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Oligonucleotide-Based

Therapeutics ConferenceOctober 28-30 | North Bethesda, MD

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Clinical Development of microRNA Inhibitors

© 2019 DIA, Inc. All rights reserved.

Diana M Escolar, MD, FAAN

SVP, Clinical Science

miRagen Therapeutics

October 28, 2019

Page 2



Disclaimer

Page 3

The views and opinions expressed in the following PowerPoint slides are those of

the individual presenter and should not be attributed to DIA, its directors, officers,

employees, volunteers, members, chapters, councils, Communities or affiliates,

or any organization with which the presenter is employed or affiliated.

These PowerPoint slides are the intellectual property of the individual presenter

and are protected under the copyright laws of the United States of America and

other countries. Used by permission. All rights reserved. DIA and the DIA logo are

registered trademarks or trademarks of Drug Information Association Inc. All other

trademarks are the property of their respective owners.


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. Actual results or events could differ materially from the

plans, intentions and expectations disclosed in the forward-looking statements that we make due to a number of important factors,

including those risks discussed in “Risk Factors” and elsewhere in our Annual Report on Form 10-K for the year ended December

31, 2018 and our other reports filed with the U.S. Securities and Exchange Commission. 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.


microRNAs have been evolutionarily selected to regulate networks of genes

microRNAs are dysregulated in many diseases

Dysregulation of microRNAs is associated with alteration of downstream gene networks and disease

microRNA-targeted therapy is focused on disease modification by restoring homeostasis to dysregulated processes

microRNA therapeutics may be particularly suited for complex, multigenic disorders


microRNAs Regulate Network Biology to Maintain Homeostasis

Page 5

A

Conventional Therapies

(Small molecules, Antibodies, siRNA, etc)

Single molecule as target

microRNA-based Therapies

Network (pathway) as target

% IN

HIB

ITIO

N

100

50

0


Opportunities and Challenges for miRNA Therapeutics

Many diseases are multigenic, complex disorders.

Modulation of miRNAs may offer multiple opportunities

to intervene in disease-relevant pathways

miRNAs are homeostatic and therefore miRNA

therapeutics do not appear to adversely affect normal

tissues/systems

miRNA therapeutics can be administered without

exotic formulations, thereby potentially improving their

safety profile

6

Safety of formulated miRNA therapeutics has been

poor to date.

• Safety concerns may be mitigated with unique

chemistry and delivery approaches

PD biomarker identification efforts are required to

identify genes and networks affected by a miRNA

therapeutic

• Identification of translatable PD biomarkers

• Proving selectivity for disease specific

pathways and not normal physiology

• Exclude candidate molecules that affect off-

target biomarkers/gene signatures

Translatability from cells → animal models →

patients

• Need to demonstrate proof of concept early in

clinical trials

Opportunities for Development of miRNA

Therapeutics

Overcoming Challenges in Development of

miRNA Therapeutics


miRagen has developed miRNA inhibitors that to date have better safety profile than other miRNA inhibitors and many other oligonucleotide drugs, by addressing: Chemistry

• LNA/DNA mixmer design appears to blunt acute inflammatory responses, hepatotoxicity, renal toxicity

• Chemical stabilization allows for long tissue half lives and relatively infrequent dosing

Delivery• miRNA inhibitors can be delivered without the use of viral vectors, liposomes, or nanoparticle

formulation, reducing immunogenicity and potential for off-target toxicity

• Molecules can be developed that are either broadly taken up by cells or that have targeted delivery conjugates

Relative specificity• Target miRNAs and their regulated gene networks selected for development are dysregulated

only in disease circumstances, thereby potentially limiting exacerbated pharmacology

• Therapeutic objective is restoration of homeostasis – miRNA therapeutics modulate but do not obliterate their targets, thereby potentially preventing toxicities associated with a complete repression of target protein expression


