Version: 160421PH Non-Confidential 1 Disclaimer Sementis We - - PowerPoint PPT Presentation

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Version: 160421PH Non-Confidential

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

Disclaimer

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• 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

Sementis

Sementis SCV platform technology

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Vaccine In General

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Vaccine Class Property Common Example Potency Adjuvant Requiring Safety Profile

Attenuated Weakened infectious pathogen Measles Mumps Rubella Oral Polio Yellow Fever

• Strong
• Life Long

immunity No

• Risk of reversion
• Rare cases of side

effects Inactivated Killed non- infectious Influenza IPV (Polio) JE

• Weak
• Requires regular

boosting (5yrs, 10yrs) Yes

• Safe
• Requires high

containment facilities during manufacturing Subunit

• Pathogen coat

protein

• Non infectious

HBV HPV (VLPs)

• Weak
• Requires regular

boosting (5yrs, 10yrs) Yes Safe

• SCV has the advantages of attenuated vaccine’s potency with the

safety of subunit vaccines

• Does not require adjuvants
• Efficient generation of immune responses
• Live virus, therefore self adjuvanting
• Stimulates antibody and T-cell responses
• Capacity to carry large and multiple antigens
• Cell line cultured in synthetic growth media so is free of animal-

derived products

• Offers potential productivity gains in large scale manufacture

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Advantages of the SCV platform

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• Develop SCV platform and manufacturing capability through

government funded initiatives

• Chikungunya vaccine
• Smallpox vaccine
• Grow pipeline in high value diseases with significant unmet medical

need

• Allergies
• License SCV platform for application in non-core therapeutic areas
• Oncology
• Infectious diseases

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Sementis strategy

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Current

• Peanut allergy
• Cat allergy
• Chikungunya
• Smallpox

Future opportunities

• Zika virus

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Sementis vaccine pipeline

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SCV Platform Technology

• Live viral vector that offers:

– the properties of attenuated vaccine – unable to multiply upon vaccination providing the added safety of inactivated vaccines – Accommodate multiple antigens to give the broad spectrum of subunit vaccines

• A manufacturing process scalability by using a proprietary genetically engineered

suspension cell substrate to produce all SCV vaccines

• The SCV cell substrate for manufacturing is CHO based – industry gold standard for

production of biologicals with the following advantages:

– Biotechnology friendly: bioreactor and processes are standardize to CHO cells – Fastest growing cell substrate, important for upscaling – Suspension culture requiring low surface are to volume culturing systems – Most characterised cell line used for the production medicinal biologicals – Well know and understood by medical control agency around the word (TGA in Australia, FDA in USA, EMEA in Europe)

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Principles of the SCV approach

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SCV Platform Vector Attenuation Profile

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SCV does not multiply in human and mammalian cells lines

A study was carried to show that SCV does not multiple or propagate in cells derived from key organs of the body after deliberate infection: Vaccinia Virus (Parent of SCV) SCV Human Bone cell High Yields of virus (expected) No virus production! Human Lung cells Human Kidney cells Human Skin cells Human Cervical cells

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SCV is non-pathogenic in severely immune deficient (SCID) mice

Study: infection of SCID mice with SCV and Vaccinia Virus Results:

• Survival:
• All SCID mice infected with SCV survived during the 100 day observation period
• All SCID mice infected with Vaccinia Virus died or were humanely euthanized by

day 21

• Dissemination:
• SCV infected mice: No live infectious virus could be recovered from Lung, Kidney,

Spleens and ovaries

• Vaccinia virus infected mice: high yields of live infectious virus could be recovery

from Lung, Kindneys, Spleens and Ovaries within days are infection

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SCV-Chikungunya vaccine Preclinical Proof-of-Concept

Chikungunya: an emerging disease

• Chikungunya virus is transmitted to humans by infected mosquitoes
• Disease is characterized by sudden onset of severe joint pain or swelling, muscle

pain, high fever, rash, headache and fatigue

• Fatigue and joint pain may last for months, chronic arthritis occurs in ~15% of cases
• Often misdiagnosed as dengue fever
• Causes loss of bone density which leads to debilitating pain and immobility
• Reports of autoimmune neuropathologies and fatal cardiac and neurological

