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Clinical Development of RXI-109
to Reduce Dermal Scarring
Pamela A. Pavco
Chief Development Officer
RXi Pharmaceuticals Corp.
TIDES / Boston
May 15, 2013
OTC: RXII
Next Generation in RNAi ®
2 Property of RXi Pharmaceuticals
Forward Looking Statements
This presentation contains forward-looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995. Such statements include, but are not
limited to, statements about the future development of RXi Pharmaceuticals
Corporation’s (the “Company”) 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 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 Property of RXi Pharmaceuticals
Corporate History
Founded as RXI Pharmaceuticals in 2007
Named changed to Galena Biopharma, Inc. and then spun out as an
independent company in April 2012 (OTC:RXII)
Approximately $50 million invested to date to develop a broad-based
RNAi technology platform and our lead compound, RXI-109
RXi received FDA clearance to begin clinical trials with
RXI-109 in mid-2012
Conducted 2 Phase 1 clinical trials with RXI-109 between
June 2012 – February 2013
Progress in ophthalmology, neurology and liver fibrosis supported by
research grants and collaborative projects
Located in the greater Boston area – Westborough/Worcester, MA
4 Property of RXi Pharmaceuticals
sd-rxRNA Combines Features of RNAi and Antisense Technologies
sd-rxRNA therapeutic compounds with drug-like properties
Conventional Antisense
Clinically relevant,
validated PK/PD
Conventional RNAi
Potent, long-lasting
activity
Medicinal Chemistry
Improved cell uptake
and PK/PD
O
sd-rxRNA
Single compound, i.e., no
delivery vehicle required
Proven robust uptake &
silencing in multiple preclinical
models
Structural diversity = novel
intellectual property
Combining positives of RNAi &
antisense, while avoiding
negatives
Provides for broad pipeline of
RNAi drugs for unmet medical
needs
5 Property of RXi Pharmaceuticals
sd-rxRNA: Structural Highlights
Single chemically-modified RNA compound
No delivery formulation required
Efficient cellular uptake and gene silencing
Potent, stable, specific
Robust, long lasting in vivo efficacy in multiple
tissues
Manufactured under GMP
<15 bp duplex 6 nt & longer tail
= standard and modified bases
= phosphorothioate linkages
= various hydrophobic moieties
= other hydrophobic linkages
= phosphodiester linkages
6 Property of RXi Pharmaceuticals
RXi’s Lead Clinical Product
Candidate: RXI-109
FDA Clearance in June 2012 to Begin Clinical
Trials with RXI-109
7 Property of RXi Pharmaceuticals
Selection of Area of Focus: Dermal Scarring Attractive Therapeutic Opportunity
Unmet need with limited competition for truly effective therapies
No prescription drugs approved
Unproven cosmeceutical products sell well >$100 million annually in USA
Large underserved market (>$1 B) in scar prevention or revision
Clear development precedent with early efficacy endpoints (Excaliard/Pfizer antisense)
Partnership potential / larger market for additional therapeutic uses of CTGF silencing in diseases with a fibrotic component
Proliferative vitreoretinopathy, liver fibrosis, surgical adhesions, wet AMD, acute spinal injury, restenosis, etc.
8 Property of RXi Pharmaceuticals
Connective Tissue Growth Factor A Central Factor in the Pathway to Fibrosis
RXI-109
Connective Tissue Growth Factor Central player in the balance between healthy
healing and excessive fibrosis
Cellular Effects
Pathologic Effects
Pulmonary
Fibrosis
Acute Spinal
Injury Restenosis
Ocular
Scarring
Liver
Fibrosis
Collagen Deposition Adhesion Migration Proliferation Differentiation
Excessive
Fibrosis
Tissue
Regeneration
Dermal
Anti-Scarring
Property of RXI Pharmaceuticals 8
9 Property of RXi Pharmaceuticals
RXI-109 Overview: Target Selection and Rationale
Numerous studies implicate Connective Tissue Growth
Factor (CTGF) overexpression in scarring and fibrotic
disease
RXI-109, an anti-CTGF sd-rxRNA compound, is uniquely
suited for local delivery, avoiding delivery challenges of
systemic RNA-based drugs
Preclinical data demonstrate potent, selective, dose-
dependent and long-lasting silencing of CTGF with RXI-109
Clinical validation with an anti-CTGF antisense
10 Property of RXi Pharmaceuticals
RXI-109 Efficiently Silences CTGF in vitro and in vivo
CTGF Silencing in vitro
• A549 cells were treated with RXI-109 and NTC
• Passive uptake 48 hours
• EC50 = 29.4 +/- 6.3 nM
Day 1 3 8
Harvest Excisional Wound
RXI-109 injections
0
20
40
60
80
100
120
0.01 0.025 0.05 0.1 0.5 1 NTC 1 uM
CT
GF
Exp
ressio
n, %
NT
C 1
NTC 1 uM
RXI-109 Concentration (mM)
• mRNA levels were quantified by QPCR on Day 8, normalized to the
housekeeping gene and set relative to PBS.
