RXi Pharmaceuticals Corporation

Transcription

1 RXi Pharmaceuticals Corporation Next Generation in RNAi Jefferies 2014 Global Healthcare Conference June 3, 2014 NASDAQ: RXII

2 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.

3 3 Corporate Highlights (1) RXi is a leader in development of advanced RNAi-based therapeutics with strong IP position Self-delivering technology has advantages in safety, potency & selectivity Recently received Notice of Allowance covering self-delivering (sd-rxrna ) technology platform In early 2014, granted a patent covering CTGF-targeting self-delivering RNAi compounds for the treatment of fibrosis Experienced scientific and development team (2) RXI-109, RXi s lead product, silences a clinically validated target and circumvents many challenges facing other RNAi-based drugs Reduction of CTGF with an antisense oligonucleotide correlated with improved scars in well-controlled clinical trials Delivered locally; avoiding many challenges of other RNA-based drugs > $1 billion market opportunity in scar prevention/revision (3) Multiple development opportunities based on its RNAi platform Dermatology, ophthalmology, organ fibrosis, spinal cord injury Platform potential enhanced by OPKO Health, Inc. asset purchase

4 Multiple Layers of Intellectual Property Protection 4 May 2014, granted Notice of Allowance for key patent broadly covering both the composition and methods of use of RXi's self-delivering technology platform. Key patent differentiating factor between RXi's technology and the competition Provides a powerful advantage to deliver our RNAi compounds without delivery vehicles Use of our proprietary sd-rxrna technology platform may lead to improved tolerability and thereby potentially broadening of the therapeutic window for these compounds March 2014, granted patent covering CTGF-targeting self-delivering RNAi compounds (sd-rxrna ) for the treatment of fibrosis. Complete RXi portfolio of intellectual property and licenses includes: RNAi compound design, configurations and chemical modification patterns; Innovative oligonucleotide technologies; Specific sequences for multiple therapeutic target genes; and Therapeutic methods of using rxrna and sd-rxrna to treat diseases in multiple areas.

5 5 Broad Intellectual Property Position in RNAi Compounds and Delivery RXi s Unique RNAi Platform Granted Notice of Allowance: Reduced Size Self-Delivering RNAi Compounds - Protection into 2029 RNA Duplex Length sd-rxrna sd-rxrna dsrna Conventional sirna rxrnaori Kreutzer-Limmer self-delivering compounds can enter cells and tissues to silence, without the need for an additional delivery vehicle Has several properties key to the clinical development of RNAi-based drugs (potency, selectivity/specificity, half-life) rxrnaori Similarities to classic sirna, but slightly longer duplex length The compound is highly active at picomolar levels in vitro Modified to increase resistance to nucleases and to prevent off target effects, including induction of an immune response

6 sd-rxrna Combines Features of RNAi and Antisense Technologies 6 Medicinal Chemistry Improved cell uptake and PK/PD Single compound designed to not require delivery vehicle Conventional RNAi Potent, long-lasting activity O Conventional Antisense Clinically relevant, validated PK/PD Robust uptake & silencing in multiple preclinical models Structural diversity = novel intellectual property Combining many positives of RNAi & antisense, while avoiding many negatives sd-rxrna Provides for broad pipeline of RNAi drugs for unmet medical needs sd-rxrna therapeutic compounds with drug-like properties

7 sd-rxrna: Robust Cellular Uptake in vitro and in vivo 7 Keratinocytes human primary ARPE-19 retinal pigment epithelium SH-SY5Y neuroblastoma Macrophages primary mouse Hepatocytes primary mouse Delivery and silencing demonstrated in many different cell types Human, Primate, Rat, Mouse, Adherent, Non-adherent, Primary, Transformed Efficient delivery of sd-rxrna to multiple tissues in vivo upon local and systemic administration Alveolar Skin Eye Spinal cord macrophages Liver

