1. Targeting Inflammation in Duchenne Muscular Dystrophy: Non-mutation specific approaches in developing therapies for DMD
Joanne M. Donovan, M.D., Ph.D.
Chief Medical Officer
Catabasis Pharmaceuticals

2. Forward Looking Statements
This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including statements regarding our expectations and beliefs about our business, future financial and operating performance, clinical trial plans, product development plans and prospects. 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 identifying words.
The forward-looking statements contained in this presentation and in remarks made during this presentation and the following Q&A session are subject to important risks and uncertainties that may cause actual events or results to differ materially from our current expectations and beliefs, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of our product candidates; availability and timing of results from 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; availability of funding sufficient for our foreseeable and unforeseeable operating expenses and capital expenditure requirements; other matters that could affect the availability or commercial potential of our product candidates; and general economic and market conditions. These and other risks are described under the caption “Risk Factors” in our Quarterly Report Form 10-Q for the three months ended June 30, 2015, which is on file with the Securities and Exchange Commission, and in other filings that we may make with the Securities and Exchange Commission in the future.
In addition, the forward-looking statements included 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 specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this presentation.

3. Preventing Disease Progression in Duchenne
Muscle replacement by fat and fibrosis
Muscle intact
Progressive functional impairment
Kinali, 2011

4. Absence of Dystrophin plus Mechanical Stress Results in DMD Disease Progression
Drugs primarily targeting inflammation:
Steroids: prednisone, deflazacort
CAT-1004
Verolone (VB-15)
IMO-8400
NEMO peptides
Inflammation
Toll-like receptors NF-kB
satellite stem cell
myoblasts
Drives Muscle Degeneration
Promotes Inflammation
and Fibrosis
Inhibits Muscle Regeneration

5. In Duchenne, Inflammation (NF-kB) Is Present at an Early Age and During Symptomatic Disease
NF-κB Activation in Muscle in Infancy in DMD:
What are the earliest changes that are seen in Duchenne?
Eric Hoffman’s group looked at gene expression changes before birth, in infancy and in boys aged 5 to 12
Dystrophin is absent at all ages
Changes in gene expression related to inflammation – TLR7, NF-kB were present in muscle soon after birth and in symptomatic boys aged 5 to 12
NF-κB nuclear staining
Control
Muscle biopsies from infants with DMD show activated nuclear NF-κB (red)
Chen et al, 2005

6. Activated NF-kB Inhibits Muscle Regeneration
Dystrophin production (red) in engrafted stem cells:
Repair of muscle damage occurs in response to injury in normal muscle and dystrophic muscle
Stem cell proliferation and differentiation into mature muscle cells is key to muscle repair
However, the local environment around stem cells has a major impact on their ability to regenerate, and inflammatory mediators inhibit muscle regeneration.
Intact NF-κB levels
Reduced NF-κB levels
8-week-old mdx/SCID mice in which p65+/– and wild-type (wt) MDSCs were implanted. Engraftment was determined by immunostaining for dystrophin (red)
Lu et al., 2012

7. Cross section of mid-thigh muscle in boys age 12 - 14
Lack of Dystrophin is Necessary but Not Sufficient for DMD Disease Progression
MRI shows replacement of muscle with fat and fibrosis
Muscles with less evidence of muscle edema and inflammation in younger boys show less disease at older ages
Muscles exposed to less mechanical stress are relatively protected from degradation
Control
DMD
Cross section of mid-thigh muscle in boys age
Gracilis muscle
Sources:
Akima et al Neuromuscul Disord (1):16-25
Hu et al., 2015

8. CAT-1004 Modulates the NF-ĸB Pathway and Has Potential to be Disease-Modifying in DMD
ABSENCE OF
DYSTROPHIN
MECHANICAL
STRESS
CAT-1004
Activated
NF-B
CAT Series
satellite stem cell
myoblasts
Drives Muscle Degeneration
Promotes Inflammation
and Fibrosis
Inhibits Muscle Regeneration

9. CAT-1004 Analog Demonstrated Significant Improvements in Muscle Function, Running Wheel Activity and Diaphragm Function
Activity on Extensor Digitorum Longus Muscle Function After 5 Contractions
CAT-1041 Activity on Muscle Endurance in the mdx Mouse Model
CAT-1041 Activity on Diaphragm Function in the mdx Mouse Model * **
% Specific Force (N/cm2) 80 60 40 20
Control
CAT- 1004
CAT- 1041
Cumulative Revolutions
800000
600000
400000
200000
Control
CAT-1041
Specific Force (N/cm2) 10 8 6 4 2
Control
CAT-1041 * *
**p=0.001
*p=0.02
*p=0.01
*p=0.02
25-week mdx mouse study
Study conducted by Prof. Lee Sweeney

10. CAT-1004 Analog Demonstrated Significant Improvements in Muscle Fibrosis and Muscle Mass
CAT-1041 Activity on Fibrosis in Quadriceps in the mdx Mouse Model
CAT-1041 Activity on Muscle Mass in the mdx Mouse Model
Muscle Mass (mg)
300
250
200
150
100 50
Gastrocnemius
Quadriceps
Heart *
CAT-1041
Control
Untreated *
Treated
*p<0.05
6-month mdx mouse study
Study conducted by Prof. Lee Sweeney

11. CAT-1004 MoveDMD Trial Design
Part A
7-day, open-label dose ranging trial
Part B
12-week, randomized, double-blind placebo-controlled trial
N = 6 per arm
N = 6-8 per arm
33 mg/kg per day
CAT-1004 Dose 1
67 mg/kg per day
CAT-1004 Dose 2
100 mg/kg per day
Placebo*
Safety, tolerability and exposure data
Efficacy data
Study Population: All mutations, ages 4 – 7, steroid naïve or off steroids for ≥6 months
* placebo followed by cross-over to 12 weeks CAT-1004
Objectives
Assess safety, tolerability and pharmacokinetics
Key Endpoints
Primary efficacy: changes in MRI of muscles
Secondary efficacy: 10 meter walk/run, 4-stair climb, time to stand
Additional efficacy assessment: muscle strength

12. Current Status in the Clinic
Phase 1
Phase 2
Phase 3
Approved
Prednisone/ prednisolone
Deflazacort
CAT-1004
Verolone (VB-15)
IMO-8400
NEMO peptides

13. Targeting NF-kB in Duchenne: The Future
Multiple pathophysiologic process including activated NF-kB are key to the process of muscle damage in Duchenne, and will be a key component of future treatments.
Treatment with glucocorticoids demonstrates that targeting inflammation has benefits in preserving ambulation and positive effects on pulmonary and cardiac function; however, these effects come with significant side effects.
Combination therapy of dystrophin / utrophin targeted therapies and NF-kB targeted therapies offer potential benefits because of differing mechanisms of action
Therapies currently in development offer the potential to inhibit the inflammation seen at all stages of Duchenne without the negative effects of steroids.

14. Thank you!