Intrahepatic Characterization of Virological and Immunological Markers in Two Distinct Populations of Chronic Hepatitis B: Baseline Assessment of Core Liver and Fine Needle Aspiration Biopsies From the Investigational INSIGHT Study
Pietro Lampertico,1,2,* Tarik Asselah,3 Ed Gane,4 Scott Fung,5 Patrick T. Kennedy,6 Thomas Vanwolleghem,7 Ewa Janczewska,8 Julian Schulze zur Wiesch,9 Mark Sulkowski,10 Hans Wils,11 Daniele Filippo Colombo,11 Nádia Conceição-Neto,11 Ewoud de Troyer,11 Koen Van den Berge,11 Hinrich W.H. Göhlmann,11 Jeroen Aerssens,11 John Jezorwski,12 Zacharias Anastasiou,13 Oliver Lenz,11 Thierry Verbinnen,11 Thomas N. Kakuda,14 Carine Guinard-Azadian,11 Marianne Tuefferd,11 Michael Biermer11
1Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; 2CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; 3Université de Paris-Cité, INSERM UMR1149, Department of Hepatology, AP-HP Hôpital Beaujon, Clichy, France; 4New Zealand Liver Transplant Unit, | |
University of Auckland, Auckland, New Zealand; 5University Health Network, Toronto, Ontario, Canada; ⁶Barts and The London School of Medicine and Dentistry, London, UK; 7University of Antwerp, Faculty of Medicine & Health Sciences, Laboratory of Experimental Medicine & Pediatrics, Viral Hepatitis Research Group, Antwerp, Belgium; 8Medical University of Silesia in Katowice, Faculty of Public Health in | |
Bytom, Bytom, Poland; 9University Medical Center Hamburg - Eppendorf, Hamburg, Germany; 10Johns Hopkins University, Baltimore, MD, USA; 11Janssen Pharmaceutica NV, Beerse, Belgium; 12Janssen Research & Development, LLC, Titusville, NJ, USA; 13Janssen-Cilag Pharmaceutical, Pefki, Greece; 14Janssen Research & Development, LLC, Brisbane, CA, USA. | *Presenting author. |
FRI-248
Key Finding
> | Contrasted intrahepatic |
distribution of liver viral | |
markers was observed when | |
comparing NCT HBeAg |
Introduction
• JNJ-73763989(JNJ-3989) is a liver-targeted small interfering |
RNA (siRNA) that targets all hepatitis B virus (HBV) RNAs |
for degradation, thereby reducing all HBV proteins and |
pregenomic RNA1 |
Figure 2. (A) Liver sample collection* and (B) intrahepatic viral and immune profiling.†
A. | B. |
FNAB | HBV RNA primers | ||
5' HBV | Polymerase | 3' HBV | |
30 | 2.4 kb2.1 kb | 0.7 kb | |
20 | |||
10 |
- HBV RNA expression was significantly higher in biopsies collected from NCT HBeAg positive versus VS HBeAg negative patients (Table 2; Figure 4), and the fraction of cccDNA positive, HBV RNA positive, and HBsAg positive cells (infected cells with active replication and HBsAg expression) was higher in NCT HBeAg positive patients
- Core biopsies from VS HBeAg negative patients were associated with a higher frequency of cccDNA negative, HBV RNA negative, and HBsAg negative cells (a proxy for non-infected hepatocytes) compared to NCT HBeAg positive patients
Figure 4. Differences in baseline HBV RNA expression and cccDNA/HBV RNA positivity in up to 90 individual hepatocytes per section picked from a subset of 4 core biopsies of NCT HBeAg positive patients and 5 biopsies of VS HBeAg negative patients.
