Pg. 1

Restoring Biological Harmony for Patients with Debilitating DiseaseRestoring Biological Harmony for Patients with Debilitating Disease

Development of MRG-110, an LNA-AntimiRTargeting miR-92a for Use in Tissue Repair and Regeneration

Rusty L. Montgomery, Ph.D.

miRagen Therapeutics, Inc.

OTS, October 2019

Pg. 2

▪ Rusty Montgomery is an employee and stock/option holder of miRagen Therapeutics, Inc.

Disclosures

Pg. 3

Cautionary Note Regarding Forward-Looking Statements

This presentation contains forward-looking statements relating to Miragen Therapeutics, Inc., including statements about our plans to obtain funding, develop and commercialize our therapeutic candidates, our planned clinical trials, the timing of and our ability to obtain and maintain regulatory approvals for our therapeutic candidates, the clinical utility of our therapeutic candidates and our intellectual property position. You can identify forward-looking statements by the use of forward-looking terminology including “believes,” “expects,” “may,” “will,” “should,” “seeks,” “intends,” “plans,” “pro forma,” “estimates,” or “anticipates” or the negative of these words and phrases or other variations of these words and phrases or comparable terminology. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. These forward-looking statements should not be relied upon as predictions of future events as we cannot assure you that the events or circumstances reflected in these statements will be achieved or will occur. The forward-looking statements in this presentation represent our views as of the date of this presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation.

This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.

Pg. 4

▪ miRagen has developed MRG-110, a single-stranded antimiR inhibitor of miR-92a, a key regulator of angiogenesis

▪ MRG-110 induces angiogenesis and tissue repair in myocardial infarction, limb ischemia, vascular injury, and wound healing in rodents

▪ MRG-110 is delivered as a naked oligonucleotide; no delivery agents are required

▪ MRG-110 is biologically active when delivered systemically or through local routes of administration

▪ MRG-110 has demonstrated:▪ PD and efficacy in rodent and porcine models of heart failure and dermal wounds

▪ Clinical proof-of-mechanism in a Phase 1 trial

▪ Safety and tolerability following single and multiple administration in Phase 1 trials

▪ MRG-110 is an advanced, clinical-stage asset for multiple indications characterized by ischemia

Overview

Pg. 5

miR-92a is a Key Regulator of Angiogenesis

Control

miR-92a

Spheroid model Network formation Matrigel plug model

Overexpression of miR-92a inhibits sprouting, network formation, and angiogenesis in multiple models

Bonauer et al., Science 2009

db/db wound healing

Control

antimiR-92a(MRG-110)

Inhibition of miR-92a induces granulation tissue formation and angiogenesis,

and accelerates wound healing in db/db model

MRG-110 is an inhibitor of miR-92a

Pg. 6

▪ Cardiovascular indications that can benefit from angiogenic therapy also include:

▪ Acute myocardial infarction

▪ Chronic heart failure/angina

▪ Vascular injury – inhibition of neointimal formation after balloon angiography

▪ Peripheral artery disease

▪ Ischemia is a major contributing factor to slow/ineffective wound healing in:

▪ Burn wounds

▪ Grafts

▪ Diabetic foot ulcers

▪ Pressure ulcers

▪ Acute wounds in the elderly (e.g. pretibial lacerations)

▪ Increased angiogenesis may increase the rate of wound healing in all of the above, plus:

▪ Graft donor sites

▪ Complicated laparotomy closure

Clinical Problem Addressed

Pg. 7

Chronic Myocardial Ischemia Model in Pig

• Reduction stent implanted at day 0 resulting in 75% occlusionleading to 100% occlusion at day 28

• LNA-92a (MRG-110) or Control administered retrograde at day 28• 5 mg/kg heart weight, single dose

• Assess cardiac function, perfusion, and histology at day 56

Pg. 8

MRG-110 Increases Angiogenesis and Collateral Growth in Chronic Myocardial Ischemia in Pigs

MR

G-1

10

Co

ntr

ol

MRG-110Control

MRG-110Control MRG-110Control

Day 56

Markers of new blood vessel formation

Pg. 9

MRG-110 Improves Global Myocardial Function in Chronic Myocardial Ischemia in Pigs

