Update on Phase 2a Clinical Trial Results of RXI-109 Treatment to Reduce the Formation of Hypertrophic Dermal Scars and Keloids

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1 Update on Phase 2a Clinical Trial Results of RXI-109 Treatment to Reduce the Formation of Hypertrophic Dermal Scars and Keloids Presenter: Pamela A. Pavco, PhD Chief Development Officer RXi Pharmaceuticals Corporation June 9, 2015 FC-07 Wound Healing 23 rd World Congress of Dermatology

2 Overview and Learning Objectives At the conclusion of this talk you will understand: the potential for RNA interference as a dermal therapeutic the key role of CTGF in dermal scarring and keloid formation results of initial Phase 1 and 2a trials with RXI-109, a proprietary, self-delivering RNAi compound that targets CTGF key learnings from the early and ongoing RXI-109 trials, and the next steps for clinical studies with RXI-109.

3 Therapeutic Development of RNA Interference

4 First Development Area: Dermal Scarring Addressing significant unmet medical need with large market potential Targeting Connective Tissue Growth Factor (CTGF) CTGF plays a key role in tissue regeneration & repair, overexpression leads to scarring Unmet need with limited competition for truly effective therapies No prescription drugs approved Trials initiated with RXi s first clinical candidate: RXI-109 RXI-109 is an sd-rxrna compound developed to reduce dermal and retinal scarring Large market in scar prevention/revision 42.3 million surgical procedures per year in the United States* 177,000 scar revision surgeries per year in the United States** *US anti-scarring market The Nemetz Group December 2009 **2014 Plastic Surgery Statistics Report, American Society of Plastic Surgeons Type of Skin Surgery Cosmetic Reconstructive Moles Trauma Elective (office) Elective (hospital) TOTAL Annual Number of Procedures 6.0 million 3.9 million 3.4 million 9.0 million 9.6 million 10.4 million 42.3 million

5 Key Role of Connective Tissue Growth Factor (CTGF) CTGF in Dermal Scarring Tissue Regeneration Connective Tissue Growth Factor Central player in the balance between healthy healing and excessive fibrosis Excessive Fibrosis RXI-109 Cellular Effects Collagen Deposition Adhesion Migration Proliferation Differentiation Pathologic Effects Pulmonary Fibrosis Acute Spinal Injury Dermal Scarring Restenosis Ocular Scarring Liver Fibrosis

6 Abnormal Skin Healing Hypertrophic Scarring: Raised, often hyperpigmented scar Excess collagen deposition resulting from traumatic injury to deep dermal layers Keloid Disorder: Large, raised scars that grow beyond the boundary of original injury Often hyperpigmented; most common on chest, back, shoulders (areas of tension) & earlobes, usually recur Both have a genetic component More common in persons with darker skin pigmentation (higher Fitzpatrick phototype) Keloid prevalence is <0.1% in Great Britain; 16% in the Congo 1 Hypertrophic scarring can be 40-70% following surgery, higher following burns 2 1. Kelly AP Keloids. Dermatol Clin (3): Gauglitz GG Hypertrophic scarring and keloids. Mol Med (2):

7 The Wound Healing Cascade Normal Proliferation Remodeling A Hypertrophic Proliferation Remodeling B C Keloid Proliferation Acute Inflammation post trauma (~2 Weeks) Months 1 Year A Bayat, A et al. BMJ 2003;326; doi: /bmj B Property of RXi Pharmaceuticals C Courtesy of skincareguide.ca

8 Results of Phase 1 Clinical Trials Phase 1: Healthy Volunteers (N = 30 in 2 studies) Dose escalation, dosing via intradermal injection Compared RXI-109 vs. placebo Study 1201: Single dose (at two 2-cm incision sites) Study 1202: Multi-dose (three doses at four 2-cm incision sites) Safety Treatment on Days 1, 8, 15 No significant local effects (local effects of erythema, slight pain), no indication of accumulation, MTD not reached Biomarker Analysis (supports RNAi mechanism of action) Significant dose dependent reduction CTGF protein 84 days post single dose Significant dose dependent reduction of CTGF mrna 3 days post third dose

