Introduction

The phase 3 QUASAR maintenance study (NCT04033445) evaluated the efficacy and safety of guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64 (a receptor on cells that produce IL-23), in patients (pts) who achieved clinical response to 12 weeks of IV GUS. Here we present results for effects of GUS maintenance on histologic and combined histologic and endoscopic outcomes at Week 44.

Aims & Methods

At maintenance baseline, clinical responders following 12 weeks of GUS IV induction from the QUASAR Phase 2b and 3 induction studies were randomized 1:1:1 to GUS 200 mg SC q4w, GUS 100 mg SC q8w, or GUS withdrawal (PBO SC). Colonic biopsies were collected during endoscopy at maintenance baseline and Week 44 to evaluate treatment effect on histology measured using Geboes, Robarts, and Nancy Histological Index. Histologic improvement, histologic remission, the combination of histologic improvement and endoscopic improvement (histo-endoscopic mucosal improvement; HEMI), the combination of histologic remission and endoscopic improvement, and the combination of histologic remission and endoscopic normalization (remission) were evaluated at Week 44 (see Table for definitions).

Results

Of the 568 pts randomized (at induction baseline: mean age, 40.7yrs; mean UC disease duration, 7.8yrs; mean modified Mayo score, 6.9 [63.9% with severe disease]; Mayo endoscopy subscore of 3, 66.4%), 190 were receiving GUS 200 mg q4w, 188 receiving GUS 100 mg q8w, and 190 receiving PBO. Baseline characteristics were similar across treatment groups. Histologic activity at maintenance baseline was similar for the GUS 200 mg q4w, GUS 100 mg q8w, and PBO treatment groups (mean continuous Geboes total score: 6.7, 6.8, and 6.9, respectively).

Improvements in histologic activity at Week 44 were observed in pts treated with GUS 200 mg q4w and GUS 100 mg q8w, while pts assigned to PBO worsened (mean change from maintenance baseline in continuous Geboes total score at Week 44: -1.0, -1.2, and 2.2, respectively [both nominal P<0.001]). At Week 44, a significantly greater proportion of pts treated with GUS 200 mg q4w and GUS 100 mg q8w achieved HEMI compared to PBO (47.9% and 43.6% vs 16.8%, respectively; both P<0.001). Greater proportions of pts in both GUS treatment groups achieved other relevant endpoints at Week 44 compared to PBO-treated pts as presented in Table. Across biologic/JAK inhibitor therapy history subpopulations, greater proportions of GUS-treated pts achieved the assessed endpoints compared to PBO.

Table. Summary of Histologic and Combined Histologic and Endoscopic Outcomes at Week 44
	GUS Withdrawal (Placebo)	GUS 100 mg SC q8w	GUS 200 mg SC q4w
Primary analysis population, N	190	188	190
Histologic improvement, n (%) (Neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system [ie, Geboes histologic score ≤3.1]) Adjusted treatment difference (95% CI) Nominal p-value	58 (30.5) -	122 (64.9) 33.6 (24.3, 42.9) P<0.001	122 (64.2) 32.6 (23.3, 41.9) P<0.001
Histologic remission, n (%) (Absence of neutrophils from the mucosa [both lamina propria and epithelium], no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system [ie, Geboes histologic score ≤2 B.0])a Adjusted treatment difference (95% CI) Nominal p-value	51 (26.8) -	111 (59.0) 31.2 (21.9, 40.5) P<0.001	115 (60.5) 32.6 (23.5, 41.8) P<0.001
Histo-endoscopic mucosal improvement (HEMI), n (%) (Achieving a combination of histologic improvement and endoscopic improvement [Mayo endoscopy subscore of 0 or 1 with no friability]) Adjusted treatment difference (95% CI) Multiplicity-controlled p-value	32 (16.8) -	82 (43.6) 25.7 (17.1, 34.3) P<0.001	91 (47.9) 29.6 (21.1, 38.0) P<0.001
Histologic remission and endoscopic improvement, n (%) (Geboes histologic score ≤2 B.0 and endoscopic improvement) Adjusted treatment difference (95% CI) Nominal p-value	30 (15.8) -	78 (41.5) 24.7 (16.2, 33.2) P<0.001	89 (46.8) 29.6 (21.3, 38.0) P<0.001
Histologic remission and endoscopic normalization (remission), n (%) (Geboes histologic score ≤2 B.0 and Mayo endoscopy subscore of 0) Adjusted treatment difference (95% CI) Nominal p-value	27 (14.2) -	59 (31.4) 16.2 (8.2, 24.3) P<0.001	62 (32.6) 16.9 (9.2, 24.7) P<0.001
a Results for histologic remission by alternative definitions using Robarts Histopathology Index (RHI ≤ 3, with subscores of 0 for lamina propria neutrophils and neutrophils in the epithelium and without ulcers or erosion) and Nancy Histological Index (NHI ≤ 1) were identical. Note: Patients who had a prohibited change in UC medication, an ostomy or colectomy, a dose adjustment (including sham dose adjustment), discontinued study agent due to lack of therapeutic effect or due to an AE of worsening of UC, or due to other reasons except for COVID-19 related reasons (excluding COVID-19 infection) or regional crisis in Russia and Ukraine prior to Week 44 were considered not to have achieved the endpoint. Patients who had an unevaluable biopsy (ie, a biopsy that was collected, but could not be assessed due to sample preparation or technical errors) or were missing the endoscopy subscore (if applicable) or any of the histology components pertaining to an endpoint at Week 44 were considered not to have achieved the endpoint. The adjusted treatment difference and confidence intervals were based on the Wald statistic with Cochran-Mantel-Haenszel (CMH) weight. The p-values were based on the CMH chi-square test, stratified by clinical remission status at maintenance baseline (Yes/No), and induction treatment (guselkumab 400 mg IV, guselkumab 200 mg IV, placebo IV crossover to guselkumab 200 mg IV).