• **p=0.0015, ***0.0001 (relative to the dose-matched NTC)
• PBS = Phosphate Buffered Saline (Vehicle Control)
• NTC = Non-Targeting Control sd-rxRNA
NTC
(1 mM)
0
20
40
60
80
100
120
140
160
180
RXI-109 (21204.8)
300ug
RXI-109 (21204.8)
600ug
NTC (20489.6)
300ug
NTC (20489.6)
600ug
PBS
CT
GF
Exp
ressio
n, %
PB
S RXI-109 (21204.8) 300ug
NTC (20489.6) 300ug
PBS
51% 67%
300 mg 600 mg 300 mg 600 mg PBS
RXI-109 NTC
CTGF Silencing in vivo in Rat Skin
** ***
RXI-109
NTC
11 Property of RXi Pharmaceuticals
CTGF Silencing Does Not Delay Early Wound Healing in a Rodent Model
Dose ID 48 hr before
wound
Dose ID at wounding
Dose ID7 days post
wound
ExcisionalWound
Harvest Group 1
5 days post wound
Harvest Group 2
9 days post wound
Harvest Group 3
15 days post wound
Days
0
0.2
0.4
0.6
0.8
1
1.2
RXI-109 PBS
CT
GF
mR
NA
- R
ela
tiv
e t
o P
BS
Silencing of CTGF mRNA (Day 5 post wound)
0
20
40
60
80
100
120
Day 5 Day 15
% R
e-e
pit
helializati
on
Wound Re-epithelialization
RXI-109
PBS
*
0
10
20
30
40
50
60
70
80
90
100
6 7 8 Rela
tiv
e W
ou
nd
Wid
th (
% D
ay 0
)
Days Post Wounding
Wound Width
RXI-109
PBS
**
* * *
12 Property of RXi Pharmaceuticals
RXI-109 Phase 1: Clinical Development Plan
Study 1201 (First in Man):
Phase 1 single center, randomized, single dose, double-blind, ascending dose, within-subject controlled study of RXI-109 for the treatment of incision scars
Study 1202:
Phase 1 single center, randomized, multi-dose double-blind, ascending dose, within-subject controlled study of RXI-109 for the treatment of incision scars
Parameters evaluated:
- Safety & side effect assessment versus vehicle
- Pharmacokinetic parameters after local intradermal injection
- Photographic comparison versus vehicle
- Histological comparison of the scar sites versus vehicle
13 Property of RXi Pharmaceuticals
RXI-109-1201: Overview
RXI-109 vs. PBS administered on separate sides of the abdomen
Single intradermal dose
Dose levels: 5 cohorts of 3 subjects each
1, 2.5, 5, 7.5 and 10 mg per 2 cm incision site
Endpoints
PK Parameters
Safety assessed throughout the 3-month study period
Photographs
Biomarker / histology assessment at end of study, Day 84
Abdominoplasty on Day 84
14 Property of RXi Pharmaceuticals
RXI-109-1201: Abdominal Incision Layout
A o B
1
2
Wound
Addresses
Column
A
(Right)
Column
B
(Left)
Row 1 1A 1B
Row 2 2A 2B
• Four injections and incisions (2 cm in length) were made on the abdomen.
