Provisional American College of Rheumatology (ACR) Combined Response - PowerPoint PPT Presentation

Provisional American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) Score Correlates with Changes (Δ) in Patient-reported Outcomes (PROs) Robert Spiera, Laura Hummers, Lorinda Chung, Tracy Frech, Robyn Domsic, Vivien Hsu, Daniel E. Furst, Jessica Gordon, Maureen Mayes, Robert Simms, Elizabeth Lee, Scott Constantine, Nancy Dgetluck, Quinn Dinh, Brad Bloom, and Barbara White

Disclosures • Grants/Research Support • Consulting - Roche-Genetech - Roche-Genetech - GSK - GSK - BMS - CSL Behring - Boehringer Ingelheim - Sanofi - Cytori - Janssen - Chemocentryx - Chemocentryx - Corbus - Formation Biologics - Formation Biologics - Sanofi - Inflarx

Background • ACR CRISS score is a composite outcome developed to assess the likelihood of improvement from baseline in clinical trials in subjects with dcSSc • Several trials have reported positive outcomes using ACR CRISS score as a primary, secondary, or post-hoc efficacy outcome • Primary efficacy outcomes should reflect clinical benefit, that is how the patient feels, functions, or survives 3

Objective Determine whether ACR CRISS score reflects patient-reported outcomes, including two that are part of the ACR CRISS score itself (HAQ-DI and PtGA), Systemic Sclerosis Skin Symptoms Patient-reported Outcome 1 (SSPRO) and PROMIS-29 domain scores over 12 months 4

Methods • Determine Spearman correlation coefficients between ACR CRISS score and change in PROs in a phase 2 study of lenabasum in dcSSc - Months 3 and 4 in double-blind placebo control Part A of study (n = 38 each) and months 6, 12, 18, and 24 in open-label extension of study (N = 36, 31, 30, and 29, respectively) • Baseline was time of the first dose in Part A or the first dose in the OLE • For description purposes, correlations coefficients (r) are categorized as: - no (0 to 0.19) - low (0.20 to 0.34) - moderate (0.35 to 0.59) - strong (0.60 to 0.79) 5

Results: ACR CRISS Score and Change in PtGA (Overall Health) DBPC OLE Lenabasum DBPC OLE Lenabasum Week of Treatment 12 16 28 52 76 108 0.00 -0.05 Correlation Between PtGA and ACR CRISS Score -0.10 -0.15 -0.20 -0.21 -0.25 -0.30 -0.32 -0.35 -0.35 * P < 0.05 -0.40 * -0.38 -0.40 -0.40 * -0.45 * * Low to moderate correlations 6

Results: ACR CRISS Score and Change in HAQ-DI (Function) DBPC OLE Lenabasum DBPC OLE Lenabasum Weeks of Treatment 12 16 28 52 76 108 0 Correlation Between HAQ-DI -0.1 and ACR CRISS Score -0.15 -0.2 -0.3 -0.4 -0.42 -0.45 -0.5 -0.46 * * P < 0.05 ** -0.50 ** ** P < 0.01 ** -0.6 *** P < 0.001 -0.64 -0.7 *** Moderate to strong correlations after week 16 7

Results: ACR CRISS Score and Change in PROMIS-29 Social Role and Physical Function Domains (Function) ** 0.56 0.6 DBPC OLE Lenabasum ** Correlation Between Social Role 8 Mean Change from Baseline 0.50 * 0.5 0.46 and ACR CRISS Score Social Role Improves * * 5.9 0.39 0.39 6 5.2 3.9 4.1 4.5 4.8 5 4.9 0.4 4.5 4.3 3.8 3.6 3.2 0.3 4 1.8 0.2 1.7 Moderate 1.6 Placebo 2 Lenabasum Double-blind 0.1 to strong 0 0 Lenabasum OLE 0 0 correlations 0 4 8 12 0 4 20 36 60 76 92 108 0.8 Week *** Correlation Between Physical 0.67 0.7 5 Physical Function *** * P < 0.05 4.7 4.3 ** 3.73.94.2 0.60 and ACR CRISS Score 3.83.9 3.9 0.57 ** P < 0.01 0.6 Improves Mean Change from Baseline 4 ** 3.2 *** P < 0.001 0.47 2.8 3 Function 0.5 3 2.32.5 2.2 0.4 2 0.28 1.4 0.3 Placebo 1 0.2 0 0 Lenabasum Double-blind 0 0.1 Lenabasum OLE -0.7 0 -1 12 28 52 72 108 0 4 8 12 0 4 20 36 60 76 92 108 Week Week of Treatment

