Kyntra Bio, Inc. · NASDAQ:KYNB
Kyntra Bio — Fibrogen — Technical Presentation (September 2017)
21 slides from Kyntra Bio's technical presentation, Sep 13, 2017
Slide 1: The PRAISE Study
The PRAISE Study A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pamrevlumab (FG-3019) in Patients with Idiopathic Pulmonary Fibrosis Prof. Luca Richeldi, MD Policlinico A. Gemelli, Catholic University, Rome FIBROGEN STUDY#: FGCL-3019-067 ClinicalT
Slide 2: PRAISE Background: Pamrevlumab (FG-3019), a Human MAb Targeting CTGF
PRAISE Background Pamrevlumab (FG-3019) A Human MAb Targeting CTGF Preclinical Data Supportive of Reversal of the Process of Fibrosis1 Decline in lung density over 8 weeks of therapeutic administration in a mouse Radiation-Induced Lung Fibrosis (RILF) model with durable effects after treatment cessa
Slide 3: PRAISE Study Design
PRAISE Study Design Randomized, Double-Blind, Placebo-Controlled Lung Function Assessments: Every 12 weeks Main: 39 sites in 7 countries; 62% US Sub-Study: 20 sites in US only Safety Sub-Study (N=57) Main Study (N=103) Placebo + SoC (Pirfenidone or Nintedanib) 24 weeks Pamrevlumab (30 mg/kg q3W) + S
Slide 4: Study Design Eligibility
PRAISE Study Design Eligibility Age: 40–80 years Diagnosis of IPF as per International Guidelines* Definite UIP, or Possible UIP+SLB Additionally, High Resolution Computerized Tomography should confirm: ≥10% and <50% Fibrosis <25% Honeycombing FVC: ≥55% percent of predicted DLCO: ≥30% percent of pre
Slide 5: Study Population
PRAISE Study Population Subjects Screened (n) 214 Subjects Randomized (n) 103 (Pamrevlumab=50; Placebo=53) Main Reasons for Screen Failures*: Overall US Ex-US - Non-qualifying FVC 34% 10% 24% - Not meeting UIP criteria 26% 14% 12% - Non-qualifying Dlco 18% 9% 9% - PI judgment 10% 2% 8% - ≥10-50% fib
Slide 6: Demographics and Baseline Characteristics, Safety Population
PRAISE Demographics and Baseline Characteristics, Safety Population Source: t-14-1-dm-saf; t-14-1-4-1-pft-saf Variable* Pamrevlumab (N=50) Placebo (N=53) Age (years) 68.3 ±7.05 68.4 ±7.20 Male Gender, n (%) 33 (66.0) 43 (81.1) Race White, n (%) 41 (82.0) 44 (83.0) Weight (Kg) 80.16 ±17.427 86.86 ±17
Slide 7: Demographics and Baseline Characteristics, Safety Population (cont.)
PRAISE Demographics and Baseline Characteristics, Safety Population (cont.) Source: t-14-1-4-2-blgap-saf ; t-14-1-1-enroll-rand Variable* Pamrevlumab (N=50) Placebo (N=53) GAP Stage I / II / III (%) 46 / 48 / 6 45 / 51 / 4 GAP Score: mean ± SD 3.6 ± 1.34 3.6 ± 1.24 Enrollment by Country (%) U.S. 58.
Slide 8: Safety Overview: Treatment Emergent Adverse Events
Safety Overview Treatment Emergent Adverse Events* Source: t-14-3-1-teae-sum-saf Patients, n (%) Pamrevlumab (N=50) Placebo (N=53) Any Adverse Event 48 (96.0) 52 (98.1) Grade 3 10 (20.0) 8 (15.1) Grade 4 1 (2.0) 2 (3.8) Any Serious Adverse Event 12 (24.0) 8 (15.1) All Reported Deaths 3 (6.0) 6 (11.3
Slide 9: Most Common Treatment Emergent Adverse Events
Most Common Treatment Emergent Adverse Events* Source: t-14-3-1-teae-inc10-saf + t-14-3-1-teae-saf Patients, n (%) Pamrevlumab (N=50) Placebo (N=53) Respiratory Tract Infection 15 (30.0) 11 (20.8) Cough 14 (28.0) 23 (43.4) Dyspnea 14 (28.0) 11 (20.8) Idiopathic Pulmonary Fibrosis 10 (20.0) 9 (17.0)
Slide 10: TESAEs were Infrequent and Mostly Respiratory-Related
TESAEs* were Infrequent During the Study and Mostly Respiratory-Related Source: t-14-3-2-tesae-saf; t-14-3-1-teae-ifurel-saf Patients, n (%) Pamrevlumab (N=50) Placebo (N=53) Interstitial Lung Disease 2 (4.0) 0 Pulmonary Embolism 2 (4.0) 0 Cardiac Arrest 0 2 (3.8) Idiopathic Pulmonary Fibrosis 0 4 (
Slide 11: All-Cause Mortality Rate PRAISE vs GAP
