Benitec Ltd

www.benitec.com

1

Benitec’s Gene Silencing Platform Technology – An overview

Non-Confidential Presentation

Benitec Ltd

www.benitec.com

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This presentation contains forward looking statements that involve risks and uncertainties. Although we believe that the expectations reflected in the forward looking statements are reasonable at this time, Benitec can give no assurance that these expectations will prove to be correct. Actual results could differ materially from those anticipated. Reasons may include risks associated with drug development and manufacture, risks inherent in the regulatory processes, delays in clinical trials, risks associated with patent protection, future capital needs or other general risks or factors.

Benitec Ltd

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Table of Contents

ddRNAi Technology Investment Thesis 4

Benitec Corporate Overview 5

RNA Interference Background 9

Introduction to the ddRNAi Technology 10

Current ddRNAi Programs 13

Benitec Intellectual Property Portfolio 19

Investment Opportunity Summary 23

Contact Information 24

Benitec Ltd

www.benitec.com

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ddRNAi Technology

Investment Thesis

DNA-directed RNA interference (ddRNAi) is a novel technology platform capable of achieving long-term targeted gene silencing.

Benitec is developing a a range of products that utilize the ddRNAi technology to treat and cure life threatening severe conditions in infectious disease, cancer and CNS areas.

Benitec’s cancer areas include drug resistant non-small cell lung cancer and relief of cancer-associated neuropathic pain.

Benitec’s infectious disease areas include programs in chronic hepatitis infection, including hepatitis B and C.

Functional gene silencing constructs for all of the programs have been created. Preclinical in vivo studies proving the safety and efficacy of the products are in progress.

Benitec’s technology platform is applicable to a large number of other therapeutic areas In which up-regulation of a gene is associated with a disease or disorder, including genetic diseases.

Benitec Ltd

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Benitec Corporate Overview

Based in Sydney, Australia, Benitec is a biopharmaceutical company developing a novel

DNA-directed RNA interference (ddRNAi) platform for therapeutic use. The company

is listed on the Australian stock exchange (ASX: BLT) with a market cap of ~AU$25M

and AU$7M cash at hand.

Benitec is pursuing licensing, partnering and co-development activities for its

transformational, proprietary ddRNAi platform technology for human therapeutics

and research.

Benitec has a strong management team with deep scientific and clinical resources

and extensive experience with the commercialization of biological intellectual property.

Benitec is currently utilising ddRNAi technology internally across multiple therapeutic

areas where there is a significant unmet need to develop ddRNAi-based

therapeutic products for a range of conditions including lung cancer, neuropathic

pain, and infectious disease (hepatitis B and hepatitis C).

Business Overview

Business Strategy

Management Team

Product Strategy

Benitec has a robust patent portfolio protecting their platform technology across the

major pharmaceutical markets with patent coverage extending through 2027. Intellectual Property

Benitec Ltd

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Benitec Corporate Strategy

to Build Value

ddRNAi Technology

Human Therapeutics Research Tools

Partner Individual Therapeutics

Develop the ddRNAi therapeutic product

pipeline in-house through pre-clinical

and early stage clinical studies, and

potentially partner products for late-

stage development and

commercialization

Partner Therapeutic Platform

Partner the technology platform for a

wide range of therapeutics in the near

term for development and

commercialization

Partner Technology For Research

License the ddRNAi platform

technology as a research tool to

research institutions, pharmaceutical

and biotech companies

Benitec has a value-building strategy based on to partnering its proprietary ddRNAi technology with

pharmaceutical and biotechnology companies both as research tools and as potential therapeutics.

Benitec Ltd

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Benitec Senior Leadership Team

CEO

Peter French, PhD

Cell and molecular biologist with an MBA in

Technology Management. Founder of stem cell

storage company Cryosite Ltd, launched six

new probiotic-based products with Probiomics.

CFO, Company Secretary

Greg West

Chartered Accountant, Director and audit

committee chairman of ITC Ltd, IDP

Education Pty Ltd, Education Australia Ltd,

and Sydney International Film School Pty Ltd.

Board of Directors

Peter Francis LLB Grad Dip

(Intellectual Property) Non-

executive Chairman

Partner at Francis Abourizk

Lightowlers (FAL), a legal

specialist in the areas of

intellectual property and licensing

and provides legal advice to a

large number of corporations and

research bodies.

