PHASE 2 STUDY IN SYSTEMIC SCLEROSIS NASDAQ:CRBP | CORBUSPHARMA.COM - PowerPoint PPT Presentation

JBT101-SSC-001 PHASE 2 STUDY IN SYSTEMIC SCLEROSIS NASDAQ:CRBP | CORBUSPHARMA.COM

TRIAL DESIGN 2

JBT101-SSc-001 PHASE 2 TRIAL DESIGN • Double-blind, randomized, placebo-controlled, Phase 2 study (Part A) • 9 clinical sites in the U.S. • Adults ages 18 to 70 with diffuse cutaneous systemic sclerosis (SSc) • Inclusive eligibility criteria • Disease duration ≤ 3 years with any modified Rodnan skin score (mRSS), or • Disease duration > 3 and ≤ 6 years if mRSS ≥ 16, mRSS increased ≥ 5 points in the last 6 months, or elevated IL-6 or CRP • Immunosuppressive medications allowed • ClinicalTrials.gov identifier NCT02465437 3

DURATION AND DOSING • 2:1 overall ratio of JBT-101:placebo • 16 week study, 12 weeks of active dosing • Weeks 1-4: Dose response for biomarkers, plasma concentrations, and safety. JBT-101 5 mg once a day, JBT-101 20 mg once a day, JBT-101 20 mg twice daily or placebo in 2:2:2:3 randomization. Overall 2:1 randomization of JBT-101:placebo • Weeks 5-12: Single high dose JBT-101 to test efficacy and safety, JBT-101 20 mg twice daily or placebo, 2:1 randomization of JBT-101:placebo • Weeks 13-16: Follow-up off drug • Safety Assessments: Day 1, Weeks 2, 4, 8, 12, and 16 • Efficacy Assessments: Weeks 4, 8, 12, and 16 4

OBJECTIVES Primary Objectives • Evaluate safety and tolerability • Evaluate efficacy, using the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score Secondary Objectives • Evaluate efficacy using categories of CRISS response and each CRISS domain • Evaluate efficacy with other patient-reported outcomes 5

CRISS SCORE Description Advantages Single number between 0-1 or 0-100% that indicates overall Measures overall improvement, not just improvement from baseline. Has floor and ceiling for responses improvement in skin or lungs Developed to reflect physician assessment of overall Endorsed by the American College of improvement Rheumatology (Khanna et al, Arthritis Rheumatol. 2016; 68:299) Score includes change from baseline in five domains Rewards for improvement in more than one • Two physician assessments – skin thickness (mRSS) and domain and penalizes for worsening in any physician global assessment (MDGA) domain. Subject must improve more than • Two patient assessments – Health Assessment Questionnaire worsen to achieve CRISS score > 0. Disability-Index (HAQ-DI) and patient global assessment (PtGA) • Forced vital capacity (FVC) The domains of mRSS, FVC, % predicted, MDGA, and HAQ-DI all are associated with survival (Tyndall et al, Ann Rheum Dis 2010;69:1809; Harel et al, J Rheumatol 2016; 43:1510; Sultan et al, Rheumatology 2004;43:472) 6

SAMPLE SIZE Efficacy • Not formally powered for efficacy • Small, first-in-SSc Phase 2 study of JBT-101. Efficacy would be unexpected in such a trial • No JBT-101 experience upon which to calculate sample size • Improvement, not worsening, is expected effect of JBT-101 on SSc, therefore one-sided statistical analyses are justified in this small, first-in-SSc trial Safety • At least 95% probability of detecting adverse events that occur at a true rate of 12% or higher over 12 weeks dosing 7

SUBJECT DISPOSITION AND BASELINE CHARACTERISTICS 8

SUBJECT DISPOSITION Intent to Treat 43 Randomized N = 43 1 withdrawn by physician decision Safety Population 15 Dosed with 27 Dosed with JBT-101 Placebo N = 42 1 withdrawn by physician decision Efficacy 15 Completed ≥ 26 Completed ≥ 1 Population 1 Efficacy Efficacy evaluation evaluation N = 41 1 withdrew consent 1 withdrew consent 1 withdrew for AE of Completer moderate dizziness 14 Completed Population 24 Completed study study N = 38 1/27 (3.7%) subjects dosed with JBT-101 withdrew for an adverse event 9

BASELINE CHARACERISTICS OF SUBJECTS Safety Population Efficacy Population Meta-analysis of six previous clinical Characteristic trials 2 JBT-101 Placebo JBT-101 Placebo P-value P-value N = 629 n = 27 n = 15 n = 26 n = 15 Female, % 85.2% 60.0% NS 3 84.6% 60.0% NS 82% 48.8 ± 10.6 46.7 (11.2) Age, mean (SD) 48.7 (10.4) 46.5 (11.1) NS NS 46.5 (11.8) Caucasian, % 81.5% 80.0% NS 80.8% 80.0% NS Not Hispanic of Latino, % 81.5% 93.3% NS 80.8% 93.3% NS Disease duration 1 , months, mean (SD) 37.1 (19.0) 40.6 (19.5) NS 38.7 (19.2) 40.6 (19.5) NS 19.4 (15.9) Usually prohibited Concomitant immunosuppressive or 92.9% 80.0% NS 100.0% 80.0% P = 0.043 except low dose immuno-modulating drugs, n (%) corticosteroids 1 Since first non- Raynaud’s symptom. 2 Alpha interferon, d-penicillamine, relaxin Ph 2 and 3, methotrexate, minocycline, anti-TGFbeta, Merkel et al, Arthritis Rheum 2012;64:3420. 2 NS = Not statistically significant, P > 0.05, two-tailed t test for continuous data or two- tailed Fisher’s exact test for categorical data • Subjects have a broader range of disease duration and greater use of concomitant immunosuppressive/ modulating drugs than subjects enrolled in previous trials in SSc • Slightly higher use of immunosuppressive/ modulating drugs in JBT-101 group may indicate a more refractory population 10

