusion Criteria

• Patients 18-75 years old with acquired bilateral hearing loss

• Minimal residual hearing (< 110 dB)

• Stable pure tone thresholds for at least 6 months

• Pure tone threshold > 50 dB for lower frequencies and > 70 dB for higher frequencies

• Patients eligible for general anesthesia and surgery

Key Exclusion Criteria

• Known genetic disease associated with hearing loss

• Known cause of hearing loss that is associated with structural damage

• Unilateral vestibular dysfunction in the non-treatment ear

Key Inclusion/Exclusion Criteria


Drug Delivery Intra-Labyrinthine (IL)


Drug Product Infusion Device Infusion Pump

CGF166 Delivery System


CGF166 Overview

A Novel Therapy for Hearing Loss

Demonstrated ability to deliver material to cochlea and vestibular system

Demonstrated efficacy in various models (explants and in vivo)

Ongoing Phase 1/2 clinical study designed to evaluate safety and efficacy


TheraBiologics Collaboration

Neural Stem Cell Mediated Cancer Therapy

Benefits of Neural Stem Cells (NSCs): • Inherent ability to track down cancer cells

• Able to cross blood brain barrier

• Able to penetrate tumor mass

• Provide an efficient vehicle to deliver a therapeutic payload within the tumor and metastatic sites


NSCs

bv

NSCs penetrate

main tumor mass

NSCs selectively target invasive

tumor cells

NSC Tumor Cell

NSCs target new blood

vessels

December 2015


Neural Stem Cell CE Cancer Therapy


NSCs transduced by proprietary GenVec adenovector express and secrete carboxylesterase (CE) within the tumor

Secreted CE enzyme provides radius of action throughout the tumor

CE converts irinotecan to SN-38, which is 1,000x more toxic to tumor cells than irinotecan alone

NSC Secrets CE

Irinotecan

SN-38

Tumor cell killing

NSC

Conversion to SN-38

December 2015


Pre-clinical Efficacy in Neuroblastoma Model


0 100 200 300 400

0

50

75

25

100

Days After NB injection

Pe

rce

nt

Surv

ival

Untreated

NSC.CE + Irinotecan

Irinotecan only

December 2015

Adenovector Advantages

Excellent safety profile facilitated by additional viral genome deletions

Efficient transduction in dividing and non-dividing cells

Low probability of disturbance of vital cellular genes due to the non-integrating transgene

Grow in high titers to support product manufacturing and commercialization


GenVec’s Proprietary Technology Platform

AdenoVerse™

GenVec’s adenovectors have superior performance characteristics for therapeutics and vaccines: • Vectors with no or very low seroprevalence in the

human population

• Featuring Tunable Tropism technology to allow cell-type specific gene delivery

• Large packaging capacity (>12 kb) with multiple expression cassettes


GenVec’s capabilities to support vector development and manufacturing:

• Proprietary vector construction methodology

• Extensive cGMP manufacturing expertise

• Proprietary packaging cell lines supported by FDA Master File

December 2015

Transduction of Cells in Culture

Enhanced Vector Performance F

old

En

ha

nc

em

en

t R

ela

tive

to

Ad

5

GenVec Vectors

0

20

40

60

80

100

120

140

A B C D E F G H I J K L M N

Cell Type A

Cell Type B

Ad5


Applications of the AdenoVerse™ Platform

GenVec Technology

Pioneering the value and versatility of

adenovector gene delivery solutions

for

A broad spectrum of applications across

indications and therapeutic areas

AdenoVerse™

Platform

Regenerative Medicine

Vaccines

Therapeutic Gene

Delivery

Immuno-therapy

Nucleic Acid Therapeutics

Gene Editing

Oncolytics

Cell Therapy

Current / active program areas Potential program areas


Proprietary Vectors, Excellent Performance

Non-Human GC Vectors

Discovered and developed proprietary novel adenoviral vectors with outstanding properties

Productive pre-IND meetings with the FDA for two product candidates

GC vectors include gorilla vectors with distinct advantages for molecular vaccines