positive to VS HBeAg |
negative patients, which |
was reflected in peripheral |
viral markers |
• | JNJ-56136379(JNJ-6379; bersacapavir) is a capsid assembly |
modulator-empty(CAM-E) that interferes with HBV | |
replication by causing the formation of structurally normal | |
empty capsids that are devoid of HBV DNA and RNA2 | |
• | Recent studies investigating the combination treatment |
t-SNE2 | 0 | Single-cell RNAseq | |||||||||||||||||||||||||||||||||||||||||||
-10 | (BD Rhapsody™) | ||||||||||||||||||||||||||||||||||||||||||||
3.5 kb | |||||||||||||||||||||||||||||||||||||||||||||
-20 | |||||||||||||||||||||||||||||||||||||||||||||
DR2 DR1 PAS | |||||||||||||||||||||||||||||||||||||||||||||
-30 | DR1 | ||||||||||||||||||||||||||||||||||||||||||||
-30-20-10 | 0 | 10 | 20 | 30 | |||||||||||||||||||||||||||||||||||||||||
t-SNE1 | |||||||||||||||||||||||||||||||||||||||||||||
A. | 8 | B. | 1.0 |
0.9 | |||
copies + 1 | 6 | hepatocytes | 0.8 |
0.7 | |||
0.6 | |||
4 | 0.5 | ||
C. | 1.0 |
0.9 | |
hepatocytes | 0.8 |
0.7 | |
0.6 | |
Conclusions
regimen of JNJ-3989 and nucleos(t)ide analogues (NAs), |
with or without JNJ-6379, have demonstrated profound |
reductions in HBV viral serum markers in patients with |
3,4 |
Core liver biopsies
% HBsAg positive hepatocytes
% HBcAg positive cells/biopsy
cccDNA, covalently closed circular DNA; LOD, limit of detection.
*Liver sample collection was standardized across sites. Samples were cryopreserved at the sites and shipped to a central laboratory for analysis. FNAB profiling was performed by single-cell RNAseq using BD Rhapsody™ whole transcriptome analysis to assess variation in intrahepatic immune cells; core biopsies were analyzed by IF staining to assess the fraction of HBsAg positive hepatocytes and HBcAg positive cells per sample. In a subset of core biopsy
RNA | of | 0.4 | |
Log HBV | Fraction | ||
2 | 0.3 | ||
0.2 | |||
of | 0.5 |
0.4 | |
Fraction | |
0.3 | |
0.2 | |
chronic hepatitis B (CHB) |
Objective
• The phase 2 INSIGHT study (ClinicalTrials.gov Identifier: |
NCT04585789) will assess the changes in intrahepatic viral |
and immune markers in response to JNJ-3989-containing |
IF staining
(HBsAg/HBcAg, CK18, DAPI)
cccDNA presence/absence
Plasmid-Safe™,
TempliPhi™
HBV RNA quantification
DNase I |
samples (n = 9), up to 90 hepatocytes per sample were individually picked (RareCyte® CyteFinder® II) for deep viral characterization (HBsAg positivity, cccDNA presence/absence, and HBV RNA quantification for each individual hepatocyte). The LOD of the HBV RNA assay was 1.6 copies/cell.
†Primers were designed for single-cell droplet PCR at the 3' end of HBV genome to enrich for cccDNA-derived HBV RNAs.
0 | 0.1 |
0 | |
NCT HBeAg | VS HBeAg | NCT HBeAg | VS HBeAg |
positive patients | negative patients | positive patients | negative patients |
cccDNA positive/HBV RNA positive cccDNA negative/HBV RNA positive
cccDNA positive/HBV RNA negative cccDNA negative/HBV RNA negative
0.1 |
0 |
NCT HBeAg | VS HBeAg |
positive patients | negative patients |
cccDNA positive/HBV RNA positive/HBsAg positive Other
cccDNA positive/HBV RNA positive/HBsAg negative cccDNA negative/HBV RNA negative/HBsAg negative
combination regimens by comparing intrahepatic status |
between 2 distinct populations at baseline: virologically |
suppressed (VS) hepatitis B e antigen (HBeAg) negative and |
not currently treated (NCT) HBeAg positive patients with CHB |
HBsAg, CK18, DAPI staining | Single-cell droplet PCR |
combined with single-cell picking | |
up to 90 cells per sample | |
(RareCyte® CyteFinder® II) | |
- Violin plot representing the distribution of HBV RNA copies. (B) Joint distribution of cccDNA positive and HBV RNA positive (HBV infected and actively replicating) hepatocytes, cccDNA negative and HBV RNA positive hepatocytes, cccDNA positive and HBV RNA negative (silent) hepatocytes, and cccDNA negative and HBV RNA negative (non-infected) hepatocytes. (C) Joint distribution of cccDNA positive, HBV RNA positive, and HBsAg positive hepatocytes (infected and actively expressed HBV RNA and HBsAg) and cccDNA negative, HBV RNA negative, and HBsAg negative hepatocytes. The LOD for cccDNA positivity and HBV RNA positivity is 1.6 copies/cell. Other includes any combination of cccDNA, HBV RNA, and HBsAg not listed in the other 3 categories.