• The A and B ‘columns’ were at least 4 cm lateral to the midline of the abdomen.
• Rows were spaced at least 4 cm apart.
• Treatment at each incision site was made by intradermal injection according to a predetermined randomization pattern for each subject.
• Half of the sites were treated with RXI-109, half with placebo.
15 Property of RXi Pharmaceuticals
RXI-109-1201: Preliminary Safety Summary
Comparison of Treatment-Related Adverse Events by Study Day
Local Skin
Assessment1
Study Day
Day 1 Day 2 Day 3 Day 5 Day 8 Day 12 Day 28 Day 56 Day 84
Erythema 14 (23%) 23 (38%) 52 (87%) 30 (50%) 46 (77%) 47 (78%) 60 (100%) 60 (100%) 60 (100%)
Tenderness 2 (3%) 16 (27%) 33 (55%) 14 (23%) 14 (23%) 16 (27%) 0 0 0
Induration 16 (27%) 11 (18%) 14 (23%) 0 0 0 0 0 0
Pain 0 0 4 (17%) 0 0 0 0 0 0
Urticaria/Pruritis 4 (7%) 1 (2%) 11 (18%) 16 (27%) 29 (48%) 21 (35%) 4 (7%) 6 (10%) 0
Systemic Adverse
Events2
Study Day
Day 1 Day 2 Day 3 Day 5 Day 8 Day 12 Day 28 Day 56 Day 843
Rash 1 (7%) 0 0 0 0 0 0 0 0
Xerostomia 1 (7%) 1 (7%) 1 (7%) 1 (7%) 1 (7%) 0 0 0 0
Fever 1 (7%) 0 0 0 0 0 0 0 0
Nausea 1 (7%) 0 0 0 0 0 0 0 0
Joint Pain 1 (7%) 0 0 0 0 0 0 0 0
1 Local skin assessments based on a total of 60 treatment sites (i.e., 15 subjects, 4 sites each) 2 Systemic AEs based on a total of 15 subjects. All systemic AEs are Grade 1, except for Fever (Grade 2).
3 Post Day 84: 1 wound infection 4 days post abdominoplasty (SAE, Grade 3) requiring hospitalization and parenteral
antibiotic treatment and 2 instances of seroma (Grade 1)
AEs are graded based on Common Terminology Criteria for Adverse Events (CTCAE)
16 Property of RXi Pharmaceuticals
0
10
20
30
D 1
D 2
D 3
D 5
D 8
D 12
D 28
D 56
D 84
D 1
D 2
D 3
D 5
D 8
D 12
D 28
D 56
D 84
D 1
D 2
D 3
D 5
D 8
D 12
D 28
D 56
D 84
D 1
D 2
D 3
D 5
D 8
D 12
D 28
D 56
D 84
D 1
D 2
D 3
D 5
D 8
D 12
D 28
D 56
D 84
Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5
# o
f In
cid
en
ce
s
Day 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84
Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5
ERYTHEMA TENDERNESS INDURATION PAIN
A. Summary of skin assessments, all grades
0
2
4
6
8
10
1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 Day 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84 1 2 3 5 8 12 28 56 84
Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5
B. Summary of skin assessments, ≥ Grade 2
# o
f In
cid
en
ce
s
(≥ G
rad
e 2
) RXI-109-1201: Preliminary Safety Summary by Cohort and Grade
17 Property of RXi Pharmaceuticals
Protocol RXI-109-1201: Pharmacokinetic Parameters Following Intradermal Dosing
0
50
100
150
200
250
0 20 40 60 80 100 120
ng
/ml
Hours
2 mg
5 mg
10 mg
15 mg
20 mg
Cohort Total Dose
(mg) Tmax (hr) Cmax (ng/mL) AUClast (hr*ng/mL)
1 2 10.0 ± 2.0 21.2 ± 8.8 579 ± 461
2 5 10.6 ± 1.1 81.6 ± 4.2 2409 ± 130
3 10 16.3 ± 7.5 108 ± 21.2 3485 ± 506
4 15 9.3 ± 1.2 141 ± 15.9 5060 ± 331
5 20 20.6 ± 7.4 155 ± 63.5 8671 ± 3394
18 Property of RXi Pharmaceuticals
Protocol RXI-109-1201: No Complement Activation After Intradermal Dosing
0.00
0.20
0.40
0.60
0.80
1.00
1.20
1.40
1.60
1.80
2.00
0.00 0.50 1.00 1.50 2.00
Po
st-
do
se
(B
b m
g/m
L)
Pre-dose (Bb mg/mL)
Individual Bb Levels
4
24
4 hr
24 hr
No evidence of an RXI-109-related increase in Bb in any subject at any dose level.
