Pliant Therapeutics, Inc. · NASDAQ:PLRX
Pliant Therapeutics — AASLD: The Liver Meeting 2023
18 slides from Pliant Therapeutics's conference presentation, November 2023
Slide 1: Oral αvβ6/αvβ1 Integrin Inhibition in Primary Sclerosing Cholangitis: INTEGRIS-PSC Interim Analysis
Oral αvβ6/αvβ1 Integrin Inhibition in Primary Sclerosing Cholangitis: 12-week Interim Safety and Efficacy Analysis of INTEGRIS-PSC, A Phase 2a Trial of Bexotegrast Gideon M. Hirschfield1, Kris V. Kowdley2,3, Michael Trauner4, Palak J. Trivedi5, Éric A. Lefebvre6, Johanna Schaub6, Martin Decaris6, An
Slide 2: Disclosure Statement
Disclosure Statement Advisor • Advanz Pharma • CymaBay Therapeutics • GSK • Intercept Pharmaceuticals • Ipsen • Kowa Pharmaceuticals • Mirum Pharmaceuticals • Pliant Therapeutics © 2023 PLIANT THERAPEUTICS
Slide 3: αvβ6/αvβ1 Integrins Promote Biliary Fibrosis by Activating TGF-β
αvβ6 / αvβ1 Integrins Promote Biliary Fibrosis by Activating TGF-β Fibrotic PSC In PSC: • αVβ6 is specifically expressed on injured cholangiocytes and αVβ1 on HSC/fibroblasts1,2 • Loss or inhibition of αVβ6 or αVβ1 reduces fibrosis in preclinical models of biliary and hepatic fibrosis1-5 • Therefore
Slide 4: Enhanced Liver Fibrosis (ELF) Score Prognostic Biomarker
Enhanced Liver Fibrosis (ELF) Score Prognostic Biomarker • Established ELF thresholds (7.7, 9.8) have been shown to predict transplant free survival in PSC1 • Worsening of ELF associated with increased risk of PSC-related clinical events2 • Measuring ELF is suggested for annual surveillance of PSC3
Slide 5: INTEGRIS-PSC: Study Design and Objectives
INTEGRIS-PSC: Study Design and Objectives RANDOMIZATION Bexotegrast 3:1 Placebo PRIMARY AND SECONDARY ENDPOINTS • Safety and tolerability Placebo • Pharmacokineticsa END OF STUDY SCREENING Bexotegrast 40mg EXPLORATORY ENDPOINTS • Change in liver fibrosis markers: ELF Bexotegrast 80mg score and PRO-C
Slide 6: Key Eligibility Criteria
Key Eligibility Criteria Trial Enriched for Participants with Suspected Liver Fibrosis INCLUSION EXCLUSION • Large duct PSC • Small duct PSC • Suspected liver fibrosis (moderate to • Cirrhosis severe) with at least one of the following: • Worsening liver chemistry during screening ⎼ ELF score ≥7.7 •
Slide 7: Participant Disposition
Participant Disposition SCREENED n=179 SCREEN FAILURE n=49 RANDOMIZED AND TREATED n=85 BEXOTEGRAST PLACEBO n=64 n=21 Safety Population n=64a Safety Population n=21a With UDCA n=42 (65.6%) With UDCA n=13 (61.9%) Discontinued Treatment Discontinued Treatment n=4b (6.3%) n=2c (9.5%) aSafety population
Slide 8: Baseline Demographics
Baseline Demographics Bexotegrast Bexotegrast Bexotegrast Bexotegrast Placebo Characteristic 40 mg 80 mg 160 mg All (n=24)c (n=20)c (n=20)c (n=64) (n=21) Male sex, n (%) 17 (70.8) 16 (80.0) 14 (70.0) 47 (73.4) 17 (81.0) Age (yr), mean (SD) 46.9 (15.06) 40.5 (15.32) 45.1 (12.65) 44.3 (14.46) 45.6 (12
Slide 9: Baseline Characteristics
