RXi Pharmaceuticals. BioPharm America September 26, 2017 NASDAQ: RXII. Property of RXi Pharmaceuticals

Transcription

1 RXi Pharmaceuticals BioPharm America September 26, 2017 NASDAQ: RXII

2 Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of Words such as believes, anticipates, plans, expects, indicates, will, intends, potential, suggests and similar expressions are intended to identify forward-looking statements. These statements are based on RXi Pharmaceuticals Corporation s (the Company ) current beliefs and expectations. Such statements include, but are not limited to, statements about the future development of the Company s products (including timing of clinical trials and related matters associated therewith), the expected timing of certain developmental milestones, the reporting of unblinded data, potential partnership opportunities, the Company s competition and market opportunity and pro forma estimates. The inclusion of forward-looking statements should not be regarded as a representation by the Company that any of its plans will be achieved. Actual results may differ from those set forth in this presentation due to risks and uncertainties in the Company s business, including those identified under Risk Factors in the Company s most recently filed Quarterly Report on Form 10-Q and in other filings the Company periodically makes with the U.S. Securities and Exchange Commission. The Company does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this presentation. 2

3 RXi Pharmaceuticals Overview Developing Innovative RNAi Therapeutics - For a Better Life Proprietary Technology Therapeutic self-delivering RNA ( ) compounds Harnessing naturally occurring RNAi process Innovation Freedom to Operate Extensive patent estate 3

4 Novel Self-delivering RNAi ( ) Platform 4 Provides for Broad Pipeline of RNAi Drugs for Unmet Medical Needs Single compound incorporates gene silencing activity & cellular uptake Robust uptake & silencing in multiple preclinical models Demonstration of safety and activity in a clinical setting Can be used alone or in combination with cellbased therapeutics Best RNAi technology for enhancement of cell-based therapeutics Potential to expand cell therapy beyond its current reach, e.g. CAR-T cells for solid tumors 4

5 Keratinocytes human primary : Robust Cellular Uptake ARPE-19 retinal pigment epithelium In vivo and in vitro SH-SY5Y neuroblastoma Hepatocytes primary mouse T-cells Uptake and silencing demonstrated in many different cell types Human, Primate, Rat, Mouse, Adherent, Non-adherent, Primary, Transformed Efficient uptake of (red) to multiple tissues in vivo upon local and systemic administration Skin Eye Spinal cord Liver 5

6 RXi Pharmaceuticals Development Pipeline Description Indication Discovery Pre-Clinical Phase 1 Phase 2 Phase 3 Dermal Scarring RXI-109 targeting CTGF Retinal Scarring Corneal Scarring *In ACT RXI-762 RXI-804 targeting PD-1* targeting TIGIT* Immuno-oncology Solid tumors Immuno-oncology Solid tumors Undisclosed targeting undisclosed targets Immuno-oncology Samcyprone Small molecule DPCP Cutaneous Warts Description Application Functional and Safety Testing Consumer / User Testing RXI-231 targeting tyrosinase Uneven skin tone / pigmentation RXI-185 targeting MMP1 Wrinkles / skin laxity 6

7 in Adoptive Cell Transfer * Transient silencing of differentiation targets with during cell production Immune checkpoint silencing by ex-vivo treatment of cells with * Lim and June, Cell (2017) 168:

8 in Adoptive Cell Transfer Modulation of Immune Effector Cells with RNAi Checkpoint Inhibition 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. 8

9 : Best RNAi technology for ACT High Transfection Efficiency with High Cell Viability Nearly 100% transfection efficiency combined with high cell viability 98.6% 9

10 Targeting Multiple Immunosuppression Pathways* in a Single Therapeutic Entity Simultaneous Silencing of Multiple Genes is a Major Competitive Advantage of PD-1 *Extracellular TIGIT LAG-3 *Intracellular Undisclosed Target Gene Expression, % of non-targeting control (NTC)

11 Silencing by : Long-Term Effect in vivo Reduced in vivo Tumor Growth Using CAR T-cells Treated ex vivo with PD1 targeting Meso CAR T-cells 1 : T-cells engineered to target mesothelin, overexpressed on many solid tumors Meso CAR T-cells were pretreated with ex vivo and injected into human ovarian cancer tumors in mice * Pvalue <0.01 (compared to PBS control arm) * Reduction of tumor growth is significantly improved by anti- PD1 treatment at one month Anti-PD1 Control 1 CAR T-cells = chimeric antigen receptor T-cells 11

12 Silencing by : Long-Term Effect in vivo 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 12

13 PD1 Silencing by in TILs Enhances Killing of Autologous Tumor Cells In Vitro Tumor Infiltrating Lymphocytes (TILs) Against Melanoma TILs isolated from melanoma patient 13 TILs treated with PD1 in a clinically used Rapid Expansion Protocol (REP) Tumor cell killing by TILs was measured by chromium release assay in vitro 13

14 Improving ACT by Impacting Cell Differentiation with Improving Antitumor Efficacy and Self Renewal Properties of Therapeutic T-cells by Enhancing Long-term Survival and Metabolic Fitness Seeking to partner and collaborate with leading ACT companies Ideal RNAi technology to affect cell differentiation during manufacturing Multiplexing: simultaneous modulation of multiple differentiation mechanisms: Signaling pathways Metabolic targets Transcription factors Epigenetic regulators Figure adapted from: Gattinoni L, et al: T memory stem cells in health and disease. Nat Med ;23(1):

15 Benefits of Using in ACT Gene Editing Antibodies No direct off-tumor side effects No persisting rogue cells in the body * Moderate cost of goods Targeting multiple checkpoints *Potentially further complicated by increased evidence of off-target mutations - Schaefer, K. A., Wu, W., Colgan, D.F., Tsang, S.H, Bassuk, A.G., & Mahajan, V.B. (2017). Unexpected mutations after CRISPR Cas9 editing in vivo. Nature Methods, 14, doi: /nmeth

16 Additional Advantages with in ACT Single Therapeutic Agent Single therapeutic agent with one or multiple immune checkpoints or differentiation targets attenuated Streamlined Regulatory Path Ex vivo application of No multiple combination clinical trials required Newly discovered checkpoint targets or differentiation can be rapidly tackled Clinically proven safety of Ease of Manufacturing Only small alterations needed in cell manufacturing process Facilitates adaptation of existing cell technologies 16

17 Immuno-Oncology Clinical Development with Two self-delivering RNAi ( ) compounds selected for preclinical development RXI-762, targeting PD-1 RXI-804, targeting TIGIT Manufacturing facility selected to initiate production of cgmp grade material, initially for RXI-762 to support moving into clinical development as early as 2018 as part of an ACT therapy. 17

18 RXi Pharmaceuticals Upcoming Milestones Therapeutic Development Description Indication Next milestone RXI-109 targeting CTGF Dermal Scarring Retinal Scarring Q4 2017: Phase 2 Readouts Q1 2018: Phase 1/2 Readouts RXI-762 targeting PD-1* Immuno-oncology Solid tumors Q4 2017: Update on preclinical checkpoint inhibiting RXI-804 targeting TIGIT* Immuno-oncology Solid tumors H2 2017: Publish in vitro results on use of with TILs in melanoma Samcyprone Small molecule DPCP Cutaneous Warts Q4 2017: Phase 2 Readouts *In ACT RXI-231 Description Application Next Milestone targeting tyrosinase Consumer Product Development Uneven skin tone / pigmentation 18 Q4 2017: Readouts on consumer testing