9 Overview of Phase 2a Clinical Trial Protocols Phase 2a: Treatment with RXI-109 Following Revision Surgery Dosing initiated at start of inflammation or proliferation phase Study 1301: Hypertrophic Scars (3 5 mg/cm; 4, 5, 6 cm) N = 22 patients, 2 cohorts RXI-109 treatment on 4, 5 or 6 cm on one side of scar, vehicle on other Double-blind treatment on Days 1, 8 and 15 (Cohort 1) or Days 14, 21 and 28 (Cohort 2) Pilot Study 1401: Keloids (4 10 mg/cm, up to 3 cm) N = 16 patients, 2 cohorts To Prevent Formation of Dermal Scars or Keloids RXI-109 treatment of one revision site, placebo on other Single-blind treatment on Days 1, 8, 15 and 22 (Cohort 1) or Days 15, 22, 29 and 36 (Cohort 2)

10 RXI : Blinded Panel Evaluation First P2a Study: RXI-109 vs. Placebo after Scar Revision Surgery At 3 months, improved results were obtained when treatment with RXI-109 was started two weeks post-surgery 100% 80% p < 0.001* 60% 40% 20% 0% 3 month 3 month Treatment Start Day 1 Treatment Start Day 14 RXI-109 better Placebo better or no difference between sides

11 RXI : Scar Comparison at 3 Months First Phase 2a: RXI Placebo RXI-109 First Two Subjects Subject #1 Subject #2

12 RXI : Scar Comparison at 3 Months Widened scar with keloidal character First Phase 2a: RXI Pre-scar revision surgery PLACEBO 3 months post-scar revision surgery *White dots are markers used in clinical photography. RXI-109

13 Key Learnings from Initial RXI-109 Trials Studies 1301 & 1401: Enrollment and treatment complete 3 doses in 2 weeks for hypertrophic scars; 4 doses in 1 month for keloids Continue follow-up as per protocol (9 and 6 months, respectively) Safety in Phase 2a is similar to Phase 1 Increased dose (amount and number of doses) in Phase 2a Main local effects are mild erythema, slight pain; limited urticaria with no sequelae RXI-109 scored a positive clinical effect on hypertrophic scars at 3 months post surgery Treatment initiating at 2 weeks, at start of proliferation phase of wound healing, is beneficial vs. starting immediately on surgery day Longer treatment duration is indicated Conclusions

14 Next Steps with RXI-109 Study 1402: Hypertrophic Scars Ongoing Dosing initiated at 2 weeks, after the inflammation phase and at start of proliferation phase Increased dosing occasions from 3 to a total of 6 doses Dosing extends well into proliferation phase of wound healing Dosing on Days 14, 21, 28, 35, 56, mg/cm and 5 mg/cm are being compared RXI-109 vs. untreated Enrollment of first group of 20 patients (2 cohorts) almost completed Follow-on Keloid Study Planned Will include an extended dosing schedule

15 Authors and Conflict of Interest Declaration RXi Pharmaceuticals Employees (Marlborough, MA) Pamela Pavco, PhD Karen Bulock, PhD Lyn Libertine, MD Mike Byrne, PhD Margo McKinlay Katherine Holton Laurie Barefoot, CNP, CCRC Pathi Pandarinathan, PhD Geert Cauwenbergh, Dr. Med. Sc. James Cardia, PhD Investigators (funded by RXi Pharmaceuticals to conduct RXI-109 trials) Georgina Nelly Paz, MD, Hospital y Clinica Bendana, Honduras V. Leroy Young, MD, Mercy Research, St. Louis MO (Member of RXi SAB) Ynca Nina Vasquez, MD, Instituto Dermatológico y Cirugía de Piel, DR