Mel Bridges BAppSc FAICD

Non-executive Director

More than 30 years experience

in the global biotechnology and

healthcare industry. During this

period, he founded and

managed successful

diagnostics, biotechnology and

medical device businesses.

John Chiplin PhD

Non-executive Director

His most recent accomplishment

was the corporate reengineering

of Arana Therapeutics, a world

leading Antibody developer,

which resulted in the acquisition

of the company by Cephalon for

a significant premium to market.

Iain Ross BSc ChD

Non-executive Director

Over 30 years experience in the

international life sciences sector.

Following a career with Sandoz,

Fisons, Hoffman La Roche, and

Celltech he has undertaken and

had input to a number of

company turnarounds and

start‐ups

Benitec’s management team has demonstrated experience and expertise in developing and licensing novel

therapeutic technology.

Benitec Ltd

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Indication Discovery Pre- clinical Human Clinical

Collaborator/ Licensee

Collaboration Status

Cancer-associated pain

University of Queensland (Australia)

Benitec has contracted with TetraQ to generate data to be able to conduct a clinical trial on terminally ill cancer patients suffering from pain.

Drug resistant lung cancer

University of New South Wales (Australia)

Researchers are collaborating with Benitec to develop a ddRNAi-based therapy to overcome chemotherapy resistance in non-small cell lung cancer.

Hepatitis B Biomics (China) Benitec is working with Biomics to develop ddRNAi candidates for hepatitis B silencing for preclinical testing and a China-based clinical trial.

Hepatitis C Tacere (Pfizer)

(US)

Benitec’s preclinical hepatitis C program was outlicenced to Tacere in 2006, and then outlicensed by Tacere to Pfizer in 2008. In 2010, Pfizer exercised an option to further develop and commercialize Tacere’s Hepatitis C compounds as a result of favorable primate and mouse efficacy and toxicity studies. The companies observed no maximum tolerated dose, no safety signals, viral inhibition and >90% penetration of human hepatocytes.

Licensed program

Benitec has a pipeline of ddRNAi-based therapeutics targeted for indications where their technology provides

a significant competitive advantage.

Benitec funded programs Partnered program

ddRNAi Product

Development Timeline

Benitec Ltd

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RNAi Mechanism

RNA Interference

Technology Background

RNAi is a technology which silences targeted genes through a natural mechanism, the discovery of which

earned Andrew Fire and Craig Mello the Nobel Prize in Physiology and Medicine in 2006.

Sources: Datamonitor. RNA Therapy. October 2008; Business Insights. The Future of RNAi Therapeutics. August 2008.

Source: The Nobel Prize in Physiology or Medicine 2006. Nobelprize.org. Accessed October 2011.

Technology Background

RNA therapies can be divided into RNAi therapies, which are

mediated by the RISC enzyme, and antisense therapies,

which are RISC-independent agents.

Antisense oligonucleotides were initially used primarily as an

in vitro research tool but have been developed as a means of

modifying RNA levels in human therapeutic applications.

RNAi was subsequently found to offer up to 1000 x more

efficient silencing than antisense agents.

Modern RNAi therapeutic approaches utilize short, chemically

synthesized RNA duplexes that mimic natural products.

The RNAi mechanism allows protein function to be modulated

by controlling the translation of mRNA.

Gene

Therapy

RNA

Therapy

Small Molecules

mAbs

DNA RNA Protein

Modulating

Agent:

Target:

The Dicer endonuclease cuts

double stranded RNA into

short pieces (siRNA)

The antisense strand is

loaded into the RNA-induced

silencing complex (RISC) and

links the complex to the

mRNA strand by base pairing

The RISC complex cuts the

mRNA strand and the mRNA

is subsequently degraded

Benitec Ltd

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Benitec’s Novel

RNA Interference Technology

ddRNAi Mechanism of Action Benitec technology

ddRNAi DNA construct

Sources: Zou W et al., Intrathecal Lentiviral-Mediated RNA Interference Targeting PKCγ Attenuates Chronic Constriction Injury–Induced Neuropathic Pain in Rats. Human Gene Therapy. 22:465–475 (April 2011)

Benitec’s ddRNAi technology platform utilizes a self-inactivating lentiviral vector to express shRNA molecules

which silence a targeted gene of interest.

