Joanne Donovan, MD, PhDCatabasis Pharmaceuticals, Cambridge, MA

Targeting NF-κB with Edasalonexent for Muscle and Bone Health in Duchenne Muscular Dystrophy

2

Disclosures

This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including statements regardingour expectations and beliefs about our business, future financial and operating performance, clinical trial plans, product development plans and prospects,including statements about future clinical trial plans including, among other things, statements about our single global Phase 3 PolarisDMD trial in Duchennemuscular dystrophy, or DMD, to evaluate the efficacy and safety of edasalonexent for registration purposes, our plans to continue to evaluate data from the open-label extension of our MoveDMD® clinical trial of edasalonexent for the treatment of DMD, and our plans to combine edasalonexent treatment with other DMDtreatments such as gene therapy and other dystrophin-targeted approaches. The words “believe”, “anticipate”, “plans,” “expect”, “could”, “should”, “will”, “would”,“may”, “intend” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifyingwords.

The forward-looking statements contained in this presentation and in remarks made during this presentation and the following Q&A session are subject toimportant risks and uncertainties that may cause actual events or results to differ materially from our current expectations and beliefs, including: uncertaintiesinherent in the initiation and completion of preclinical studies and clinical trials and clinical development of our product candidates; availability and timing of resultsfrom preclinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials;expectations for regulatory approvals to conduct trials or to market products, including our expected target product profile for edasalonexent in DMD; availability offunding sufficient for our foreseeable and unforeseeable operating expenses and capital expenditure requirements; other matters that could affect the availabilityor commercial potential of our product candidates; and general economic and market conditions and other factors discussed in the “Risk Factors” section of ourAnnual Report on Form 10-Q for the period ended March 31, 2019, which is on file with the Securities and Exchange Commission, and in other filings that we maymake with the Securities and Exchange Commission in the future. In addition, the forward-looking statements included in this presentation represent our views asof the date of this presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to updatethese forward-looking statements at some point in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not berelied upon as representing our views as of any date subsequent to the date of this presentation.

Joanne Donovan is an employee of Catabasis Pharmaceuticals, Inc.

Edasalonexent is an investigational agent that is not approved in any territory.

Chen et al., Neurology 2005 65: 826Fiorillo et al., Physiol Genomics 2018 50:735 3

Activation of NF-κB in Muscular Dystrophy Is a Key Factorin Disease Progression in Skeletal and Cardiac Muscle

No Dystrophin + Mechanical Stress

Disease Progression

ActivatedNF-κB

Kumar et al., FASEB J 2003 17:386Akima et al., Neuromuscul Disord 2012 22: 16

Degeneration MuRF1/MAFbx

Control DMD

Cross section of mid-thigh muscle in 12-14 YO boys

Dystrophin and Membrane Stability

b-Dystroglycan

Actin

Dystrophin

MMP-9

miRNA

NF-κB decreases dystrophin production, suggesting inhibition could increase dystrophin with dystrophin-targeted therapies

Inflammation in Infancy

Cytokines

Fibrosis

Inflammation

Regeneration

Satellite Cell

Myoblasts

Myotube

Cyclin D1

MyoD

Edasalonexent Inhibits NF-κB, a Key Driver of Muscle Disease in DMD

‣ Inhibiting NF-κB slows disease progression in animal models of DMD

– Oral administration of edasalonexent or analog (CAT-1041) reduces muscle inflammation and improves function in mdx mice and GRMD dog

‣ Edasalonexent is an orally-administered small molecule that is not a steroid

‣ Being developed for patients with DMD regardless of mutation, both as monotherapy and potentially to be combined with dystrophin-targeted therapies

Decreased Cardiac FibrosisReduced Inflammation in mdx12 month-old GRMD

Untreated CAT-1041

Masson’s Trichrome Staining

Re

lati

ve P

rote

in C

on

ten

t (A

U)

2.5

2

1.5

1

0.5

0OPN IL-6 IL-4

p=0.02

p=0.01

p=0.04

Control

CAT-1041

Increased Diaphragm Specific Force in mdx

Sp

eci

fic

Fo

rce

(N

/cm

2)

10

8

6

4

2

0Control CAT-1041

Control

CAT-1041

p=0.02

Means + SEM

Hammers et al., 2016 JCI Insight

4

5

DMD Boys Are Shorter From an Early Age

3 4 5 6 7 8 9

8 0

1 0 0

1 2 0

1 4 0

S te ro id -N a iv e D M D B o y s a r e

C o n s is te n t ly S h o r te r

fo r T h e ir A g e

( 1 0t h

, 5 0t h

, a n d 9 0t h

p e r c e n t i le s )