Results: ACR CRISS Score and Change in SSPRO and PROMIS-29 Pain Interference Domains (Symptoms) OLE Lenabasum DBPC DBPC OLE Lenabasum Week of Treatment 12 28 52 72 108 0.00 Correlation Between SSPRO -0.05 and ACR CRISS Score -0.10 Improves -0.15 -0.20 -0.20 -0.20 -0.25 -0.30 Low to -0.35 -0.31 moderate -0.40 -0.36 -0.39 -0.45 * 0 correlations 0 0 * Mean Change from Baseline 0 -2.5 -2.1 * P < 0.05 Correlation Between Pain -2 -2.8 -2.8 and ACR CRISS Score -0.1 ** P < 0.01 -3.6 -3.6 -3.6 Improves -4 -4.3 Interference -0.2 -4 -4.9 -5.3 -5.3 -5.3 -5.4 -0.23 -5.8 -0.3 -6.1 -6 Placebo -0.36-0.35 -0.4 Lenabasum Double-blind -0.40 Lenabasum OLE * -8 * -0.5 0 4 12 0 4 20 36 60 76 92 108 -0.48 Week ** -0.6 9

Correlations of ACR CRISS Score vs. Change in mRSS with Change in PRO Overall Function Symptoms 0.4 * P < 0.05 Between HAQ-DI 0.20 0.2 0.30 Correlation 0 Correlation Between PtGA Correlation Between 0.10 0.20 -0.2 0.10 0.00 -0.4 0.00 SSPRO * * * * -0.6 -0.10 -0.10 * -0.8 -0.20 Correlation Between Physical Function 0.8 * -0.20 * -0.30 * 0.6 * -0.40 * -0.30 * 0.4 -0.50 0.2 * -0.40 * * * 0 -0.2 -0.50 12 16 28 52 76 108 Correlation Between 0.2 -0.4 Week of Treatment Pain Interference 0.1 -0.6 0 * Blue – ACR CRISS 0.6 Correlation Between * * -0.1 * * Orange - mRSS 0.4 -0.2 Social Role -0.3 0.2 ACR CRISS score has -0.4 * * 0 -0.5 * stronger correlations with -0.6 12 28 52 72 108 -0.2 PROs than change in Week of Treatment 12 28 52 72 108 -0.4 mRSS Week of Treatment

Summary and Conclusions • The composite ACR CRISS score consistently correlated with patient-reported function and symptoms outcomes, including patient-reported outcomes not captured in the ACR CRISS score calculation • ACR CRISS score correlated with these PRO more strongly than change in mRSS, a physician measurement of skin thickness • ACR CRISS score may serve as an efficacy outcome that broadly reflects how the patient feels and functions 11

Investigators and study coordinators Principal Investigator Study Coordinators Institution Jesse Ojeda Robert Spiera Sarah Jinich Weill Cornell Medical College Jessica Gordon Anna Yusov Lorinda Chung Joel Nicholus Stanford University School of Medicine Robyn Domsic Jennifer Peat-Fircak University of Pittsburgh School of Medicine Tracy Frech Jennifer Godina University of Utah School of Medicine Daniel E. Furst Omar Aly Pacific Arthritis Care Center Vivien Hsu Deborah McCloskey Robert Wood Johnson Medical School Gwen Leatherman Laura Hummers Johns Hopkins School of Medicine Margaret Sampedro Maureen Mayes Patricia Gonzales University of Texas, Houston Eric Stratton Robert Simms Boston University Connor Buchholz 12