MRG-110Control MRG-110Control

MRG-110 shows improved hemodynamics and cardiac function in chronic ischemia

Pg. 10

Data to Date in Wound Healing – MRG-110 Increases Angiogenesis in Mice to Men

Species Data

Rodent ▪ Accelerated wound healing in db/db mice

▪ Increased CD31+ vessel formation in db/db mice

Porcine ▪ Improved perfusion and rate of wound closure in farm pigs

▪ Dose-dependent decrease in contracture of healed wounds

▪ Accelerated wound healing in burn model

Human ▪ Increased angiogenesis and perfusion in treated subjects

▪ Decreased fibroblast/myofibroblast α-SMA expression at

Day 29

Pg. 11

SH

AM

48H

R

96H

R

1W

K

2W

K

0

2

4

6

8

R a t E x c is e d S k in ; M R G -1 1 0 B io m a rk e r D is c o v e r y

m iR -9 2 a L e v e ls S k in (R ig h t/2 n d )

RQ

miR-92a is Increased in Rodent Excised Skin and Human Chronic Wounds

Human tissue samples were obtained from patients presenting with healing (day 14–30 days post surgery, n=6) and non-healing (venous leg ulcers, n=6) skin wound….Lucas et al., Nat Comm., 2017

miR92a levels post-excision in rat

Pg. 12

MRG-110 Accelerates Wound Healing and Angiogenesis in db/db Mice

† = p<0.05, Kruskal-Wallis

†† = p<0.01, Kruskal-Wallis

†††† = p<0.0001, Kruskal-Wallis

Wound Healing

Gallant-Behm et. al., Wound Repair Regen., 2018

0.0

0.5

1.0

1.5

Gra

nu

lati

on

tis

su

e a

rea

(m

m2)

† † †††††† †

PBS VEGF PDGF 10 30 100 10 30 100

nmol MRG-110 nmol antimiR-92a

#2

0.0

0.1

0.2

0.3

0.4

Gra

nu

lati

on

tis

su

e t

hic

kn

es

s (

mm

)

††† †† †††† ††† ††† †

PBS VEGF PDGF 10 30 100 10 30 100

nmol MRG-110 nmol antimiR-92a

#2

0.0

0.5

1.0

1.5

Gra

nu

lati

on

tis

su

e a

rea

(m

m2)

† † †††††† †

PBS VEGF PDGF 10 30 100 10 30 100

nmol MRG-110 nmol antimiR-92a

#2

0.0

0.1

0.2

0.3

0.4

Gra

nu

lati

on

tis

su

e t

hic

kn

es

s (

mm

)

††† †† †††† ††† ††† †

PBS VEGF PDGF 10 30 100 10 30 100

nmol MRG-110 nmol antimiR-92a

#2

PBS MRG-110

CD

31 im

mun

osta

inin

g

PBS PDGF 10 nmolMRG-110

100 nmolMRG-110

0

50

100

150

200

250

CD

31

+ c

ou

nts

****

PBS PDGF 10 nmolMRG-110

100 nmolMRG-110

0.000

0.005

0.010

0.015

0.020

0.025

CD

31

+ a

rea

(m

m2)

††††

PBS PDGF 10 nmolMRG-110

100 nmolMRG-110

0

50

100

150

200

250

CD

31

+ c

ou

nts

****

PBS PDGF 10 nmolMRG-110

100 nmolMRG-110

0.000

0.005

0.010

0.015

0.020

0.025

CD

31

+ a

rea

(m

m2)

††††

Angiogenesis

Pg. 13

Dermal Tolerability and Wound Healing Studies in Pigs

▪ Pig skin architecture and healing processes are similar to those in humans, which make pigs one of the best animal models for wound healing and skin tolerability studies

▪ GLP local tolerability and wound healing study in Farm Pigs▪ Six MRG-110 treated pigs and 2 control pigs each received eight 2.5 x 2.5 cm full thickness

wounds on the back

▪ 3, 12, 48 mg/wound intradermally per dose day compared to no treatment except dressing changes (SOC) and vehicle treated wounds

▪ Wounds were treated 3 times a week for 2 weeks then followed to complete wound closure at Day 49

▪ All doses were well-tolerated and led to improved wound healing as assessed by histology, wound closure measurements, and laser Doppler.