A g e (y )

He

igh

t (c

m)

D M D (W e s t, e t . a l . )

C D C (2 0 0 0 )

‣ Normal length at birth

‣ Progressive divergence in the difference in stature (compared to healthy controls)

‣ ~5% difference in height from healthy controls

West et al., 2013 J Peds

6

‣ RANK-ligand mediated NF-κB activates osteoclast differentiation and function

– Drives bone loss

‣ NF-κB activation additionally inhibits osteoblast maturation

– Inhibits new bone growth

NF-κB Activity Mediates Inflammation-induced Bone Loss(R

ach

ne

r, e

t. a

l., L

an

cet

20

11

)

(Kru

m, e

t. a

l., N

atu

re R

ev R

heu

m 2

01

0)

Inhibition of NF-κB has the potential to reduce bone loss and enhance new bone growth in patients affected by DMD

7

‣ Inflammatory stimuli that activate NF-κB cause reduced bone lengths

– (in situ fetal mouse metatarsals)

Persistent NF-κB Activation Reduces Bone Length

Landman, et. al., Arthritis Research and Therapy 2013

8

‣ Corticosteroid molecules enhance osteoblast apoptosis and reduce ossification

‣ Steroid-induced increase in RANK-ligand and decrease in Osteoprotegerin leads to enhanced bone resorption and osteoporosis

Corticosteroid Activity Favors Bone Resorption

(Baschant et. al., Nature Rev Rheum 2012)

‣ Clinical consequence is an increased risk of fractures with minimal mechanical stress

(Joseph et. al., JAMA Neurology 2019)

9

Bone Sparing Effect of Edasalonexent in mdx MiceCompared to bone loss seen with prednisolone

‣ No bone metabolism defects in young mdx mice relative to WT (measured by peripheral quantitative CT)

‣ Prednisolone treatment (5mg/kg daily) for ~6 weeks significantly reduced bone length and density

‣ With edasalonexent treatment bone length and density are normal

Femur Length Cortical Density

**** P<0.0001 vs mdx control

10

‣ Long-term low dose corticosteroid is sufficient to induce bone loss and reduced femur lengths

Edasalonexent Maintains Bone Sparing Effect in mdx Mice AfterLong Term Treatment

3-month treatment1 mg/kg Prednisolone

6-month treatment1 mg/kg Prednisolone

Femur Length Cortical Density

W T

c t r l

m d x

c t r l

m d x

e d a s a

m d x

p r e d

0

4

8

1 2

1 6

2 0

F e m u r L e n g th

Fe

mu

r L

en

gth

(m

m)

W T

c t r l

m d x

c t r l

m d x

e d a s a

m d x

p r e d

0

4

8

1 2

1 6

2 0

F e m u r L e n g th

Fe

mu

r L

en

gth

(m

m)

N S

N S

* * *

W T

c t r l

m d x

c t r l

m d x

e d a s a

m d x

p r e d

0 .0

0 .4

0 .8

1 .2

C o rtic a l D e n s ity

Co

rti

ca

l D

en

sit

y (

mg

/mm

2)

N S

N S

* * * *

W T

c t r l

m d x

c t r l

m d x

e d a s a

m d x

p r e d

0 .0

0 .4

0 .8

1 .2

C o rtic a l D e n s ity

Co

rti

ca

l D

en

sit

y (

mg

/mm

2)

****p<0.0001, ***p<0.005

‣ Study Objectives

– Proof of concept using MRI to assess changes in muscle health

– Long-term study to enable Phase 3

‣ Key Inclusion / Exclusion criteria

– Age 4 to 8th birthday not on corticosteroids for at least 24 weeks

Design of MoveDMD, a Phase 2 Trial with Open-Label Extension

Phase 1n=17

Off-Treatment Periodn=16

Phase 2n=31

Open-Label Extensionn=31

‣ Analysis Plan

– 12-week placebo control period

– Compare changes during off-treatment control period with changes after initiation of edasalonexent

1 week ~6 months prior to Phase 2 12-week placebo-controlled period

>72 weeks

11

12

Range of Endpoints to Demonstrate Proof of Concept and Support Design of Phase 3

NF-κB Target Engagement Biomarkers Muscle MRI Functional

▸ Inhibition of

NF-κB targeted

gene set in

peripheral blood

▸ CRP, biomarker of

inflammation

▸Muscle enzymes

▸MRI T2 of upper

and lower leg

▸MRS muscle fat

▸North Star

Ambulatory

Assessment and

Timed Function

Tests

13

‣ Declines in function in natural history study were similar to those observed in the MoveDMD trial off-treatment