Intrahepatic Immune Composition
Methods
Study Design and Patients
- The phase 2, open-label,parallel-group, multicenter (across
Results
Demographic and Disease Characteristics
• Baseline liver samples were collected from 20 patients (10 per group; Table 1) |
Table 2. Baseline Intrahepatic HBV Viral Markers in the 2 Populations of Patients Enrolled in INSIGHT
- Limited differences in intrahepatic cell composition were observed when comparing FNABs from NCT HBeAg positive patients and VS HBeAg negative patients (Figure 5)
- A trend for higher CD8+ effector memory T cells in NCT HBeAg positive patients was observed - No significant change was detected in the normalized cell abundance of each cell population in FNABs collected from NCT HBeAg positive and VS HBeAg negative patients
- A trend for enrichment was observed in the expression of interferon-stimulated genes in CD8+ effector memory T cells of samples collected in NCT HBeAg positive compared to VS HBeAg negative patients (associated with a false discovery rate [FDR] <10%; Figure 6 and Table 3)
- Tumor necrosis factor (TNF) expression in mucosal-associated invariant T cells (MAIT) is associated with peripheral HBsAg categories (1,000 IU/mL and 10,000 IU/mL; Figure 7)
9 countries in Europe, North America, and Oceania) INSIGHT study includes patients with CHB who are NCT HBeAg positive or VS by NA and HBeAg negative (Figure 1)
- Patients are receiving JNJ-3989 and NA, with or without JNJ-6379, for 48 weeks
Figure 1. Study design and INSIGHT cohorts.
NCT HBeAg positive patients | JNJ-3989 200 mg Q4W ± JNJ-6379 250 mg QD + NA (n = 10) | Follow-up | |||||||
VS HBeAg negative patients | JNJ-3989 200 mg Q4W ± JNJ-6379 250 mg QD + NA (n = 10) | Follow-up | |||||||
Liver biopsy | Liver biopsy | ||||||||
0 | 12 | 24 | 36 | 40 | 48 | 60 | 72 | 84 | 96 |
Weeks |
Key inclusion criteria:
- Age 18-65 years
- Active CHB with HBsAg >100 IU/mL
- Non-cirrhotic(fibrosis stage F0-F2)
- Countries: Belgium, Canada, France, Germany, Italy, New Zealand, Poland, United Kingdom, United States
- NCT HBeAg positive patients (n = 10)
- HBV DNA ≥20,000 IU/mL
- ALT <10 ULN
- VS HBeAg negative patients (n = 10)
- HBV DNA <60 IU/mL
- ALT <2 ULN
- NA* treatment for ≥6 months
• For NCT HBeAg positive and VS HBeAg negative patients, the mean age was |
33.4 and 43.4 years, respectively, and 50% of patients in each group were female; |
the NCT HBeAg positive group had a higher number of patients who were Asian |
versus the VS HBeAg negative group (80% vs 30%; Table 1) |
Table 1. Baseline Demographic and Disease Characteristics of NCT HBeAg Positive and VS HBeAg Negative Patients Enrolled in the INSIGHT Study
NCT HBeAg | VS HBeAg | |||
N (%) or mean (SD) | positive patients | negative patients | ||
Analysis set: ITT | n = 10 | n = 10 | ||
Demographic characteristics | ||||
Age, years | 33.4 (14.73) | 43.4 (12.63) | ||
Female | 5 | (50%) | 5 | (50%) |
Asian | 8 | (80%) | 3 | (30%) |
Disease characteristics | ||||
Virologically suppressed | 0 | 10 | (100%) | |
HBeAg positive | 10 | (100%) | 0 | |
HBeAg, log10 IU/mL* | 2.80 (0.52) | - | ||
HBsAg, log10 IU/mL | 4.47 (0.64) | 3.40 (0.59) | ||
HBsAg ≥1,000 IU/mL | 10 | (100%) | 8 | (80%) |
HBV DNA, log10 IU/mL | 8.01 (0.66) | 0.84 (0.23) | ||
HBV DNA <> | 0 | 10 | (100%) |
NCT HBeAg | VS HBeAg | |
Mean (SD) | positive patients negative patients | |
Analysis set: ITT | n = 9 | n = 10 |
HBsAg positive hepatocytes, % | 69.4 (39.6) | 16.1 (16.5) |
HBcAg positive cells, % | 84.3 (19.9) | 6.6 (8.5) |
HBV RNA positive hepatocytes, % | 96.6 (5.3) | 19.5 (9.1) |
cccDNA positive hepatocytes, % | 46.9 (33.3) | 46.3 (15.2) |
cccDNA positive HBV RNA negative (silent) | 1.9 (3.7) | 36.4 (10.1) |
hepatocytes, % | ||
The viral markers reported were measured in core liver biopsies. Percentages of positive HBsAg (median = 11,252; range: 640-31,051)
and HBcAg (median = 13,095; range: 1,648-33,998) cells were based on IF staining; percentages of cccDNA and HBV RNA positive cells were based on single-cell digital droplet PCR from up to 90 hepatocytes picked from a section (LOD = 1.6 copies/cell).