Pg. 14

MRG-110 Improves Wound Perfusion and Rate of Wound Closure in Healthy Farm Pigs

Wound Perfusion

▪ MRG-110 improved perfusion as assessed by laser Doppler imaging at day 14 for all 3 doses

▪ On Day 35, complete wound closure was achieved in 7 of 12 wounds (58%) with low dose MRG-110 compared

to 0 of 8 (0%) Standard of Care (wound dressing changes only) and 1 of 8 (12%) vehicle control treated wounds

▪ All doses appeared active suggesting low dose (3 mg/wound; ~2 mg/cm2) is at the top of dose response curve

Percent of Wounds Open Over TimeMean Days to 50% Closure of Each Wound

SOC VC LowDose

MidDose

HighDose

0

50

100

150

200

Laser Doppler Assessment

Pe

rfu

sio

n u

nit

s

† † ††

MRG-11010 12 14 16 18 20 22 24

High Dose

Mid Dose

Low Dose

VC

SOC

Median Days to 50% Wound Closure

MR

G-1

10

0 100

10

20

30

40

50

60

70

80

90

100

27 30 33 36 39 42 45 48

Day

Pe

rce

nt

Op

en

Wo

un

ds

SOC

VC

Low Dose

Mid Dose

High Dose MR

G-1

10

† = p<0.05, Kruskal-Wallis

†† = p<0.01, Kruskal-Wallis Gallant-Behm et. al.

Wound Repair Regen

2018

Pg. 15

MRG-110 Improves Vascularization and Decreases Contracture in Healthy Farm PigsAssessed on Day 49

602 SOC: Granulation Tissue (dashed line) Dermal: 1+ Subcutaneous: 2+

605 High Dose: Granulation Tissue (dashed line) Dermal: 4+

Subcutaneous: 4+

SOC VC LowDose

MidDose

HighDose

0

1

2

3

Vascularization

His

tolo

gic

al

Sc

ore

† †

MRG-110

SOC VC LowDose

MidDose

HighDose

0

1

2

3

4

Epithelial Thickness

His

tolo

gic

al

Sc

ore

MRG-110

SOC VC LowDose

MidDose

HighDose

0

1

2

3

4

Granulation Tissue - Dermal

His

tolo

gic

al

Sc

ore

†† ††

MRG-110

SOC VC LowDose

MidDose

HighDose

0

1

2

3

4

Granulation Tissue - Subcutaneous

His

tolo

gic

al

Sc

ore

†† †††

MRG-110

Gallant-Behm et. al.

Wound Repair Regen

2018

† = p<0.05, Kruskal-Wallis

†† = p<0.01, Kruskal-Wallis

Pg. 16

Dose-dependent Decrease in Contraction of Healed Wounds in MRG-110 Treated vs. Vehicle or Standard of Care Treated Wounds

Vehicle control SOC High Dose (48 mg)Mid Dose (12 mg)Low Dose (3 mg)

Pg. 17

▪ 9 female domestic Yorkshire crossbred pigs (~ 45 kg)

▪ Group 1: 3 pigs receiving vehicle only (105 mM Phosphate buffer diluted with 0.9% normal saline)

▪ Group 2: 6 pigs receiving 3 weekly 1.5 mg/kg MRG-110 intravenous injections (slow bolus over 10 minutes) on days 1, 8 and 15

▪ Twelve 2.5 x 2.5 cm deep partial thickness burns per pig

▪ 4 burns created 72 hours before Day 1 dosing

▪ 4 burns created 48 hours before Day 1 dosing

▪ 4 burns created on Day 1

▪ PK samples taken after last dose at predose, 5 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr, 24 hr, 48 hr, and 7 days

▪ Laser Doppler imaging, wound assessments (size, exudate, erythema, edema, re-epithelialization) and photographs done every week on a M, W, F schedule through Day 29

▪ Biopsies▪ Days 7, 14, and 29 post burn

▪ Data are pending

Pig Burn Study Design

Day 7 4mm Biopsyin formalin for IHC

Day 7 4mm Biopsy Snap Frozen for Biodistribution

Day 14 4mm Biopsyin formalin for IHC

Day 14 4mm BiopsySnap Frozen for Biodistribution

Day 29 Biopsy at necropsyin formalin for IHC

Day 29 4mm BiopsySnap Frozen for Biodistribution2.5 x 2.5 cm Burn Wound

Pg. 18

MRG-110 Treatment Increased Wound Closure Rate in Porcine Burn Model

Vehic

le

MRG

-110

Day

1 B

urn

MRG

-110

-48

Hr Burn

MRG

-110

-72

Hr Burn

0

10

20

30

40

50

60

70

80

90

100

% W

ou

nd

s C

los

ed

on

Da

y 2

9

n=24 n=24 n=24n=36

<0.0001p

******** **

****

** p=0.0057

Chi-squared Analysis

Pg. 19

▪ MRG-110 increased angiogenesis and left ventricular function in a porcine chronic ischemia model

▪ MRG-110 increased angiogenesis and wound healing in db/db mice▪ Increased re-epithelialization and granulation tissue formation