19 Property of RXi Pharmaceuticals
RXI-109-1201: Examples of Preliminary Blinded Histology Data
12 Weeks Post-Treatment
Normal Skin 1A
2A
1B
2B
• Preliminary blinded data
• Trichrome staining of incision sites
from one of three subjects in Cohort 4
• Single injection of 7.5 mg
• Images taken at 20X magnification
• Full analysis will provide wound area
assessments on all subjects
20 Property of RXi Pharmaceuticals
RXI-109-1201, Single Dose Cohort 4: Area (mm2) of Scar Tissue (BLINDED)
A and B sides are treated with RXI-109 or placebo – Blinded data
Average of 31% Difference between Sides
Example of blinded data from the lower 2 sites on each subject
(reported as sum of area from three sections per site)
8.14
11.97
17.29
15.94
9.62
13.34
0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00
18.00
8.14
15.94
11.97
9.62
17.29
13.34
Sca
r A
rea
(m
m2
)
01-18 01-19 01-20
A B A B A B
21 Property of RXi Pharmaceuticals
RXI-109-1201: Example of Preliminary Blinded Biomarker Data
2A
Trichrome
CTGF
a-SMA
2B
• Treatment per side is still blinded
• Smaller wound area appears to track
with lower CTGF expression levels
• Images of CTGF and Trichrome taken at
20X magnification
• a-SMA image collected at 40X
magnification and from adjacent
sections
Subject 01-18
Cohort 4
22 Property of RXi Pharmaceuticals
RXI-109-1202: Overview
RXI-109 vs. PBS administered on separate sides of the abdomen
Three intradermal doses over 2 weeks
Dose levels: 3 cohorts of 3 subjects each
2.5, 5 and 7.5 mg per 2 cm incision site
Endpoints
PK parameters after 1st and 3rd dose
Safety assessed throughout the 3-month study
Photographs
Biomarker / histology assessment early (after 2 week dosing period) and late (at end of study, Day 84)
23 Property of RXi Pharmaceuticals
RXI-109-1202: Abdominal Incision Layout
Wound
Addresses
R
(Right)
L
(Left)
Row 1 1R 1L
Row 2 2R 2L
• 8 injections and incisions (2 cm in length) were made on the abdomen – each incision received 3 injections over a given time period.
• The R and L incisions were at least 4 cm lateral to the midline of the abdomen.
• Rows were spaced at least 4 cm apart.
• Treatment at each incision site was made by intradermal injection according to a predetermined randomization pattern for each subject.
• Half of the sites were treated with RXI-109, half with placebo.
R o L
1
2
24 Property of RXi Pharmaceuticals
RXI-109-1202: Preliminary Safety Summary
Dose escalation study w/ three doses and twice the number of sites compared to the first study
To date:
Local skin observations are not increased in number or severity over a single dose
Mild bilateral erythema is common
No skin assessment observations >Grade 1
1 AE (Grade 1): folliculitis (resolved with medication)
No SAEs
25 Property of RXi Pharmaceuticals
Preliminary Plan for Phase 2 Program for RXI-109
2-3 randomized, double-blind, within-subject controlled studies
Potential indications include:
Hysterectomy scar revision
Cesarean section scar revision
Scar revision following cosmetic breast surgery
Bilateral keloid scar revision
Study objectives include:
Determination of optimal dose and schedule
Demonstration of safety and efficacy
Planned initiation in H2 of 2013
26 Property of RXi Pharmaceuticals
RXI-109 Phase 1: Summary of Observations to Date
First studies aimed at showing safety and initial indications of clinical efficacy within 12-18 months of study initiation with limited number of subjects
First P1 single dose study started in June 2012; last dose administered in September 2012
Multi-dose volunteer P1 study started December 2012; last dose administered February 2013
Tolerance and safety considered excellent by investigators & volunteers. No negative effect of RXI-109 on wound healing.
