PLIANT THERAPEUTICS, INC. Phase 2a Collagen PET Study of Bexotegrast Topline Results
MAY 2024
© 2024 PLIANT THERAPEUTICS
Quantification of Collagen in the Lung using PET Imaging
Healthy Control | IPF Patient |
- 68Ga-CBP8 is a PET probe that binds type I collagen with high specificity1
- IPF patients have higher standardized uptake values (SUV) compared to healthy volunteers2
- The probe binds to both freshly synthesized and mature collagen
- 68Ga-CBP8 previously detected treatment response to anti-fibrotic therapy in a mouse model of pulmonary fibrosis1
68GA-CBP8:peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope
SUV: standardized uptake value; SUV measures the ratio of the uptake of a radiotracer in tissue 1Désogere et al, Sci Trans Med. 2017; 2Montesi Am J Respir Crit Care Med 200:2 2019
Note: Uptake in the heart and vasculature as well as in the liver is to be expected based on the probe's half-life and biodistribution
© 2024 PLIANT THERAPEUTICS | 2 |
Design and Objectives
Quantification of Type 1 Collagen in the Lung using PET Imaging
SCREENING
RANDOMIZATION
Bexotegrast
2:1
Placebo
Placebo (n=3)
Bexotegrast 160 mg (n=7)
Stratified for the use of SoC (nintedanib or pirfenidone)
END OF STUDY
PRIMARY AND SECONDARY ENDPOINTS
- Change in whole lung standardized uptake value (SUV) of 68GA-CBP8(type-1 collagen probe)
- Safety and tolerability
EXPLORATORY ENDPOINTS
- Changes in FVC and FVCpp
- Change in VAS for cough severity
- Changes in fibrosis biomarkers
INCLUSION CRITERIA
- Diagnosis of IPF (within 8 years)
- FVC percent predicted ≥ 45%
- DLCO ≥ 30%
• Estimated glomerular filtration rate ≥ 50mL/min
Day -28Baseline | Last dose Week 14 |
Day 1 | Week 12 |
FVC: forced vital capacity, FVCpp: forced vital capacity percent predicted; SoC = Standard of care; VAS: visual analog scale
68GA-CBP8:peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope
© 2024 PLIANT THERAPEUTICS | 3 |
Participant Disposition
SCREENED
n=14
SCREEN FAILURE
n=49
RANDOMIZED AND TREATED
n=10
BEXOTEGRAST | PLACEBO | |
Safety Population3 n=7 | Safety Population3 n=3 |
With SoC n=6 (86%) | With SoC=2 (67%) |
Efficacy Intent-to Treat Analysis n=7 | Efficacy Intent-to Treat Analysis n=3 |
Discontinued Treatment | Discontinued Treatment | ||
n=0 | n=0 | ||
SoC = Standard of care
© 2024 PLIANT THERAPEUTICS | 4 |
Baseline Demographics
Characteristic | Bexotegrast | |
160mg | Placebo | |
(n=7) | (n=3) | |
Male sex, n (%) | 6 (85.7) | 3 (100) |
Age (yr), median (IQR) | 70 (64 - 72) | 74 (72 - 76) |
Weight (kg), median (IQR) | 81.2 (79.0 - 88.5) | 78.0 (77.6 - 85.3) |
BMI (kg/m2), median (IQR) | ||
25.7 (23.7 - 30.4) | 26.4 (24.0 - 30.3) | |
Race, n (%) | ||
White | 6 (85.7) | 3 (100) |
Black | 0 | 0 |
Asian | 1 (14.3) | 0 |
Other / Not Reported / Unknown | 0 | 0 |
IQR = Interquartile range (Q1, Q3); BMI = Body Mass Index
© 2024 PLIANT THERAPEUTICS | 5 |
Baseline Disease Characteristics
Characteristic | Bexotegrast | ||
160mg | Placebo | ||
(n=7) | (n=3) | ||
Time since diagnosis of IPF (mo), median (IQR) | 50 (22 - 70) | 9 (7 - 72) | |
Standard of Care Use, n (%) | |||
Nintedanib | 5 | (71.4) | 1 (33.3) |
Pirfenidone | 1 (14.3) | 1 (33.3) | |
Duration of Standard of Care at Randomization (mo), median (IQR) | 34.5 | (17 - 55) | 40.0 (6 - 74) |
FVC | |||
Absolute (mL), median (IQR) | 2,750 (2,400 - 3,080) | 2,250 (1,700 - 2,640) | |
Percent of predicted value (%), median (IQR) | 66.0 (56.0 - 92.0) | 58.0 (49.0 - 69.0) | |
Percent of predicted DLCO, corrected for the hemoglobin level (%), median (IQR) | 49 (40.0 - 58.0) | 43 (36.5 - 45.0) | |
GAP Stage, n (%) | |||
GAP Stage I | 4 | (57.1) | 0 |
GAP Stage II | 2 | (28.6) | 2 (66.7) |
GAP Stage III | 1 | (14.3) | 1 (33.3) |
GAP Index score derived from Gender, Age, FVC, % Predicted and DLCO, % Predicted.