▪ Increased angiogenesis as assessed by histology

▪ MRG-110 increased angiogenesis and wound healing rates in healthy farm pigs▪ Increased perfusion as assessed by laser Doppler imaging at day 14 for all

3 doses tested in excisional wound in pigs

▪ Increased vascularity as assessed by histology

▪ Improved wound closure

▪ Reduced contracture following healing

▪ MRG-110 increased wound healing in a pig burn model

▪ GLP toxicology studies show that IV doses are safe and could lead to efficacious levels of drug in multiple tissue types

Summary of Preclinical Results

Pg. 20

Two Phase 1 trials for MRG-110 - Completed

▪ Single ascending dose study to assess safety and PK of systemic administration▪ Healthy volunteers. Systemic administration in 49 subjects• Assessment of safety, tolerability, and pharmacokinetics• Biomarkers of drug activity on target gene pathways

▪ Dermal revascularization▪ Single and multiple dose ascending study to assess safety, PK and mechanistic proof-of-

concept. Assessments included:▪ Laboratory, ECG, Adverse events reporting, Physical exam▪ PK ▪ Exploratory pharmacodynamic effects

▪ On-target activity in humans▪ Effects on direct target gene and protein expression from skin biopsy samples

▪ Angiogenesis▪ Histology assessment of new vessel formation

▪ Improved blood flow/perfusion▪ Non-invasive Laser Speckle Perfusion Imaging over time

▪ Wound healing▪ Granulation tissue formation by histology, α-SMA expression▪ Photographs, wound measurements over time

Development Overview for MRG-110

Pg. 21

Intravenous SAD Study Design

▪ 7 cohorts of 7 subjects each (5 active and 2 placebo): 0.01 mg/kg to 1.5 mg/kg

▪ Endpoints:

▪ Safety

▪ Tolerability

▪ PK

▪ PD biomarkers

MRG-110/Placebo

Pg. 22

Study Endpoints

▪ Safety/Tolerability

▪ Pharmacokinetics and local tissue exposure

▪ Pharmacodynamics

▪ Wound healing

▪ Angiogenesis and tissue perfusion

▪ Local and systemic pharmacodynamic biomarker expression

Intradermal SAD Study Design

Pg. 23

Intradermal MAD Study Design

4 mm punch biopsy

4 mm punch biopsy

PlaceboDrug

Day 1Wound creationDrug treatment

4 mmBiopsy

4 mmBiopsy

Day 11 Biopsy for drug distribution/PD

6 mmBiopsy

6 mmBiopsy

Day 8Drug treatment

PlaceboDrug

Day 15Drug treatment

PlaceboDrug

Day 29Biopsy for drug distribution/PD

6 mmBiopsy

6 mmBiopsy

-28 to -1 3 4StudyDay

Screening Treatment Follow-up at 22, 29, 36 days

1 5 6 7 8

Enroll next cohort

9 10 11

PK

2 15

Drug

12-1 18 43 50

Safety labs

16

Biopsy

13 20

Perfusion and/or wound assessments

Pg. 24

▪ MRG-110 is safe and generally well-tolerated when given as a single intravenous dose up to 1.5 mg/kg ▪ No dose-related effect on the occurrence of EAEs, and no clinically significant abnormal

values were observed in the MRG-110 treatment group for biochemistry, hematology, coagulation, complement activation, safety biomarkers, urine chemistry, urine biochemistry, vital signs, or ECG

▪ MRG-110 is safe and generally well-tolerated when given as 3 weekly intradermal doses up to 4.5 mg/dose (0.08 mg/kg per dose in a 60 kg person)▪ No drug-related SAEs observed

▪ Incidence of AEs in SAD and MAD parts were similar between Placebo and MRG-110/Saline treatment groups

MRG-110 Administered by Intravenous or Intradermal Injection is Well Tolerated at All Doses Tested

Pg. 25

▪ Biphasic plasma concentration vs. time curves

indicative of multi-compartmental kinetics

▪ Cmax increases proportionally between 0.15

and 1.5 mg/kg following intravenous dosing

▪ Median Tmax after ID dosing ranged between

30 min and 2 hours

▪ Minimal evidence of accumulation after

multiple ID doses

▪ Low interindividual variability in mean plasma

concentrations and PK parameters

MRG-110 PK Parameters Are Typical for Oligonucleotide Therapeutics SAD Intravenous Dosing