(encephalitis) manifestations

• Epidemics occur in tropical and temperate regions
• Prevalent in Asia and Africa
• Recent outbreaks in Pacific Islands, Caribbean
• Current prevention focusses on vector control

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• Cases in Europe and the Americas have primarily been imported by travellers

returning from areas with high incidence rates

• From 2013-2015, there were 2,524 confirmed cases of chikungunya reported among US

travelers

• Virus has adapted to globally distributed Asian tiger mosquito (Aedes albopticus)
• Locally acquired cases reported in both Europe and the Americas
• Conservative estimate of global market is US$150-200 million
• Travellers = 65%, military = 15%, endemic = 20%
• Potential for endemic infections in developed markets
• Opportunity to access government and NGO funds to progress development

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Chikungunya: an emerging market

• pportunity

Chikungunya vaccine

• Sementis CHIKV vaccine expresses multiple Chikungunya

antigens which induce cross protection across all strains

• Protection is antibody mediated
• 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 and protects against virus-induced arthritis in mice

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Mice  Vaccination  30 days later CHIKV Challenge  observation period  30 days later detection for low level persistent CHIKV

Study outcomes:

• Immunogenicity:
• Vaccination with Sementis’ totally attenuated SCV-CHIKV vaccine (SCV305) can stimulated anti-CHIKV

immune response in terms of total antibody responses and neutralization antibody response.

• Efficacy of protection from CHIKV challenge:
• Vaccination was sufficient to protect mice from a CHIKV infection challenge.
• Prevention of Persistence of CHIKV infection
• Vaccination was sufficient to protect mice from persistent CHIKV infection.

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Sementis’ SCV-CHIKV vaccine efficacy study in mice

Smallpox: a bioterrorism threat

• Caused by variola virus and is transmitted by direct person-to-person contact
• There is no effective treatment, with mortality rates of up to 30%
• Smallpox was endemic throughout the world
• Prior to initiation of the global eradication program in the 1950s,

~ 50 million cases of smallpox occurred annually

• Smallpox accounted for ~10% of deaths in the world each year
• Eradication of smallpox was achieved in 1980 following a global immunization

program by the WHO

• Although smallpox infection has been eradicated, the variola virus is not extinct
• Smallpox remains of concern as a biological weapon
• Currently, no licensed vaccine is commercially available

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Medical countermeasures smallpox vaccine

• Ectromelia (mousepox) virus (ETCV) is an animal model for smallpox
• Vaccination of mice with vaccinia (pox virus) protects them from

ETCV infection

• Sementis smallpox vaccine expresses protein antigens common to

all pox viruses

• Protection induced by the Sementis smallpox vaccine is

T-cell rather than antibody based

• Vaccination with Sementis smallpox SCV vector and SCV-CHIKV

vaccine protects mice from ETCV

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Medical countermeasures smallpox vaccine

Ectromelia (mousepox) virus (ETCV) mouse study:

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Mice Vaccination

• SCV
• SCV-CHIKV
• Vaccinia Virus
• Placebo

ECTV Lethal Challenge 14 day Observation Period 30 days Results: Vaccinia Virus: total protection SCV Vector only: total protection SCV-CHIKV: total protection Placebo: No Protection Conclusion: In a surrogate mouse model for smallpox infection SCV and SCV-CHIKV can protect mice from mousepox virus (Ectromelia) infection!

Smallpox vaccine development plan

• Leverages Chikungunya vaccine development program
• Uses same vaccine construct (“dual purpose” vaccine)
• Uses same scale up to GMP manufacture activities
• Uses same development activities from preclinical and toxicology to

phase II

• Additional primate challenge model (planning underway)
• Protection against monkey pox.
• Targets early development stockpiling orders from

government.