Conclusion

In this phase 3 maintenance study, pts with UC treated with GUS 200 mg SC q4w or GUS 100 mg SC q8w experienced clinically meaningful improvements in histologic and combined histologic and endoscopic outcomes at Week 44 compared to PBO-treated pts.

Disclosure

JP: AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman.
AD: Abivax, AbbVie, Bristol Myers Squibb, Dr Falk Foundation, Galapagos, Gilead, Janssen, Pfizer, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Celltrion, Ferring Pharmaceuticals, Fresenius Kabi, Lilly, MSD, Pharmacosmos, Roche, Sandoz, Stada, Takeda, Tillotts, Vifor Pharma, CED Service GmbH, High5MD, Materia Prima, MedToday, Thieme, and UniMed Verlag.
TH: AbbVie, Daiichi-Sankyo, EA Pharma Co, Ltd. JIMRO, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmacuetical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Co., Ltd., and Janssen Research & Development, LLC.
SY, KGH, MG, SS, PB, RW, and HZ: Johnson & Johnson.
FM: AbbVie, Arena, Celltrion, Eli Lilly and Company, Ferring, Fresenius, Galapagos, GlaxoSmithKline, Janssen, Merck, Pfizer, Prometheus Biosciences, Roche, Sandoz, Tillots, Takeda, and Teva.
VJ: AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion, and Shire.
BGF: AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc, Arena Pharma, Avoro Capital Advisors, Atomwise, BioJamp, Biora Therapeutics, Boehringer-Ingelheim, Boxer, Celsius Therapeutics,Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Hot Spot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, LifeSci Capital, Lument AB, Millennium, MiroBio, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd., Viatris, Ysios, Ysopia, Zealand Pharma, Morgan Lewis and Lenczner Slaght, Ecor1Capital, and Axio Research.
GRL: Abbvie, Allergan, American College of Gastroenterology, American Gastroenterological Association, American Regent, Celgene, Chemed, Eli Lilly, Endo Pharmaceuticals, Ferring, Gastroenterology and Hepatology, Gilead, IMEDEX, Ironwood, Janssen/ Janssen Orthobiotech, MedEd Consultants, Merck, Morphic Therapeutics, Pfizer Pharmaceuticals, Professional Communications, Inc., Prometheus Laboratories, Inc, Romark, Sandoz, Salix Pharmaceuticals/Valeant, Shire Pharmaceuticals, SLACK, Inc, Springer Science and Business Media, Takeda, University of Kentucky, UCB, Up-To-Date, Vindico, and Virgo.
DTR: Takeda, AbbVie, Altrubio, Allergan, Inc., Arena Pharmaceuticals, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Ltd., Bristol Myers Squibb, Celgene Corp/Syneos, Connect BioPharma, GalenPharma/Atlantica, Genentech/Roche, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Eli Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda, Techlab, Inc, and Cornerstones Health, Inc
BES: Abbvie, Adiso Therapeutics, Agomab, Alimentiv , Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Envied Biosciences, Evommune, Ferring, Fresenius Kabi, Fiat, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, Abivax, Lilly, Bristol Myers Squibb, Janssen, Pfizer, Takeda, Theravance Biopharma, and Ventyx Biopharma.

