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Vaxil BioTherapeutics Ltd. 1 Developing the next generation Of therapeutic vaccines.

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Presentation on theme: "Vaxil BioTherapeutics Ltd. 1 Developing the next generation Of therapeutic vaccines."— Presentation transcript:

1 Vaxil BioTherapeutics Ltd. 1 Developing the next generation Of therapeutic vaccines

2 Vaxil BioTherapeutics Ltd. 2 Overview

3 Vaxil BioTherapeutics Ltd.  Vaxil has developed VaxHit, a technology to identify Vaccine Candidate (VCs) with the ability to induce specific, robust and broader T-cell immunity for different cancers and key infectious diseases.  Lead product ImMucin, a MUC1 cancer vaccine is being evaluated in a Phase I/II clinical trial in MM patients (HMC, Jerusalem).  Trial regulatory approval covers all MUC1 positive cancers (>90% of cancers).  A second vaccine MTbuVax for Tuberculosis is in preclinical stage of development.  Partnering can be achieved at pre-clinical stage.  VaxHit in-silico technology has been used to identify a pool of potential VCs.  Currently several academic collaborations and one with industry (Immunovaccine: TSX IMV).  Looking for other partners for out-licensing/joint development.  All IP is company owned. Vaxil BioTherapeutics: Overview

4 Vaxil BioTherapeutics Ltd. 4 Technological and therapeutic advantages

5 Vaxil BioTherapeutics Ltd. 5 Vaccines for Adoptive immunity: Rational & Challenges Goal: Obtain Robust and Comprehensive CD4+ plus CD8+ response but maintain antigen specificity Antigen selection is the first and most critical parameter in designing any type of vaccine

6 Vaxil BioTherapeutics Ltd.  CD8 + and CD4 + T-cells recognize their target antigen (epitope/s) in association with MHC class I and class II molecules.  Hundreds of MHC alleles with different binding properties - every individual has a different set of between 6 and 12 MHC alleles.  For a vaccine to work, it must be able to bind these MHC molecules in different individuals.  There are currently two main approaches for achieving this goal:  Approach 1: use larger sequence/s (entire pathogen/cancer cell/antigen). Statistically contain more epitopes which can bind more combinations of MHC molecules. This reduces the specificity of response >> reduced efficacy and lead to higher side-effects.  Approach 2: identify epitope/s on the target antigen that bind to one more abundant MHC allele e.g. HLA-A2.1. This leads to a specific but weak immune response, applicable only to that proportion of the population with that MHC molecule. T-cell Vaccines : Rational & Challenges

7 Vaxil BioTherapeutics Ltd. The research hypothesis in Vaxil’s new paradigm: “Do specific defined protein domains have different epitope densities?” T- cells Vaccine: A new paradigm Can the advantages in these two approaches be combined? Kovjazin et al., Mol. Immunol, April 2011

8 Vaxil BioTherapeutics Ltd. Vaccine design: A new paradigm Kovjazin et al., Mol. Immunol, 2011  Signal peptides (SP) and trans-membrane (TM) domains have exceptionally high MHC epitope densities in all human or mouse protein domains. (when TAP wasn't used, P<1.e-8 in human and P<0.05 in mouse genome, t-test between each group and the overall mean of all sampled domains with Bonferroni).  The high epitope density of SP but not TM is corroborated by a high percentage of identified SP epitope in the IEDB (immune epitope) database. Frequency is X3 higher than expected from the distribution of SP in the proteins containing the epitopes (chi square test, p<1.e-6).  The improved MHC binding of these domains relies on their hydrophobic nature but in SP, also on their specific sequence. Only the SP domains had a significantly higher MHC binding compared to their scrambled counterparts (p<0.05), for TAP and Tapasin-independent allele.

9 Vaxil BioTherapeutics Ltd. Vaxil’s technological approach : VaxHit (I)  Vaxil offers a different approach, combining the advantages of current approaches.  Using VaxHit, we can easily identify the key VCs sequence (entire SP domains) on any given antigen which has the following characteristics:  Small highly defined sequence: VCs that generate a specific immune response with lower side-effects.  Multiple MHC activation: VCs that bind a large proportion of the individual’s MHC repertoire (promiscuous binding). High coverage for both Class I and Class II.  applicable for the majority of the population worldwide.  induces more robust antigen specific CD4 + and CD8 + T-cell activation.  TAP-independent presentation: VCs have a the ability to overcome “immune escape” attempts by tumour cells/intracellular pathogens >>reduces tumor/pathogens resistance. Kovjazin et al., Mol. Immunol, April 2011

10 Vaxil BioTherapeutics Ltd.  VaxHit derived VCs vaccines have the following additional properties:  Stand alone products  Delivery: VCs with the ability to efficiently pass through cell membranes in order to be presented to immune cells via MHC binding.  Adjuvant: VCs hydrophobic properties have antigen specific stimulation properties which reduce the dependency for external adjutants. Vaxil’s technological approach : VaxHit (II) Kovjazin et al., Mol. Immunol, April 2011

11 Vaxil BioTherapeutics Ltd. 11 Therapeutic vaccines: The essentials Target: the antigen Delivery: presenting the antigen Adjuvant: boosting the immune response Vaxil’s vaccines uniquely provide a solution for all 3 requirements using a single sequence

12 Vaxil BioTherapeutics Ltd. 12 Vaxil’s approach: Comparison vs. current solutions  Score:  Score: +Poor, ++Moderate, +++Excellent solution

