movedmd phase 1 2 trial of edasalonexent an nf b

MoveDMD: Phase 1/2 Trial of Edasalonexent, an NF- B Inhibitor, in 4 - PowerPoint PPT Presentation

MoveDMD: Phase 1/2 Trial of Edasalonexent, an NF- B Inhibitor, in 4 to 7-Year Old Patients with Duchenne Muscular Dystrophy Richard Finkel, MD 1, ; Krista Vandenborne, PT, PhD. 2 , H Lee Sweeney, PhD. 2 , Erika Finanger, MD 3 , Gihan Tennekoon,

  1. MoveDMD: Phase 1/2 Trial of Edasalonexent, an NF- κ B Inhibitor, in 4 to 7-Year Old Patients with Duchenne Muscular Dystrophy Richard Finkel, MD 1, ; Krista Vandenborne, PT, PhD. 2 , H Lee Sweeney, PhD. 2 , Erika Finanger, MD 3 , Gihan Tennekoon, MBBS, MRCS, LCRP 4 , Perry Shieh, MD, PhD 5 , Sabrina Yum, MD 4 , Maria Mancini, MHP 6 , Pradeep Bista, PhD 6 , Andrew Nichols, PhD 6 , Joanne Donovan, MD, PhD 6 1 Nemours Children’s Health System, Orlando, FL; 2 University of Florida Health, Gainesville, FL; 3 Oregon Health Sciences University, Portland, OR; 4 The Children's Hospital of Philadelphia, Philadelphia, PA; 5 University of California, Los Angeles, Los Angeles, CA; 6 Catabasis Pharmaceuticals, Cambridge, MA March 22, 2017

  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 Annual Report on Form 10-K for the year ended December 31, 2016, 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. Conflict of interest: Joanne Donovan, Maria Mancini, Pradeep Bista and Andrew Nichols are employees of Catabasis 2

  3. Background and Objective ‣ NF- κ B is activated from infancy in DMD, driving inflammation, muscle degeneration and inhibiting muscle regeneration. Edasalonexent, an oral small molecule that inhibits NF- κ B, has shown positive preclinical effects on skeletal muscle, including the diaphragm, and heart in DMD models. ‣ Objective of the study: – To assess safety and efficacy of edasalonexent (CAT-1004) in boys with Duchenne muscular dystrophy (DMD) not yet on steroids 3

  4. Positive Effects of NF- κ B Inhibitors, CAT-1041 and Edasalonexent (CAT-1004), Observed in mdx Mice CAT-1041 has positive effects on: Muscle mass Fibrosis Muscle specific tension Hammers et al, JCI Insights (2016) * p <0.05 Edasalonexent increases dystrophin expression in combination with exon skipping wild type/saline mdx /saline mdx/ edasa mdx/ M23D mdx/ M23D/edasa Merge Laminin Dystrophin M23D: exon skipping specific for mdx ; Nelsa Estrella, Sarepta (Unpublished observations) * p <0.05 4

  5. MoveDMD Trial Design Study Population: All DMD mutations, ages 4 – 7, steroid naïve or off steroids for ≥ 6 months Part A Part B Part C 7-day, open-label 12-week, randomized, double-blind 36-week, open-label dose-ranging trial placebo-controlled trial treatment period N ~ 6 per arm N ~ 10 per arm N ~ 10 per arm 100 Edasalonexent 67 mg/kg/day Edasalonexent 67 mg/kg/day mg/kg/day 67 Edasalonexent 100 mg/kg/day Edasalonexent 100 mg/kg/day mg/kg/day 33 Placebo Edasalonexent 100 mg/kg/day or 67 mg/kg/day mg/kg/day ‣ Assess the safety ‣ Assess the safety and ‣ Measure the same safety and efficacy parameters as and PK of efficacy of edasalonexent in Part B of the trial to assess treatment effects over edasalonexent in versus placebo using MRI as a longer time ~18 boys with an early biomarker; trial was Duchenne powered only for the primary end point of change ‣ Showed positive PK, from baseline in MRI T2 of NF- κ B biomarker composite of lower leg effects, safety and muscles tolerability ‣ Other measures: timed function tests (10-meter walk/run, 4-stair climb, time to stand), NSAA, muscle strength, PODCI and MRI fat fraction 5

