RXi Pharmaceuticals. Bio Investor Forum San Francisco, CA NASDAQ: RXII. October 21, Property of RXi Pharmaceuticals

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1 RXi Pharmaceuticals NASDAQ: RXII Bio Investor Forum San Francisco, CA October 21, 2015

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 RXII: Developing Innovative Therapeutics Innovation For a Better Life Pioneer in the development of novel, self-delivering RNAi (sd-rxrna ) therapeutics Direction Creating therapeutics in dermatology and ophthalmology Value Creation Research, develop, partner and license RXI-109 sd-rxrna Platform Samcyprone

4 Proprietary Self-delivering RNAi (sd-rxrna ) Platform The sd-rxrna Advantage Novel, self-delivering RNAi therapeutic compounds Single compound incorporates activity and delivery Structural diversity = novel intellectual property Robust uptake & silencing in multiple preclinical models Combines many positives of RNAi & antisense, while avoiding many negatives Reduces the expression of mrnas and long non-coding RNAs (lncrnas) in a target specific manner sd-rxrna Provides for broad pipeline of RNAi drugs for unmet medical needs

5 Rx Discovery Preclinical RXI-109 Hypertrophic Scars & Keloids Samcyprone Alopecia Areata, Warts, Cutaneous Metastases Melanoma Anti-Collagenase Aging, Chronic wounds Dermatology Franchise sirna Therapeutics and Immunotherapy Agents - Clinical and Cosmeceutical Development Clinical Phase 1 Phase 2 Phase 3 Anti-Tyrosinase Melasma, PIH, Lentigines Cosmetic Lead Identification Functional and Safety Testing Consumer/User Testing RXI-185 Target: Collagenase (MMP1) RXI-231 Target: Tyrosinase (TYR)

6 Dermal Clinical Program: RXI-109 An sd-rxrna in Development to Reduce Dermal Scarring Validated Target: CTGF Market Potential: $1-3B RXI-109 targets Connective Tissue Growth Factor (CTGF) Regulatory component of fibrosis and scar formation, plays a key role in tissue regeneration and repair Approximately 45M surgical procedures per year in the U.S. No FDA-approved targeted therapies in the U.S. for the treatment and prevention of scars Clinical Trials: Phase 2 clinical trials ongoing Safe and well tolerated: Approximately 100 subjects have been treated with RXI-109 by intradermal injection in all trials to date Positive visible effect on scar appearance and clinical endpoints

7 RXI-109: Developed to Reduce the Recurrence of Hypertrophic Scars Hypertrophic Scars: abnormal scars that are raised above the normal skin surface and can be reddened or darker than the existing skin tone The incidence of hypertrophic scarring following surgery is reported to be at least 40% in the general population 3 and up to 70% in certain Asian populations 4. RXI-109: self-delivering RNAi therapeutic compound (sd-rxrna) that silences CTGF Primary Endpoint: Improved visual appearance of revised scar after scar revision surgery (statistical difference in revised scar, treated vs. control) 3 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,

8 RXI-109 Treatment Scores Better Than Control Investigator Scar Scores and Visual Analogue Scale (VAS) Scores for RXI-109 Treated Scars After Scar Revision Surgery are Better than Control (3-month time point, p < 0.05) RXI-109 treated scar is better RXI RXI RXI-109 treated scar is better B 25 B A Cohort 2 (5 mg/cm) Control scar is better Cohort 1 (10 mg/cm) A Cohort 1 (10 mg/cm) Control scar is better Investigator Scar Assessment Score VAS Score Results calculated using scores from completed Patient and Observer Scar Assessment Scale (POSAS)*, which includes: Vascularity, pigmentation, thickness, relief, pliability, surface area and overall Investigator opinion A measure of the Investigator's opinion of the appearance of a scar on a scale of = fine line scar 10 = worst scar imaginable

9 Investigators and Panel Agree on Improved Appearance RXI-109 Treated Scars Have Improved Appearance Over Control Following Blinded Review of All 3-Month Scars Available to Date (5 mg/cm cohort) 100% RXI % 18% 20% 80% 70% 14% 18% 60% 50% 40% 30% 68% * 62% * 20% 10% 0% Panel * Investigators * RXI-109 better Control better Not different * p < Photographs of scars at 3-months available to date were blinded and provided to a panel of non-clinicians and a panel of clinicians (trial investigators and KOLs) Blinded Panel and Investigators were asked: Scar A looks better? Scar B looks better? or Not different? Panel s opinions in agreement with Investigator's opinions (not statistically different)

