1 Disclaimer Sementis We believe that the information in this - - PowerPoint PPT Presentation

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Disclaimer

We believe that the information in this presentation is correct and any opinions and conclusions are reasonably held or made, based

• n the information available at the time of its compilation, but no

representation or warranty, either expressed or implied, is made

• r provided as to accuracy, reliability or completeness of any

statement made in this presentation. Sementis Limited does not accept any liability for any loss or damage arising out of the use of all or any part of this presentation. This presentation has been prepared without taking into account the objectives, financial situation or needs of any particular individual.

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Sementis

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Sementis SCV platform technology

• Proprietary vaccine platform technology for delivery of

antigens

• Live virus vector derived from attenuated strains of vaccinia

virus

• Enables development of new vaccines in the field of

infectious diseases, allergies and oncology

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Advantages of the SCV platform

• Attenuated virus vector is non-replicating
• Efficient generation of immune responses
• Live virus
• Stimulates antibody and T-cell responses
• Genetic manipulation can be used to modify immune

modulation capability

• Large antigen carrying capacity
• Cell line cultured in synthetic growth media so is free of

derived animal products

• Offers potential productivity gains in large scale manufacture
• Vector has potent adjuvant effects and is suitable for dose-

sparing strategies

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Sementis vaccine pipeline

Current

• Peanut allergy therapeutic vaccine
• Chikungunya prophylactic vaccine
• Smallpox prophylactic vaccine

Future opportunities

• Prostate cancer therapeutic vaccine
• Melanoma (skin cancer) therapeutic vaccine
• Q Fever prophylactic vaccine
• Ebola prophylactic vaccine

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Principles of the SCV approach

• Normally, a virus infects a cell and replicates using the cellular machinery;

having been multiplied in number the virus exits the cell to infect new cells

• The SCV viral vector is unable to replicate in the cell because Sementis has

removed the genes which allow it to be fully reproduced. Instead, the infection results in release of non-replicating virus proteins and antigens which stimulate the therapeutic or prophylactic immune response

• To manufacture the non-replicating SCV virus, Sementis has designed a cell

line which has the missing genetic information inserted into its genome

• The “rescue” CHO cell line allows complete multiplication of the active virus
• Thus, the SCV viral vector can not replicate in man but can deliver the antigens

to the immune system to stimulate the desired response

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SCV only replicates in the Sementis SCV rescue cell line

Cell line Description Virus Production

Vaccinia MVA SCV

CHO

Chinese hamster ovary cell line

  

SCV-CHO- Rescue

CHO cell line expressing SCV viral assembly protein

  

BHK21

Baby hamster kidney cell line clone 21

  

Vero

African Green Monkey kidney cell line

  

HEK-293

Human embryonic kidney cell line

  

143B

Human bone cell line

  

MRC-5

Human lung fibroblast cell line

  

A431

Human skin epidermis cell line

  

: no virus production; : trace production level; : low production level; : moderate production level; : high level of production

The results above are from a multistep viral amplification experiment studying the level of virus production after 2 days of infection. The overall conclusion is that the attenuated SCV virus vector is TOTALLY attenuated in all cell lines tested except for the rescue cell line used in production (SCV-CHO-Rescue).

Small pox vaccine

• Ectromelia (mouse pox) virus (ETCV) is an animal model for

small pox

• Vaccination of mice with vaccinia (pox virus) protects them

from ETCV infection

• Sementis small pox vaccine expresses protein antigens

common to all pox viruses

• Protection induced by the Sementis small pox vaccine is

T-cell rather than antibody based

• Vaccination with Sementis small pox vaccine protects mice

from ETCV

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SCV vaccination protects mice from ECTV

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Score Symptoms

Coat condition Normal Eye condition Movement Limb condition

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Coat condition Slightly rough Eye condition Mild discharge Movement Abnormal, uncoordinated Limb condition Swelling

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Coat condition Dishevelled, lesions forming Eye condition Severe discharge Movement Walking on tiptoe, reluctant to move Limb condition Abnormal limbs

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Coat condition Bleeding or irritated lesions, severe hair loss Movement Staggering, paralysis Limb condition Severe necrosis

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Mice were either vaccinated with Sementis attenuated-SCV (SCV104) at two different doses or vaccinia virus (VACV) also at two different doses or a placebo (PBS). Mice were challenged 4 weeks later with mousepox virus (ECTV). Clinical symptoms observed after ECTV challenge were quantified and plotted. Results show that mice vaccinated with either attenuated-SCV or the positive control VACV were protected from mousepox disease, unlike the mice that received placebo, which became ill after ECTV infection.

Chikungunya vaccine

• Protection is antibody mediated
• Sementis CHIKV vaccine expresses Chikungunya

antigens which induce cross protection across all strains

• Antibody responses in mice are thought to be

indicative of protection

• Foot pad swelling in mice is a model for Chikungunya

virus-induced arthritis in man

• Vaccination with Sementis Chikungunya vaccine

prevents virus replication in mice and protects against virus-induced arthritis

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Vaccine SCV301C protects mice against CHIKV infection (viral load)

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Mice were vaccinated either with vaccine expressing Chikungunya antigens (SCV301C), vaccinia virus (VACV) or a placebo (PBS) and then challenged 3 weeks later with Chikungunya virus (CHIKV). The graph shows the level of CHIKV replication in the blood stream of each challenged mouse over a 5 day period post challenge. SCV301C vaccination prevented CHIKV replication and viral spread via the blood stream whereas the vaccinia virus and placebo groups showed CHIKV replication and spread via the blood stream.

