Phio Pharmaceuticals Corp. · NASDAQ:PHIO
Phio Pharmaceuticals — RXi Pharmaceuticals — 2nd Annual Oligonucleotide and Peptide Therapeutics Conference (March 2017)
27 slides from Phio Pharmaceuticals's conference presentation, Mar 29, 2017
Slide 1: Targeting Immune Checkpoints Using Self-Delivering RNAi (sd-rxRNA) Technology
RXi Pharmaceuticals NASDAQ: RXII Targeting Immune Checkpoints Using Self-Delivering RNAi (sd-rxRNA®) Technology Alexey Eliseev, PhD 2nd Annual Oligonucleotide and Peptide Therapeutics Conference, Cambridge, MA March 29, 2017 Exhibit 99.1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “believes,” “anticipates,” “plans,” “expects,” “indicates,” “will,” “intends,” “potential,” “suggests” and similar expressions ar
Slide 3: Promise to Cure Cancer: The Story of Immunotherapy
Promise to Cure Cancer The Story of Immunotherapy Survival Conventional therapy Immunotherapy Time Next-generation immunotherapeutic treatments
Slide 4: Adoptive Cell Transfer (ACT) Leading Direction in Immunotherapy
Adoptive Cell Transfer (ACT) Leading Direction in Immunotherapy Clinical Breakthroughs in ACT: Over 50% complete response in some hematological malignancies 20-30% complete response in metastatic melanoma
Slide 5: Clinical Success of ACT
Clinical Success of ACT Business and Industry Development Large Pharma Enter ACT Field Through Major Deals with Biotech and Academia IPOs of ACT Companies: Average Market Cap $1.5B
Slide 6: Immunosuppression Major Hurdle for ACT in Solid Tumors
Immunosuppression Major Hurdle for ACT in Solid Tumors Initial clinical trials of CAR T in solid tumors show limited success One of the major issues is immunosuppressive tumor microenvironment Multiple inhibitory receptors - immune checkpoints - are responsible for immunosuppression Clinical and com
Slide 7: Overcoming Immunosuppression
Overcoming Immunosuppression sd-rxRNA pre-treatment of cells can be used to silence one or more immuno-suppressive genes (such as PD-1 and other checkpoints). Results in fewer suppressive receptors on the immune cell surface, which boosts their ability to detect and destroy tumor cells. Therapeutic
Slide 8: RXi's sd-rxRNA: Best RNAi Technology for Adoptive Cell Transfer
RXi’s sd-rxRNA: Best RNAi Technology for Adoptive Cell Transfer One of the main challenges of RNAi technologies is the delivery of hydrophilic siRNA molecules to target cells Commonly used delivery techniques (lipid formulations, electroporation) are not optimal for ex-vivo treatment of therapeutic
Slide 9: sd-rxRNA Technology Provides Simple and Effective RNAi Delivery for ex-vivo Applications
sd-rxRNA Technology Provides Simple and Effective RNAi Delivery for ex-vivo Applications No delivery formulation required for local therapeutic applications Delivery not limited to a specific cell type Single chemically-modified RNA compound with improved drug-like properties Potent, stable, specifi
Slide 10: sd-rxRNA: Robust Cellular Uptake in vivo and in vitro
sd-rxRNA: Robust Cellular Uptake in vivo and in vitro T-cells ARPE-19 retinal pigment epithelium Hepatocytes primary mouse Keratinocytes human primary SH-SY5Y neuroblastoma Skin Eye Spinal cord Uptake and silencing demonstrated in many different cell types Human, Primate, Rat, Mouse, Adherent, Non-a
Slide 11: Immuno-oncology Program with sd-rxRNA
Immuno-oncology Program with sd-rxRNA Selection of lead sd-rxRNA compounds against six different extracellular and intracellular immune check points Demonstrated silencing of all tested checkpoint targets in vitro, singly and in combinations Efficient and long-lasting silencing of immune checkpoints
Slide 12: Immuno-oncology Program: Nearly 100% Transfection Efficiency
Immuno-oncology Program Nearly 100% transfection efficiency… sd-rxRNA is uniquely suited for checkpoint modulation in cellular immuno-oncology therapies 98.6% … combined with high cell viability sd-rxRNA sd-rxRNA Provides Highly Effective Transfection of Human T-Cells
Slide 13: Identification of sd-rxRNA Compounds Against Human PD-1
Identification of sd-rxRNA Compounds Against Human PD-1 RXi Uses a Proprietary Algorithm to Rapidly Identify and Validate Lead sd-rxRNA Compounds for New Checkpoint Targets - Average Lead Generation Time is 3-4 Months
Slide 14: Reduction of PD-1 Expression in Human Primary T-cells