  6. MoveDMD Part A Results: Safety and Tolerability ‣ Generally well tolerated – No serious adverse events, no discontinuations – All patients able to take edasalonexent capsules – Adverse events (AE) predominantly mild, most common Edasalonexent Tic-Tac AE was diarrhea 100mg ‣ Assessments: – Laboratory: no trends or safety issues in liver, renal, Edasalonexent M&M 250mg hematology – Physical exam, EKG, vitals: no safety issues ‣ Adverse events over 7 days: 33 mg/kg 67 mg/kg 100 mg/kg Total n=5 n=6 n=6 n=17 Diarrhea 0 0 4 4 Soft feces 1 1 1 3 Abdominal pain upper 1 0 1 2 6

  7. Part B Key Study Metrics and Efficacy End Points Key Study Metrics ‣ Enrolled total of 31 boys at 5 sites for Part B of the trial, 16 of whom also participated in Part A. In Part B, patients were randomized to: Edasalonexent 67 mg/kg/day given as twice per day dosing − Edasalonexent 100 mg/kg/day given as three times per day dosing − Placebo − ‣ All 31 patients who enrolled completed the trial Primary Efficacy End ‣ Average change from baseline to week 12 in MRI T2 relaxation time Point (milliseconds) for the composite of lower leg muscles: Soleus (Sol) − Medial gastrocnemius (MG) − Tibialis posterior (TP) − Tibialis anterior (TA) − Peroneals (Per) − Additional Efficacy End ‣ Speeds and times for timed function tests (TFTs): Points Completing the 10-meter walk/run (10MWR) − Climbing 4 stairs (4SC) − Standing from supine (time to stand: TTS) − ‣ North Star Ambulatory Assessment (NSAA) ‣ Other MRI/MRS measures in lower and upper leg muscles ‣ Muscle strength testing Knee extension − Plantar flexion − ‣ Pediatric outcomes data collection instrument (PODCI) 7 MRS: Magnetic Resonance Spectroscopy

  8. MoveDMD Trial Part B Patient Disposition Discontinuations Screened Screen Failed n=0 n=33 n=2 Randomized n=31 PBO Edasa PBO Edasa Treatment 67 mg/kg 67 mg/kg 100 mg/kg 100 mg/kg Groups n=5 n=10 n=6 n=10 n = 2 n = 6 n = 2 n = 6 From Part A ‣ All 31 patients completed the study and were included in the per protocol population. 8

  9. MoveDMD Trial Part B Baseline Demographics and Values Edasalonexent Edasalonexent Overall Treatment Group Placebo 67 mg/kg/day 100 mg/kg/day Edasalonexent (n =11) (n =10) (n =10) (n =20) Age at Week 0 (years) 1 6.3 6.0 6.0 6.0 Age at Symptom Onset (years) 2 3.7 3.0 2.0 2.5 Age at Diagnosis (years) 2 4.6 3.5 3.0 3.3 Weight at randomization (kg) 21.4 22.1 22.0 22.1 10-meter walk/run (10MWR in seconds) 1 6.9 6.3 6.8 6.6 4-stair climb (4SC in seconds) 2 5.0 4.5 6.3 5.4 Time to stand (TTS in seconds) 2 6.5 7.0 12.0 9.4 Values shown are means Patients were all male and steroid-naive and predominantly Caucasian 1 Patient randomization was stratified for baseline age and 10-meter walk/run 2 On average, patients in the edasalonexent 100 mg/kg/day group were symptomatic at a younger age and did not perform as well on the 4-stair climb and the time to stand function tests at baseline; characteristics consistent with more advanced disease 9

  10. MoveDMD Trial Part B Results Primary Efficacy End Point Change in MRI T2 from Baseline to Week 12 in Composite of 5 Lower Leg Muscles Smaller increase in MRI T2 1 . 0 correlates with less muscle inflammation Change in MRI T2 0 . 8 P = NS (milliseconds) 0 . 6 0 . 4 0 . 2 0 . 0 P l a c e b o 6 7 m g / k g 1 0 0 m g / k g P o o l e d E d a s a l o n e x e n t No significant change in the primary end point, average change from baseline to ‣ Week 12 in the MRI T2 measure for a composite of lower leg muscles for the pooled edasalonexent treatment groups vs. placebo. Error bars in chart denote SEM 10

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