RXi Pharmaceuticals - Jefferies · Second Development Area: Topical Immunotherapy Samcyprone™ - RXi’s second clinical candidate A proprietary topical formulation of diphenylcyclopropenone

RXi PharmaceuticalsNASDAQ: RXII

2015 Jefferies Healthcare Conference

®

Q2 2015_JUN04

2Property of RXi Pharmaceuticals

Forward Looking Statements

This presentation contains forward-looking statements within the meaning of the PrivateSecurities Litigation Reform Act of 1995. Words such as “believes,” “anticipates,” “plans,”“expects,” “indicates,” “will,” “intends,” “potential,” “suggests” and similar expressions areintended to identify forward-looking statements. These statements are based on RXiPharmaceuticals Corporation’s (the “Company”) current beliefs and expectations. Suchstatements include, but are not limited to, statements about the future development of theCompany’s products (including timing of clinical trials and related matters associatedtherewith), the expected timing of certain developmental milestones, the reporting ofunblinded data, potential partnership opportunities, the Company’s competition and marketopportunity and pro forma estimates. The inclusion of forward-looking statements should notbe 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 anduncertainties in the Company’s business, including those identified under “Risk Factors” in theCompany’s most recently filed Quarterly Report on Form 10-Q and in other filings theCompany periodically makes with the U.S Securities and Exchange Commission. TheCompany does not undertake to update any of these forward-looking statements to reflect achange in its views or events or circumstances that occur after the date of this presentation.


Corporate Highlights

Leader in development of advanced RNAi-based therapeutics Novel, self-delivering RNAi (sd-rxRNA®) platform provides improved cellular uptake,

safety, potency and selectivity over classic siRNA

Developing innovative therapeutics in dermatology and ophthalmology Discovery and clinical development programs based on proprietary RNAi technology

and immunotherapy agents

RXI-109: sd-rxRNA compound initially being developed to reduce or inhibit scar formation in the skin and retina

Samcyprone™: immunomodulator initially being developed for the treatment of alopecia areata, warts, and cutaneous metastases of melanoma

Numerous clinical and business development opportunities Extensive patent portfolio covering sd-rxRNA platform and additional compounds

Discovery and clinical pipeline with substantial market potential


Recent Accomplishments

Strengthened Balance Sheet Public offering raised gross proceeds of $10.4M of common stock and warrants

Broadened Patent Portfolio Granted notice of allowance for lead compound, RXI-109, for use in the eye.

Core patent broadens coverage of RXi's self-delivering platform and provides coverage of RXI-109 for the treatment of ocular fibrosis

Advanced Research and Discovery Programs sd-rxRNA compounds identified to silence collagenase and tyrosinase, enzymes with

relevance in major disease areas Tyrosinase targeting sd-rxRNA compounds resulted in a visible reduction of

pigmentation in vitro

Executed Licensing Agreements Cell-based therapies to treat cancer: exclusive license for RXi's self-delivering

(sd-rxRNA) technology to MirImmune Immunotherapy: global exclusive license for Samcyprone completed, adding second

Phase 2 asset to RXi


Leader in the Development of Advanced RNAi-based Therapeutics

sd-rxRNA therapeutic compounds with drug-like properties

Conventional AntisenseClinically relevant, validated PK/PD

Conventional RNAiPotent, long-lasting

activity

Medicinal ChemistryImproved cell uptake

and PK/PD

O

sd-rxRNA

The sd-rxRNA Platform

Proprietary sd-rxRNA® (‘self-delivering’ RNAi) compounds combine features of RNAi and Antisense technologies

Single compound incorporatesactivity and delivery

Robust uptake & silencing in multiple preclinical models

Structural diversity = novel intellectual property

Combining many positives of RNAi & antisense, while avoiding many negatives

Provides for broad pipeline of RNAi drugs for unmet medical needs


sd-rxRNA: Robust Cellular Uptake in vitro and in vivo

Hepatocytesprimary mouse

ARPE-19retinal pigment

epitheliumMacrophagesprimary mouse

Keratinocyteshuman primary

SH-SY5Yneuroblastoma

Skin Eye LiverSpinal cord

Delivery and silencing demonstrated in many different cell typesHuman, Primate, Rat, Mouse, Adherent, Non-adherent, Primary, Transformed

Efficient delivery of sd-rxRNA to multiple tissues in vivo upon local and systemic administration

Alveolarmacrophages

The sd-rxRNA Platform


Dermatology Franchise

Program Discovery Preclinical

RXI-109(Hypertrophic Scars &

Keloids)Samcyprone™

(Alopecia Areata, Warts, Cutaneous Metastases

Melanoma)