10 RXI-109 Treatment Scores Better than Control Representative Photos from 5 mg/cm Cohort at 3 Months RXI-109 RXI Control

11 Dose Optimization Results in Progressive Improvement Adjusting Timing and Number of Doses of RXI-109 Treatment Improves the Outcome at 3 Months (5 mg/cm) 100% 80% RXI-109 better 60% 40% 20% 54% 68% 24% 0% Study doses starting immediately post surgery Study doses starting 2 weeks post surgery Study doses starting 2 weeks post surgery Graph represents the percentage of observations that the RXI-109 treated scar was selected as better than control scar by a blinded panel reviewing photos at 3 months

12 RXI-109: On Track - Adaptive Approach Defined best time to start treatment 2 weeks post scar revision surgery P P doses Days 14, 21, 28 Evaluating 5 mg/cm, two (2) dosing regimens Selected better dose level 5 mg/cm 6 5 mg/cm Days 14, 21, 28, 35, 56, 84 3 doses Days 1, 8, mg/cm Days 14, 21, 28, 35, 56, 84 Evaluating two (2) dose levels, 5 mg/cm and 10 mg/cm, using an extended dosing regimen Next step: Define best treatment length (initiate Q4 2015) P doses Days 14, 28, 42, 56, 84 Month 4, 5, 6 9 doses Days 14, 21, 28, 35, 56, 84 Month 4, 5, 6 Evaluating two (2) dosing 5 mg/cm

13 Samcyprone : Topical Immunotherapy Proprietary Samcyprone is a proprietary, topical formulation of diphenylcyclopropenone (DPCP) Immunomodulator DPCP is a topical immunomodulator that works by eliciting a T-cell response Effective Efficacy reported in peer-reviewed journals with DPCP for the three target indications: warts, alopecia areata and cutaneous metastasis of melanoma Orphan-drug designation For malignant melanoma stage IIb to IV Market Potential: Combined, estimated >$1B Major competitors for treatment of warts: Aldara and Picato

14 Treatment with DPCP Active Ingredient in Samcyprone Warts (refractory plantar & periungual) Alopecia Areata Cutaneous Metastases of Melanoma (refractory) Choi, Y et al. Ann Dermatol. 2013, 25 4: >350 patients treated for weeks Response rates of 80-85% Cotellessa, C et al. JAAD 2001;44:73-6 >200 patients treated for several months Response rates of 67-78% Damian, DL et al. J Surg Oncol 2014, 109: patients with mean of 15 months treatment 46% complete clearance and 38% partial clearance

15 Samcyprone : Clinical Development Plan Cutaneous Warts Initiate: Phase 2 trial Q Indication: Cutaneous warts Expected preliminary readouts: H Estimated start of Phase 3: 2018 Value Creation: Evaluate other indications for potential new trial(s) using Samcyprone

16 Ophthalmology Franchise sirna Therapeutics Program Discovery Preclinical RXI-109 Retinal scarring, Macular Degeneration Clinical Phase 1 Phase 2 Phase 3 Corneal scarring (Topical) Self-Delivering ( sd ) Adaptation to acquired OPKO estate New targets

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

18 RXI-109: Dose-dependent Reduction of CTGF in 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 % Positive CTGF Staining * ** PBS 0.1 mg 0.33 mg 1 mg Treatment Dose 0.1 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 *

19 Ophthalmology Clinical Program: RXI-109 An sd-rxrna in Development to Reduce Retinal Scarring Initiate: Phase 1/2 trial Q Objective: Block the formation of sub-retinal scarring in patients with wet AMD Goal: to maintain vision for a longer period of time than anti-vegf treatment alone Market Potential: >$1B in US; Global $5B Target: CTGF RXI-109 targets Connective Tissue Growth Factor (CTGF) A key regulator of fibrosis and scar formation in the skin and the eye Dermal safety demonstrated by intradermal injection; dose levels for Phase 1/2 ocular study determined in toxicology studies via intraocular injection

20 Value Creation: Research Programs Advancing Towards Preclinical and Cosmeceutical Development Collagenase (MMP1) MMP1 enzyme involved in breakdown of extracellular matrix Potent MMP1 sd-rxrnas identified for potential preclinical development for treatment of skin aging disorders including photo aging Tyrosinase (TYR) TYR is key enzyme in synthesis of melanin Potent TYR sd-rxrnas identified for potential preclinical development. Potential indications include cutaneous hyperpigmentation disorders, lentigines (age spots, liver spots, freckles) OPKO RNAi Assets Acquired estate provides multiple development opportunities Novel potent sd-rxrna compounds targeting VEGF for potential intra-ocular therapy for age-related macular degeneration Other targets - discovery stage efforts ongoing