Overcoming Challenges in the Clinical Development of miRNA Therapeutics - Safety

Page 7


miRagen believes it has addressed the challenges of identifying PD biomarkers for miRNA inhibitors that result in relatively minor expression changes for many genes simultaneously by: Focusing on miRNAs that are highly evolutionarily conserved and whose target gene

networks/pathways are biologically relevant to disease

Identifying the PD biomarker “fingerprint” for each miRNA inhibitor• Assess PD biomarkers in stressed settings that mimic disease

• Using unbiased screening approaches (e.g. RNAseq) to identify pharmacodynamic targets that are reciprocally regulated by promiRs and antimiRs for the same miRNA

• Pathway analysis to identify pharmacodynamic targets that are conserved within a network or pathway

• Utilization of kinetics experiments to identify both direct and indirect downstream targets within the same pathway

• Identification of lead candidates that are potent, selective

Select the most disease relevant genes for translation to mechanistic proof of concept studies in early stage clinical trials


Overcoming Challenges in the Clinical Development of miRNAs Therapeutics - Pharmacodynamics

Page 8


miRagen believes it has addressed the challenges in the translation going from cells → animal models → patients by: Improving translatability from preclinical to clinical studies

• Perform research in the most relevant species or disease model

• Identify the pharmacodynamic “fingerprint” using preclinical studies

• Validate assays (Nanostring, QRT-PCR, ISH, IHC or other) for translation to the clinic

Derisking the clinical program by incorporating mechanistic and/or clinical proof-of-concept studies in first-in-human trials:

• Incorporate mPOC endpoints such as PD biomarker regulation into first in human trials to confirm biological activity in humans

• Assess disease-relevant endpoints (e.g. CAILS and mSWAT assessments) to address cPOCearly in the clinical program

• Initially focus on localized delivery (e.g. intradermal administration) and collect target tissue samples to assess compound activity in humans

• Follow with IV or SC administration to assess safety, efficacy

• Conduct comparative PK for each route of administration


Overcoming Challenges in the Clinical Development of miRNAs Therapeutics – Translation and Clinical Development

Page 9


miRagen Clinical Development Programs

MRG-106/Cobomarsen

MRG-110

© 2019 DIA, Inc. All rights reserved. Page 10


Cobomarsen, a miR-155 Inhibitor for Potential Treatment of Hematologic Malignancies




miR-155 Regulates Gene Pathways Implicated in Mycosis Fungoides

Page 12

↑ miR-155

Proliferation

Apoptosis

T-cell activation

Conventional Therapy

(e.g., idelalisib)

Cobomarsen

Multiple survival and

immune pathways activated

One survival

pathway inactivatedMultiple survival and immune

pathways inactivated

idelalisib

Proliferation

Apoptosis

T-cell activation

Proliferation

Apoptosis

T-cell activation

PI3K/AKT

JAK/STAT

NF-kB

RAS/MAPK

PI3K/AKT

JAK/STAT

NF-kB

RAS/MAPK

PI3K/AKT

JAK/STAT

NF-kB

RAS/MAPK


© 2019 DIA, Inc. All rights reserved. Page 13© 2019 DIA, Inc. All rights reserved. Page 13

miR-155 is overexpressed

in CTCL skin lesions and is

involved in tumor

progression

The miR-155 inhibitor

cobomarsen impacts

proliferation and cell survival

in MF cells

0 2 4 6 8 10 120

200

400

600

2000

4000

6000

8000

10000

Days

% C

han

ge C

om

pare

d t

o U

ntr

eate

d a

t D

ay 1

0 2 4 6 8 10 120

200

400

600

800

Days

% c

han

ge c

om

pare

d t

o u

ntr

eate

d a

t D

ay 1

0 2 4 6 8 10 120

200

400

600

2000

4000

6000

8000

10000

Days

% C

han

ge C

om

pare

d t

o U

ntr

eate

d a

t D

ay 1

Untreated

Bexarotene

Cobomarsen

0 2 4 6 8 10 120

200

400

600

2000

4000

6000

8000

10000

Days

% C

han

ge C

om

pare

d t

o U

ntr

eate

d a

t D

ay 1

Untreated

Bexarotene

Cobomarsen

PROLIFERATION APOPTOSIS

N=10 N =13 N =21N =13

*In collaboration with Madeleine Duvic (MD Anderson)

