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Disclaimer Sementis We believe that the information in this presentation is correct and any opinions and conclusions are reasonably held or made, based on the information available at the time of its compilation, but no representation or warranty, either expressed or implied, is made or 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. 2 2
Sementis SCV platform technology Sementis • 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 3
Advantages of the SCV platform Sementis • 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 4
Sementis vaccine pipeline Sementis 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 5
Principles of the SCV approach Sementis • 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 6 6
SCV only replicates in the Sementis SCV Sementis rescue cell line Cell line Description Virus Production Vaccinia MVA SCV CHO Chinese hamster ovary cell line SCV-CHO- CHO cell line expressing SCV viral assembly protein Rescue 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). 7
Small pox vaccine Sementis • 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 8 8
SCV vaccination protects mice from ECTV Sementis Score Symptoms Coat condition Eye condition Normal 0 Movement Limb condition Coat condition Slightly rough Eye condition Mild discharge 1 Movement Abnormal, uncoordinated Limb condition Swelling Coat condition Dishevelled, lesions forming Eye condition Severe discharge 2 Movement Walking on tiptoe, reluctant to move Limb condition Abnormal limbs Coat condition Bleeding or irritated lesions, severe hair loss 3 Movement Staggering, paralysis Limb condition Severe necrosis 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. 9
Chikungunya vaccine Sementis • 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 10 10
Vaccine SCV301C protects mice against CHIKV infection (viral load) Sementis viral load 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. 11 11
Vaccine SCV301C protects mice from CHIKV- induced arthritis Sementis 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. 12 12
Peanut allergy vaccine - background Sementis • 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 13 13
SCV-peanut allergy vaccine may switch the immune response to peanuts from an allergic Sementis 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 14 14
Results of exploratory study of prophylactic SCV-peanut allergy vaccine in sensitized mice (1) 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 • IFN- γ is central to TH1 Response to peanut challenge • IL-5 only occurs for TH2 p<0.005 Placebo Vaccine • IL-4 helps create TH2 Relative cytokine response • IL-2 commands the response of the immune system • Results show that after vaccination, the immune response is redirected to a 0 peanut-specific TH1 IFN-gamma IL-5 IL-4 IL-2 response 15
Results of exploratory study of prophylactic SCV-peanut allergy vaccine in sensitized mice (2) Sementis • Compared with non-vaccinated peanut sensitized mice, the vaccinated peanut sensitized mice showed: – Increased IFN γ 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 16 16
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