‣ Decreases in function correlate with increases in composite lower leg MRI T2 as well as muscle fat fraction

Steroid-Naïve Boys in Age Range 4 to 8th Birthday Are Declining in Function and Progressing on MRI

Functional Decline in Boys Not Receiving Steroids or Edasalonexent

MRI Shows Disease Progression

Finkel et al., World Muscle Society, 2018; Vandenbourne et al., World Muscle Society, 2018

An

nu

alize

d R

ate

of

Ch

an

ge

(m

s/ye

ar)

6

4

2

An

nu

alize

d R

ate

of

Ch

an

ge

(%

/ye

ar)

4

3

2

1

An

nu

alize

d R

ate

of

Ch

an

ge

(%

/ye

ar)

20

15

10

5

Lower Leg Composite MRI T2 Soleus Fat Fraction VL Fat Fraction

An

nu

alize

d R

ate

of

Ch

an

ge

(ta

sks/

s/ye

ar)

0.00

-0.05

-0.10

-0.15

10-meter walk/run 4-stair climb Time to stand

Natural History: ImagingDMD Prior to treatment: MoveDMD

Means + SEM

14

‣ Composite of 5 lower leg muscles MRI T2 used to encompass muscles at various stages of disease progression and minimize variability

‣ Following 72 weeks of edasalonexent, the rate of increase in the composite MRI T2 in the five lower leg muscles decreased as compared to the rate of increase during the off-treatment control period

In Phase 2 MoveDMD Trial and Open-Label Extension:

Edasalonexent Improved Rate of Change of MRI T2 Compared to Off-Treatment Control Period

MRI T2: Composite of 5 Lower Leg Muscles

Weeks on Edasalonexent

12 483624

* **

*

Edasalonexent

100 mg/kg

Off-treatment control

*

72

Better

An

nu

alize

d R

ate

of

Ch

an

ge

(m

se

c/ye

ar)

6

4

2

0

-4

Means + SEM; mixed model comparison with off-treatment period * Week 12: p=0.002, n=16; Week 24: p=0.004, n=14; Week 36: p=0.032, n=13; Week 48: p=0.018, n=12; Week 72: p=0.052, n=9

15

In Phase 2 MoveDMD Trial and Open-Label Extension:

All Assessments of Function Stabilized on Edasalonexent Compared to Off-Treatment Control

North Star Ambulatory Assessment

NS

AA

Sco

re

25

20

15

10

5

-36 -24 -12 0 12 24 36 48 60 72

Edasalonexent

100 mg/kg

Control Period

Sp

ee

d (

1/S

eco

nd

s)

0.4Edasalonexent

0.3

0.2

0-36 -24 -12 0 12 24 36 48 60

100 mg/kg

Control Period

0.1

4-Stair Climb

72

Tim

e (S

eco

nd

s)

5

1015

10-Meter Walk/Run

Sp

ee

d (

1/S

eco

nd

s) Tim

e (S

eco

nd

s)

0.20

0.18

0.16

0.14

0.12

5

10-36 -24 -12 0 12 24 36 48 60 72

Edasalonexent

100 mg/kg

Control Period

Better

Weeks

WeeksWeeks

Time to Stand

Sp

ee

d (

1/S

eco

nd

s)

Tim

e (S

eco

nd

s)

0.3

-36 -24 -12 0 12 24 36 48 60 72

Edasalonexent

100 mg/kg

0

0.2

0.1

5

10

Control Period

15

Weeks

Means ± SEM shown. Includes data of all boys initially started on 100 mg/kg dose (n=16) with 11 boys participating through 72 weeks.

