BioMmune Technologies Inc. Corporate Presentation 2015

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1 BioMmune Technologies Inc Corporate Presentation 2015

2 * Harnessing the body s own immune system to fight cancer & other autoimmune diseases

3 BioMmune Technologies Inc. (IMU) ABOUT A public biopharmaceutical company based in Vancouver Canada (TSX.V: IMU) Focus on discovery of new anti-cancer drugs which are designed to unmask cancer cells allowing the body to attack them And the development of drug compounds for the treatment of autoimmune diseases

4 IMU HAS THREE KEY PROGRAMS MHC 1 Ca Channel Blockers CD74 New methods for identification, discovery and development of drugs that can enhance and restore the immunogenicity of cells, which evade immunosurveillance. Identify new calcium channel regulators (blockers) which activate the immune system to combat cancers, infections and autoimmune diseases. Use of a chaperone protein CD74 to design better vaccines to fight against infections and other diseases.

5 MHC Class 1 Molecules Program 1 Cancer cells often evade immunorecognition due to their lack of expression of MHC class I antigens at their cell surface. This lack of expression of MHC I is the result of the down regulation of potential multiple factors such as transporters (TAP), Proteasome components (LMP) and other accessory proteins important in the antigen presentation and processing pathway Simply put; find a way to increase MHC class I expression on a cancer cell and your immune system may well be able to treat and kill the cancer.

6 MHC Class 1 Molecules Down-regulation of MHC class I antigen processing machinery results in Escape from immune surveillance Normal cells Cancer cells Escape of abnormal cells from immune surveillance Cancer cells with additional mutations No additional Mutations Mutations Escape immune system Recognized and killed by the Immune System

7 MHC Class 1 Molecules Normal cells Cancer cells Escape of abnormal cells from immune surveillance Cancer cells with additional mutations Drug Treatment restores MHC class I antigen presentation resulting in immuno-recognition No additional Mutations Mutations Escape immune system Restoration of MHC I Expression by BioMmune s New Drug Recognized and killed by the Immune System Recognized and killed by the Immune System

8 MHC Class 1 Molecules Development of a Screening Assay This proprietary screening assay was designed by BioMmune to discover compounds that have the ability to restore immune recognition of tumours leading to an anti-tumoral effect To develop a phenotypic screening assay to identify compounds which up-regulate MHC 1

9 MHC Class 1 Molecules Isolation of Active Compounds Marine natural product library has revealed promising lead compounds Ultimate Goals: Determination of the chemical structure has been done for 4 isolated active compounds. Synthesize the pharmacophore involved in the observed phenotype (Dr. Raymond Andersen s group) has been done for one so far. Four additional analogs have been synthesized All these active compounds have been tested in-vitro for increase of MHC I at the cell surface of A9 tumor cells

10 MHC Class 1 Molecules Initial Library Screening Marine natural product library has revealed promising lead compounds Ultimate Goals: To isolate the active compound, determine the chemical structure and identify/synthesize the pharmacophore involved in the observed phenotype (Dr. Raymond Andersen s group) To evaluate the biological activity as well as the mechanism of action of the active compound(s) / synthesized molecules To discover and develop new anti cancer drugs that result in cancer treatement

11 MHC Class 1 Molecules Using the Screen to Identify New Active Structures : 1.Determine whether marine extracts which induce TAP: reporter gene expression can also induce an increase in MHC-I expression on the cell surface. 2.Determine whether marine extracts will induce an increase in MHC-I expression on lung carcinoma cell surface. 3.Determine whether marine extracts restore T cell recognition of cancer cells.

12 MHC Class 1 Molecules New Compound and Analogs Marine natural product library has revealed promising lead compounds Advantages: First very active compound to be isolated from the screening of the marine natural library. This compound can be easily synthesized in a chemistry lab at low cost Four additional analogs have been synthesized in addition to curcuphenol with low costs All these active compounds have been tested in-vitro for increase of MHC I at the cell surface of A9 tumor cells and have showed high activity and low cytotoxicity

13 MHC Class 1 Molecules Future Work and Goal for 2015 Curcuphenol and Analogs Efficacy in mice implanted SC with A9 cells (Lung Cancer Cells) Testing curcuphenol and analogs on a mice implanted with pancreatic cancer. Additional Active Compounds: 3 new active structures identified and synthesis of enough of each with analogs to be tested in-vitro and in-vivo (Ray Andersen) In-vivo Efficacy testing in mice implanted SC with A9 cells of three additional compounds Identify the specific structures of the additional hits identified 5-7 hits.