MIR-155 COPY NUMBER BY

LESION TYPE


Cobomarsen Observed to Reverse the Disease Gene Signature in Mycosis Fungoides

T cell activation, survival signaling, and cytokine

signaling genes ↑ in MF lesions

REDUCED by cobomarsen

Cell cycle checkpoint genes ↓ in MF lesions

INCREASED by cobomarsen


GENES REGULATED IN MF LESIONS

COMPARED TO NORMAL SKIN

Patch PlaqueTumorMF Cells+ Cobo

T cell activation,

survival signaling,

cytokine signaling

Cell cycle

checkpoint

regulation



Cobomarsen Clinical Program in Hematological Malignancies

Page 15

Dose, Schedule Optimization

and Response Durability in CTCL

Pa

ralle

l In

dic

ation

Exp

an

sio

n in

Ph

1

mPoC cPoC Futility

AnalysisPART B/C

SYSTEMIC

PART A

LOCAL

ATLL

DLBCL

CLL

Ph 1 CTCL Ph 2 CTCL

Ph 2 in NHL / Leukemia

CTCL MYCOSIS FUNGOIDES

MIR-155-HIGH NON-HODGKINS

LYMPHOMA (NHL)/LEUKEMIA


Cobomarsen Clinical DevelopmentPhase I Results in CTCL




Cobomarsen: Two-part Phase 1 CTCL Clinical Trial

Page 17

PART A

Intra-tumoral delivery

of cobomarsen

(75 mg dose)

PART B

Systemic SC or IV delivery

to determine optimal

potential dose (300, 600

and 900 mg+ dose)

OBJECTIVES

+ PRIMARY Safety and

tolerability

+ SECONDARY PK

+ EXPLORATORY PD,

histopathology, lesion

morphology

PRETREATMENT

BIOPSY

PRETREATMENT

BIOPSY

PLACEBO COBOMARSEN

PLACEBO

BIOPSY

COBOMARSEN

BIOPSY BIOPSY

COBOMARSEN

SC or IV

PART A PART B



Cobomarsen Shows Favorable Tolerability

Page 18

No serious adverse events attributed to

cobomarsen in CTCL

No acute inflammatory toxicities

No significant abnormalities found in liver, kidney or blood

In Total, 68 Patients

(CTCL, ATLL, DLBCL,

and CLL from Ph1 and

CTCL SOLAR) Have

Been Exposed to

Cobomarsen for up to

2.25 Years

+ COBOMARSEN HAS BEEN GENERALLY SAFE

and well tolerated

o Multiple patients receiving more than a year

of therapy

o Total of 1254 cumulative doses

(across 68 patients)

+ NO SIGNIFICANT LAB ABNORMALITIES found

in liver function, kidney function, thyroid function

and platelet counts

+ NO EVIDENCE OF METABOLIC or

HEMATOLOGICAL toxicities

+ NO EVIDENCE OF GLOBAL

IMMUNOSUPPRESSION

+ NOVEL OLIGONUCLEOTIDE drug class

(Data Cutoff July 23, 2019)



Cobomarsen Observed to Reverse the Disease Gene Signature and Reduce Malignant Cell Clonality in Mycosis Fungoides Patients

Page 19

Survival

signaling



Phase I CTCL Thirty-three of Thirty-six Patients (92%) Treated Systemically with Cobomarsen Have Shown mSWAT Score Improvement

Page 20

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

0

10

20

30

Be

st

Ch

an

ge

in

mS

WA

T S

co

re (

%)