Figure 3. Baseline HBsAg and HBcAg IF staining.
A.
B.
Figure 5. Projection of single-cell RNAseq FNAB profiling (UMAP5 fastMNN6 corrected) at baseline.
10 | • CD4 naïve T cells | ||||
• CD4 T | |||||
2 | B cell | ||||
• CD4 Treg | |||||
corrected | CD4+ T | ||||
5 | CD8 + T | • CD8 early activated T cells | |||
CD14+ | • CD8 effector memory T cells | ||||
CD16+ | • CD8 exhausted T cells | ||||
cDC2 | • CD8 naïve cells | ||||
fastMNN | CLEC9A-DC | • CD8 memory stem cells | |||
NK GZMB+ | |||||
0 | GD T | ||||
MAIT | |||||
NK | |||||
UMAP | NK-T | ||||
-5 | NK-T GZMB+ | ||||
pDC | |||||
Proliferating | |||||
Treg | |||||
10 |
-10
-10 | -5 | 0 | 5 | 10 |
UMAP fastMNN corrected 1
cDC2, type-2 conventional dendritic cell; DC, dendritic cell; GZMB+, granzyme B positive; NK, natural killer; pDC, plasmacytoid dendritic cell; Tfh, T follicular helper.
19 FNAB samples collected at baseline were successfully profiled, with approximately 2,000 genes/cell quantified (NCT HBeAg positive patients, n = 9; 15,828 liver resident cells; VS HBeAg negative patients, n = 10; 21,925 liver resident cells). On average, 1,988 cells per sample were profiled, varying from 282 to 5,200 cells. 24 major immune cell populations could be identified based on their transcriptome.
Table 3. Differentially Expressed Genes at Baseline in Detected Cell Populations in Samples From NCT HBeAg Positive and VS HBeAg Negative Patients
FDR-adjusted | |||
Cell population | Gene | Direction | P value |
CD8+ T cells | EPSTI1 | NCT HBeAg+ | 0.027 |
MAIT | GBP1 | NCT HBeAg+ | 0.047 |
MAIT | GBP4 | NCT HBeAg+ | 0.047 |
NK cells GzmB+ | STAT1 | NCT HBeAg+ | 0.060 |
NK cells GzmB+ | SPON2 | NCT HBeAg+ | 0.060 |
CD8+ T cells | TAP1 | NCT HBeAg+ | 0.069 |
CD8+ T cells | ITM2C | NCT HBeAg+ | 0.069 |
CD8+ T cells | JAK3 | NCT HBeAg+ | 0.069 |
CD8+ T cells | JAML | NCT HBeAg+ | 0.069 |
CD8+ T cells | MPP6 | VS HBeAg- | 0.076 |
CD8+ T cells | STAT1 | NCT HBeAg+ | 0.076 |
CD8+ T cells | ARHGAP9 | NCT HBeAg+ | 0.085 |
CD8+ T cells | MYO6 | VS HBeAg- | 0.085 |
HBeAg-, HBeAg negative; HBeAg+, HBeAg positive.
An FDR of 10% was used as the cutoff within each population. Pseudobulk analysis was performed with edgeR.7 The group associated with enrichment in a specific gene is listed under "Direction."
ALT, alanine transaminase; ETV, entecavir; HBsAg, hepatitis B surface antigen; Q4W, every 4 weeks; QD, daily; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; ULN, upper limit of normal.
*NA = ETV/TAF/TDF according to label.
