Protagonist Therapeutics, Inc. · NASDAQ:PTGX
Protagonist Therapeutics — Technical Presentation (October 2018)
14 slides from Protagonist Therapeutics's technical presentation, Oct 22, 2018
Slide 1: Disclosures
Disclosures Dr. Sandborn reports consulting fees from Abbvie, Akros Pharma, Allergan, Ambrx Inc., Amgen, Ardelyx, Arena Pharmaceuticals, Atlantic Pharmaceuticals, Avaxia, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Conatus, Cosmo Technologies, Escalier Biosciences, Ferring, Ferring
Slide 2: PTG-100 Oral α4β7-specific, GI-restricted, Targeted Therapy for IBD
PTG-100 Oral 47-specific, GI-restricted, Targeted Therapy for IBD Briskin M, et al Am J Pathol. 1997;151:97-110 3 • First-in-class potential as a GI-restricted 47-specific blocker – Small constrained peptide – ~2.5 kDa • 47 integrin, a clinically validated IBD target • Oral, once daily dosing • Bloo
Slide 3: Phase 2 PROPEL Study in Ulcerative Colitis
Phase 2 PROPEL Study in Ulcerative Colitis Randomized, double-blind, placebo-controlled adaptive parallel design • • 12 week induction study, QD dosing Primary endpoints: Clinical remission, safety and tolerability Score * change of one or more from baseline of clinical remission 4 Interim Analysis
Slide 4: Baseline Demographics
Baseline Demographics Interim Analysis Dataset (n = 65) • Patients were balanced across all treatment arms 5 Demographic Placebo 150 mg 300 mg 900 mg Age (mean) 42.4 45.2 43.7 40.9 Gender (% M) 57 72 46 35 BMI (kg/m2) 23.4 25.7 24.4 24.4 Duration of UC (years) 7.5 5.1 6.9 5.6 Baseline Total Mayo Sco
Slide 5: Interim Analysis Futile Outcome Driven by Unusually High Placebo Rates
Interim Analysis Futile Outcome Driven by Unusually High Placebo Rates • • Interim outcome (n=65) declared futile by DMC and trial was No safety concerns were noted discontinued • A comprehensive data review was undertaken – – Operational misconduct and trial design issues were ruled out Issues with
Slide 6: Re-analysis Based on Endoscopy Re-Reads: Interim dataset
Re-analysis Based on Endoscopy Re-Reads Interim dataset summary (n = 65) Response • • 1/17 (5.9%) placebo rate of remission; this indicated non-futile outcome Efficacy observed in PTG-100 higher dose arms 7 Remission Endoscopic 150 mg 1/16 (6%) 1/16 (6%) 300 mg 2/16 (13%) 2/16 (13%) 900 mg 3/16 (19%
Slide 7: Re-analysis Based on Endoscopy Re-Reads: Full Dataset
Re-analysis Based on Endoscopy Re-Reads Full Dataset Summary (n = 83) • • Placebo remission rate in line with historical norms (1/21, 4.8%) Efficacy observed in PTG-100 higher dose arms –900 mg arm showed 11% delta over PBO 8 Criteria Placebo 150 mg 300 mg 900 mg # Patients 21 22 21 19 Clinical Remi
Slide 8: PTG-100 is Safe and Well-Tolerated
PTG-100 is Full Analysis Safe and Well-Tolerated Set (n=98) •All SAEs and AEs leading to discontinuation were due to worsening of UC •Cause of death in placebo patient: – Mesenteric ischemia due to complications of UC surgery 9 PBO (n=21) 150 mg (n=22) 300 mg (n=25) 900 mg (n=20) Subjects with at le
Slide 9: Histopathology Analysis
Histopathology Analysis Robarts Histopathology Index (RHI) • Four components – – – – Chronic Inflammatory Infiltrate Lamina Propria Neutrophils Epithelial Neutrophils Erosions/Ulcerations • • Included patients with disease activity at baseline (RHI > 3) Histologic remission defined as an RHI score <
Slide 10: Dose-dependent Increase in Rates of Histologic Remission
Dose-dependent Increase in Rates of Histologic Remission Defined as an RHI score < 3 at Week 12 50 45 40 44% 35 30 25 20 15 10 5 0 PBO (n=13) 150 mg (n=13) 300 mg (n=9) 900 mg (n=16) 11 % Histologic Remission 22% 15% 0
Slide 11: PTG-100 Does Not Require 100% Target Engagement in Blood
PTG-100 Does Not Require 100% Target Engagement in Blood for Clinical Efficacy 100 150mg 300mg 900mg Placebos 80 60 40 20 0 -20 -40 0 14 28 42 Day 56 70 84 • • The above data is consistent with previous pre-clinical colitis and Phase 1 PD results Receptor occupancy in blood and in the GI tissue are
Slide 12: PTG-100 Phase 2 PROPEL Study Conclusions
PTG-100 Phase Conclusions 2 PROPEL Study These data must be interpreted with caution given that the re-read was post hoc, the sample size is relatively small, and changes in the outcome of a small number of patients led to different conclusions PTG-100 is safe and well-tolerated, and the totality of
Slide 13: Thanks to the patients, families and investigators
14 Thanks to the patients, families and investigators for their participation in the PROPEL study.
Slide 14: Thanks to the patients, families and investigators
Thanks to the patients, families and investigators for their participation in the PROPEL study.
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