The ddRNAi-based product consists of a third-generation

vesicular stomatitis virus G (VSV-G) pseudotyped self-

inactivating lentiviral vector containing a novel gene

construct.

The construct expresses a short hairpin RNA (shRNA)

molecule intended to silence the selected gene of

interest.

The expressed shRNA integrates into the host’s native

RNAi process where it is separated into single strands

and binds to the target mRNA.

– This results in cleavage of the target RNA and

silencing of the gene of interest.

ddRNAi Mechanism of Action

Benitec Ltd

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Differences between ddRNAi

and Conventional siRNA

While siRNA has demonstrated considerable limitations for clinical use, ddRNAi has the potential to

overcome many of the delivery obstacles previously faced by siRNA.

Source: Datamonitor. Gene Therapy. December 2009.

Differences Between ddRNAi and siRNA

Property ddRNAi siRNA Description

Origin Double stranded RNA for siRNA must be manufactured, while in ddRNAi, the

shRNA is continuously expressed by the host cell.

Potency ddRNAi-generated shRNA is up to 250x more potent than siRNA and thus requires

less material to silence a gene.

Off-Target Effects

Off-target effects are common and problematic with siRNA. ddRNAi results in minimal off-target effects due to its expression being restricted to the transfected cell type.

Delivery

ddRNAi is capable of utilising a range of established delivery options including viral, non-viral and stem cell vectors, while siRNA must be modified for systemic or targeted delivery.

Duration of Action Unlike siRNA, which is capable of only short-term silencing, ddRNAi has a variable

duration of action including the potential for long-term silencing.

Targeting Options Multiple targets can be targeted with a single DNA construct using ddRNAi, while

only a single target can be targeted with each siRNA.

Cost Production of the shRNA DNA construct and delivery system is low cost, while

siRNA requires expensive custom synthesis Positive Attribute

Neutral Negative Attribute

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Proof of Concept Study for ddRNAi

in AIDS Lymphoma Patients (Phase I)

The advantages of the ddRNAi technology were demonstrated in a pilot study (phase I clinical trial) to assess

the safety and feasibility of using a lentiviral RNA vector encoding multiple targets in stem cells of AIDS

lymphoma patients.

Results of the AIDS Lymphoma Study

ddRNAi therapy is safe and feasible.

The therapy is long-lasting (at least two years) from a single treatment.

Patients are able to rebuild a new and resistant immune system following treatment.

Lentiviral-mediated

transduction of CD34

Pool and infuse

Patient follow-up

Healthy HIV positive

or chemo-responsive

AIDS lymphoma

GCSF

Stem-cell enrichment Apheresis

CD34+ PBPC

Study Design

GCSF – Granulocyte colony-stimulating factor

PBPC – Peripheral blood progenitor cell

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Preclinical in vivo studies have been conducted

successfully showing the efficacy of PKCγ-targeted

ddRNAi on pain inhibition.

Current ddRNAi Programs:

Cancer Pain Product

Utilizing the ddRNAi platform, Benitec has developed their gene silencing technology for the treatment of pain

in terminal cancer patients.

Rationale:

PKCγ has been shown to play a major role in the

transmission of neuropathic pain and in overcoming

tolerance to morphine.

The restricted spinal cord location of the PKCγ-

containing interneurons allows a selective inhibitor to

inhibit nerve injury-induced neuropathic pain.

KOLs see strong potential for the ddRNAi cancer pain

product to be used in terminal patients suffering from all

types of cancer.

Market Size:

There are approximately 11.7 million people in the US

with cancer. Approximately 65% of all cancer

patients experience pain.

The cancer pain ddRNAi product may be used in up to

65% of cancer patients receiving invasive pain therapy.

Cancer Pain

Collaborator:

Status:

Benitec has planned a phase I/II study of the ddRNAi-

based product in terminal cancer patients with intractable

pain and a quick timeline to approval is expected.

Benitec Ltd

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Of 5000 potential sequences, 14 RNA sequences

have been identified by Biomics that provide ≥70%

knockdown of HBV gene mRNA.

Current ddRNAi Programs:

Hepatitis B

The ddRNAi technology is also being developed for HBV under collaboration with Biomics.

Rationale:

Successful ddRNAi delivery to the liver has been

demonstrated.

The targeted enzyme is key to HBV replication.