300 mg

600 mg

900 mg

* treatment ongoing

*

*

56

0

12

6

68

NE

NE

49

5

21

4

58

2

39

315

4

35

7

18

1

48

52

NE

14

8

IV Infusion IV BolusSC

STAGE

BASELINE mSWAT

DOSES

1A 2A 1B 1B 2B 1A 2B 1B 1B 2B 2B 1B 2B 3A 1B 2A 2B 1B 2B 2B 2B 1B 1B 1B 1B 1B 1A 1A 2B 2A 1B 3B 2A 2A 1B 1B

6 103 43 20 2 2 47 17 22 18 20 33 9 178 100 78 58 18 6 11 178 43 82 54 27 180 6 5 86 85 54 71 59 18 132 66

9 3 6 6 6 6 6 85 79 6 7 17 11 14 12 9 6 13 6 11 9 56 29 34 27 77 26 41 5 10 6 10 27 32 9 33

*



Phase I CTCL Cobomarsen Substantially Reduces Lesion Severity Following IV Administration

Page 21

C1D1 Pretreatment

CAILS: 12

C3D1

CAILS: 3

C6D1

CAILS: 0

C12D1

CAILS: 0


Cobomarsen Clinical Development:Phase I Results in ATLL




Cobomarsen Clinical Experience in ATLL

Page 23

PART F:

Open-label, dose-ranging, multiple dose trial of cobomarsen in ATLL

OVERALL TRIAL DESIGN

+ INCLUSION CRITERIA

o Acute, lymphomatous, chronic, and smouldering

subtypes

o Relapsing or in PR/CR after prior therapy

o Progressed on, or refractory to, at least one prior

therapy

+ DOSING AND DURATION

o SQ or IV

o 3 loading doses the first week

o Weekly dosing thereafter

o Discontinue if subject becomes intolerant, develops

clinically significant side effects, or progresses

OBJECTIVES

+ PRIMARY: Safety and tolerability

+ SECONDARY: PK

+ EXPLORATORY: PD, histopathology, lesion morphology



Subject 101-008 Acute ATLL in Partial Remission

Page 24

+ Diagnosed Dec 2016 with acute ATLL

+ Relapsed after treatment with zidovudine, interferon ɑ-2b, lenalidomide and EPOCH chemotherapy

+ Cobomarsen monotherapy initiated Nov 2017o Stable abnormal ATL cells for

> 16 moo Normalization of residual enlarged

lymph node after chemotherapy (1.0 to 0.8 cm), which remained normal as of last imaging Nov 2018

o Reduction in biomarkers of cell activation and proliferation (Ki67, CD69 and HLA-DR)

+ Subject remains on treatment and has completed Cycle 18, missing only 1 dose due to sciatic pain

2/2

2/1

7

7/1

9/1

7

8/1

2/1

7

9/8

/17

10/1

2/1

7

11/6

/17

12/1

3/1

7

1/3

1/1

8

3/1

8/1

8

5/9

/18

7/2

5/1

8

10/1

0/1

8

12/2

6/1

8

3/2

0/1

9

0

3

6

9

1 2

1 5

1 8

2 1

2 4

2 7

3 0

3 3

Ce

lls

x 1

0^

3 /

L

L a s t E P O C H d o s e

F irs t c o b o m a rs e n d o s e

A Z T /IF NL e n a lid o m id e

E P O C H

c o b o m a rs e n

A b n o rm a l T c e lls

W B C

m is s e d

d o se

(Data Cutoff March 15, 2019)



Subject 101-008 Cobomarsen Appears to Decrease Activation and Proliferation Status of Circulating Tumor Cells in ATLL