16

In Phase 2 MoveDMD Trial and Open-Label Extension:

Muscle Enzymes Significantly Decreased on Edasalonexent, Supporting a Positive Drug Effect

Weeks on 100 mg/kg Edasalonexent

IU/m

L

0

-5000

-10000

-15000

-20000

-25000

IU/m

L

0

-50

-100

-150

-200

Alanine Aminotransferase

12 36 724824 60

IU/m

L

0

-50

-100

-150

-200

-250

Aspartate Aminotransferase

12 36 724824 60

IU/m

L

0

-200

-400

-600

-800

Lactate Dehydrogenase

12 36 724824 60

Creatine Kinase

*

12 36 724824 60

*

* *

Plasma muscle enzymes are elevated 10 to 100 fold in DMD, indicative of leakage from damaged myocytes

Means ± SEM shown; * p<0.05 for mean change from baseline after 12 weeks

17

In Phase 2 MoveDMD Trial and Open-Label Extension:

Edasalonexent Showed Potential for Cardiac Benefits in DMDB

ea

ts p

er

min

ute

0

-5

-10

-15

Heart Rate: Change from Baseline

0 20 40

Weeks on Edasalonexent

8060

* p<0.01

Thomas, et al. Pediatr Cardiol. 2012 33(7):1175-9.Hammers, et al. JCI Insight 2016 1(21): e90341Fleming, et al., Lancet 2011 377: 1011-18Means ± SEM shown;

Baseline99 beats/min

‣ Elevated resting heart rate is initial manifestation of cardiac disease in DMD

– Cardiac failure is a leading cause of mortality in DMD

– Elevated heart rate triples the risk of cardiomyopathy several years later

‣ Edasalonexent analog had positive effects on fibrosis in mdx and GRMD models

– Edasalonexent tissue levels in heart > skeletal muscle

‣ In MoveDMD trial, mean resting heart rate significantly decreased, approaching age-normative heart rate ~92 beats per minute

100

75

50

25

0

18

‣ 50+ patient years of exposure

‣ Well tolerated, with majority of adverse events mild in nature

– Most common related adverse event was diarrhea, which did not require discontinuation

– No adverse trends in chemistry, hematology, or measures of adrenal function (cortisol and ACTH)

‣ Boys on edasalonexent grew 2.1 inches/ year, similar to unaffected boys

In Phase 2 MoveDMD Trial and Open-Label Extension:

Safety: Growth Continues as Expected

Percentiles Compared to CDC Growth Charts

BMI 100

75

50

25

0

Weight 100

75

50

25

0

Height

Pe

rce

nti

le

Weeks on Edasalonexent

Means ± SEM shown

0 12 24 36 48 60 72 0 12 24 36 48 60 720 12 24 36 48 60 72

‣ Preclinical data support potential for NF-κB inhibition to support bone health in DMD

‣ In Phase 2 MoveDMD trial and open-label extension, edasalonexent, an oral NF-κB inhibitor, showed:

– MRI measures supportive of positive edasalonexent treatment effects

– Muscle MRI T2 rate of change improved with edasalonexent treatment versus off-treatment control period progression

– Well-tolerated with growth along expected growth curves

– Clinically meaningful slowing of disease progression on edasalonexent compared to off-treatment control period

– North Star Ambulatory Assessment and all timed function tests stabilized

‣ Preclinical and clinical data support design of Phase 3 registration trial

19

Targeting NF-κB with Edasalonexent Has Potential for Benefit of Skeletal and Cardiac Muscle as well as Supporting Growth and Bone Health in DMD

20

– Enrolling approximately 125 4-to-<8 year-old boys not on steroids for 6 months

– Primary endpoint: NSAA

– Secondary endpoints: age-appropriate timed functional tests

‣ Bone-related measures:

– Standardized lumbosacral spine films to assess for fractures

– DXA: bone density and body composition

‣ Top-line results anticipated in second half of 2020

Phase 3 Polaris Clinical Trial Currently Ongoing

12-month, randomized, double-blind placebo-controlled trial

Open-label extension

Edasalonexent

Primary Endpoint

Placebo

Edasalonexent 100 mg/kg

21

Acknowledgements

‣ Patients and families

‣ Patient groups

‣ Nemours Children’s Hospital

– Richard Finkel, MD

‣ ImagingDMD & University of Florida

– Krista Vandenborne, PT PhD

– H. Lee Sweeney, PhD

– Rebecca J. Willcocks, PhD

– Glenn Walter, PhD

– Sean C. Forbes, PhD

– William T. Triplett, BSc

‣ Oregon Health Sciences University

– Erika L. Finanger, MD

– William Rooney, PhD

‣ The Children’s Hospital of Philadelphia

– Gihan I. Tennekoon, MD

– Sabrina W. Yum, MD

‣ University of California

– Perry Shieh, MD PhD

‣ Catabasis Pharmaceuticals

– Maria Mancini, MHP

– Angelika Fretzen, PhD

– Pradeep Bista, PhD

– Andrew Nichols, PhD

– James MacDougall, PhD