The strategy provides treatment of the existing infection

and long-lasting protection from re-infection.

Market Size:

There are about 400 million people worldwide with

chronic HBV infection.

Carriers of HBV are up to 300 times more likely to

develop liver cancer than non-carriers, and HBV causes

60-80% of the world’s primary liver cancers.

Hepatitis B Virus

Collaborator:

Status:

Benitec is working with Biomics to evaluate RNAi

candidates for hepatitis B silencing for preclinical testing

and a China-based clinical trial.

Benitec Ltd

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Current ddRNAi Programs:

Hepatitis C

Benitec has sub-licensed its technology platform to Tacere to develop a ddRNAi-based therapeutic targeting

the Hepatitis C viral genome.

Hepatitis C Virus

Rationale:

Successful ddRNAi delivery to the liver has been

demonstrated.

The strategy provides treatment of the existing infection

and long-lasting protection from re-infection.

Multi-target construct (three sequences) to prevent viral

escape in a single drug “cocktail”

Market Size:

Over 170 million people worldwide, are chronically

infected with HCV, with 3-4 million new infections

occurring each year.

Licensed to Tacere Therapeutics Inc. - USD$143M deal

with Pfizer Inc. Benitec has an equity stake in Tacere.

Collaborator:

Status:

Pfizer have closed the Sandwich facility,

uncertain status of program

Tacere have demonstrated both efficacy and safety

with their AAV8-delivered ddRNAi-based therapeutic

in non-human primates

Benitec Ltd

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Development Plan and Timeline for

Current ddRNAi Programs

Current ddRNAi Programs Clinical Development Timeline

Program 2011 2012 2013 2014 2015

Hepatitis B

Cancer Pain

Additional clinical studies to be planned in both HepatitisB and Cancer Pain

Proof of concept in pre-clinical model of pain

Toxicology studies

IND Preparation and Submission

Phase I/II Trial (cancer patients with intractable pain)

Target Sequence Efficacy

Design vector-expressed constructs

Preclinical testing (in vitro and in vivo models)

Benitec Ltd

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Current ddRNAi Programs:

Drug Resistant NSCLC

Benitec is collaborating with University of New South Wales researchers to develop a ddRNAi-based

therapeutic targeting a gene associated with chemotherapy resistance.

Non-small Cell Lung Cancer (NSCLC)

Rationale:

βIII-tubulin has been shown to be associated with drug

resistance in non-small cell lung cancer (NSCLC).

Silencing βIII-tubulin using ddRNAi increases the killing

of NSCLC cells by chemotherapy agents.

Market Size:

Lung cancer is the leading form of cancer worldwide in

terms of incidence and mortality.

NSCLC account for >80% of all lung cancers and has a

high mortality rate due to rapid development of

resistance to chemotherapy drugs.

Collaborator:

Status:

Researchers are using Benitec’s technology to develop a

ddRNAi-based therapy to overcome chemotherapy

resistance in NSCLC cells.

In vitro results show highly effective silencing of

βIII-tubulin and effective targeting of NSCLC cells

with the ddRNAi construct.

Benitec Ltd

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Development Plan and Timeline for

NSCLC ddRNAi Program

NSCLC ddRNAi Programs Clinical Development Timeline

Program 2011 2012 2013 2014

NSCLC

Animal model (lung)

In vivo Toxicology

Phase I Clinical Trial

IND Preparation and Submission

Benitec Ltd

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Benitec Intellectual Property

Portfolio

Benitec has an extensive patent estate for the ddRNAi product that spans key pharmaceutical markets with

coverage through 2027 with additional exclusivity anticipated for biologic upon launch.

Graham&family&patents'!

"revocable)license)from)CSIRO!for$the$human$field)!

Patent&Number Description! !Jurisdiction

Genetic'constructs'for'delaying'or'repressing'the'expression'of'a'target&gene

Sense strand

Hair pin

Complementary strand

A family of patents that covers Benitec’s gene silencing platform technology in

expressed RNA interference.

Generally the patents cover a double stranded DNA construct which comprises:

• one or more sequences directed to one or more targets

• sequences of around 20 to 30 nucleotides in length

• sequences substantially identical or identical to the target gene sequence

• target is either exogenous or endogenous genes

• in mammalian cells, preferably human

Widely!granted!in!countries!including!Australia,!