14 Ca Channel Blockers Program 2 Identifying new calcium channel regulators (blockers) which activate the immune system to combat cancers, infections and autoimmune diseases. Activities of these channels regulate the concentration of calcium (Ca) in cells resulting ultimately in the regulation of the activity of cells involved in the immune system.

15 Ca Channel Blockers Properties of Calcium Channels Ca V 1.4 contributes to T cell development in the thymus as well as naïve T cell homeostasis Ca V 1.4 is involved in regulating TCRinduced Ca 2+ fluxes Ca V 1.4 contributes to naïve T cell survival Ca V 1.4 is important for generation of functional immune responses

16 Ca Channel Blockers Why the Focus on Calcium Channels? Development of new drugs that target calcium channels expressed on lymphocytes to regulate their activity. One application is to suppress the immune system for the treatment of autoimmune diseases and the prevention of transplant rejection.

17 Ca Channel Blockers Identifying Unique Channel Sequences to Use as Targets for Making Mouse Monoclonals Picking the unique peptide sequences: at least one peptide per CaV1 channel. Ideal target sequence: unique to the particular channel exposed on portion of channel that is positioned on outside of cell; antigenic found in both mouse and human Ab will affect channel activity when bound

18 Ca Channel Blockers Development of new drugs that target calcium channels expressed on lymphocytes to regulate their activity. Achievements: Generated monoclonal antibodies reacting with specific Cav1 channels: Identified specific epitopes (peptides) expressed on Cav1.1, Cav1.2, Cav1.3 and Cav1.4 Ca channel, exposed on the surface of lymphocytes and common sequence in human and mice cells Peptides have been identified and synthesized Monoclonal antibodies (mabs) have been selected which bind to the specific peptides as measured by ELISA 36 mabs are have selected for further development for binding to lymphocytes as measured by FACS. Functional tests are developed to assess the activity and reactivity of these mabs: HEK293 cells that overproduce Cav1.1, Cav1.2, Cav1.3 or Cav1.4 Proliferation assays and assessment of calcium current.

19 Ca Channel Blockers Application of these active mabs Future Developments: Development of new drugs that target calcium channels expressed on lymphocytes to regulate their activity. Use as potential new treatments against leukemias. Testing to see whether these antibodies modulate inflammation Affect immune function in animal models of human disease such as transplant rejection, allergy and autoimmune diseases

20 Ca Channel Blockers Future Plans and Goals for 2015: Characterize mabs reacting with Cav channels by downregulation of cell proliferation by May 2015 Manufacture enough mabs to test in animal mice models developed previously first batches by June 2015 Efficay testing in mice models for leukemias and autoimmune diseases by June 2015 Selection of positive antibodies presenting efficacy and therapeutic potential for the treatment of leukemias or other autoimmune diseases By End 2015

21 CD74 Program 3 Finding compounds that take advantage of the CD74 pathway to improve our immune systems ability to combat infections, cancers and autoimmune diseases. Identifying new compounds to enhance expression of CD74 will result in a better way to fight inflammation, infections and other related immune disorders This technology is associated with the discovery around CD74, a protein chaperone associated with the presentation of endogenous and exogenous peptides by MHC molecules involved in the immune system and its regulation.

22 CD74 Using antigenic proteins incorporated in CD74 in order to design better vaccines to treat infections Approach: Using antigenic proteins that take advantage of the CD74 pathway to improve our immune systems ability to combat infections, cancers and autoimmune diseases. Test wether CD74 bound to antigenic proteins can enhance Dendritic Cells (DC) cross presentation of antigens and doing so make better vaccines.