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SCV-Peanut Hypoallergy vaccine Preclinical Proof-of-Concept

Peanut allergy

• IgE-mediated food allergy that causes severe and occasionally fatal reactions in those

sensitized to peanuts

• Symptoms of peanut-induced allergic reactions range from hives, angioedema and

flushing to life-threatening anaphylaxis

• Prevalence is increasing worldwide, greatest in developed countries
• ~ 1% of general population
• ~ 2% of children aged under 18 years
• Affects 25.5% of American children aged 6-10 years
• Most commonly diagnosed between 6-24 months of age and reactions usually become

more severe with age

• Management of peanut allergy is currently limited to avoidance and rapid treatment

with autoinjectable epinephrine (adrenaline)

• Estimated global market is ~US$2 billion

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• SCV-PHAV 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

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Peanut allergy vaccine

Published scientific evidence to show desensitization to peanut is linked to a change from Th2 to Th1 immune profile

References: Turcanu etal (2003) Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts. J. Clin. Invest. 111: 1065-1072

Study conclusion: “Acquisition of tolerance in children previously allergic to peanuts (outgrown) is accompanied by a shift in the cytokine phenotype of peanut-specific lymphocytes from a Th2 to a Th1 profile.” PA: Peanut Allergic NA: Non-allergic IFNγ: Th1 cytokine IL2: Th2 cytokine

SCV-PHAV Preclinical Proof-of-Concept in Mice

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Study Design:

• Vaccinate mice  sensitization protocol  challenge with peanut protein  extract T-cells
• Culture T cells in the presence of peanut protein  measure cytokine secretion

Results:

IFN-g secretion (TH1 marker): greater in SCV-PHAV vaccinated mice than the Placebo vaccinated mice IL4 secretion (Th2 marker): less in SCV-PHAV vaccinated mice than in the Placebo vaccinated mice IL5 secretion (Th2 marker): less in SCV-PHAV vaccinated mice than in the Placebo vaccinated mice Results show that after vaccination, the immune response is redirected to a peanut-specific TH1 response

Study conclusion

• 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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SCV-PHAV Preclinical Proof-of-Concept in Mice

The objective was to show in a “test tube” that vaccination of white blood cells

• btained from peanut allergic individuals does NOT exacerbate the already existing

peanut specific Th2 immune response upon exposure to peanut protein extract. Results:

In the presence of soluble peanut protein extract, the SCV-PHAV (SCV204) vaccinated DCs caused a decrease in the number of IL-4 producing CD4+ T-cells from 0.24% of the total T-cell population to 0.19%

i.e., 1.3 fold decrease in Th2-T cell numbers in response to peanut protein mediated by vaccinated DCs In the presence of soluble peanut protein extract, the SCV-PHAV (SCV204) vaccinated DCs caused an increase in the number of IFNγ producing CD4+ T-cells from 0.56% of the total T-cell population to 0.83% i.e., 1.5 fold increase in Th1-T cell numbers in response to peanut protein mediated by vaccinated DCs

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“Test tube” vaccination of blood samples taken from peanut allergic individuals

• Interest in licensing the manufacturing rights for the technology from a

contract manufacturing organization

• If successful, will develop production methods for Chikungunya and

smallpox vaccines

• Manufacture Chikungunya and smallpox vaccines for initiation of

toxicology studies

• 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

• Cat hypoallergy vaccine construction and proof-of-concept studies

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Outlook 2016

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Longer Term Outlook

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• Manufacturing Process Development for SCV vaccines
• Adventitious viral clearance study to validate manufacturing process
• Manufacturing and biosafety testing of clinical batches for:

– Cat hypoallergy Vaccine – Peanut hypoallergy vaccine – Chikungunya vaccine

• Toxicology studies for:

– Cat hyoallergy vaccine – Peanut hypoallergy vaccine – Chikungunya vaccine

• Double blinded placebo controlled Phase 1/2a clinic trials for:

– Cat hypoallergy vaccine – Peanut hypoallergy vaccine – Chikungunya vaccine

• 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 Co-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, utilising his extensive knowledge, experience and networks in the areas of antigen design and discovery, proof of concept studies in animal models, GLP preclinical and toxicology studies, process development and cGMP manufacturing, regulatory affairs and first in man studies concerning live viral vectored vaccines.

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Board and management

Contact:

Dr Jane Ryan CEO Email: jane.ryan@sementis.com.au Phone: +61 (0)419 541 623 Website: www.sementis.com

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