21 Value Creation: Research Programs Lead Selection for Cosmeceutical Development MMP1 TYR Target Selection Bioinformatics Compound Synthesis In vitro Screening File IP Chemical Optimization Test in Relevant Models Cosmeceutical Lead Candidate Identification

22 Value Creation: Path to Cosmetic Development Cosmeceuticals: Compounds that affect the appearance of the skin May have a faster development path to market Targets: MMP1 and TYR Collagenase (MMP1) and Tyrosinase (TYR) have great potential as cosmeceutical targets in the near term Market Potential: Combined global market potential ~$200B for skin lightening and skin rejuvenation Next Steps: Form of topical delivery is required

23 sd-rxrna Compound Targeting MMP1 Identified for Cosmeceutical Development: RXI-185 MMP-1 mrna Levels, % of Control 120% 100% 80% 60% 40% 20% 0% MMP1 mrna Levels Lead 2 Original Lead 2a RXI-185 Optimized 0.01 um um 0.1 um 0.5 um 1.0 um Passive transfection in HT-1080 cells RXI-185 EC50 = 330 nm MMP1 Matrix metalloproteinase involved in the breakdown of extracellular matrix Specifically cleaves collagens I, II, and III MMP1-targeting sd-rxrna may improve the appearance of: Wrinkles due to skin aging disorders, including photo-aging Acne scarring

24 RXI-185: Reduction of MMP1 Expression Results in Reduction of MMP1 Activity in vitro MMP1 mrna Levels MMP1 Enzyme Activity 120% 120% MMP-1 Expression, % of Control 100% 80% 60% 40% 20% 0.1 um 0.5 um 1.0 um MMP-1 Protein, % of Control 100% 80% 60% 40% 20% 0.1uM 0.5 um 1uM 0% Control NTC RXI-185 Optimized 0% Control RXI-185 Dose dependent reduction in MMP1 mrna levels observed when HT-1080 cells are treated with RXI-185 Dose dependent reduction in MMP1 enzyme activity observed when HT-1080 cells are treated with RXI-185

25 RXI-185: Reduced Migration Rate of A549 Lung Carcinoma Cells in vitro - Targeting MMP1 Reduced migration rate with RXI h RXI-185 NTC UTC Comparison of A549 Cell Migration after Treatment with MMP1 Targeting sd-rxrna 24 h h 48 h h Migration Distance (um) h h NTC UTC NTC UTC NTC UTC 24 h 48 h 72 h Scratch migration assay - A549 non-small cell lung carcinoma cell line Cells in culture treated with RXI-185 targeting sd-rxrna, non-targeting control (NTC), or untreated control (UTC) Reduced migration in the scratch assay may indicate a reduction in the invasive nature of the cancer cell due to MMP1 reduction as a result of sd-rxrna treatment

26 sd-rxrna Targeting TYR Identified for Cosmeceutical Development: RXI % TYR mrna Levels Tyrosinase TYR mrna Levels, % of Control 120% 100% 80% 60% 40% 20% 0% Lead Original Lead 1A RXI um um 0.05 um 0.1 um 0.5 um 1.0 um Oxidase that controls the ratelimiting step in melanin production Tyrosinase targeting sd-rxrna may approve the appearance of: Cutaneous hyperpigmentation Passive transfection in SK-MEL-5 cells RXI-231 EC50 = 400 nm Lentigines (freckles)

27 RXI-231: Reduction of TYR Expression Results in Reduction of TYR Activity in vitro TYR Expression in Melanocytes TYR Activity in Melanocytes 120% 120% 100% 100% TYR Expression, % of Control 80% 60% 40% 0.01 um um 0.1 um 0.5 um 1.0 um TYR Activity, % of Control 80% 60% 40% NTC RXI % 20% 0% RXI % Day 3 Day 5 Day 7 Dose dependent reduction in TYR mrna levels observed when primary human melanocytes are treated with RXI-185 Reduction in TYR enzyme activity observed when primary human melanocytes are treated with RXI-185

28 RXI-231: Reduction of TYR Expression Results in Reduction of Melanin in vitro Tyrosinase Expression In MelanoDerm Melanin Content in MelanoDerm TYR Expression, % of Control uM 2.5uM Melanin Content, % of Control uM 2.5uM NTC RXI-231 Control 0 RXI-231 Control NTC MelanoDerm 3-dimensional epidermal culture model containing melanocytes Seven day culture with TYR-targeting RXI-231 added to culture media