8 8 Therapeutic Franchises: Dermatology and Ophthalmology RXi s Next Steps RXi development focus for past two years: Dermatology and skin scarring RXI-109 to reduce expression of CTGF Well positioned to enter next stage of growth RXI-109 Phase 2 clinical trials underway Attractive therapeutic targets in dermatology and ophthalmology Formation of two therapeutic franchises within RXi Dermatology Ophthalmology

9 9 Dermatology Franchise RXI-109: The first self delivering sirna (sd-rxrna) to reduce the expression of CTGF protein in a dose dependent manner after intradermal injections Identify sd-rxrnas against key targets for dermatology indications Ongoing process to identify and access additional Phase 2 clinical compound

10 CTGF Expression, % NTC Property of RXi Pharmaceuticals CTGF Expression, % PBS 10 RXI-109 Efficiently Silences CTGF in in vitro and in vivo Preclinical Experiments CTGF Silencing in vitro RXI NTC 1 um CTGF Silencing in vivo in Rat Skin RXI-109 ( ) 300ug NTC ( ) 300ug PBS 51% 67% ** *** NTC 1 um RXI-109 Concentration (mm) NTC (1 mm) RXI-109 mg RXI mg 300 NTCmg 600 NTCmg PBS ( ) ( ) ( ) ( ) RXI-109 NTC 300ug 600ug 300ug 600ug RXI-109 injections Day A549 cells were treated with RXI-109 and NTC Passive uptake 48 hours EC50 = /- 6.3 nm Excisional Wound mrna levels were quantified by QPCR on Day 8, normalized to the housekeeping gene and set relative to PBS. **p=0.0015, *** (relative to the dose-matched NTC) PBS = Phosphate Buffered Saline (Vehicle Control) NTC = Non-Targeting Control sd-rxrna Harvest

11 11 Selection of Area of Focus: Dermal Scarring Attractive Therapeutic Opportunity Unmet need with limited competition for truly effective therapies No prescription drugs approved Clear development precedent (Excaliard antisense) Large market in scar prevention/revision 42.3 million surgical procedures per year in the U.S.* Courtesy of Dirk M Elston MD Courtesy skincareguide.ca *US anti-scarring market The Nemetz Group December 2009

12 RXI-109 Phase 1 Clinical Trials Safety Pharmacokinetics Biomarkers Single dose use in volunteers (dose ascending 5 doses) 2. Multi-dose in volunteers (dose ascending 4 doses/5 cohorts) Parameters Evaluated Results Safety & side effect assessment vs. vehicle Photographic comparison vs. vehicle Histological comparison of the scar sites vs. vehicle Pharmacokinetics with local intradermal use CTGF protein & mrna levels No toxicity; minor erythema No impaired wound healing in volunteers No impaired wound healing Systemic exposure 5% of dose given Dose dependent reduction in protein and mrna

13 5.0% 0.0% Dose Dependent Reduction in CTGF Protein and mrna Study 1201: Reduction in CTGF Protein (as a percentage of placebo dosed sites) RXI-109 P1 Studies -5.0% -10.0% -15.0% -20.0% Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 mg/incision Paired t-test p-values 13% 17% % 0% -25% Study 1202: Reduction in CTGF mrna (as a percentage of placebo dosed sites) 43% 43% 50% -50% * Cohort 1 Cohort 2 Cohort 3 Cohort 4 mg/incision Paired t-test p-values Property of RXi Pharmaceuticals Note: No additional benefit was seen on CTGF mrna reduction in Cohort 5 (delayed dosing regimen, 10 mg per incision) 13

14 14 Ongoing Phase 2 Program for RXI randomized, within-subject controlled studies Indications include: Lower abdominal scar revision (RXI ) Initiated Q4, 2013 Keloid scar excision (RXI ) Initiated Q2, 2014 Scar revision following cosmetic breast surgery Study objectives include: Determination of optimal dose and schedule Demonstration of efficacy and safety