Introduction

The small intestine (SI) microbiome plays a crucial role in nutrient absorption and emerging evidence indicates that fecal microbiome is insufficient to represent SI microbiome. Ingestible sampling capsule technologies are emerging. However, potential contamination becomes a major limitation of these devices [1].

Aims & Methods

We previously reported the Small Intestinal MicroBiome Aspiration (SIMBA) capsules as effective means for sampling, sealing and preserving SI luminal contents for 16s rRNA sequencing analysis [2,3]. A subset of the DNA samples, including SI samples collected by SIMBA capsules (CAP) and the matched saliva (SAL), fecal (FEC) and duodenal endoscopic aspirate (ASP) and brush (BRU) samples, from 16 participants recruited for an observational clinical validation study [3] were sent for shotgun metagenomic sequencing. The aims are: 1) to compare the sampling performance of the capsule (CAP) compared to endoscopic aspirates (ASP) and 850 small intestine, large intestine and fecal samples from the Clinical Microbiomics data warehouse (PRJEB28097), and 2) to characterize samples from the 4 different sampling sites in terms of species composition and functional potential.

Results

4/80 samples (1/16 SAL, 2/16 ASP, 0/16 BRU, 1/16 CAP and 0/16 FEC) failed library preparation and 76 samples were shotgun sequenced (average of 38.5 M read pairs / sample). Quality assessment showed that despite the low raw DNA yield of CAP samples, they retained a minimal level of host contamination, in comparison to ASP and BRU (mean 5.27 % vs. 93.09 - 96.44% of average total reads per sample). 3/14 ASP and all BRU samples have too few reads per sample mapping to genes, failed the rarefaction procedure and were excluded from analysis.

Site	Total (read pairs)	Host %	High Quality Non-Human (HQNH, %)	HQNH	Mapped to Gene Catalog
SAL	37.59 M	70.30	26.07	9.58 M	7.22 M
BRU	34.80 M	96.44	0.13	0.04 M	0.03 M
ASP	39.81 M	93.09	5.43	1.98 M	1.48 M
CAP	36.53 M	5.27	88.01	32.06 M	24.98 M
FEC	43.74 M	2.71	85.26	37.35 M	29.54 M

CAP samples shared majority of the species with ASP samples and a big fraction of CAP species detected in the terminal ileum samples. ASP and CAP sample composition was more similar to duodenum, jejunum and saliva and very different from large intestine and stool samples. Functional genomics further revealed GI regional-specific differences: In both ASP and CAP samples we detect a number of Gut Metabolic Modules for carbohydrate digestion and short-chain fatty acids. However, probiotic species, and species and genes involved in the bile acid metabolism were mainly prevalent in CAP and FEC samples and could not be detected in ASP samples.

Conclusion

CAP and ASP microbiome are compositionally similar despite of the high level of host contamination of ASP samples. CAP appears to be of better quality to reveal GI regional-specific functional potentials than ASP. This analysis demonstrates the great potential for the SIMBA capsule for unveiling the SI microbiome.

References

[1] Yersin S and Vonaesch P. Small intestinal microbiota: from taxonomic composition to metabolism. Trends in Microbiology, 2024, https://doi.org/10.1016/j.tim.2024.02.013
[2] Wang G, Menon S, Wilsack L, Rehak R, Lou L, Turbide C, et al. Spatially and Temporally Precise Microbiome Profiling in the Small Intestine using the SIMBA Capsule with X-ray tracking. MedRxiv 2024:2024.04.02.24305212. https://doi.org/10.1101/2024.04.02.24305212.
[3] Wang G, Bundalovic-Torma C, Menon S, Bruehlmann S, et al. Clinical Sampling of Small Intestine Luminal Content for Microbiome Multi-Omics Analysis: A Performance Analysis of The Small Intestine Microbiome Aspiration (SIMBA) Capsule and Benchmarking Against Endoscopy. MedRxiv 2024:04.07.24305299. https://doi.org/10.1101/2024.04.04.24305299.

Disclosure

G.W, C.BT and S.B are employees of Nimble Science. G.W, C.BT, S.B. and C.N.A. are shareholders and hold stock options of Nimble Science.

Introduction

Tumor necrosis factor–like cytokine 1A (TL1A) promotes inflammation and fibrosis. PRA023 is an anti-TL1A monoclonal antibody in development for multiple inflammatory/fibrotic diseases. ARTEMIS-UC was a phase 2 multicenter, double-blind, placebo-controlled trial of PRA023 in adults with moderately to severely active ulcerative colitis (UC). The primary endpoint of clinical remission was statistically significantly higher in the PRA023 arm compared with the placebo arm. Here, we report the impact of PRA023 on endoscopic and histologic outcomes.

