Medicinova, Inc. · NASDAQ:MNOV
Medicinova — International Symposium on ALS/MND 2018
35 slides from Medicinova's conference presentation, December 2018
Slide 1: Novel Composite Endpoint Extended Analysis During Extension of Ibudilast Phase 1b/2a Clinical Trial
NCT02238626 C22 Novel Composite Endpoint Extended Analysis During Extension of Ibudilast Phase 1b / 2a Clinical Trial Better Predicts Post-Wash-Out Survival Benjamin Rix Brooks 1, 6 MD, Elena K Bravver 1,6 MD, Mohammed Sanjak 1, 2, 6 PhD, PT, Velma L Langford 1 RT, Donna C Graves1, 6 MD, Linda A Moo
Slide 2: Disclosures
C22 NCT02238626 Disclosures Benjamin Rix Brooks MD received grant support from MediciNova, Cytokinetics, Acceleron, ITF Pharma, Avanir, Biogen, RTI Research, Santhera, Orion, Center for Disease Control. Elena K Bravver MD received grant support from MediciNova, Cytokinetics, Acceleron, RTI Research,
Slide 3: Outline
NCT02238626 C22 Ibudilast - Glial Pathology MS, ALS, Glioblastoma Treatment Development Ibudilast Pharmacology - Target Engagement Adaptive Protocol - Early Cohort (EC) - DB - OLE -12 months - Vital Status post Ibudilast Washout CONSORT Diagram - DB - OLE -12 months Adaptive Protocol - Loss of Muscl
Slide 4: Ibudilast - Glial Pathology MS, ALS, Glioblastoma Treatment Development
C22 NCT02238626 Ibudilast - Glial Pathology MS, ALS, Glioblastoma Treatment Development
Slide 5: NCT02238626 MS ALS
=a NCT02238626 “t NRABG Inhibit microgli Glial ‘ahibiPatial acaivatl , : nate ay u pial a SPRINTFMS minocycline isopropylpyrazolo-[1,5- ALS a]pyridine] (Ibudilast) [Bos ete vay tne Microglia N ClinicalTrials, gov A Y ~N- Pro-inflammatory, \ Sa pg a cytokines ws ‘2m Inhibit toll-like \ Pa sone trocyt
Slide 6: SPRINT-MS Phase II Trial of Ibudilast in Progressive MS: Top-Line Results
SPRINT-MSINN 102 Phase II Trial of lbudilast in Progressive MS: Top-Line Results snis = R.J. Fox, C.S. Coffey, M.E. Cudkowicz, T. Gleason, A. Goodman, E.C. Klawiter, K. Matsuda, M. McGovern, R. Conwit R. Naismith, ‘A. Ashokkumar, D. Eckund, E. Klinger, M. Koepp, S. Natarajan, B. Thornell, J. Yankey,
Slide 7: The challenges associated with molecular targeted therapies for glioblastoma
Slasgew C22 ‘J Neuroancol (2016) 127:427-434 ‘DOT 10.1007411060.016.2080-6 conti The challenges associated with molecular targeted therapies for glioblastoma ‘Toni Rose Jue’ » Kerrie L. McDonald" ‘Received: 30 September 2015 / Accepted: 15 Februsry 2016 / Published online: 22 Febrazry 2016 (© Spring
Slide 8: Ibudilast Pharmacology Target Engagement
C22 NCT02238626 Ibudilast Pharmacology Target Engagement
Slide 9: Background: Riluzole Pharmacology
NCT02238626 Background C22 Riluzole Pharmacology Riluzole currently slows the rate of loss of ALSFRS-R by 25-28% when administered at 50mg-twice-daily to achieve levels of 30-1552 ng/mL corresponding to 0.15-6.6 µM ( Groeneveld, 2003 ). Tissue levels are 10-fold higher ( Milane, 2009 ) providing in
Slide 10: Background: Enhance Riluzole Pharmacology
NCT02238626 Background C22 Enhance Riluzole Pharmacology Both riluzole and some PDE inhibitors reduce infarct size following transient cerebral artery occlusion ( O’Neill, 1997 ). Ibudilast, achieves this reduced infarct size at serum levels achievable in humans ( Lee, 2011 ). Decreased Cytokine Pro
Slide 11: Ibudilast Pharmacology - Target Engagement
NCT02238626 C22 Ibudilast Pharmacology - Target Engagement Ibudilast Biochemistry IC50 Chronic daily oral administration of Ibudilast at 30mg twice-daily in humans can achieve peak PDE4A - 0.05 µM [ 0.25 µM ] and trough [ 0.15 µM ] serum levels PDE4B - 0.06 µM ( Yoon, 2009 ). Brain and spinal cord l
Slide 12: Adaptive Protocol
C22 NCT02238626 Adaptive Protocol - Early Cohort (EC) - DB - OLE -12 months - Vital Status post Ibudilast Washout
Slide 13: Inclusion/Exclusion Criteria
NCT02238626 C22 Methods Inclusion/Exclusion Criteria Inclusion: • Age 18-80 years • Diagnosis of familial or sporadic ALS • ALS with onset of ≤ 5 yrs for EC • SVC ≥ 60% • Currently on stable dose of Riluzole Exclusion: • Use of Tracheostomy, invasive mechanical ventilation, Non- invasive ventilation