15 15 Ophthalmology Franchise Multiple RNAi assets in preclinical pipeline Limited financial runway to advance these assets Expressed interest from investment funds to support RXi s ophthalmology developments Preclinical data in vivo in retinal scarring and retinoblastoma Completed dose range finding ocular toxicity study for RXI-109 in non-human primate Need to complete GLP toxicity for RXI-109 intraocular injection File IND

16 *Van Geest, et al Br J Ophthalmol 2012:96: RXi Ocular Programs Areas of focus have been identified for targeted ocular therapeutics Ocular Scarring Retinal scarring in Proliferative Vitreoretinopathy (PVR) Occurs in approximately 8-10% of patients who develop a retinal detachment File an IND cross-referencing the RXI-109 anti-scarring IND with ocular toxicity studies Scarring after Glaucoma surgery Neovascularization/fibrotic disorders VEGF targeting compound either alone or in combination with a CTGF targeting sd-rxrna for retinopathy disorders Therapeutics relying on suppression of VEGF address the neovascularization component of these disorders but not the subsequent retinal scarring that often occurs* Retinoblastoma Retinoblastoma is childhood cancer that originates in the retina Goal is to develop compounds against retinoblastoma therapeutic targets

17 17 Ophthalmology Franchise Multiple Development Opportunities Program Discovery Preclinical Clinical PVR Phase 1 Phase 2 Phase 3 Macular Degeneration Retinoblastoma Self Delivering ( sd ) Adaptation to Acquired OPKO Estate Core focus Projected next steps

18 sd-rxrna: In Ophthalmology: Improved Delivery vs. Stabilized RNAi Byrne et al., JOPT. December 2013, 29(10): sd-rxrna Stabilized Placebo sirna Mouse immediately post-dose Mouse at 24 hours post-dose Mouse at 24 hours post-dose Rabbit at 24 hours post-dose sd-rxrna chemistry is required for robust uptake to the cells of the eye No overt toxicity observed after sd-rxrna treatment to the eye Dosing by intravitreal injection to mouse or rabbit eye Dy547-labeled sd-rxrna, stabilized sirna or placebo

19 PPIB Expression, % of NTC sd-rxrna: Extended Silencing in vivo in the Rodent Eye Byrne et al., JOPT. December 2013, 29(10): Duration of Silencing Induced by PPIB Targeting sd-rxrna % ** 45% ** 32% ** Time after injection, days 22% ** PBS NTC PPIB 3 mg PPIB or NTC administered by intravitreal injection (in 1 ml) to mouse eyes mrna levels were quantified by Quantitative PCR (QPCR) and normalized to b-actin Data assembled from 5 different studies to enable sufficient n for each data point (n=5-8); graphed +/- SD relative to PBS in each study; * p 0.05, ** p 0.01 PBS = Phosphate Buffered Saline (Placebo) NTC = Non-Targeting Control sd-rxrna PPIB = Anti-cyclophilin B sd-rxrna

20 Byrne et al., JOPT. December 2013, 29(10): sd-rxrna: Preliminary Safety Evaluation Color Fundus Photography No RPE degeneration No overt signs of retinal damage Fluorescein Angiography No leakage of retinal/choroidal blood vessels 5 µg (1 µl) of sd-rxrna targeting MAP4K4 was administered by intravitreal injection to mouse eyes

21 Byrne et al., JOPT. December 2013, 29(10): sd-rxrna: Preliminary Safety Evaluation ERG Recordings No loss of retinal function following dosing with sd-rxrna or PBS Optical Coherence Tomography No changes in retinal morphology through 4 weeks post administration 5 µg (1 µl) of sd-rxrna targeting MAP4K4 was administered by intravitreal injection to mouse eyes

22 22 Areas of Focus for CTGF Protein Evaluation Retina Cynomolgus Monkey Whole Eye Cornea vitreous lens Back Front

