RXi Pharmaceuticals. October 2017 NASDAQ: RXII. Property of RXi Pharmaceuticals

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1 RXi Pharmaceuticals October 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 (sd-rxrna ) compounds Harnessing naturally occurring RNAi process Innovation Freedom to Operate Extensive patent estate 3

4 Novel Self-delivering RNAi (sd-rxrna ) 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 sd-rxrna: Robust Cellular Uptake In vivo and in vitro Keratinocytes human primary ARPE-19 retinal pigment epithelium 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 sd-rxrna (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 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 Description Application Functional and Safety Testing Consumer / User Testing RXI-231 sd-rxrna targeting tyrosinase Uneven skin tone / pigmentation RXI-185 sd-rxrna targeting MMP1 Wrinkles / skin laxity 6

7 Anti-Scarring Programs RXI-109 (Eye and Skin) 7

8 Selection of Lead Candidate RXI-109 Numerous studies implicate Connective Tissue Growth Factor (CTGF) overexpression in scarring and fibrotic diseases RXI-109, an anti-ctgf sd-rxrna compound, is delivered locally, avoiding delivery challenges of systemic RNAbased drugs Preclinical data demonstrate potent, selective, dosedependent and long-lasting silencing of CTGF with RXI- 109 RXI-109 addresses a large market opportunity in scar prevention/revision, in dermatology and ophthalmology applications 8

9 RXI-109: sd-rxrna in Clinical Development to Reduce Dermal Scarring (Phase 2) RXI objective is to reduce the formation of hypertrophic scars following scar revision surgery Market Potential: $1-3B 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 Validated Target: RXI-109: sd-rxrna silences CTGF Design of current study based on clinical observations of two earlier Phase 2a studies 9

10 RXI : Clinical Development to Reduce Dermal Scarring (Phase 2) Study Design: Open-Label, Multi-Center, Prospective, Within-Subject Controlled Subjects with hypertrophic scar(s), dosing via intradermal injection Evaluating multiple dosing regimens 4 cohorts Study Status: Patient enrollment & follow-up completed. Data collection and analysis ongoing. Proven safe and well tolerated in a clinical setting Improved scar appearance over control in preliminary blinded reviews Expected full readouts Q

11 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 % 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 *

12 RXI-109: Clinical Development to Reduce Retinal Scarring (Phase 1/2) RXI : The objective is to block the formation of subretinal scarring in patients with advanced wet age-related macular degeneration (AMD) Goal: to maintain vision for a longer period of time than current standard of care (i.e. anti-vegf treatments) alone Market Potential: > $1B Approximately 11 million individuals are affected with AMD in the U.S. alone, with a global prevalence of 170 million No FDA-approved targeted therapies in the U.S. for the treatment and prevention subretinal scarring in advanced wet age-related macular degeneration 12 Pennington KL, DeAngelis MM:. Epidemiology of age-related macular degeneration. Eye Vis (Lond) ;3:34.

13 RXI : Clinical Development to Reduce Retinal Scarring (Phase 1/2) 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 Day 1 Fundus angiograph image showing retinal scarring Study Status: Enrollment completed, drug dosing completed, patient follow-up ongoing No dose limiting or serious toxicities have been noted, and no study drug related AEs have been reported to date Q readouts 13

14 RXI-109: In Development to Reduce Corneal Scarring RXI-109: The objective is to block the formation of corneal scarring in patients with corneal injuries. Goal: Prevent permanent damage to the cornea - the clear protective tissue in the front of the eye and prevent vision impairment Market Potential: 2.4 million eye injuries / year in the US Partial or full-thickness 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 Image Source: University of Basel, Center for 14 Medical Image Analysis & Navigation - CIAN

15 Consumer Product Development RXI-231 RXI

16 RXI-231: Cosmetic Ingredient that may Improve the Appearance of Uneven Skin Tone and Pigmentation RXI-231 A cosmetic ingredient based on sd-rxrna that targets tyrosinase (TYR), a key enzyme involved in synthesis of melanin Goal The development as a cosmetic ingredient that may improve the appearance of uneven skin tone and pigmentation Market potential Combined global market potential ~$200B for skin lightening and skin rejuvenation 16