Intrahepatic Assessments
- Paired percutaneous core liver biopsies and fine needle aspiration biopsies (FNABs) are being collected pre-baseline and at Week 40 of treatment using standardized collection procedures and storage protocols across sites (Figure 2A)
- The quality of the samples is being assessed during collection (capturing the size and volume of the sample and potential blood contamination) and with profiling at a central laboratory
- Viral intrahepatic markers, including HBsAg, hepatitis B core antigen (HBcAg), and HBV RNA, are being assessed by immunofluorescent (IF) core biopsy staining combined with single-cell digital droplet polymerase chain reaction (PCR) from fresh frozen tissue sections (Figure 2A)
- Immune cells are characterized by single-cell RNA sequencing (RNAseq) from FNABs (Figure 2B)
HBV RNA <> | 0 | 5 | (50%) |
HBcrAg, log10 U/mL | 8.41 (0.80) | 3.53 (0.99) | |
HBcrAg <>§ | 0 | 4 | (40%) |
ALT ≤ULN | 4 (40%) | 10 | (100%) |
ALT ≤ULN and DNA >7 log10 IU/mL | 3 (30.0%) | 0 | |
FibroScan® score, kPa | 5.49 (1.51) | 4.84 (1.30) | |
Type of NA at study entry: TDF/TAF/ETV‖ | - | 5 (50%)/2 (20%)/3 (30%) | |
Duration of NA at baseline, years‖ | - | 6.2 (3.12) | |
2 (20%) GT-B, | |||
HBV genotype | 6 (60%) GT-C, | 2 (20%) GT-D¶ | |
2 (20%) GT-E |
HBcrAg, hepatitis B core-related antigen; ITT, intention-to-treat; LLOQ, lower limit of quantification; SD, standard deviation. The viral markers and ALT reported in this table are serum based (ie, peripheral).
*Among NCT HBeAg positive patients. †For HBV DNA, LLOQ = 1.3 log10 IU/mL. ‡For HBV RNA, LOD ≈ 1.4 log10 cp/mL.
§For HBcrAg, LLOQ = 3.0 log10 U/mL. ‖Among VS HBeAg negative patients.
¶2 of 10 patients with available HBV genotype data based on historical information.
Intrahepatic Viral Markers
- Higher expression of intrahepatic viral markers was observed in biopsies from NCT HBeAg positive compared to VS HBeAg negative patients (Table 2; Figures 3 and 4)
- A significantly lower fraction of HBsAg positive hepatocytes and HBcAg positive cells was observed in VS HBeAg negative patients compared to NCT HBeAg positive patients (beta binomial model; Figure 3)
C. | 100.00 | 100.00 | ||||
75.00 | 75.00 | |||||
50.00 | 50.00 | |||||
% | 20.00 | % | 20.00 | |||
10.00 | 10.00 | |||||
hepatocytes, | hepatocytes, | |||||
1.00 | 1.00 | |||||
positive | positive | |||||
HBsAg | 0.10 | HBcAg | 0.10 | |||
0.01 | 0.01 | |||||
NCT HBeAg | VS HBeAg | NCT HBeAg | VS HBeAg | |||
positive patients | negative patients | positive patients | negative patients |
Representative examples of multiplex IF staining of a core biopsy collected in (A) NCT HBeAg positive and (B) VS HBeAg negative patients showing contrasted fraction and distribution of infected cells (with clusters of HBsAg positive cells in samples collected in VS HBeAg negative patients). (C) Overall proportion of detected HBsAg positive hepatocytes and HBcAg positive cells comparing NCT HBeAg positive and VS HBeAg negative patients (P<0.01 in both comparisons, applying a beta binomial model). A median of 11,251 (range: 1,309-22,430) hepatocytes were analyzed per biopsy.
Figure 6. Normalized cell abundance of each cell population in FNABs collected at baseline from NCT HBeAg positive and VS HBeAg negative patients.
NCT HBeAg positive patients | VS HBeAg negative patients |
2 | |
cell abundance | 0 |
Normalized | |
-2 |
B cell | CD14+ | CD16+ | CD4 naïve | CD4 Tfh | CD4 Treg | CD8 early activity | CD8 effector memory | CD8 exhaustion | CD8 naïve | CD8 stem cell memory | cDC2 | CLEC9A-DC | GD T | MAIT | NK GZMB + | NK GZMK + | NK-T GZMB + | NK-T GZMK + | pDC | Proliferating |
Negative binomial model with an FDR of 5%.
Figure 7. Relationship between baseline TNF expression in MAIT cells and peripheral HBsAg levels.