Page 25

C1D

1

C1D

5

C1D

27

C2

C4

C6

C8

C10

C12

C14

C16

0 .0

0 .5

1 .0

1 .5

Fo

ld C

ha

ng

e f

ro

m B

as

eli

ne

K i-6 7

H L A -D R

C D 6 9

C1D

1

C1D

5

C1D

27

C2

C4

C6

C8

C10

C12

C14

C16

0

2 0

4 0

6 0

8 0

%C

ell

s P

os

itiv

e f

or M

ark

er

% K i-6 7 +

% H L A -D R +

% C D 6 9 +

FLOW CYTOMETRIC ASSESSMENT of ACTIVATION and PROLIFERATION

Biomarkers’ Expression in Circulating ATLL Cells

7%

Ac

tiva

tio

n M

ark

ers

Pro

life

rati

on

35% 25% 5% 5% 7%

CD69

C1D1

HLA-DR

C1D5 C1D27 C2D22 C6D22 C14D22

SS

C

Ki-67

SS

C

50%

1179

71%

2880

67%

214856%

1264

53%

1129

50%

1283

Percent

MFI

19%

3436

13%

21058%

1885

8%

1900

8%

2011

Percent

MFI7%

1810

C1D1 C1D5 C1D27 C2D22 C6D22 C14D22

SS

C

Percent

MFI: Median Fluorescence Intensity, ATL cells: CD3+CD4+CD8-CD25+CD127-

ATL cells: CD3+CD4+CD8-CD7-CD25+CD45RA-

% CELLS POSITIVE FOR BIOMARKERS

CHANGE FROM BASELINE IN BIOMARKERS




Cobomarsen Appears to Decrease the Activation and Proliferation of Circulating Tumor Cells

Page 26

C1D

1

C1D

5

C1D

27

C2

C4

C6

C8

C10

C12

C14

C16

0 .0

0 .5

1 .0

1 .5

2 .0A c tiv a tio n M a rk e rs A T L T u m o r C e lls

Av

era

ge

Fo

ld C

ha

ng

e o

f

% C

ell

s P

os

itiv

e f

ro

m B

as

eli

ne % C D 6 9 +

% H L A -D R +

n = 4 n = 4

n = 3n = 4

n = 4

n = 3 n = 2

n = 2

n = 2 n = 2

C1D

1

C1D

5

C1D

27

C2

C4

C6

C8

C10

C12

C14

C16

0 .0

0 .5

1 .0

1 .5P ro life ra tio n In d e x A T L T u m o r C e lls

Av

era

ge

Fo

ld C

ha

ng

e o

f

% C

ell

s P

os

itiv

e f

ro

m B

as

eli

ne

% K i-6 7 +

n = 4 n = 4

n = 3

n = 4

n = 4

n = 3

n = 2n = 2

n = 2

n = 2

ACTIVATION MARKERS ATL TUMOR CELLS PROLIFERATION INDEX ATL TUMOR CELLS



SOLAR: A Phase II Clinical Trial of Cobomarsen in Mycosis Fungoides




SOLAR Phase 2 Clinical Trial

Page 28

A Randomized, Open-Label, Parallel-group,

Active Comparator, Global Trial in Patients

with Stage IB-III Mycosis Fungoides (MF)

Primary Endpoint

+ Overall Response Rate of Four Months (ORR4)

using Global Response Criteria

Secondary Endpoints

+ Progression-free Survival

+ Patient Reported Outcomes

OPEN LABEL RANDOMIZE TO:COBOMARSEN IV

INFUSION VS. VORINOSTAT

RANDOMIZE

COBOMARSEN (282 MG IV INFUSION)

N=63 SUBJECTS

VORINOSTATN=63 SUBJECTS

FOLLOW UNTIL PROGRESSION

FOLLOW UNTIL PROGRESSION

OPEN LABEL EXTENSION

PRISM



SOLAR Study Participating Countries

Page 29

+ Austria

+ Australia

+ Belgium

+ Canada

+ France

+ Germany

+ Italy

+ Netherlands

+ Spain

+ United Kingdom

+ United States

126 Subjects at ~60 Sites

Across 11 Countries


MRG-110, a miR-92a Inhibitor for Potential Treatment of Cardiovascular Disease and Wound Healing