17 RXI-231: Cosmetic Ingredient that may Improve the Appearance of Uneven Skin Tone and Pigmentation Product Development: RXi developed a proprietary formulation that allows for the penetration of sdrxrna compounds to the epidermaldermal junction where TYR-producing melanocytes reside sd-rxrna Topical Formulation Consumer Testing Program: Initiated June 2017 Positive data from two safety studies (irritation and sensitization potential) Ongoing study assessing the impact of RXI-231 on the appearance of skin pigmentation induced by UV exposure Q readouts 17 Penetration of fluorescently labelled sd-rxrna (red) through stratum corneum of porcine ear skin explants

18 Samcyprone (DPCP) Small Molecule, Topical Immunomodulator 18

19 Samcyprone Small molecule in Development to Treat Cutaneous Warts Samcyprone - small molecule that is a proprietary topical formulation of diphenylcyclopropenone (DPCP) DPCP is a topical immunomodulator that works by eliciting a T-cell response Efficacy in the three target indications, alopecia areata, warts, and cutaneous metastasis of melanoma, reported in peer-reviewed journals with DPCP Orphan-drug designation of Samcyprone granted by FDA for the treatment of malignant melanoma stage IIb to IV A number of patients with Stage IIb to IV malignant melanoma develop cutaneous metastases. Samcyprone is developed for treatment of these metastases. Market potential: Combined market for three indications estimated >$1B Major competitors for treatment of warts: Aldara (Imiquimod) and Picato (Ingenol mebutate) 19

20 RXI-SCP-1502: Clinical Development for Treatment of 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 enrollment completed, treatment phase ongoing Safe and well tolerated with a high rate of skin sensitization is achieved, a prerequisite for a therapeutic response Promising wart clearance rates in early reviews Expected readouts Q

21 Immuno-oncology Programs RXI-762 RXI

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

23 sd-rxrna in Adoptive Cell Transfer Modulation of Immune Effector Cells with RNAi Checkpoint Inhibition 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. 23

24 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 24

25 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)

26 Silencing by sd-rxrna: Long-Term 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 26

27 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 27 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 27

28 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 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):

29 Benefits of Using sd-rxrna in ACT sd-rxrna 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

30 Additional Advantages with sd-rxrna 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 sd-rxrna No multiple combination clinical trials required Newly discovered checkpoint targets or differentiation can be rapidly tackled Clinically proven safety of sd-rxrna Ease of Manufacturing Only small alterations needed in cell manufacturing process Facilitates adaptation of existing cell technologies 30

31 Immuno-Oncology Clinical Development with sd-rxrna Two self-delivering RNAi (sd-rxrna ) compounds selected for preclinical development RXI-762, sd-rxrna targeting PD-1 RXI-804, sd-rxrna 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. 31

32 RXi Pharmaceuticals Upcoming Milestones Therapeutic Development Description Indication Next milestone RXI-109 sd-rxrna targeting CTGF Dermal Scarring Retinal Scarring Q4 2017: Phase 2 Readouts Q1 2018: Phase 1/2 Readouts RXI-762 sd-rxrna targeting PD-1* Immuno-oncology Solid tumors Q4 2017: Update on preclinical checkpoint inhibiting sd-rxrna RXI-804 sd-rxrna targeting TIGIT* Immuno-oncology Solid tumors H2 2017: Publish in vitro results on use of sd-rxrna with TILs in melanoma Samcyprone Small molecule DPCP Cutaneous Warts Q4 2017: Phase 2 Readouts *In ACT RXI-231 Description Application Next Milestone sd-rxrna targeting tyrosinase Consumer Product Development Uneven skin tone / pigmentation 32 Q4 2017: Readouts on consumer testing

33 Financial Overview Cash and cash equivalents* (a/o 6/30/2017) Burn rate Cash runway (Assuming current NASDAQ limitations) Cash runway (Assuming full use of $15M equity line available) Common shares outstanding (a/o 8/2017) Market Cap (a/o 8/2017) ~$7.7M ~$2.5M/quarter Q Q ~24M ~$13.5M *Unaudited 33

34 RXi Pharmaceuticals Leadership Board of Directors Chairman of the Board Robert Bitterman Management Team President and CEO Geert Cauwenbergh, DrMedSc Scientific Advisory Board Ocular Peter Campochiaro, MD Directors Keith Brownlie Geert Cauwenbergh H. Paul Dorman Jonathan Freeman, PhD Curtis Lockshin, PhD Chief Development Officer Gerrit Dispersyn, DrMedSc Vice President of Research Karen Bulock, PhD Dermatology Jeannette Graf, MD Leroy Young, MD Immuno-oncology James Griffin, MD Rolf Kiessling, MD Oligonucleotide development Pamela Pavco, PhD 34