TNF expression in MAIT cells
8
millionpercounts | 6 |
Log | 4 |
2 |
≤1,000 >1,000-10,000 >10,000
Serum HBsAg levels (IU/mL)
NCT HBeAg positive patients
VS HBeAg negative patients
> | Compared to patients | |
with VS HBeAg negative | ||
CHB, NCT HBeAg positive | ||
patients had | ||
> | A higher proportion | |
of HBsAg positive | ||
hepatocytes | ||
> | ||
A higher proportion | ||
of HBcAg positive | ||
hepatocytes | ||
> | ||
A higher proportion | ||
of cccDNA/HBV | ||
RNA double-positive | ||
> | hepatocytes | |
In all VS HBeAg negative | ||
patients, the majority of | ||
hepatocytes were either | ||
cccDNA and HBV RNA | ||
negative (non-infected) or | ||
cccDNA positive and HBV | ||
> | RNA negative (silent) | |
In NCT HBeAg positive | ||
patients, a trend was | ||
observed for | ||
> | A lower abundance | |
of effector memory | ||
CD8+ T cells | ||
> | ||
An enriched expression | ||
of interferon-stimulated | ||
genes in CD8+ T cells | ||
References | Acknowledgments | Disclosures | |
1. | Gane E, et al. Presented at: European Association for the Study of the Liver (EASL) | The authors thank the patients who participated in the INSIGHT study. This study was supported by Janssen Research & Development, LLC. | PL serves on the advisory board/speakers bureau for Bristol Myers Squibb, Roche, Gilead, GSK, AbbVie, MSD, Arrowhead, Alnylam, Janssen, Spring Bank, MYR, Eiger BioPharmaceuticals, Antios Therapeutics, Aligos, and Vir Biotechnology. TA is a speaker and investigator for Antios Therapeutics, AbbVie, Eiger BioPharmaceuticals, ENYO, Gilead, Janssen, Roche, and Vir Biotechnology. EG is a member of scientific advisory boards for AbbVie, Abbott Diagnostics, Aligos, Arbutus, Arrowhead, Assembly Biosciences, Avalia, |
Digital International Liver Congress™; August 27-29, 2020; Virtual. Oral GS10. | Editorial support was provided by Kim Caldwell, PhD, of Lumanity Communications Inc., and was funded by Janssen Global Services, LLC. | ClearB Therapeutics, Dicerna, Gilead, GSK, Intellia, Janssen, Merck, Novartis, Genentech-Roche, Vaccitech, Vir Biotechnology, and Virion Therapeutics; and is a speaker for AbbVie, Abbott Diagnostics, Gilead, and Intellia. SF received investigator-initiated research funding from Gilead; received advisory board/consulting fees from Gilead, AbbVie, Janssen, Pfizer, and Novo Nordisk; and received speaker fees from Gilead, AbbVie, and Lupin. PTK reports relationships with Abbott, Aligos, Antios Therapeutics, Assembly | |
2. | Berke JM, et al. Antimicrob Agents Chemother. 2020;64(5):e02439-19. | Biosciences, Gilead, Janssen, GSK, Immunocore, and Drug Farm. T Vanwolleghem receives grants from Gilead and Bristol Myers Squibb; and serves as a consultant for Janssen Pharmaceuticals, Gilead, and AbbVie. EJ receives fees for clinical trials from Janssen-Cilag, GSK, Immunocore, Bristol Myers Squibb, Novo Nordisk, Inventiva, CymaBay, Dr. Falk, Grifols, Cellaïon, MSD, Exelixis, Calliditas, Sagimet, and Axcella; and serves on advisory boards for Novo Nordisk and Cellaïon. JSzW serves as a consultant for Gilead. | |
3. | Yuen MF, et al. Lancet Gastroenterol Hepatol. 2023. Accepted manuscript. | MS serves as a consultant for AbbVie, Atea, Antios Therapeutics, Aligos, Gilead, F2G, Virion Therapeutics, and Precision Bio; receives grants from Janssen, Vir Biotechnology, and GSK (directed to Johns Hopkins University); and reports relationships with DSMB Gilead (HIV) and Immunocore (HBV). HW, DFC, NC-N, EdT, KVdB, HWHG, JA, JJ, ZA, OL, T Verbinnen, TNK, CG-A, MT, and MB are employees of Janssen and may hold stock in Johnson & Johnson. | |
4. | Yuen MF, et al. J Hepatol. 2022;77(5):1287-1298. | ||
5. | Narayan A, et al. Nat Biotechnol. 2021;39(6):765-774. | ||
6. | Tran HTN, et al. Genome Biol. 2020;21(1):12. | ||
7. | Robinson MD, et al. Bioinformatics. 2010;26(1):139-140. |
Presented at the European Association for the Study of the Liver (EASL) International Liver Congress™; June 21-24, 2023; Vienna, Austria.
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Arrowhead Pharmaceuticals Inc. published this content on 23 June 2023 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 23 June 2023 18:09:54 UTC.