Anti-Collagenase (Aging, Chronic wounds)

Anti-Tyrosinase(Melasma, PIH, Lentigines)

Phase 1 Phase 2 Phase 3

Clinical

Multiple Development Opportunities


First Development Area: Dermal ScarringAddressing Significant Unmet Medical Need with Large Market Potential

Targeting Connective Tissue Growth Factor (CTGF) CTGF plays a key role in tissue regeneration and repair

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**


Type of Skin Surgery Annual Number of Procedures

Cosmetic 6.0 million

Reconstructive 3.9 million

Moles 3.4 million

Trauma 9.0 million

Elective (office) 9.6 million

Elective (hospital) 10.4 million

TOTAL 42.3 million

*US anti-scarring market – The Nemetz Group –December 2009**2014 Plastic Surgery Statistics Report, American Society of Plastic Surgeons


Normal

Hypertrophic

Keloid

Proliferation

Proliferation

Proliferation

Remodeling

Remodeling

Acute Inflammation post trauma(~2 Weeks)

Months 1 Year

Dermal Scarring: The Wound Healing CascadeUp to One Year

A

B

C

A Bayat, A et al. BMJ 2003;326;88-92. doi:10.1136/bmj.326.7380.88B Property of RXi PharmaceuticalsC Courtesy of skincareguide.ca



RXI-109 Dermal Clinical ProgramsKey Findings to Date

Trials evaluate safety and clinical effect of treatment with RXI-109 to reduce recurrence of hypertrophic scars or keloids

Top-line 3-month results have shaped the ongoing and future clinical development strategy

Phase 1 RXI-109-1201 & RXI-109-1202 - Completed• Multiple dermal injections were well tolerated at all dose levels• RXI-109 caused dose-dependent silencing of CTGF mRNA and protein in the treated

areas compared to placebo

Phase 2a RXI-109-1301, RXI-109-1401 & RXI-109-1402 - OngoingEarly, positive observations show:1. RXI-109 has a clinical effect in the hypertrophic scar target population2. Initiating treatment with RXI-109 two weeks post scar revision surgery, during the

proliferation phase of the wound healing process, is beneficial versus initiating treatment immediately (inflammation phase)

3. Longer treatment duration is indicated following hypertrophic scar revision and keloidectomy

Based on these observations, an extended dosing regimen was included in RXI-109-1402.



Phase 2a: Scar Comparison at 3 MonthsTreatment with RXI-109 Initiated Two Weeks Post Scar Revision Surgery

Phase 2a: RXI-109-1301

Pre-scar revision surgery

3 monthspost-scar revision surgery

PLACEBO RXI-109

*White dots are markers used in clinical photography.


RXI-109 Dermal Clinical ProgramDermatology Franchise

Phase 1

RXI-109-1201Single dose: safety and biomarker analysis Complete – 15 volunteers

RXI-109-1202Multi-dose: safety and biomarker analysis Complete – 15 volunteers

Phase 2aRXI-109-1301(Hypertrophic scars)

Enrollment and treatment complete. Subjects to be evaluated through Month 9 – 22 patients

RXI-109-1401(Keloids)

Enrollment complete. Dosing and data collectionongoing – 16 patients

RXI-109-1402 (6 doses over 3 months)(Hypertrophic scars)

Extended dosing regimen based on previous clinical observations - 85% enrolled (17 of 20 patients)

Phase 2bProjected initiation 2016

Phase 3Projected initiation 2018


Second Development Area: Topical Immunotherapy

Samcyprone™ - RXi’s second clinical candidate 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

Market exclusivity is expected for Samcyprone™ post approval

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.

Combined market for three indications estimated >$1B Major competitors for treatment of warts: Aldara™ (Imiquimod) and Picato®

(Ingenol mebutate)



Treatment with Diphencyprone (DPCP)DPCP is the Active Ingredient in Samcyprone™

Alopecia Areata

Cotellessa, C et al. JAAD 2001;44:73-6

• >200 patients treated for several months• Response rates of 67-78%

Warts(refractory plantar & periungual)

Choi, Y et al. Ann Dermatol. 2013, 25 4:434-439

• >350 patients treated for 12 – 24 weeks• Response rates of 80 - 85%

Cutaneous Metastases of Melanoma (refractory)

Damian, DL et al. J Surg Oncol 2014, 109:308-313• 50 patients with mean of 15 months

treatment• 46% complete clearance and 38% partial

clearance



Samcyprone™Next Steps

Complete closing of agreement to Samcyprone™

Complete process with FDA to transfer IND to RXi

Continue and complete Phase 2a trials

Initiate Phase 2b trials

Evaluate other indications for potential new trial(s) using Samcyprone™



Research and Development ProgramsNew Targets for Potential Preclinical Development

