RXi Pharmaceuticals. sd-rxrna Demonstrate Robust Efficacy in the Eye. Dr. Geert Cauwenbergh President & CEO OTCQX: RXII. Next Generation in RNAi

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1 RXi Pharmaceuticals sd-rxrna Demonstrate Robust Efficacy in the Eye Next Generation in RNAi Dr. Geert Cauwenbergh President & CEO OTCQX: RXII

2 2 Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of Such statements include, but are not limited to, statements about the future development of RXi Pharmaceuticals Corporation s products. These forward-looking statements about future expectations, plans and prospects of the development of the Company's products are subject to a number of risks and uncertainties, including those identified under Risk Factors in the Company s most recently filed Annual Report on Form 10-K, Quarterly Report on Form 10-Q and in other filings the Company periodically makes with the SEC. 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.

sd-rxrna Combines Features of RNAi and Antisense Technologies 3 Medicinal

require delivery vehicle Conventional RNAi Potent, long-lasting activity O

& silencing in multiple preclinical models Structural diversity = novel

avoiding many negatives sd-rxrna Provides for broad pipeline of RNAi drugs

3 sd-rxrna Combines Features of RNAi and Antisense Technologies 3 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

4 sd-rxrna: In Ophthalmology: Improved Delivery vs. Traditional RNAi Byrne et al., JOPT. November 2013, published online ahead of print 4 sd-rxrna Conventional 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 with Dy547- labeled sd-rxrna, conventional sirna or placebo

5 PPIB Expression, % of NTC sd-rxrna: Extended Silencing in vivo in the Rodent Eye Byrne et al., JOPT. November 2013, published online ahead of print 5 Duration of Silencing Induced by PPIB Targeting sd-rxrna % ** 45% ** 32% ** Time after injection, days 22% ** PBS NTC PPIB Single intravitreal administration of 3 µg of sd-rxrna results in sequence-specific reduction of PPIB mrna levels for 14 days 3 µg (1 µl) of sd-rxrna targeting PPIB was administered by intravitreal injection to mouse eyes

Color Fundus Photography No RPE degeneration No overt signs of retinal damage

6 Byrne et al., JOPT. November 2013, published online ahead of print 6 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

Recordings No loss of retinal function following dosing with sd-rxrna or PBS Optical Coherence

7 Byrne et al., JOPT. November 2013, published online ahead of print 7 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

8 *Van Geest, et al Br J Ophthalmol 2012:96: RXi Ocular Programs Three areas of focus for the development of targeted therapeutics for ocular indications have been identified Retinal Scarring Proliferative Vitreoretinopathy (PVR) Occurs in approximately 8-10% of patients who develop a retinal detachment Potential to file an IND cross referencing the RXI-109 anti-scarring IND with minimal ocular toxicity studies Retinoblastoma Retinoblastoma is a cancer that originates in the retina and primarily affects young children Our goal is to develop compounds against novel retinoblastoma therapeutic targets 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*

9 In Vivo Silencing of CTGF and Uptake in Model of Retinal

uptake in rat retinal detachment model In vivo cellular

silences CTGF in a normal rat retina 48 hours post

In all retinal layers in the presence and absence of a

9 9 In Vivo Silencing of CTGF and Uptake in Model of Retinal Detachment Retinal Scarring In vivo silencing In vivo retinal uptake in rat retinal detachment model In vivo cellular uptake by reactive cells involved in retinal scarring RXI-209 silences CTGF in a normal rat retina 48 hours post intravitreal administration fl-rxi-109 (red) is detectable: In all retinal layers in the presence and absence of a detachment at 24 hours At 14 days in a detached retina In Müller cells and photoreceptors

10 Twenty-four Hours Post Injection sd-rxrna

Retinoblastoma = tumor cells = sd-rxrna + Subretinal

retina and tumor cells 24 hr post injection Retina

retinoblastoma cells 10 µg of DY547-labeled sd-rxrna

10 10 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

11 Conversion of Bevasiranib to a Self Delivering RNAi Compound Age Related Macular Degeneration (AMD) Passenger Strand Guide Strand Bevasiranib Configuration 19 bp duplex Key = standard

11 11 Conversion of Bevasiranib to a Self Delivering RNAi Compound Age Related Macular Degeneration (AMD) Passenger Strand Guide Strand Bevasiranib Configuration 19 bp duplex Key = standard ribonucleotide bases = 2 deoxyribose bases = phosphodiester linkages Phase III Clinical Trial of Bevasiranib was initiated in 2007 NDA not filed with FDA Conversion of Bevasiranib into a sd-rxrna Reduce length of Passenger strand (<15 bp duplex) Identify optimal self delivering chemical modification pattern Add hydrophobic conjugate to Passenger strand to enhance cellular penetration Example sd-rxrna Bevasiranib Configuration Passenger Strand Guide Strand <15 bp duplex 5 nt & longer tail Key = standard and modified bases = various hydrophobic moieties = phosphodiester linkages = phosphorothioate linkages = other hydrophobic linkages

12 Ophthalmology Franchise Multiple Development Opportunities Program Discovery Preclinical Clinical Ophthalmology (PVR) Ophthalmology (Macular Degeneration) Ophthalmology (Retinoblastoma) Ophthalmology (Bevasiranib sequence based) Phase 1 Phase 2 Phase 3 Property of RXi Pharmaceuticals Core focus Projected next steps 12

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

RXi Pharmaceuticals. Bio Investor Forum San Francisco, CA NASDAQ: RXII. October 21, Property of RXi Pharmaceuticals RXi Pharmaceuticals NASDAQ: RXII Bio Investor Forum San Francisco, CA October 21, 2015 Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private