29 RXI-231: Visible Reduction of Pigmentation in vitro Targeting TYR RXI-231 NTC Light microscopy Histological cross section with staining for melanin Samcyprone MelanoDerm 3-dimensional epidermal culture model containing melanocytes Fourteen day culture with TYR-targeting RXI-231 added to culture media

30 Next Steps: Delivery to Skin Approach: Evaluation of technologies to achieve topical delivery Mechanical Microporation Microderm-abrasion Micro-needling Formulation Skin penetration enhancers Nanocarriers Combination approaches Porcine skin ex vivo: Microporation followed by application of 100 ug fl-sd-rxrna. Cellular uptake pattern appears similar to those obtained by intradermal injection Red (DY547) - labeled sd-rxrna Blue (Hoescht) cell nuclei Work done in collaboration with Pantec Biosolutions

31 Craig Mello, Ph.D. Chairman of RXi Pharmaceuticals' Scientific Advisory Board and co-recipient of the 2006 Nobel Prize in Medicine for RNAi "This discovery is a significant advancement for RXi's proprietary self-delivering RNA platform. lncrnas represent a diverse class of promising therapeutic targets. Currently, researchers must use multiple oligonucleotide platforms to reduce expression of lncrnas depending on the subcellular localization of the target. Biogazelle's findings suggest that RXi's technology can efficiently silence lncrnas regardless of their subcellular localization." October 20, 2015

32 Targeting lncrnas: Expanding sd-rxrna Platform Therapeutic Potential and Applicability What are long non-coding RNAs (lncrnas)? Diverse class of non-protein coding RNA transcripts > 200 nucleotides in length lncrnas are involved in critical biological processes: Control of gene expression Post transcriptional regulation Cell to cell communication lncrnas are being identified and explored as therapeutic targets in several diseases such as cancer, cardiovascular and neurological disorders Broadening therapeutic potential of sd-rxrna platform: Recent studies suggest significantly more lncrna genes (60,000) vs. protein coding genes (20,000) (Iyer et al. Nature 47, 2015) lncrna genes vs. protein coding genes 60,000 Protein coding RNA Transcribed non-coding RNA 20,000

33 Identification of Potent sd-rxrnas Targeting lncrnas Collaboration with Biogazelle Screened sd-rxrnas against 11 lncrna targets Identified potent sd-rxrnas (> 60% silencing) for 10 out of 11 lncrnas, with an overall hit rate of 21% sd-rxrna platform demonstrated potent and target-specific silencing of multiple lncrnas, including lncrnas that are strictly localized in the nucleus such as MALAT1 lncrna 2 Relative Expression MALAT 1 Relative Expression

34 Value Creation: Develop, Partner, License RXi s unique sd-rxrna platform allows for rapid identification of lead compounds for multiple targets in different therapeutic areas RXi s Strategic Core Focus Dermatology Scarring (fibrosis) Hyperpigmentation disorders Photo aging Ophthalmology Retinal scarring AMD, PVR Corneal scarring Local Delivery Arthritis Endometriosis Lung Fibrosis Chronic wounds Open for Partnering/Licensing Cell Therapy Exclusive license to platform for cell-based immunotherapies in cancer Other therapeutic areas for cell therapy still available Systemic & Cancer Liver fibrosis Kidney fibrosis Cancer sd-rxrna Platform

35 RXII: Driving Growth and Innovation Research & Development Communicate preliminary read-outs for RXI Phase 2a for Hypertrophic Scars Initiate Phase 1/2 trial in ophthalmology with RXI-109 Q Initiate Phase 2 trial for cutaneous warts with Samcyprone Q Identify lead sd-rxrna candidates targeting Collagenase (MMP1) and Tyrosinase (TYR) Business Development Collaborate Form research partnerships with other companies create proprietary sd-rxrna compounds against targets of their choice Maximize IP - Out-license/Create spin-out outside of RXi s core strategic areas. Maximize potential of platform and pipeline in exchange for equity in the receiving company (e.g. MirImmune license) Partner - Generate larger deals with equity investment by strategic regional partners

36 Financial Overview As of October 19, 2015* Cash and cash equivalents Burn rate ~$12.0 million ~$2.0M/quarter Cash runway Q Common shares outstanding ~65 million Closing share price $0.45 Market Cap ~$29 million *Unaudited

37 RXII: Developing Innovative Therapeutics Innovation For a Better Life Pioneer in the development of novel, self-delivering RNAi (sd-rxrna ) therapeutics Direction Creating therapeutics in dermatology and ophthalmology Value Creation Research, develop, partner and license RXI-109 sd-rxrna Platform Samcyprone