RXi Pharmaceuticals. Biotech Showcase. San Francisco, CA. January 8, 2018 NASDAQ: RXII. Property of RXi Pharmaceuticals

Transcription

1 RXi Pharmaceuticals Biotech Showcase San Francisco, CA January 8, 2018 NASDAQ: RXII Property of RXi Pharmaceuticals

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. Property of RXi Pharmaceuticals 2

3 Self-delivering RNAi Technology Platform sd-rxrna RNAi is a naturally occurring biological process that inhibits gene expression Property of RXi Pharmaceuticals 3 1 RNAi compound (sd-rxrna) administered sd-rxrna cell membrane 2 sd-rxrna enters cells 3 RISC sd-rxrna loads into RNA-induced silencing complex (RISC) 4 mrna Target mrna is cut & destroyed RXi developed a novel sd-rxrna platform designed to use the RNAi pathway to specifically target disease proteins Robust development pipeline includes dermatology, ophthalmology and cell-based immuno-oncology Numerous business development and out-licensing opportunities exist cleaved mrna Disease protein expression is blocked

4 Key Features of sd-rxrna Provide for Broad Applicability to Drive Value 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 cell-based 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 Delivery is not cell-type specific Property of RXi Pharmaceuticals 4 Freedom to operate with broad IP protection

5 RXi Pharmaceuticals Development Pipeline Description Indication Discovery Pre-Clinical Phase 1 Phase 2 Phase 3 Dermal Scarring RXI-109 sd-rxrna targeting CTGF Retinal Scarring Corneal Scarring *In ACT RXI-762 RXI-804 sd-rxrna targeting PD-1* sd-rxrna targeting TIGIT* Immuno-oncology Solid tumors Immuno-oncology Solid tumors Undisclosed sd-rxrna targeting undisclosed targets Immuno-oncology Samcyprone Small molecule DPCP Cutaneous Warts RXI-231 RXI-185 Description sd-rxrna targeting tyrosinase sd-rxrna targeting MMP1 Application Uneven skin tone / pigmentation Wrinkles / skin laxity Property of RXi Pharmaceuticals 5 Functional and Safety Testing Consumer / User Testing

6 Property of RXi Pharmaceuticals Dermatology Franchise

7 RXI-109: In Development to Reduce the Recurrence of Hypertrophic Scars Hypertrophic scars are abnormal scars raised above the normal skin surface that can be reddened or darker than the existing skin tone Market potential - $1-3B Approximately 42M surgical procedures per year in the U.S. The incidence of hypertrophic scarring: following surgery is reported to be at least 40% in the general population 1 and up to 70% in certain Asian populations 2. Clinically validated target: Connective tissue growth factor (CTGF) A key regulator of fibrosis and scar formation, and plays a key role in tissue regeneration and repair. 1 Gauglitz, G.G., Kortin, H.C., Pavicic, T., Ruzicka, T., & Jeschke, M.G. Hypertrophic scarring and keloids: pathomechanisms and current emerging treatment strategies. Mol Med 2011; 17(1-2): Li-Tsang, C.W., Lau, J.C. & Chan, C.C. Prevalence of hypertrophic scar formation and its characteristics among the Chinese population. Burns 2005; 31, Property of RXi Pharmaceuticals 7

8 RXI-109: Positive Phase 2 Results Primary, Secondary and Exploratory Objectives Successfully Achieved RXI-109 demonstrates improved visual appearance for treated scar over control for one of the treatment arms Statistically significant results using Investigator Scar Assessment Scale at all follow-up time points, for one of the treatment arms: - 3 months (p=0.028), 6 months (p=0.013), 9 months (p=0.013) Statistically significant results using Visual Analog Scale for all follow-up time points, for the same treatment arm: - 3 months (p=0.012), 6 months (p=0.004), 9 months (p=0.017) 88% of the patients, and 86% of the investigators, indicate RXI-109 treated scar looked better over control RXI-109 is safe and well tolerated There were no drug-related serious adverse events (SAEs) Most other treatment emergent adverse events (AEs) were those commonly found with intradermal injections Property of RXi Pharmaceuticals 8