• High-level, durable antibody responses

• High-level T cell responses

• Repeat administration boosts responses

Highly Immunogenic

Low Human

Prevalence

Highly Productive


16

32

64

128

256

512

1024

0 2 4 6 8 10 12 14 16 18 20 22 24 26

PR

NT

titer

(IC

50

)

Weeks post-immunization

GC46.F0 109 pu

Single Administration

Superior Antigen Responses High-level, Durable Antibody Response


Malaria genetic vaccine

Superior Antigen Responses

%

C

D8+

IF

Ng+

T-C

ells

0

2

4

6

8

10

12

AdNull Ad5 GC44 GC45 GC46

Single administration

High-Level T Cell Response


Superior Antigen Responses Repeat Administration Boosts Response

Ad Prime

Ad Boost

GC45 1E9

-

-

GC45 1E9

GC45 1E9

GC45 1E9

0

10

20

30

Prime/Boost 12 Week Interval

% C

D8

+ IF

Ng+

T C

ells


RSV Vaccine A Critical, Unmet Medical Need

RSV infection is a significant cause of serious respiratory illness globally Most affected are children, elderly, and high-risk adults No approved vaccine available Market is only partially addressed by Synagis®, which provides passive immunity and is indicated only for high-risk infants


GC Vector for RSV Vaccine Durable Neutralizing Antibody from a Single Dose

16

32

64

128

256

512

1024

0 2 4 6 8 10 12 14 16 18 20 22 24 26

PR

NT

titer

(IC

50

)

Weeks post-immunization

GC46.F0 109 pu

GC46.F0 107 pu

FI-RSV

RSV Genetic Vaccine


Single Administration Protects Upper and Lower Airways Against RSV Challenge

Serum neutralizing antibody

Day 0 Day 28 Day 56

109

GC46.F0 (pu)

RSV FFB Control

FI-RSV 4

5

6

7

8

10

9

• Lung and nasal titers of RSV were reduced to undetectable levels

Geo

Mea

n L

og 2

Tit

ers

(IC

-60

)

Protection against RSV

109

GC46.F0 (pu)

RSV FFB Control

FI-RSV 2.0

2.5

3.0

3.5

4.0

5.0

4.5

5.5

Lung Nasal

Lung LOD

Nasal LOD

Geo

Mea

n L

og1

0 T

iter

s (p

fu/g

)


RSV Genetic Vaccine Summary

Encouraging preclinical data

• Upper and lower respiratory tracts protected

• Good breadth of RSV neutralization

• No evidence of RSV disease potentiation

• Intra-muscular route of administration effective

Lead vaccine (GV2311) selected

Productive pre-IND meeting with FDA


Financial Summary

• 17.3 million shares Common Shares

Outstanding1

• NASDAQ: GNVC Exchange: Symbol

• $40.9 million Market

Capitalization2

• $9.9 million Cash and

Investments3

• 15 Employees

1As of October 31, 2015; 2Stock price as of December 3, 2015; 3As of September 30, 2015


Pioneering biotechnology company focused on leveraging its AdenoVerse™ gene delivery platform to develop a pipeline of cutting-edge therapeutics and vaccines

Clinical stage hearing loss program partnered with Novartis

GenVec therapeutics and vaccines safely administered to over 3,000 clinical study subjects

AdenoVerse™ platform provides multiple opportunities for product development and licensing, and is supported by strong IP

Investment Highlights


GenVec’s Proprietary Technology Platform

AdenoVerse™


AdenoVerse™

Platform

High Transduction

Efficiency

Very Low Human

Prevalence

High Production

Yield

High Packaging Capacity

Tunable Tropism

Significant Clinical

Experience

Enhanced Safety

Non Replicating

December 2015

www.genvec.com

Documents

Corporate Overviewcontent.equisolve.net/genvec/media/cf148f344865a9ffc78789c610f0… · Corporate Overview 3 Discovery Preclinical Phase 1 Phase 2 Phase 3 Approved Hearing Loss [Novartis]