Side effects minimal with injection site redness as possibly drug related; the redness was NOT dose related
Based on human and animal exposure intradermal injection provides <5% maximum systemic exposure as compared to intravenous injection
Differences between R & L sites can be seen but studies are still blinded
27 Property of RXi Pharmaceuticals
RXi Pharmaceuticals - 2013 Milestones
Q2 2013: Unblinded data on RXI-109 single dose Phase 1 (safety, side effects, PK, clinical & histology)
mid-2013: Unblinded data on RXI-109 multi-dose Phase 1:
H2 2013: Start Phase 2 studies with RXI-109 in scar revision
Partnering activities in additional areas
28 Property of RXi Pharmaceuticals
RXi’s Product Pipeline
Program Discovery Preclinical Clinical
Anti-Scarring
(RXI-109)
Ophthalmology
(PVR)
Liver disease / Liver
fibrosis
(RXI-209)
Ophthalmology
(Macular Degeneration)
Ophthalmology
(Retinoblastoma)
CNS
(ALS)
core focus strategic interest projected next steps
Phase 1 Phase 2 Phase 3
29 Property of RXi Pharmaceuticals
sd-rxRNA: Delivery Technology Results in Robust Cellular Uptake in vitro and in vivo
Hepatocytes primary mouse
ARPE-19 retinal pigment
epithelium Macrophages primary mouse
Keratinocytes human primary
SH-SY5Y neuroblastoma
Skin Eye Liver Spinal column
Delivery and silencing demonstrated in many different cell types Human, Primate, Rat, Mouse, Adherent, Non-adherent, Primary, Transformed
Efficient delivery of sd-rxRNA to multiple tissues in vivo upon
local and systemic administration
Alveolar macrophages
30 Property of RXi Pharmaceuticals
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
• Dosing by intravitreal injection to mouse
or rabbit eye with Dy547-labeled sd-
rxRNA, conventional siRNA or placebo
sd-rxRNA: Improved Retinal Delivery vs. Stabilized RNAi Compounds
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
31 Property of RXi Pharmaceuticals
sd-rxRNA: Extended Silencing in vivo in the Rodent Eye
• 3 mg PPIB or NTC administered by intravitreal injection (in 1 ml) to mouse eyes
• mRNA levels were quantified by Quantitative PCR (QPCR) and normalized to b-actin
• Data assembled from 5 different studies to enable sufficient ‘n’ for each data point (n=5-8); graphed +/- SD relative to PBS in each study
• PBS = Phosphate Buffered Saline (Placebo)
• NTC = Non-Targeting Control sd-rxRNA
• PPIB = Anti-cyclophilin B sd-rxRNA
20
30
40
50
60
70
80
90
100
110
120
1 2 4 7 14 21 28
PP
IB E
xp
res
sio
n, %
of
NT
C
Time after injection, days
PBS
NTC
PPIB
↓51%
** ↓45%
** ↓32%
** ↓22%
**
Duration of Silencing Induced by PPIB Targeting sd-rxRNA
* p ≤ 0.05
** p ≤ 0.01
32 Property of RXi Pharmaceuticals
Acknowledgements
RXi Pharmaceuticals
Geert Cauwenbergh – CEO
Pamela Pavco – CDO
Karen Bulock – VP Research
Lyn Libertine – VP Medical Affairs/Safety Assessment
Michael Byrne – Scientist II
Pathi Pandarinathan – Scientist II
James Cardia – Manager, Platform Technology
Katherine Holton – Associate Scientist
Tamara McGrillen – Manager, Operations and Administration
Caitlin Kontulis – Controller, Finance
Scientific Advisory Board
Craig Mello – UMass Medical School
Leroy Young – General / Plastic Surgery, Director BodyAesthetic Research Center, PI for RXI-109-1201
Jeannette Graf – Clinical and Research Dermatologist, Assistant Clinical Professor of Dermatology, Mount Sinai School of Medicine