9 RXI-109: Reduce the Recurrence of Hypertrophic Scars - Next Steps A large amount of data was collected allowing for additional analyses that are currently ongoing RXI-109 can be confidently moved to Phase 2b of clinical development Property of RXi Pharmaceuticals 9

10 RXI-231: Cosmetic Ingredient to Improve Skin Appearance RXI-231: targets Tyrosinase (TYR), a key enzyme in synthesis of melanin Cosmetic ingredient that may improve the appearance of uneven skin tone and pigmentation Product that could play a significant role in this market Global Industry Analysts, Inc. Research Report Findings 1 Market Potential The global market for skin lighteners is projected to reach US $31B by Property of RXi Pharmaceuticals

11 RXI-231: Positive Consumer Testing Results Topical gel formulation developed by RXi Gel formulation allows RXI-231 to penetrate into the skin layers where the melanin producing cells reside Major accomplishment to deliver an oligonucleotide that is relatively large (9-12 kda) and negatively charged Three studies confirm safety and positive results The first two studies confirmed: - No irritation and sensitization Third study confirmed: - RXI-231 containing gel, as compared to vehicle gel, can reduce a change of skin tone triggered by UV (p < 0.04) Property of RXi Pharmaceuticals 11

12 Samcyprone : Small molecule in Development to Treat Cutaneous Warts Proprietary ointment formulation of diphenylcyclopropenone (DPCP) Efficacy in warts but also alopecia areata and cutaneous metastasis of melanoma, reported in peerreviewed journals with DPCP Orphan-drug designation of for the treatment of malignant melanoma stage IIb to IV Robust Patient Base More than 30M patients annually seek treatment for common warts 1 Market Potential Estimated treatment market for warts is approximately $2-4B annually 1 Property of RXi Pharmaceuticals

13 Samcyprone : Small molecule in Development to Treat Cutaneous Warts Study Design: Open-Label, Multi-Center, Prospective Subjects with common warts, dosing with topical ointment Evaluating two dosing regimens 2 cohorts Study Status: Patient participation completed, data collection and analysis ongoing High rate of skin sensitization is achieved, a prerequisite for a therapeutic response Promising wart clearance rates in early reviews Expected full readouts Q1-Q Property of RXi Pharmaceuticals 13

14 Summary of Dermatology Franchise RXI-109 (anti-ctgf): Phase 2 asset with proven efficacy, using intradermal injections, in treating recurrence of hypertrophic scars after scar revision surgery. Estimated market size USD $1-3B. RXI-231 (anti-tyrosinase): Topical cosmeceutical asset that suppresses the production of pigmentation, capable of lowering the visibility of excess pigment in the epidermis. Estimated size of the market: multi-billion. Samcyprone (topical immuno-therapy): Phase 2 asset with proven efficacy in cutaneous warts. Estimated market size USD $2-4B. Proprietary topical formulation that has been shown to deliver RNAi compounds (9-12kD) through the epidermis to the dermal epidermal junction where the melanin producing cells reside. Access to the self-delivering platform for human therapeutic and diagnostic use, providing access to new compounds targeting proteins of relevance for the treatment of skin diseases. Property of RXi Pharmaceuticals 14

15 Property of RXi Pharmaceuticals Ophthalmology Franchise

16 RXI-109: In Development to Reduce Retinal Scarring Goal: to maintain vision for a longer period of time than current standard of care (i.e. anti-vegf treatments) alone Block: formation of subretinal scarring in patients with advanced wet age-related macular degeneration (AMD) Day 1 Fundus angiograph image showing retinal scarring Market Potential > $8B 1 In US and major European markets. No FDA-approved targeted therapies in the U.S. for the treatment and prevention of subretinal scarring in advanced wet age-related macular degeneration Property of RXi Pharmaceuticals

17 RXI-109: Dose-dependent Reduction of CTGF in NHP Retina and Cornea Retina Cornea PBS CTGF protein levels are reduced in a dose dependent manner 7 days following a single intravitreal injection of RXI-109 in non-human primate Property of RXi Pharmaceuticals % Positive CTGF Staining * ** PBS 0.1 mg 0.33 mg 1 mg Treatment Dose mg 0.33 mg 1 mg % Positive CTGF Staining * p < 0.05, ** p < 0.01 PBS 0.1 mg 0.33 mg 1 mg Treatment Dose *