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viral load

Vaccine SCV301C protects mice from CHIKV- induced arthritis

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These result shows the effect of Chikungunya (CHIKV) infection in each group mice that were either vaccinated with SCV301C (expressing CHIKV antigens), or vaccinia virus or with placebo (PBS). CHIKV infection of mice causes arthritis related foot swellings and the above results shows the SCV301C vaccinated group of mice did not suffer from viral induce arthritis unlike the vaccinia virus or placebo vaccine groups.

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• SCV201 vaccine contains Sementis proprietary vaccine

technology

• The immune system generates two different responses: TH1

and TH2 – TH1 cytokine profile is characterised by IFNɣ production – TH2 cytokine profile is characterised by IL4 and IL5 production

• In people allergic to peanuts, a TH2 immune response occurs

which can cause anaphylaxis

• The Sementis peanut allergy vaccine approach aims to

switch the allergic response to peanuts from TH2 to TH1

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Peanut allergy vaccine - background

SCV-peanut allergy vaccine may switch the immune response to peanuts from an allergic TH2 response to a TH1 response

• In an initial prophylaxis study, mice were administered with either

SCV-peanut allergy vaccine or placebo and sensitized to peanuts, then were challenged with peanuts

• Results are consistent with Sementis peanut allergy vaccine

inducing a cytokine profile that is consistent with a shift from a TH2 to a TH1 immune response

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Results of exploratory study of prophylactic SCV-peanut allergy vaccine in sensitized mice (1)

• IFN-γ is central to TH1
• IL-5 only occurs for TH2
• IL-4 helps create TH2
• IL-2 commands the

response of the immune system

• Results show that after

vaccination, the immune response is redirected to a peanut-specific TH1 response

Response to peanut challenge

IFN-gamma IL-5 IL-4 IL-2 Relative cytokine response Placebo Vaccine

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Sementis Comparison of the cytokine profiles that signal TH1 and TH2 responses for groups of five mice vaccinated with SCV-peanut allergy vaccine or placebo

p<0.005

• Compared with non-vaccinated peanut sensitized mice,

the vaccinated peanut sensitized mice showed:

– Increased IFNγ production following challenge with peanut antigen (vaccine vs. placebo p<0.005), characteristic of a TH1 response – Trends towards lower IL4 and IL5 production following challenge with peanut antigen, characteristic of a TH2 response

• Studies are underway to further elucidate these

preliminary results and to examine the potential therapeutic response to vaccination

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Results of exploratory study of prophylactic SCV-peanut allergy vaccine in sensitized mice (2)

Outlook 2015

• Interest in licensing the manufacturing rights for the

technology from a contract manufacturing

• rganisation- if successful will develop production

methods for Chikungunya and small pox vaccines

• Manufacture Chikungunya and small pox vaccines for

initiation of toxicology studies

• Construct development-ready peanut allergy vaccine
• Complete testing of properties of peanut allergy

vaccine in mice

• Complete ex vivo testing of peanut allergy vaccine in

human cells as a proof of concept

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Board and management

• Maurice O’Shannassy, Non-Executive Chairman

– Maurice spent 25 years in the financial services industry in Australia and overseas. He currently holds a number of directorships in a variety of industries and not for profit organisations.

• Jane Ryan PhD, CEO Elect

– Jane has many years of international experience in the pharmaceutical and biotechnology industry where she has managed research and development programs, as well as having key roles in business development and alliance management. She successfully negotiated a $231M US government contract with BARDA to support product development in the infectious diseases field.

• Tom Quirk MSc DPhil MA SMP, Non-Executive Director

– Tom has interests in venture capital, investment management and business advisory and brings the experience of many biotech start-ups (including Biota and Peptech), most recently as Chairman of Virax Holdings.

• Paul Howley PhD, Chief Scientist and Founder

– Paul’s scientific background is in the field of molecular virology, specialising in viral vector systems and vaccinology. Paul is the inventor of the Sementis SCV platform vaccine delivery technology and

• f a number of vaccines in development. He directs and manages the vaccine development

programs for Sementis.

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Board and management

• Jim Ackland PhD, Regulatory Affairs Consultant

– Jim has over 30 years experience in the manufacture, quality control, development and international regulatory requirements for biopharmaceutical products. He has provided regulatory and product development advice and assistance to large and small companies. Prior to establishing Global Bioscience Solutions, Jim was employed at CSL Limited as Head of Regulatory Affairs.

• Dino Dina MD, Strategic Adviser

– Dino has made an impressive contribution to the vaccine industry. He has served as President and CEO

• f Dynavax Technologies Corporation and was an employee of Chiron Corporation for 15 years,

ultimately in the role of President at Chiron Vaccines. Dino was previously employed at Albert Einstein College of Medicine as assistant professor of genetics. He received his MD from the University of Genova Medical School in Italy.

• Joy Hewitt BPharm MAppSci MBA MCommLaw, Business Development Consultant

– Joy has broad experience in business strategy and technology commercialisation and licensing in the biopharmaceutical sector. Most recently, Joy worked as Director of Business Development at Biota and has previously worked in business development roles at EQiTX, CSL and AMRAD.

• Anthony Mason PhD, Molecular Biologist

– Anthony is a molecular biologist with many years experience in biotechnology and specific expertise in CHO cell lines. He has worked at Genetech, Serono, Biota and St Vincent's Research Institute where he currently manages the business development activities for the research institute.

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Research Team