MMP1 enzyme involved in breakdown of extracellular matrixCollagenase (MMP1)

• Potent MMP1 sd-rxRNAs identified for potential for preclinical development such as skin aging disorders including photo aging

TYR key enzyme in synthesis of melaninTyrosinase (TYR)

• Potent TYR sd-rxRNAs identified for potential discovery and preclinical development. Potential indications include cutaneous hyperpigmentation disorders, lentigines (age spots, liver spots, freckles)

Acquired estate provides multiple development opportunitiesOPKO RNAi Assets

• Novel potent sd-rxRNA compounds targeting VEGF for potential intra-ocular therapy for age-related macular degeneration

• Other targets - discovery stage efforts ongoing

Combined multi-billion dollar global market potential Market Potential



Research and Development ProgramsNew Targets for Potential Preclinical Development

MMP1 TYR VEGF DISCOVERY

Target Selection In Progress

Bioinformatics Pending

Compound Synthesis Pending

In vitro Screening Pending

File IP Pending

Chemical Optimization Pending Pending

Test in Relevant Models (in vitro and in vivo) In Progress In Progress Pending Pending

Lead Candidate Identification Pending Pending Pending Pending



MMP1 and TYR Compound Potency Improved by Chemical Optimization

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

26061 26198

Original Optimized

TYR

mR

NA

Leve

ls

TYR mRNA Levels

0.01 uM

0.025 uM

0.1 uM

0.5 uM

1.0 uM

EC50 = 800 nM

EC50 = 380 nM

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

26051 26185

Original Optimized

MM

P1 m

RN

A Le

vels

MMP1 mRNA Levels

0.01 uM

0.025 uM

0.1 uM

0.5 uM

1.0 uM

EC50 = 414 nM

EC50 = 236 nM



NTC UTCMMP-26038

0 h

24 h

48 h

72 h

MMP1 – Targeting sd-rxRNA CompoundsReduced Migration Rate of A549 Lung Carcinoma Cells in vitro

0

100

200

300

400

500

600

700

800

900

1000

2603

8

NTC

UTC

2603

8

NTC

UTC

2603

8

NTC

UTC

Mig

ratio

n D

ista

nce

(um

)

Comparison of A549 Cell Migration after Treatment with MMP1 Targeting sd-rxRNA

48 h24 h 72 h48 h24 h 72 h

• Scratch migration assay - A549 non-small cell lung carcinoma cell line• Cells in culture treated with MMP1 – 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


TYR – Targeting sd-rxRNA CompoundsLead to a Visible Reduction of Pigmentation in vitro

NTCTYR - 21698TYR - 26231

• MelanoDerm™ 3-dimensional epidermal culture model containing melanocytes • Fourteen day culture with TYR-targeting sd-rxRNA added to culture media

Light microscopy


Histological cross section with staining for melanin


VEGF-Targeting sd-rxRNABased on Bevasiranib Target Sequence

0%

20%

40%

60%

80%

100%

120%

VEGF sd-rxRNA Bevasiranib

VE

GF

Exp

ress

ion,

%C

ontro

l

Passive Transfection of a VEGF-targeting sd-rxRNA and Bevasiranib

0.025 uM

0.05 uM

0.1 uM

0.5 uM

1.0 uM

VEGF-26015 Bevasiranib

• Passive transfection (no delivery vehicle) in HEK293 cells• Next steps

• Continued chemical optimization• Preclinical studies alone and/or in combination with CTGF targeting sd-rxRNA



Ophthalmology Franchise

RXI-109 - retinal scars (intraocular) and corneal scars (topical)→ IND-supporting toxicity testing of RXI-109 in the eye is in progress→positive pre-IND interaction with the FDA → IND preparation in progress for retinal scarring

Retinal scarring(Macular Degeneration)

Corneal scarring(Topical)

“Self-Delivering” (“sd”) Adaptation to acquired

OPKO estate

New targets

Program Discovery PreclinicalPhase 1 Phase 2 Phase 3

Clinical



sd-rxRNA Stabilized PlacebosiRNA

Mouse immediately post-dose

Mouse at24 hours post-dose

Mouse at24 hours post-dose

Rabbit at24 hours post-dose

• Dosing by intravitreal injection to mouse or rabbit eye

• Dy547-labeled sd-rxRNA, stabilized siRNA or placebo

sd-rxRNA: In OphthalmologyImproved Delivery vs. Stabilized RNAi

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

Byrne et al., JOPT. December 2013, 29(10): 855-864.