18 RXI-109: In Development to Reduce Retinal Scarring Study Design Single center (Johns Hopkins) Subjects with retinal scarring associated with advanced neovascular AMD Dose escalation (3 dose cohorts) & 4 doses at monthly intervals followed by 3-month observation period Study Status Patient participation completed, data collection ongoing. No dose limiting or serious toxicities have been noted, and no study drug related AEs have been reported to date Q readouts Property of RXi Pharmaceuticals 18

19 RXI-109: Preclinical Development to Reduce Corneal Scarring Objective: Block the formation of corneal scarring in patients with corneal injuries. Market Potential - 2.4M eye injuries / year in the US - Partial or fullthickness corneal injuries are common and can lead to corneal infection, erosion and scarring. If severe, may require corneal transplant to restore vision - ~50,000 corneal transplants / year in the US Property of RXi Pharmaceuticals 19

20 RXI-109: Successful Topical Delivery to Cornea sd-rxrna (red) in a Corneal Wound Model in vivo in Rabbit Property of RXi Pharmaceuticals 20

21 Summary of Ophthalmology C Franchise RXI-109 (anti-ctgf): Phase 1/2 asset with proven safety, using intra-ocular injections in patients with wet age-related macular degeneration that have developed retinal scarring. Estimated market size USD $3-5 B. Preclinical data package including CTFG protein reduction in retina and cornea in non-human primates following intra-ocular injection and delivery in a corneal wound model in rabbit demonstrating the potential for topical delivery of RXI-109 for the prevention of corneal scarring. Patented set of sequences against a variety of relevant proteins for targeting ocular disorders (acquired from OPKO in 2013). In addition, sequences against MDM2 which may be involved in Retinoblastoma. Preclinical intra-ocular asset (sd-rxrna targeting VEGF) with dose dependent effects and tolerability demonstrated in a mouse model. Access to the self-delivering platform for human therapeutic and diagnostic use, providing ready access to new compounds targeting proteins of relevance for the treatment of ophthalmic diseases. Property of RXi Pharmaceuticals 21

22 Property of RXi Pharmaceuticals Immuno-oncology Franchise

23 sd-rxrna for Immuno-oncology Improved Development Landscape for Cancer Therapeutics Active government support (Cancer Moonshot) Expedited Reviews by FDA per recent guidance sd-rxrna - Best RNAi technology for ACT - Can target multiple immunosuppression pathways in a single therapeutic entity - Demonstrated efficient uptake of sd-rxrna to immune cells - Silencing by sd-rxrna - long-term effect in vivo - Clinically proven safety of sd-rxrna - Established cgmp manufacturing Recent approvals in ACT Well positioned for success with safe and proven sd-rxrna platform Market Potential T-cell Immunotherapy Market ~$25B by Property of RXi Pharmaceuticals

24 Broad Potential Applicability of sd-rxrna In Cell Therapy for Oncology Human T Cells Number one Number two Number three TILs for ovarian cancer or melanoma HSCT for modulation of GvHD γ/δ T cells Engineered T Cells Number one Number two Number three CAR T TCR Checkpoint inhibition and optimization for persistence and fitness of T cells Human NK Cells Dendritic Cells Autologous or Allogeneic Natural Killer (NK) cells Cytokine Induced Killer (CIK) cells for hematological and solid tumor malignancies Engineered NK or CIK Property of RXi Pharmaceuticals 24 Dendritic cell cancer vaccines

25 Cell Based Therapy- Immuno-oncology Areas for Continued and Expanded Growth Internal Programs and Collaborations Expanding Partnerships and Collaboration with Industry and Academia Optimize Existing Treatment Paradigms New Technology / Engineered Cells Hematopoietic Stem Cells NK Cells TILs CAR T TCR Engineered NK Property of RXi Pharmaceuticals 25