SAD vs MAD Intradermal Dosing

Pg. 26

▪ Saline injected, contralateral wounds on MRG-110 treated subjects show dose responsive inhibition of miR-92a detection by qPCR in biopsies collected on Day 11, which is not seen with miR-191-5p

▪ MRG-110 PK data shows Tmax in systemic circulation is between 30 min and 1 hour post intradermal dosing around the two MRG-110 treated wounds

▪ A 4.5 mg total MRG-110 dose (~0.08 mg/kg in a 60 Kg person) is sufficient to provide systemic drug levels ( Cmax ~142 ng/mL; AUC ~582 ng*hr/mL) capable of inhibiting miR-92a detection in contralateral wound sites

miR-92a Copy Number Demonstrates MRG-110 Distribution to Contralateral Wounds

Pla

ce

bo

Su

bje

cts

0.5

0 m

g M

RG

-11

0

1.5

mg

MR

G-1

10

4.5

mg

MR

G-1

10

All

Do

se

Le

ve

ls

0

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

1 2 0 0

1 4 0 0

1 6 0 0

1 8 0 0

2 0 0 0

2 2 0 0

2 4 0 0

3 0 0 0

4 0 0 0

5 0 0 0

6 0 0 0

7 0 0 0

8 0 0 0

9 0 0 0

m iR -9 2 a -3 p

miR

-92

a c

op

y n

um

be

r

pe

r 1

0 p

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ota

l R

NA

C o n tra la te ra l

W o u n d s

M R G -1 1 0 T re a te d

W o u n d s

Pla

ce

bo

0.5

mg

MR

G-1

10

1.5

mg

MR

G-1

10

4.5

mg

MR

G-1

10

All

Do

se

Le

ve

ls

0

5 0

1 0 0

1 5 0

2 0 0

2 5 0

3 0 0

3 5 0

4 0 0

4 5 0

5 0 0

5 5 0

6 0 0

m iR -1 9 1 -5 p

miR

-19

1-5

p c

op

y n

um

be

r

pe

r 1

0 p

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NA

C o n tra la te ra l

W o u n d s

M R G -1 1 0 T re a te d

W o u n d s

Pg. 27

▪ Day 11 biopsies from Cohorts 1 and 2 show increases in CD31 and CD49e (ITGA5) positive lumen in the MRG-110 treated wounds compared to Placebo.

▪ Saline injected wounds on treated subjects showed dose response in CD31 and CD49e + lumen suggesting active levels of compound in saline injected wounds due to systemic recirculation

▪ Laser Speckle data correlates well with CD31 data

Early Time Points (Before Wound Closure) Demonstrate Increased Angiogenesis and Perfusion in Treated Subjects Compared to Placebos

C1: Cohort 1C2: Cohort 2

Pla

ceb

o

Salin

e C

1

MR

G-1

10 C

1

Salin

e C

2

MR

G-1

10 C

2

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

C D 3 1 + L u m in a

CD

31

+ L

um

ina

p = 0.0198

Pla

ceb

o

Salin

e C

1

MR

G-1

10 C

1

Salin

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2

MR

G-1

10 C

2

0

1 0

2 0

3 0

4 0

5 0

6 0

C D 4 9 e + L u m in a

CD

49

e+

Lu

min

a

Pla

ceb

o

Salin

e C

1

MR

G-1

10 C

1

Salin

e C

2

MR

G-1

10 C

2

0

1 0

2 0

3 0

4 0

5 0

6 0

E R G -1 + L u m in a

ER

G-1

+ L

um

ina

Pla

ceb

o

MR

G-1

10 C

1

MR

G-1

10 C

2

0

1 0

2 0

3 0

4 0

5 0

6 0

C D 3 1 + L u m in a

CD

31

+ L

um

ina

0.0375

n = 4 n = 4n = 7

p =

Pla

ceb

o

MR

G-1

10 C

1

MR

G-1

10 C

2

0

1 0

2 0

3 0

4 0

5 0

E R G -1 + L u m in a

ER

G-1

+ L

um

ina

n = 4 n = 4n = 8

Pla

ceb

o

MR

G-1

10 C

1

MR

G-1

10 C

2

0

1 0

2 0

3 0

4 0

5 0

C D 4 9 e + L u m in a

CD

49

e+

Lu

min

a

n = 4 n = 4n = 7

p = 0 .0 6 5 0

P-value calculated using Kruskal-

Wallis test for main effect with post-

hoc assessment performed using

Dunn’s multiple comparisons test

compared to placebo. Error bars

represent standard error of the mean.

Pg. 28

▪ α-SMA expression has been associated with thicker scars and delayed wound closure.