South!Africa,!New!Zealand,!UK,!Canada,!India,!Japan,!Europe,!USA!

!

Expiry!from!June!2018!

Benitec Ltd

www.benitec.com

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Benitec Intellectual Property

Portfolio

Benitec has an extensive patent estate for the ddRNAi product that spans key pharmaceutical markets with

coverage through 2027 with additional exclusivity anticipated for biologic upon launch.

Waterhouse!family'patents'!

xclusive)worldwide!license'from'CSIRO'for'the'human'field)!

Patent&Number Description! Jurisdiction!

CN#200910206175.7#

#

Methods(And(Means(For(Obtaining(Modified(Phenotypes

Sense strand

Hair pin

Complementary strand

This patent covers a cell that contains either a double stranded DNA construct for

expressing a hairpin RNA, or a hairpin RNA itself. The hairpin comprises:

• Sense and anti-sense sequences of at least 20 nucleotides in length

• sense sequence is sequence of target

• antisense sequence is 100% identical to complement of sense sequence

China!

!

Expiry!from!June!2018!

EP#1068311#

The patent covers an RNA molecule that comprises

· a sense sequence and an anti-sense sequence of at least ten consecutive

nucleotides

· 75% to 100% sequence identity to a target sequence

· in a hairpin RNA structure

Europe!

Benitec Ltd

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Benitec Intellectual Property

Portfolio

Benitec has an extensive patent estate for the ddRNAi product that spans key pharmaceutical markets with

coverage through 2027 with additional exclusivity anticipated for biologic upon launch.

Benitec!Owned&Patents!

Patent&Number! Description! Jurisdiction!

US7,727,970;!JP4763681;!!!!!!!!!!!!!!!!!!!

EP05727680.0;!!!!!!!!!!!!!!AU2005222084;!NZ550284!

AU2006210443;!US11/883645;!US7,803,611;!NZ560936!

Expression*cassettes*for*delivery*of*ddRNAi*agents*targeting(hepatitis(C(Virus#

Two patent families covering the use of ddRNAi expressing multiple shRNAs from either single or multiple promoters, targeting sequences on the hepatitis C viral genome

!

USA,!Europe,!Australia,!Japan,!New!Zealand!

Expiry:!2025L2027!

US8,008,468;!US11/731198!

Liver(cell(specific(RNAi(expression(constructs(

Patents that cover the use of a ddRNAi expression construct which has liver specific promoter

and enhancer components to complement Benitec’s hepatitis programs US!

AU2004243347;!NZ543815;!

ZA2005/09813;!!!!SG200507474L5!

A"long"double>stranded(nucleic(acid#construct#

Patents that cover the use of a long double stranded DNA construct expressing multiple double

stranded RNA silencing molecules, each 17 to 30 nucleotides in length.

Australia,!New!Zealand,!Singapore,!South!Africa!

Expiry:!2024!

GB!2377221;!SG91678;!

ZA2002/07428!

Genetic'silencing(

A genetic construct, that reduces the translation of a target endogenous gene, comprising a

sequence of nucleotides substantially identical to a sequence of the target gene and a nucleotide sequence complementary or substantially complementary to the target gene

sequence wherein the nucleotide sequences identical and complementary to said target endogenous nucleotide sequence are separated by a spacer sequence.!

Great!Britain,!Singapore,!South!Africa!

Benitec Ltd

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Benitec Intellectual Property

Portfolio

Benitec has an extensive patent estate for the ddRNAi product that spans key pharmaceutical markets with

coverage through 2027 with additional exclusivity anticipated for biologic upon launch.

Benitec Ltd

www.benitec.com

23

Investment Opportunity Summary

ddRNAi Product Asset Summary

Extensive IP Estate Patent Coverage Through 2027

Favorable KOL Responses

Favorable preclinical data

From Extensive in vitro and in vivo Studies

Unmet Medical Need ddRNAi can treat undrugable targets

Large Market Opportunities Non-Small Cell Lung Cancer, Pain, Hepatitis

and a plethora of other opportunities

Novel Approach Novel class of therapeutics for treatment and cure

Benitec Ltd

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Contact Information

To respond to this introduction to the ddRNAi opportunity, please contact:

Dr. Peter French, Ph.D., M.B.A.

CEO Benitec Ltd.

Phone: +61 (0)412 457 595 E-mail: pfrench@benitec.com