26 sd-rxrna: Best RNAi technology for ACT High Transfection Efficiency with High Cell Viability Nearly 100% transfection efficiency combined with high cell viability 98.6% sd-rxrna Property of RXi Pharmaceuticals 26

27 Targeting Multiple Immunosuppression Pathways* in a Single Therapeutic Entity Simultaneous Silencing of Multiple Genes is a Major Competitive Advantage of sd-rxrna PD-1 *Extracellular TIGIT LAG-3 *Intracellular Undisclosed Target Gene Expression, % of non-targeting control (NTC) Property of RXi Pharmaceuticals 27

28 sd-rxrna: Long-Term Silencing Effect in vivo Reduced in vivo Tumor Growth Using CAR T-cells Treated ex vivo with PD1 targeting sd-rxrna Meso CAR T-cells 1 : T-cells engineered to target mesothelin, overexpressed on many solid tumors Meso CAR T-cells were pretreated with sd-rxrna 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 sd-rxrna treatment at one month Anti-PD1 sd-rxrna Control 1 CAR T-cells = chimeric antigen receptor T-cells Property of RXi Pharmaceuticals 28

29 PD1 Silencing by sd-rxrna in TILs Enhances Killing of Autologous Tumor Cells In Vitro Tumor Infiltrating Lymphocytes (TILs) Against Melanoma TILs isolated from melanoma patient TILs treated with PD1 sd-rxrna in a clinically used Rapid Expansion Protocol (REP) Tumor cell killing by TILs was measured by chromium release assay in vitro 29 Property of RXi Pharmaceuticals 29

30 Improving ACT by Impacting Cell Differentiation with sd-rxrna Improving antitumor efficacy and self renewal properties of therapeutic T-cells by enhancing long-term survival and metabolic fitness sd-rxrna ideal technology to affect cell differentiation during manufacturing Multiplexing: simultaneous modulation of multiple differentiation mechanisms: Signaling pathways Transcription factors Metabolic targets Epigenetic regulators Figure adapted from: Gattinoni L, et al: T memory stem cells in health and disease. Nat Med ;23(1):18-27 Property of RXi Pharmaceuticals 30

31 Summary of Immuno-oncology Franchise sd-rxrna for Cancer Therapeutics Best RNAi technology for ACT Can target multiple immunosuppression pathways in a single therapeutic entity Demonstrated efficient uptake of sd-rxrna to immune cells Silencing by sd-rxrna - long-term effect in vivo Clinically proven safety of sd-rxrna Ideal technology to affect cell differentiation during manufacturing Numerous ongoing collaborations evaluating hematopoietic stem cells, NK cells, TILS, CAR T, TCR and engineered NK cells RXI-762 and RXI-804 Solid Tumors sd-rxrna compounds targeting PD-1 and TIGIT respectively Established manufacturing of cgmp Property of RXi Pharmaceuticals 31

32 Corporate and Shareholder Update Attract long-term value investors and broaden shareholder base Executed reverse split to: - Maintain NASDAQ listing to support ongoing business development and other strategic transactions - Attract a broader range of institutional investors, mutual and pension funds with an increased share price - Reduce beta to decrease volatility in share price Property of RXi Pharmaceuticals 32

33 Business Strategy Partner / Out-license Dermatology and Ophthalmology Franchises Monetize valuable assets to promote growth in focus areas and extend financial runway Increase collaborations to advance Immuno-oncology program Accelerate development and path to market Continue global outreach for partners and outlicensing Advance growth and innovation through out-licensing in other therapeutic areas to support development of RNAi-based therapeutics using sd-rxrna Property of RXi Pharmaceuticals 33

34 Financial Overview Cash and cash equivalents* (a/o 9/30/2017) Burn rate Cash runway (Assuming current NASDAQ limitations with use of equity line) Cash runway (Assuming full use of $15M equity line available) Common shares outstanding (a/o 1/8/2018) Market Cap (a/o 1/8/2018) ~$5.4M ~$2.0-$2.5M/quarter Q Q ~2.4M ~$13.5M *Unaudited Property of RXi Pharmaceuticals 34