CTGF Protein Levels in the NHP Retina and Cornea Decrease Following Treatment with RXI-109

Retina Cornea

0

5

10

15

20

25

30

35

40

45

PBS 0.1 mg 0.33 mg 1 mg0

5

10

15

20

25

30

35

40

45

PBS 0.1 mg 0.33 mg 1 mg

% P

ositi

ve C

TGF

Sta

inin

g

% P

ositi

ve C

TGF

Sta

inin

g CTGF protein levels

are reduced in a dose dependent manner

7-days following single intravitreal injection

of RXI-109

Treatment Dose Treatment Dose

PBS

0.1 mg

0.33 mg

1 mg

***

*

* p < 0.05, ** p < 0.01



RXi’s Propriety PlatformYields Multiple Business Development Opportunities

sd-rxRNA®

Platform

RXi’s Strategic Core Focus

Local Delivery Applications

Systemic and Cancer

Cell Therapy

Business Development / Partnering Opportunities

RXi’s unique sd-rxRNA platform allows for rapid

identification of lead compounds for multiple

targets in different therapeutic areas

Dermatology Scarring (fibrosis) Hyperpigmentation disorders Photo aging

Ophthalmology Retinal scarring AMD, PVR

Corneal scarring

Arthritis Endometriosis Lung fibrosis Chronicwounds

Liver fibrosis Kidney fibrosis Cancer

Exclusive license toplatform for cell-based immunotherapies in cancer

Other therapeutic areas for cell therapy still available


Management Team, Board of Directors and Scientific Advisory Board

Geert Cauwenbergh,Dr. Med. Sc.

President & CEO and Director

Pamela Pavco, Ph.D.Chief Development Officer

Lyn Libertine, M.D.VP Med Affairs & Safety

Karen Bulock, Ph.D.VP Research

Robert BittermanChairman Board of DirectorsChairman Nominating Comm.

Keith BrownlieDirector & Chairman

Audit Committee

Curtis Lockshin, Ph.D.Director & Chairman

Governance Committee

H. Paul DormanDirector & Chairman

Nominating Committee

Craig C. Mello, Ph.D.Chairman

Leroy Young, M.D.Member

Jeannette Graf, M.D.Member

Peter Campochiaro, M.D.Member

Man

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Boa

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Dire

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oard


2015 Milestones

RXI-109-1301: study to be completed in 2015

Early results and later read-outs in Hypertrophic Scars (RXI-109-1402) and Keloid Studies (RXI-109-1401)

Samcyprone™: Closing of acquisition and continuation of Phase 2 studies

Advance additional programs from discovery into preclinical development

Broaden & diversify intellectual property portfolio

Expansion of clinical pipeline

Broaden shareholder base

File IND for ophthalmology indication with RXI-109


Financial Overview* a/o June 2, 2015

Cash (on hand)

Cash (assuming 100% exercise of warrants and purchase rights)

~$14.8 million~$27.4 million

Burn rate ~$2.0-2.5 M /quarter

Cash runway Q3 2016 (Share proceeds only)Q4 2017 (Shares & warrants)

Common shares outstanding Preferred shares outstanding

~65 million None

Closing share price $0.37

Market Cap ~$24 million

*Unaudited


2015 Financing

Broadened shareholder base: several institutional investors, large retail participation and insider supportProvides financial runway for the next 12-24 months*

Proceeds will be used, in part, for the following: New batch of drug product for RXI-109

Clinical trials Extension study for hypertrophic scars (severe cases)

New keloid study with extended dosing regimen

Ophthalmology Phase 1 / 2 trial

Samcyprone trial for warts

Additional tox studies to support continued development (ocular and dermal)

Additional headcount to support new trials

Other corporate purposes* Through Q3 2016 (with share proceeds only); through Q4 2017 (with shares & warrants)


Corporate Highlights

Leader in development of advanced RNAi-based therapeutics Novel, self-delivering RNAi (sd-rxRNA®) platform provides improved cellular uptake,

safety, potency and selectivity over classic siRNA

Developing innovative therapeutics in dermatology and ophthalmology Discovery and clinical development programs based on proprietary RNAi technology

and immunotherapy agents

RXI-109: sd-rxRNA compound initially being developed to reduce or inhibit scar formation in the skin and retina

Samcyprone™: immunomodulator initially being developed for the treatment of alopecia areata, warts, and cutaneous metastases of melanoma

Numerous clinical and business development opportunities Extensive patent portfolio covering sd-rxRNA platform and additional compounds

Discovery and clinical pipeline with substantial market potential

Documents

RXi Pharmaceuticals - Jefferies · Second Development Area: Topical Immunotherapy Samcyprone™ - RXi’s second clinical candidate A proprietary topical formulation of diphenylcyclopropenone