▪ Scar contraction is also influenced by α-SMA expression and scar thickness

Percent Fibroblasts Expressing Alpha Smooth Muscle Actin in Day 29 Wound Biopsies is Significantly Decreased in Treated Subjects

α-SMA score definitions: Rare positive = 1% - 25%

Focally positive = 26% - 50%

Variable positive = 51% - 75%

Uniformly positive = > 75%

Graphs represent average of the

ranges listed by the pathologistP

laceb

o

Salin

e

MR

G-1

10

0

2 0

4 0

6 0

8 0

1 0 0

%

-S

MA

po

sit

ive

ce

lls

0.02300.0386p = p =

Pla

ceb

o

Salin

e C

1

MR

G-1

10 C

1

Salin

e C

2

MR

G-1

10 C

2

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0

1 0 0

%

-S

MA

po

sit

ive

ce

lls

% α-SMA+ Fibroblasts/Myofibroblasts

for Cohorts 1 & 2

% α-SMA+ Fibroblasts/Myofibroblasts

for Cohorts 1 & 2 Combined

P-value calculated using Kruskal-Wallis test for main effect with post-hoc assessment performed using Dunn’s

multiple comparisons test compared to placebo. Error bars represent standard error of the mean.

Pg. 29

▪ Mean granulation tissue area is significantly decreased in treated subjects Saline and MRG-110 treated wounds on Day 11 compared to Placebo subjects’ wounds

▪ Delayed granulation tissue formation may be related to the MRG-110 meditated decrease in α-SMA positive myofibroblasts which are predominant source of type I collagen and fibrogenic/inflammatory cytokines

▪ Delayed kinetics of granulation tissue formation was not detrimental to achieving full wound closure or appropriate collagen maturation

MRG-110 Mediated Decrease in -SMA+ Myofibroblasts May Reduce Occurrence of Over-granulation in Deep Dermal/Full Thickness Wounds

Day 11

** p-value < 0.01 by Kruskal-Wallis test with Dunn’s multiple comparison test vs Placebo

Pla

ceb

o

Salin

e

MR

G-1

10

0

2

4

6

8

1 0

1 2

Gra

nu

lati

on

Tis

su

e A

re

a m

m2

n = 1 2 n = 1 4 n = 1 3

****

M R G -1 1 0 T re a te d S u b je c ts

Pla

ceb

o

Salin

e C

1

Salin

e C

2

Salin

e C

3

MR

G-1

10 C

1

MR

G-1

10 C

2

MR

G-1

10 C

3

0

5

1 0

1 5

2 0

2 5

G ra n u la t io n T is s u e A re a

Gra

nu

lati

on

Tis

su

e A

re

a m

m2

Pg. 30

▪ MRG-110 is safe and generally well-tolerated when given as a single intravenous dose up to 1.5 mg/kg or as 3 weekly intradermal doses up to 4.5 mg/dose (0.08 mg/kg per dose in a 60 kg person)

▪ In small, acute wounds on normal healthy volunteers, single and multiple doses of MRG-110 appeared to:▪ Systemically recirculate to a placebo treated contralateral wound

▪ Increase angiogenesis as assessed by CD31 immunostaining

▪ Increase peri-wound perfusion, as assessed by non-invasive Laser Speckle Perfusion Imaging

▪ Increase CD49e (ITGA5) expression, as assessed by immunostaining

▪ Reduce -SMA expression, as assessed by immunostaining

▪ These data support moving forward in cutaneous wounds of varying etiology where increased perfusion may result in improved wound closure and reduced -SMA expression may reduce scar formation and contracture as well as cardiovascular indications where enhanced vascularization would be beneficial

Data From Phase I Clinical Trials

Pg. 31

miRagen

▪ Diana Escolar

▪ Rob Hopkins

▪ Charissa Bondy

▪ Linda Pestano

▪ Corrie Gallant-Behm

▪ Brent Dickinson

▪ Kristin Schroeder

▪ Beth Brown

▪ Mark Robberson

▪ Judy Ruckman

▪ Steve Shoemaker

▪ Graciella Beyers

▪ Lisa Beshore

Acknowledgements

▪ Ann Marie Curatolo

▪ Pam Lopert

▪ Bill Perry

▪ Aimee Jackson

▪ Paul Rubin

Univ. Frankfurt

▪ Stefanie Dimmeler

▪ Rabea Hinkel

Servier

▪ Isabelle Paty

▪ Guillaume Allee

Celerion

▪ Phase 1 Unit