23 % Positive CTGF Staining % Positive CTGF Staining CTGF Protein Levels in the NHP Retina and Cornea Decrease Following Treatment with RXI-109 Retina Cornea PBS 0.1 mg Property of RXi Pharmaceuticals * ** PBS 0.1 mg 0.33 mg 1 mg Treatment Dose 0.33 mg 1 mg * p < 0.05, ** p < 0.01 PBS 0.1 mg 0.33 mg 1 mg Treatment Dose * CTGF protein levels are reduced in a dose dependent manner 7-days following single intravitreal injection of RXI

24 24 Retinoblastoma Retinoblastoma is a cancer that originates in the retina and primarily affects young children. Accounts for about 3% of cancers occurring in children younger than 15 years of age. The heritable form is driven by mutations in the retinoblastoma (RB1) gene. Expression of genes involved in the normal signaling circuitry of retinal cells are also involved. Our goal is to develop compounds against retinoblastoma therapeutic targets. Progress to date: Dose-dependent mrna silencing in retinoblastoma cell lines Uptake by human retinoblastoma tumor cells in vivo in a mouse model Funded by NIH/NCI SBIR grant

25 25 Twenty-four Hours Post Injection sd-rxrna Co-localize with Tumor Cells Throughout the Eye Retinoblastoma = tumor cells = sd-rxrna + Subretinal space Vitreous Uptake of sd-rxrna in vivo in mouse retina and tumor cells 24 hr post injection Retina Mouse eyes were seeded subretinally with Y79 retinoblastoma cells 10 µg of DY547-labeled sd-rxrna (red) was administered by intravitreal injection (1µl) 3 weeks after seeding

26 Building sd-rxrna Compounds Based on Acquired OPKO Assets Passenger Strand Guide Strand Property of RXi Pharmaceuticals Example sd-rxrna Bevasiranib Configuration <15 bp duplex 5 nt & longer tail = standard and modified bases = various hydrophobic moieties = phosphodiester linkages = phosphorothioate linkages = other hydrophobic linkages Conversion of Bevasiranib into a sd-rxrna Use bioinformatics and sequence walk to select Bevasiranib and overlapping sequences for conversion to sd-rxrna structure Synthesize and screen in vitro Chemically optimize for enhanced potency and stability Select leads for in vivo model testing Additional target sequences acquired from OPKO Involved in angiogenesis treatment of retinal diseases or cancer HIF-1a ICAM-1 Angiopoietin-2 Key 26

27 27 Corporate Goals 2014 Initiate two additional Phase 2 clinical trials with RXI-109 Advance additional programs from discovery into preclinical development Maintain appropriate cash resources to support Phase 2 studies and advance our therapeutic pipeline Broaden and diversify our intellectual property portfolio Broaden shareholder base

28 Financial Overview a/o May 30, 2014 Cash ~$12.9 million* Burn rate ~$2-2.5million/quarter Available cash with current plan Q No Debt Common shares outstanding 14 million Closing share price $2.69 Market Cap ~$38 million *Unaudited numbers Property of RXi Pharmaceuticals 28

29 29 Corporate Highlights (1) RXi is a leader in development of advanced RNAi-based therapeutics with strong IP position Self-delivering technology has advantages in safety, potency & selectivity Recently received Notice of Allowance covering self-delivering (sd-rxrna ) technology platform In early 2014, granted a patent covering CTGF-targeting self-delivering RNAi compounds for the treatment of fibrosis Experienced scientific and development team (2) RXI-109, RXi s lead product, silences a clinically validated target and circumvents many challenges facing other RNAi-based drugs Reduction of CTGF with an antisense oligonucleotide correlated with improved scars in well-controlled clinical trials Delivered locally; avoiding many challenges of other RNA-based drugs > $1 billion market opportunity in scar prevention/revision (3) Multiple development opportunities based on its RNAi platform Dermatology, ophthalmology, organ fibrosis, spinal cord injury Platform potential enhanced by OPKO Health, Inc. asset purchase