IQR = Interquartile range (Q1, Q3); DLCO= Diffusing Capacity for Carbon Monoxide; FVC = Forced Vital Capacity
© 2024 PLIANT THERAPEUTICS | 6 |
Key Findings
Bexotegrast cohort showed reduced PET ligand standardized uptake values (SUV) compared to placebo
- Reduction in SUV post-treatment indicates less total lung collagen, suggesting potential reversal of fibrosis
- Additional support of bexotegrast's antifibrotic mechanism of action
No new safety concerns identified over 12 weeks of treatment
- Most adverse events were mild with no study discontinuations observed
- No SAEs observed
Bexotegrast cohort showed improved lung function and decreased cough severity across all timepoints
- Positive FVC change compared to decline in placebo across all time points
- Decrease in cough severity observed at all time points compared to worsening seen on placebo
Biomarker results further support bexotegrast's antifibrotic mechanism
- Bexotegrast cohort showed reduced circulating PRO-C3 and Integrin Beta-6 levels at Weeks 4 and 12 compared to placebo
© 2024 PLIANT THERAPEUTICS | 7 |
Safety Overview
No serious adverse events (SAEs) occurred in the trial
Most treatment emergent adverse events (TEAEs) were mild in nature
No study discontinuations occurred
Bexotegrast continues to demonstrate a favorable safety and tolerability profile in the IPF patient population
© 2024 PLIANT THERAPEUTICS | 8 |
Bexotegrast Showed Reduced PET Tracer SUV Compared to Placebo
ITT Population
PET SUV at Week 12
Reduction in post-treatment SUV indicates a reduction in total lung collagen
Reduced post-treatment total lung collagen suggests potential reversal of fibrosis
2 Montessi AJRCCM 200:2 2019
SUV = Standardized Uptake Value; SE = Standard Error; 68GA-CBP8:peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope
SUV measures the ratio of the uptake of a radiotracer in tissue; Top quartile SUV is the mean of SUVs within the top quartile for each lung section; Whole lung is the average of the left and right lungs
© 2024 PLIANT THERAPEUTICS | 9 |
Bexotegrast Showed Improved Lung Function Compared to Placebo
ITT Population
FVC | FVCpp at Week 12 |
4%
106 mL
Bexotegrast cohort maintained a clear separation from placebo at all time points
Note: One placebo subject did not have FVC that meet quality standards per ATS guidelines at Weeks 4, 8 and 12 | ||
LS = Least Squares; SE = Standard Error; FVC = Forced Vital Capacity; FVCpp = Forced Vital Capacity Percent Predicted | © 2024 PLIANT THERAPEUTICS | 10 |
Attachments
- Original Link
- Original Document
- Permalink
Disclaimer
Pliant Therapeutics Inc. published this content on 14 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 14 May 2024 11:46:01 UTC.