All-Cause Mortality Rate PRAISE vs GAP1 1. Ley B. et al. Ann Intern Med. 2012. Source: t-14-1-4-2-blgap-saf / l-16-2-4-4-blgap-rand Full Study (N=103) Pamrevlumab Arm (N=50) Placebo Arm (N=53) Stage 1-year Risk Number Subjects Expected Number of Deaths Number Subjects Expected Number of Deaths Numbe
Slide 12: Efficacy Analysis, Primary Endpoint: Mean Change in FVC at Week 48
Efficacy Analysis, Primary Endpoint*; Mean Change from BL at Week 48 in FVC Random Coefficients Model (Linear Slope method) Source: t-14-2-1-1n-fvcpp-saf.sas t-14-2-1-11q-fvc-saf.sas Mean FVC% change +/-SE FVC%-Predicted Difference: 4.33% Relative Difference: 60% p-value = 0.0331 Absolute FVC Differ
Slide 13: Proportion of Subjects with FVC%-Predicted Decline ≥10% or Death
Visit (Weeks) P-Value* 0.1235 0.0527 0.0172 0.0103 Pamrevlumab, n (%) 3 (6.0%) 3 (6.0%) 5 (10.0%) 5 (10.0%) Placebo, n (%) 7 (13.7%) 9 (17.6%) 15 (29.4%) 16 (31.4%) Relative Diff. -56% -66% -66% -68% Proportion of Subjects with FVC%-Predicted Decline ≥10% or Death by Visit. Logistic Regression Model
Slide 14: Consistency with Prior 049 Phase 2 Open-Label Study Results
PRAISE 049 Study Placebo FVC%-Predicted Change From BL at W48 Consistency with Prior 049 Phase 2 Open-Label Study Results* Pamrevlumab Pamrevlumab *Both studies analyzed according to Linear Slope method. Study 049 with subjects BL FVC≥55% and treated with 30mg/Kg dose (N=32); FVC%-p change from BL =
Slide 15: Combination Safety Sub-Study
PRAISE Combination Safety Sub-Study Randomized, Double-Blind, Placebo-Controlled Trial with SoC Background Medication At least 3 months on stable dose of pirfenidone or nintedanib Total # of pamrevlumab (or matching placebo) doses = 8 First 2 doses at 15 mg/kg, remaining doses at 30 mg/kg 20 sites i
Slide 16: Safety Sub-Study Demographics and Baseline Characteristics
Safety Sub-Study Demographics and Baseline Characteristics Source: t-14-1-dm-saf\t-14-1-4-1-pft-saf\t-14-1-4-2-blgap-saf Pirfenidone Group N=36 Nintedanib Group N=21 Variable* Pam.+ Pirf. (N=24) Pirf. (N=12) Pam.+ Nint. (N=15) Nint. (N=6) Age (years) 68.6 ± 6.27 68.4 ± 5.50 71.1 ± 7.32 65.2 ± 4.62 M
Slide 17: Safety Sub-Study Safety Summary of TEAEs
Safety Sub-Study Safety Summary of Treatment Emergent Adverse Events Source: t-14-3-1-teae-sum-saf Pirfenidone Group N=36 Nintedanib Group N=21 Patients, n (%) Pam.+ Pirf. (N=24) Pirf. (N=12) Pam.+ Nint. (N=15) Nint. (N=6) Any TEAE 19 (79.2) 12 (100.0) 14 (93.3) 6 (100.0) Grade 3 1 (4.2) 2 (16.7) 2
Slide 18: Safety Sub-Study Most Common TEAEs in >10% of Patients
Safety Sub-Study Most Common TEAEs in >10% of Patients Source: t-14-3-1-teae-inc10-saf \ t-14-3-1-teae-saf Patients, n (%) Pam.+ Pirf. (N=24) Pirf. (N=12) Pam.+ Nint. (N=15) Nint. (N=6) Nasopharyngitis 5 (20.8) 3 (25.0) 4 (26.7) 0 Idiopathic Pulmonary Fibrosis 5 (20.8) 0 2 (13.3) 0 Cough 3 (12.5) 3
Slide 19: PK/PD Modeling Predicts Increased Efficacy with Higher Exposure
PK/PD Modeling Based on Study 049 Data Predicts Increased Efficacy with Higher Pamrevlumab Exposure In simulation, 30mg/Kg/2 weeks provides Cmin of 200ug/mL to ~80% of subjects Dose (mg/kg) q3W q2W 15 0 [0 - 1] 13 [7 - 18] 30 24 [17 - 31] 79 [72 - 86] 35 37 [29 - 47] 88 [82 - 94] 45 61 [52 - 70] 96
Slide 20: The PRAISE Phase 2 Study Summary/Conclusions
The PRAISE Phase 2 Study Summary/Conclusions Pamrevlumab shows significant benefit in lung function preservation vs placebo as measured by: FVC%-predicted FVC (mL) FVC%-predicted decline of ≥10% or death Pamrevlumab was generally well tolerated either in monotherapy or in combination with SoC PRAISE
Slide 21: Acknowledgment to PRAISE Sites and Investigators
Acknowledgment to PRAISE Sites and Investigators United States ● Anne Dixon, MD (Vermont Lung Center, Colchester, VT) ● Catherine Markin, MD (Legacy Research Institute, Portland, OR) ● Danielle D. Hosmer, MD (Legacy Research Institute, Portland, OR) ● David Lederer, MD (Columbia University Medical C