BASELINE CRISS DOMAINS Mean (SD) 1 (median, range) Domain Meta-analysis of six JBT-101 Placebo previous clinical trials 2 P-value N = 26 N = 15 N = 629 23.9 (10.4) 26.2 (11.2) 25.1 (8.2) NS 3 Modified Rodnan Skin Score (0 – 51) (ND 4 , 2 - 51) (23.5, 9 - 46) (24, 8 - 47) 4.5 (1.8) 5.2 (2.1) Physician Global Assessment (0-10) NS (4, 2 - 10) (6, 2 - 9) 4.8 (2.3) 4.9 (2.8) Patient Global Assessment (0-10) NS (5, 0 - 8) (6, 0 - 9) 1.1 (0.8) 1.5 (0.8) 1.1 (0.7) Health Assessment Questionnaire (0-3) NS (1.2, 0 - 2.5) (1.8, 0.1 - 2.6) (ND, 0 - 3.0) 85.9 (13.7) 79.6 (10.3) 84.6 (16.6) Forced Vital Capacity, % Predicted NS (87.4, 47.2 - 109.2) (79.0, 58.9 - 97.3) (ND, 36 - 144) 1 Efficacy population. 2 Alpha interferon, d-penicillamine, relaxin Ph 2 and 3, methotrexate, minocycline, anti-TGFbeta, Merkel et al, Arthritis Rheum 2012;64:3420. 3 NS = Not statistically significant, P > 0.05, two-tailed t test. 4 ND = Not done. • Baseline disease assessments are similar to those seen in other early SSc trials • No clinically or statistically meaningful difference between groups 11

CRISS RESULTS 12

DISTRIBUTION OF CRISS SCORES BY WEEK Circle = subject P 1 = 0.044 Statistical Analysis Median = black bar Interquartile Range = red bars • Statistical hypothesis is JBT-101 will JBT-101 (n = 26) Placebo (n = 15) provide clinical benefit compared 100% 100% to placebo 90% 90% • CRISS scores are not normally 80% 80% distributed (Khanna et al, Arthritis Rheumatol 2016; 68:299) 70% 70% • Use of non-parametric descriptive CRISS score, % CRISS score, % 60% 60% statistics and statistical analyses is 50% 50% indicated 40% 40% (Schlenker. Methods Mol Bio 2016;1366:271) • The mechanism of action of 30% 30% JBT-101 - activation of resolution of 20% 20% innate immune responses – may 10% 10% allow persistence of clinical benefit 0% for a time after treatment is 0% 4 8 12 16 4 8 12 16 stopped, hence, planned analysis Week Week across 16 weeks 1 Efficacy population, LOCF. 1- sided, mixed model repeated measures using rank transformed data, model includes baseline mRSS and disease duration. No effect of immunosuppressive therapy in model. 13

CRISS SCORES BY WEEK JBT-101 Previous Comparator Trial, post-hoc analysis CRISS Score 1 , % CRISS Score, % Median (Interquartile Range or IQR) 2 Median (IQR) Group Drug Week 4 Week 8 Week 12 Week 16 Week 52 Cyclophosphamide 3 JBT-101, N = 26 3.0 (0.6, 11.4) 19.0 (0.3, 69.2) 27.5 (1.9, 67.8) 33.0 (0.8, 82.1) 24.0 (0.1, 96.0) N = 45 Placebo Placebo, N = 15 1.0 (0.3, 8.8) 1.0 (0.1, 15.2) 1.0 (0.1, 60.1) 1.0 (0.1, 16.0) 0.5 (0.0, 32.0) N = 39 3 Khanna et al, personal communication. 1 Efficacy population, LOCF. 2 (25 th percentile, 75 th percentile ). The majority of JBT- 101 subjects achieve a CRISS score ≥ 20% is medically significant 14

RESULTS IN CRISS DOMAINS 15

CHANGE IN MODIFIED RODNAN SKIN SCORE • Lower score = less skin involvement. Improvement is a reduction in score. • Estimates of the minimal important improvement in mRSS are between 3.2 – 5.2 points (Khanna et al, Ann Rheum Dis 2006;65:1325). mRSS Change from Baseline Previous Comparator Trials mRSS, mean (SD) 1 change from Drug N Time Change in mRSS, LS means ±SE baseline 0 P 2 = 0.085 Active Placebo -1 Six drug trials, all 492 ~26 weeks -2.9 (7.2) -2 subjects combined 3 -3 Tocilizumab 4 77 24 weeks -3.9 -1.2 -4 Cyclophosphamide 5 84 52 weeks -5.3 -1.7 -5 24.0 (9.8) 7 Baseline Mycophenolate 6 93 -6 12 weeks 22.4 (8.9) 0 4 8 12 16 3 α interferon, d-penicillamine, relaxin Ph 2 and 3, minocycline, Week methotrexate, anti-TGF β , Merkel et al, Arthritis Rheum 2012;64:3420. JBT-101 Placebo 4 Khanna et al, Lancet 2016;387:2630. 5 Khanna et al, personal communication. 6 Le et al, Ann Rheum Dis 2011; 70: 1104. 7 Absolute 1 Efficacy population. 2 Least squares mean difference, analysis of mRSS, mean (SD), not change from baseline. covariance model, one -sided p value. • JBT-101 subjects had greater improvement in mRSS than placebo subjects • The mean degree of improvement in mRSS in JBT-101 subjects was ~ minimal important improvement • The mRSS results with JBT-101 compare favorably with data from comparator trials 16