Novantrone A_Backup_StudyDesignVersion /10/2016 A-1 Backup Visuals Presented

Novantrone A_Backup_StudyDesignVersion /10/2016 A-2 Study Number of Gd+ Lesions at Baseline No. of Patients Placebo Mito 12 Lesions at Baseline to 10 >

Novantrone A_Backup_StudyDesignVersion /10/2016 A-3 Study Summary of Relapse Data p value p value Mito 12 Mito 12 PlaceboMito 5Mito 12 vs Placebo PlaceboMito 5Mito 12 vs Placebo No. relapses No. treated relapses No. severe relapses No. relapses seen by treating physician No. relapses (adj.) No. treated relapses (adj.)

Novantrone A_Backup_StudyDesignVersion /10/2016 A-4 Study Definition of Severe Relapse New symptoms lasting  48 hours with functional status score  2 points New symptoms lasting  48 hours with functional status score  2 points Or deterioration of existing symptoms  1 point in at least one of the four following systems: pyramidal, brain stem, cerebellar, or visual. Or deterioration of existing symptoms  1 point in at least one of the four following systems: pyramidal, brain stem, cerebellar, or visual. Relapses reported by other physicians and rated as “severe” also considered severe. Relapses reported by other physicians and rated as “severe” also considered severe.

Novantrone A_Backup_StudyDesignVersion /10/2016 A-5 Study Effect of Prior Relapses on Primary Efficacy Endpoints Relapse Prior YearNo Relapse PlaceboMito 5Mito 12 PlaceboMito 5Mito 12 (n=46)(n=49)(n=45) (n=18)(n=15)(n=15) (n=46)(n=49)(n=45) (n=18)(n=15)(n=15) Mean  from baseline EDSS AI AI SNS SNS No. treated relapses (adjusted) Median time to 1st treated relapse (mo.) NR*15.0NRNR * p<0.05 Placebo vs Mito 12 * *

Novantrone A_Backup_StudyDesignVersion /10/2016 A-6 Study Concomitant MS Medications Used by  5 Patients at Baseline Treatment Group Class of DrugPlaceboMito 5Mito 12 Myorelaxants20107 Vitamins1075 Urologic Antispasmodics462 Minerals322

Novantrone A_Backup_StudyDesignVersion /10/2016 A-7 Study Gd-Enhancing Scans at Month 6 by 1.0 Point EDSS Deterioration mP Mito + mP ScanScan EDSS deteriorationNegPosNegPos No Yes0610

Novantrone A_Backup_StudyDesignVersion /10/2016 A-8 Study Correlation Between Gd+ Lesion and EDSS Score Mean correlation = 0.21 (p  0.05) Mean correlation = 0.21 (p  0.05) Mean of all patients in both groups Mean of all patients in both groups –For each patient, correlation over time of total no. of Gd+ lesions with EDSS score

Novantrone A_Backup_StudyDesignVersion /10/2016 A-9 Study Corticosteroid Use for Relapses TreatmentPatientsCourses mP1121 Mito + mP 67 Mito + mP 67

Novantrone A_Backup_StudyDesignVersion /10/2016 A-10 Study Disability Change Month 24 to EDSSAISNS Change Category Mean Change Mito 12 (n=36) Mito 5 (n=47) Placebo (n=40)

Novantrone A_Backup_StudyDesignVersion /10/2016 A-11 Study New Lesions on T2 Weighted Scans by Lesion Size mPMito + mP Lesion size(n=20)(n=20)p-value SmallMean ± SD1.7 ± ± 1.1NS Median (range)1 (0-11)0 (0-4) ModerateMean ± SD 2.3 ± ± Median (range)1 (0-17)0 (0-3) LargeMean ± SD1.6 ± ± Median (range)0.5 (0-14)0 (0-1) AllMean ± SD 5.5 ± ± Median (range)3 (0-38)1 (0-5)

Novantrone A_Backup_StudyDesignVersion /10/2016 A-12 Study Infections Number of Number (%) infections of patients infections of patients Infection (n=343 infections)(n=454) Urinary tract (33%) Upper respiratory tract77 (2%) Polysinusitis11 (<1%) Unknown4026 (6%)

Novantrone A_Backup_StudyDesignVersion /10/2016 A-13 Study Infection and Hemorrhage PlaceboMito 5Mito 12 Event(n=64)(n=65)(n=62) n % n % n % Infections Severe infections Hospitalization1 a 23 b 54 c 7 Hemorrhage Hospitalization00001 d 2 a = tonsillitis b = enteritis, UTI, viral infection c = tonsillitis, UTI (2), endometritis d = hemorrhagic cystitis

Novantrone A_Backup_StudyDesignVersion /10/2016 A-14 Study Chemistry Toxicity WHO Grade 3-4 % Patients PlaceboMito 5Mito 12 (n=64)(n=65)(n=62) (n=64)(n=65)(n=62) SGOT T. Bilirubin1.600 Alk Phosph Creatinine000

Novantrone A_Backup_StudyDesignVersion /10/2016 A-15 Study 901: Month 36 Menstruation Data % Patients PlaceboMito 5Mito 12 Parameter(n=24)(n=32)(n=21) Regular menses Irregular menses No menses8929 No data available17165 Other51818

Novantrone A_Backup_StudyDesignVersion /10/2016 A-16 Study Hospitalizations for Reasons Other Than Study Drug Administration PlaceboMito 5Mito 12 (n=64)(n=64)(n=60) No. of patients hospitalized All hospitalizations No. of hospitalizations Mean days per hospitalization MS-related hospitalizations No. of hospitalizations Mean days per hospitalization