23 CD74 CD74 Gene Constructs Control Constructs Completed CD74 alone Influenza M1 HIV nef OVA Chimera Gene Constructs Complete CD74::InfM1 CD74::HIV Nef CD74::OVA Adenovirus Vectors

24 CD74 CD74 Gene Constructs!!!!!!!!!!!I!!!!!!!!!!!!!!!!!!!!!II!!!!!!!!!!!!!!!!!!!!!!!!III!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!IV! I: CD74 Endosomal Leader sequence II: CD74 TM domain III: Three Alanine residues to add the flexibility IV: Various antigens(influenza M1, HIV Nef, and Ovalbumin)

25 CD74 CD74 Program achievements : Can CD74 bound antigenic proteins enhance the immune response against it? Achievements: Different antigenic molecules such as HIV nef, Influenza M, and ovalbumin have been cloned into CD74 protein. The different DNA constructs have been introduced into a mammalian expression system based on an adenovirus vector system from AdMax to make recombinant viral vectors. If necessary, we will clone smaller antigenic domains such as the antigenic peptides recognized. Influenza A M or OVA (SIINFEKL) T cell epitope for CD8 (MI58-66) which are recognize in association to MHCI

26 CD74 Future Plan and Goals for 2015 : Can CD74 bound antigenic proteins enhance the immune response against it? To localize gene constructs within DCs. Determine the localisation of expressed proteins linked to the CD74 localization sequence in the endolysosome of DCs. All AAV constructs, Influenza and HIV, to be tested in animal models for protection response By July 2015, first data showing protection to influenza virus infection in animal infected with AAV expressing Influenza M protein. By End 2015, other data regarding AAV-HIVnef expression in animal to protect against HIV infection.

27 MHC1, Ca Channel Blockers and CD74 IP Intellectual Property (IP) : Patent Application and Issuance: MHC1 8 Applications are pending Patent granted in Australia Application on curcuphenol and analogs done in 20 November 2014 Ca Channel Blockers: 5 applications are pending in different countries USA, Australia and other National Phases Additional provisional application and applications done on the development of specific active monoclonal antibodies CD74: 6 applications in different countries Europe, Canada, USA, China and Japan Additional provisional application will be done on the development of specific constructs and their expression in specific antigen presentation cells

28 * SUMMARY BioMmune is dedicated to the discovery and development of new compounds able to restore immunorecognition of tumor cells and to increase the efficacy of the immune system to combat infection, autoimmunities, etc

29 Corporate - Management Dr. Reinhard Gabathuler PRESIDENT Dr. Gabathuler obtained his PhD in Biochemistry at the Université de Lausanne, Switzerland, in 1982, and is considered an expert in area of immunology. BioMmune - Coproate CorporatePresentation Presentation Ms. Judi Dalling, LLB CFO Ms. Judi Dalling is a practicing lawyer with experience in corporate and securities law. She also has a strong accounting background, having been controller and business manager of a major magazine publishing enterprise for over 20 years. Dr. Wilfred Jefferies CHAIR SAB Dr. Jefferies is a Professor at the University of British Columbia and is the scientific founder of the Company. Dr. Jefferies is the inventor of the company s technology and is a renowned expert in Genetics and Immunology.

30 Corporate - Board of Directors R.B.(Rob) Hutchison Executive Chairman Mr. Hutchison serves as a director and the CEO of BiOasis Technologies Inc., a publicly traded biopharmaceutical company focused on developing and commercializing pharmaceutical products and diagnostic technologies. Dr. Karoly Nikolich Dr. Nikolich is a world renowned Neuroscientist whom has held numerous posting at Stanford University as well as held lead positions at companies such as Genentech, CEO of Circuit Therapeutics and worked with Dr. Sydney Brenner on the Human Genome project. Dr. Terry Pearson Dr. Pearson is Professor at the University of Victoria and his research for the past 29 years has focused on the molecular analysis of African trypanosomes. Currently his research team uses newly developed antibody-based technologies, protein microchemical techniques and mass spectrometry as tools for identification of molecular interactions between the parasites and their tsetse fly vectors. Mr. Craig Thomas, LLB Mr Thomas Is a partner at Thomas Rondeau and is the company s security counsel Mr. Michael Hutchison, QC Mr. Hutchison, QC is a practicing lawyer in Victoria BC Firm Smith Hutchison BioMmune - Corporate Coproate Presentation 2015

31 Corporate - Cap Table Jan Shared Issued: As at Jan 1, 2015: 22,965,000 Options: $0.23, Expire June 19, 2018

32 Thank you! please contact us for more info. Phone (604) Fax (604) Reinhard Gabathuler President

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