Reduction of PD-1 Expression in Human Primary T-cells Expression of PD-1 was Measured by FACS in Intact (Surface Expression) and Permeabilized Cells (Intracellular Expression) sd-rxRNA beads NTC beads PD-1 beads no sd-rxRNA no beads beads NTC beads NTC beads PD-1 beads PD-1 beads NTC beads PD-1 bead
Slide 15: PD-1-Silenced Healthy Human T-cells Produce More Interferon-gamma
PD-1-Silenced Healthy Human T-cells Produce More Interferon-gamma Concentration of IFN-γ was measured by ELISA OKT-3 NTC OKT-3 PD1 2 mM
Slide 16: CAR T-Cells Against Solid Tumors
CAR T-Cells Against Solid Tumors CAR T-cells targeting mesothelin, one of the most actively studied solid tumor antigens Cells treated with PD-1 sd-rxRNA and control sd-rxRNA Efficacy tested in mouse model of ovarian cancer Compared with CAR T in combination with anti-PD-1 antibody Therapeutic effec
Slide 17: sd-rxRNA Induced PD-1 Silencing Present After 1 Month in vivo
sd-rxRNA sd-rxRNA sd-rxRNA in Cell Therapy sd-rxRNA Induced PD-1 Silencing Present After 1 Month in vivo Mouse xenograft model of ovarian cancer Tumors harvested after one month and human CD45-expressing cells were extracted and analyzed for PD-1 expression by flow-cytometry
Slide 18: PD-1 Silenced TILs Highly Proliferate During Rapid Expansion Protocol
PD-1 Silenced TILs Highly Proliferate During Rapid Expansion Protocol No sd-rxRNA NTC sd-rxRNA 2 mM PD-1 sd-rxRNA 2 mM
Slide 19: PD-1 Silenced TILs Produce Higher Amount of IFN-γ
PD-1 Silenced TILs Produce Higher Amount of IFN-γ During Co-Culture with Autologous Tumor Cells (KADA) Anti-PD-1 sd-rxRNA Increases the Percentage of IFN-γ+TNF-α+ Tumor-Specific Cytotoxic T- cells During TIL Co-culture with Autologous Tumor Cells no sd-rxRNA Anti-PD-1 2 mM Control sd-rxRNA 2 mM TNF-
Slide 20: PD-1 Silencing Enhances Killing of Autologous Tumor Cells by TILs
PD-1 Silencing by sd-rxRNA Enhances Killing of Autologous Tumor Cells (KADA) by TILs PD-1 Silenced TILs Have Significantly Higher Tumor Cell Killing Activity Compared to Control TILs Cellular toxicity was measured by chromium release assay at different ratios to tumor cells to T-cells No sd-rxRNA No
Slide 21: Targeting Multiple Immunosuppression Pathways in a Single Therapeutic Entity
Targeting Multiple Immunosuppression Pathways* in a Single Therapeutic Entity * Extracellular and Intracellular Simultaneous Silencing of Multiple Checkpoint Genes in T-cells is a Major Competitive Advantage of the Technology sd-rxRNAMIX sd-rxRNAPD-1 sd-rxRNATarget 1 sd-rxRNALAG3 sd-rxRNATarget 2 NT
Slide 22: Potential Advantages of RXi's Approach to Immunotherapy
Potential Advantages of RXi’s Approach to Immunotherapy Single therapeutic agent with one or multiple immune checkpoints attenuated Streamlined regulatory path No multiple combination trials required Newly discovered checkpoint targets can be rapidly tackled Therapeutic efficacy without persisting “
Slide 23: Targeting Immunosuppression in ACT
Targeting Immunosuppression in ACT Immunosuppression Reduction in ACT Monoclonal Antibodies Combinations of cells with mAbs(e.g. anti-PD-1) Gene Editing (TALEN, CRISPR, ZFP) Checkpoint knockouts RNAi Checkpoint Silencing (sd-rxRNA) ex vivo in vivo
Slide 24: sd-rxRNA: Safe and Versatile Approach to Reduction of Immunosuppression
Off-tumor side effects Yes No No Persisting rogue cells in the body No Yes No Cost of goods High Moderate Moderate Targeting multiple checkpoints Difficult Difficult Easy sd-rxRNA: Safe and Versatile Approach to Reduction of Immunosuppression in Therapeutic Cells Antibodies Gene Editing sd-rxRNA
Slide 25: RXi Appoints Leading Oncology Experts to SAB
RXi Appoints Leading Oncology Experts to SAB Dr. James Griffin Chairman, Department of Medical Oncology, Dana-Farber Cancer Institute; Professor, Medicine, Harvard Medical School; Director, Medical Oncology, Brigham and Women's Hospital Scientific Advisory Boards: Lombardi Cancer Center at Georgetow
Slide 26: RXi Pharmaceuticals Overview
RXi Pharmaceuticals Overview Innovation RXi harnesses the naturally occurring RNAi process which has the ability to “silence” or down-regulate the expression of a specific gene that may be overexpressed in a disease condition Proprietary Technology RXi has developed a robust RNAi therapeutic platfor
Slide 27: Acknowledgements
Acknowledgements Advirna, Inc. Alexey Wolfson Taisia Shmushkovich Monica Betancur-Boissel SRI International Nathalie Scholler ProMab Biotechnologies Part of the presented results were obtained in collaboration with the following people and organizations Karolinska Institutet Rolf Kiessling Maarten L