Control

+ miR-92a

Spheroid model Network formation Matrigel plug model

Overexpression of miR-92a inhibits

sprouting, network formation, and

angiogenesis in multiple models

miR-92a mimics and inhibitors

reciprocally regulate multiple

angiogenesis-associated genes in

endothelial cells



Translatability of MRG-110 in Wound Healing:MRG-110 Observed to Increase Angiogenesis in Mice to Men

Page 32



MRG-110 Appears to Accelerate Wound Healing and Angiogenesis in db/db Mice

Page 33

† = p


MRG-110 Appears to Improve Vascularization and Decreases Contracture in Healthy Farm PigsAssessed on Day 49

Page 34

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

MRG-110 Clinical Development Phase I Results




MRG-110: Two Phase 1 Clinical Trials

Page 36

TRIAL 1

Single IV administration

(0.01-1.5 mg/kg)

Objectives


tolerability

+ SECONDARY PK

TRIAL 2

Single or multiple (3 weekly)

ID administrations around an

excisional wound

(0.25-2.25 mg/wound)

Objectives


tolerability

+ SECONDARY PK

+ EXPLORATORY wound

healing, wound perfusion,

PD, histopathology

MRG-110 IV

Trial 1

Systemic

PRETREATMENT

BIOPSIES

PRETREATMENT

BIOPSIES

PLACEBO MRG-110

PLACEBO

BIOPSY

MRG-110

BIOPSY

Trial 2

Intradermal

SINGLE OR MULTIPLE ADMINISTRATIONS

WOUND HEALING AND

PERFUSION ASSESSMENTS

OVER TIME



MRG-110 Shows Favorable Tolerability

Page 37

No serious adverse events attributed to

MRG-110

No acute inflammatory toxicities

No significant related abnormalities found in liver, kidney or blood

In Total, 65 Subjects

Have Been Exposed to

MRG-110 for up to

3 Weeks

+ MRG-110 HAS BEEN GENERALLY SAFE and

well tolerated

o IV administration up to 1.5 mg/kg

o ID administration up to 2.25 mg/wound

+ NO INJECTION SITE REACTIONS

+ NO SIGNIFICANT LAB ABNORMALITIES found

in liver function, kidney function, thyroid function

and platelet counts attributable to MRG-110

+ One Placebo subject had a Grade 4 asymptomatic elevation

in CK that was transient and did not require treatment

+ NO EVIDENCE OF DISTAL ANGIOGENESIS

+ NOVEL OLIGONUCLEOTIDE drug class



MRG-110 Observed to Increase Wound Angiogenesis and Tissue Perfusion

Page 38

Peri-wound perfusion intensity

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

e C

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


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


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


CD

49

e+

Lu

min

a

n = 4 n = 4n = 7

p = 0 .0 6 5 0

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


CD

31

+ L

um

ina

p = 0.0198

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


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


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


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


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


CD

49

e+

Lu

min

a

n = 4 n = 4n = 7

p = 0 .0 6 5 0

Angiogenesis

ITGA5

expression

(miR-92a target)


© 2019 DIA, Inc.

All rights reserved.

MRG-110 Observed to Decrease α-Smooth Muscle Actin Expression and Prevent Excessive Granulation Tissue Formation

Page 39

Pla

ceb

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

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

Granulation tissue volume reduced early after

treatment

No appreciable difference 1 month after injury –

Delayed kinetics of granulation tissue formation was

not detrimental to achieving full wound closure or

appropriate collagen maturation

α-SMA expression reduced with MRG-110 treatment


Cardiovascular indications that may benefit from angiogenic therapy Acute myocardial infarction

Chronic heart failure/angina

Vascular injury – inhibition of neointimal formation after balloon angiography

Peripheral artery disease

Wound healing, where ischemia is a major contributing factor to slow/ineffective process Burn wounds

Grafts

Diabetic foot ulcers

Pressure ulcers

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

Graft donor sites

Complicated laparotomy closure


Potential Clinical Indications

Page 40



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