13 Vaxil BioTherapeutics Ltd. ImMucin A novel therapeutic vaccine with promiscuous MHC binding for the treatment of MUC1-expressing tumors

14 Vaxil BioTherapeutics Ltd. ImMucin: Potential for “Pipeline In A Product” IndicationPatient Population Lung, Prostate, Colorectal, Breast, Ovary, Thyroid, Pancreatic, RCC, TCC, Multiple Myeloma, Leukemia (AML,ALL CML), Lymphomas Solid Tumors Non-solid Tumors Label Expansion Potential  MUC1 is a well characterized TAA with established role as potential target for Immunotherapy.  MUC1 was recently recognized by the National Cancer Institute as one of the three most important tumor proteins for vaccine development."  Current anti-MUC1 vaccines are directed to an extracellular domain on MUC1, term (TRA) Tandem Repeat Array, which so far didn’t manifested satisfactory clinical outcome.  MUC1’s wide presence in many cancer types (Expressed >90% of human epithelial tumors) including cancer stem cells combined with the unique properties of ImMucin allows label expansion potential.

15 Vaxil BioTherapeutics Ltd. ImMucin: Potential for “Pipeline In A Product” * Image from Silvia Von Mensdorff-Pouilly et al, Cancer 3 (3), Most antibodies and vaccines ImMucin vaccine  Most development programs are focused on suppressing tumor growth by directing the extracellular portion of MUC1 (TRA domain).  Success to date has been underwhelming using this approach, and tumor growth tends to restart after a short period of suppression. Since the target of these therapies is the extra cellular domain which cleaves and is shed from the cell, it’s not surprising that affected MUC1 proteins — still intact in the cytoplasm — soon regenerate and continue the process of tumor cell growth.  Vaxil approach to target the intracellular SP domain, suggest for the first time a new paradigm for targeting MUC1. Cleavage site

16 Vaxil BioTherapeutics Ltd. ImMucin (VXL100): Anti-MUC1 vaccine  A 21mer peptide containing the entire signal peptide (SP) domain of the MUC1 TAA.  Novel mechanism-of-action:  New strategy targeting MUC1’s SP vs. TRA (improved specificity>>potency ).  Broader and more robust immune activation of both CD4 + & CD8 + T-cells.  Designed to be applicable to the majority of the target patient population. (Universal).  Dual MOA: TAP-dependent and independent T-cell activation. A real answer for tumor tendency to escape specific immunity.  Internal adjuvant properties (administration with GM-CSF without additional adjutants).  Potential synergy with other modalities e.g. DC, TIL, Agonist antibodies etc. for in-vivo/ex-vivo use. Kovjazin et al., Vaccine, May 2011

17 Vaxil BioTherapeutics Ltd. 17 ImMucin: in-vitro & ex-vivo Characterization  ImMucin has a pan-HLA activation of CD4+ and CD8+ T-cells in comparison to a number of known 9mer epitopes (in naïve and primed patient-derived PBLs)  Repeated stimulation of PBL with ImMucin, increased the % of CD4+ and CD8+ population as well as of CD8+CD45RO+ and CD4+CD45RO+ memory T-cell population.  Anti-ImMucin human T-cell lines recognize the 21mer ImMucin as a set of 9mer epitopes and manifest specific response proliferation and cytokine release against them. (cross presentation).  ImMucin is presented on target cells for MUC1 specific CTL lysis.  ImMucin manifest TAP-independent presentation on TAP-deficient tumor cells.  ImMucin immunogenicity profile (proliferation) is higher and wider vs. MUC1-TRA-L (VXL25), the API of the most advanced anti-MUC1 vaccine BLP25. Kovjazin et al., Vaccine, May 2011

18 Vaxil BioTherapeutics Ltd. 18  ImMucin’s epitopes are naturally presented after vaccination of HHD-2 HLA transgenic mice and BALB/c syngeneic mice. Kovjazin et al., Vaccine, May 2011  ImMucin plus GM-CSF is sufficient for the induction of anti-MUC1 CTL in HHD-2 mice. Kovjazin et al., Vaccine, May 2011  ImMucin without any additional adjuvants is sufficient for the induction of anti- MUC1 CTL and proliferation (CD4 and CD8) in BALB/c mice. (Vaxil unpublished data)  ImMucin is more potent than MUC1-TRA-L (VXL25) in the induction of anti-MUC1 CTL and anti-metastatic response in BALB/c mice. Kovjazin et al., Vaccine, May 2011  ImMucin’s epitope (MUC1-SP-S1) is the only immunogenic epitope in HLA- A2.1/MUC1 double transgenic mice. Stepensky et al., Clin Exp Immunol., 2006  ImMucin’s epitope (MUC1-SP-S2) manifested MUC1 specific response in cancer patients Brossart et al., Blood, 2000 ImMucin: invivo Characterization

19 Vaxil BioTherapeutics Ltd. 19 ImMucin: A first in man study Principle Investigator: Prof. Michael Shapira Dept. of Bone Marrow Transplantation & Cancer Immunotherapy Hadassah University Hospital, Jerusalem 91120, ISRAEL VAXIL-001 A Phase I/II Open Label Study To Asses The Safety And Efficacy Of ImMucin In Patients with MUC1-positive, Multiple Myeloma (MM) Results Coming up 2012

20 Vaxil BioTherapeutics Ltd. 20 Thank you Lior Carmon Founder and CEO Vaxil BioTherapeutics Ltd

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