Baseline Characteristics Bexotegrast Bexotegrast Bexotegrast Bexotegrast Placebo 40 mg 80 mg 160 mg All (n=24) (n=20) (n=20) (n=64) (n=21) Serum liver tests, mean (SD) Alkaline phosphatasea, U/L 315.1 (140.26) 199.2 (81.03) 273.8 (165.63) 266.0 (140.68) 259.7 (185.76) Alanine aminotransferase, U/L 9
Slide 10: Safety and Tolerability Summary
Safety and Tolerability Summary Bexotegrast was Well Tolerated over 12 Weeks Bexotegrast Bexotegrast Bexotegrast Bexotegrast Placebo TEAE, n (%) of participants reporting 40 mg 80 mg 160 mg All (n=24) (n=20) (n=20) (n=64) (n=21) TEAE 10 (41.7) 16 (80.0) 15 (75.0) 41 (64.1) 16 (76.2) Related to stud
Slide 11: ELF Score
ELF Score Lower Mean Change in ELF with Bexotegrast vs Placebo ELF Score Change from Baseline at Week 12 * p <0.05 vs placebo All participants had baseline ELF > 7.7 (moderate to severe liver fibrosis)1 1. Vesterhus M et al. Hepatology 2015 62(1):188-197 ELF, enhanced liver fibrosis; SE, standard er
Slide 12: PRO-C3: Dynamic marker of collagen formation
PRO-C3: Dynamic marker of collagen formation Lower Mean Change in PRO-C3 with Bexotegrast vs Placebo PRO-C3 Change Over Time EOT * p <0.05 vs placebo ** p <0.01 vs placebo At 12 weeks, PRO-C3 change from baseline was significant for 40 mg and 160 mg Only participants with both a baseline and post ba
Slide 13: Gadoxetate-Enhanced MR of the Liver (Sub-Study)
Gadoxetate-Enhanced MR of the Liver (Sub-Study) • Using the MR contrast agent gadoxetate, relative enhancement is a measure of hepatocyte function1,2 • Time of arrival of gadoxetate to the common bile duct is an exploratory measure of excretory flow • Findings are suggestive of improved hepatocyte f
Slide 14: Alkaline Phosphatase
Alkaline Phosphatase Participants with Baseline ALP > ULN ALP (U/L) Change from Baseline at Week 12 ALP, alkaline phosphatase; EOT, end of treatment; SE, standard error; ULN, upper limit of normal © 2023 PLIANT THERAPEUTICS
Slide 15: Itch Numerical Rating Scale
Itch Numerical Rating Scale Itch NRS Score Change from Baseline at Week 12 * p <0.05 vs placebo Itch NRS is a patient reported outcome which assesses severity of itch, over the last 24 hours, on a scale of 0 (no itch) to 10 (worst imaginable itching) NRS: numerical rating scale; SE, standard error ©
Slide 16: Interim Analysis Conclusions
In this Interim Analysis of INTEGRIS-PSC which Evaluated Oral αvβ6/αvβ1 Integrin Inhibition with Bexotegrast in PSC: Bexotegrast was well tolerated over 12 weeks of treatment • Adverse events rates were comparable to placebo with all drug-related events mild or moderate in severity • Low rate of dis
Slide 17: Acknowledgements
Acknowledgements Study participants, their families and caregivers PSC Partners INTEGRIS-PSC Investigators, Study Coordinators and Staff: Adriaan Van der Meer Cynthia Levy Kidist Yimam Peter Fickert Akin Inderson Cyriel Ponsioen Kris Kowdley Raj Vuppalanchi Aldo Montano-Loza Daniel Pratt Lawrence Se
Slide 18: Scan the QR code to download the presentation
Scan the QR code to download the presentation AASLD: THE LIVER MEETING | November 10-14, 2023 Abstract 5008 © 2023 PLIANT THERAPEUTICS