Slide 14: Methods
NCT02238626 C22 Methods MN-166-ALS-1201 Adaptive Design Protocol
Slide 15: Baseline Characteristics
NCT02238626 C22 Baseline Characteristics Placebo Ibudilast (N=17) (N=34) Age 57.5 59.2 Female 5 (29.4%) 11 (32.4%) Ethnicity •Caucasian 15 (88.2%) 31 (91.2%) •African American 2 (11.8%) 1 (2.9%) •Asian 0% 1 (2.9%) •Unknown 0% 1 (2.9%) Baseline ALSFRS-R 39.0 39.3 Baseline SVC 97.2 92.0 Baseline MIP/N
Slide 16: CONSORT Diagram
C22 NCT02238626 CONSORT Diagram DB - OLE -12 months
Slide 17: CONSORT Subject Trajectories
CONSORT NCT02238626 Subject Trajectories C22
Slide 18: Adaptive Protocol Loss of Muscle Strength off Ibudilast
C22 NCT02238626 Adaptive Protocol Loss of Muscle Strength off Ibudilast
Slide 19: Decreased Strength off Ibudilast
NCT02238626 C22 Decreased Strength off Ibudilast
Slide 20: ALSFRS-R Responders
NCT02238626 C22 ALSFRS-R Responders
Slide 21: ALSFRS-R Responders
NCT02238626 C22 ALSFRS-R Responders
Slide 22: Adaptive Protocol Novel Composite Endpoint
C22 NCT02238626 Adaptive Protocol Novel Composite Endpoint
Slide 23: Novel Composite Endpoint
NCT02238626 C22 Novel Composite Endpoint
Slide 24: Adaptive Protocol Relation of Novel Composite Endpoint to Survival
C22 NCT02238626 Adaptive Protocol Relation of Novel Composite Endpoint to Survival
Slide 25: Composite Endpoint and Survival
NCT02238626 C22 Composite Endpoint and Survival Subjects who achieved Composite Endpoint during the DB and OLE epochs of the adaptive NCT02238626 clinical trial showed improved survival.
Slide 26: Composite Endpoint and Survival
NCT02238626 C22 Composite Endpoint and Survival Subjects who achieved Composite Endpoint during the DB and OLE epochs of the adaptive NCT02238626 clinical trial showed improved survival.
Slide 27: Adaptive Protocol Relation of Per Protocol Completion to Survival
C22 NCT02238626 Adaptive Protocol Relation of Per Protocol Completion to Survival
Slide 28: Per-Protocol and Survival
NCT02238626 C22 Per-Protocol and Survival Subjects who completed the DB and OLE epochs of the adaptive NCT02238626 clinical trial per protocol showed improved survival.
Slide 29: Per-Protocol and Survival
NCT02238626 C22 Per-Protocol and Survival Subjects who completed the DB and OLE epochs of the adaptive NCT02238626 clinical trial per protocol showed improved survival.
Slide 30: Conclusions
NCT02238626 C22 Conclusions Novel composite endpoint defined as less than 12 units (< 1 unit per month) decrease in ALSFRS-R total score and/or not losing 1 MMT unit in neck and leg muscles in the DB and OLE epochs (12 months) was analyzed.
Slide 31: Conclusions
NCT02238626 C22 Conclusions 11 / 34 ALS subjects randomized [ (intention-to- treat (ITT) ] to ibudilast compared with 2 / 17 subjects randomized to placebo (P=0.1117) showed no progression. Subjects (ITT) who showed no progression on 6 or 12 months ibudilast showed improved survival (P=0.0010) in th
Slide 32: Conclusions
NCT02238626 C22 Conclusions Subjects who completed 6 or 12 months ibuidlast treatment [ per-protocol (PP) ] showed improved survival (P=0.0025) in the 30 months post ibudilast treatment.
Slide 33: Conclusions: Multiple Myeloma, Stem Cell Therapy, Gene Therapy
NCT02238626 C22 Conclusions Multiple Myeloma treatment epoch biomarker response survival Stem Cell Therapy treatment epoch biomarker response survival Gene Therapy treatment epoch biomarker response survival
Slide 34: Carolinas Neuromuscular / ALS-MDA Care Center
Carolinas Neuromuscular / ALS-MDA Care Center C22
Slide 35: Supported by
NCT02238626 Supported by C22 CMC - Neurology Carolinas Neuromuscular / ALS-MDA Center Logistical and Statistical Support CMC - Neurology Research Division Clinical Study Drug and Placebo CHS - Office of Clinical and Translational Research Clinical Trials Grant CHS - Dickson Advanced Analytics DA2 Cl