Aims & Methods

Adults with a modified Mayo score of 4 to 9, centrally read endoscopy subscore of ≥2, rectal bleeding subscore of ≥1, and history of insufficient response, loss of response, and/or intolerance to conventional and/or advanced therapies (≤4 advanced agents from ≤3 classes allowed) were randomized 1:1 to receive placebo or intravenous PRA023 (1000 mg on day 1, and 500 mg at weeks 2, 6, and 10). Endoscopic improvement (defined as a Mayo endoscopic subscore ≤1 with no friability), endoscopic remission (defined as a Mayo endoscopic subscore of 0), histologic improvement (defined as Geboes score ≤3.1), and mucosal healing (defined as Geboes score ≤2B.1 and endoscopy subscore ≤1) were measured after 12 weeks of induction therapy. Improvements in other histologic parameters were assessed by changes in Geboes scores.

Results

Of 135 randomized patients, 60/67 (89.6%) in the placebo arm and 68/68 (100%) in the PRA023 arm completed the 12-week induction period. Baseline characteristics were similar between treatment groups. Among alpha-controlled secondary endpoints, endoscopic improvement was observed in 36.8% of PRA023-treated vs 6.0% of placebo-treated patients (Δ30.8%, p<0.0001) at week 12. Histologic improvement occurred in 46.2% of patients receiving PRA023 vs 17.5% receiving placebo (Δ28.6%, p=0.0009) and mucosal healing in 30.8% vs 3.5% (Δ27.3%, p<0.0001), respectively. The mean change (SD) from baseline in the Mayo endoscopic subscore was −0.8 (0.93) for PRA023 vs −0.2 (0.54) for placebo. Furthermore, in a post hoc analysis, a significantly greater proportion of patients who received PRA023 achieved endoscopic remission (11.8% PRA023 vs 0% placebo, Δ11.8%, p=0.004). Of the patients with eosinophils in the lamina propria (LP) at baseline, 21.8% receiving PRA023 and 5.8% receiving placebo experienced complete resolution. Similarly, the resolution rates in those with neutrophils in the LP at baseline were 41.2% and 15.4% in PRA023-treated and placebo-treated patients, respectively; and of those with neutrophils in the epithelium at baseline, values were 40.4% vs 11.3%, respectively.

Conclusion

In patients with moderately to severely active UC, PRA023 resulted in a significantly greater proportion of patients achieving endoscopic remission, endoscopic improvement, histologic improvement, and mucosal healing, endpoints associated with an improved prognosis. Resolution of eosinophil and neutrophil infiltration suggests a reduction in the inflammation associated with UC.

Disclosure

SD has received consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Eli Lilly and Company, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, and Vifor and lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
BES has served as a consultant for or received speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Connect Biopharma, Cytoki Pharma, Eli Lilly and Company, Entera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead, Genentech, GSK, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kallyope, Merck, MiroBio, Morphic Therapeutic, MRM Health, OSE Immunotherapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Sun Pharma Global, Surrozen, Synlogic, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio and has received stock options from Ventyx Biosciences.
LPB has served as a consultant for or has received fees from AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Eli Lilly and Company, Enterome, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, Hikma, Index Pharmaceuticals, Inotrem, Janssen, MSD, Mylan, Oppilan Pharma, OSE Immunotherapeutics, Nestlé, Norgine, Roche, Pandion Therapeutics, Pfizer, Pharmacosmos, Samsung Bioepis, Sandoz, sterna biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tillotts Pharma, and Vifor; has received grants from AbbVie, Fresenius Kabi, MSD, and Takeda; and has stock options from CTMA.
DTR has served as a consultant for AbbVie, AltruBio, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Chronicles, Corp/Syneos, ClostraBio, Connect Biopharma, Eco R1, Eli Lilly and Company, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido, Pfizer, Prometheus Biosciences, Reistone Biopharma, Seres Therapeutics, Takeda, Target RWE, and Trellus Health and has received grant support from Takeda, Helmsley Charitable Trust, and the Gastro-Intestinal Research Foundation.
DDN, QD, AM, JL and BD are employees and shareholders of Prometheus Biosciences.
RK has received grants from Janssen and Takeda.
TER has been a speaker for Takeda Pharmaceuticals, Janssen, Pfizer, Bristol Myers Squibb, and Abbvie; has served on advisory boards for AbbVie, Ardelyx, Arena, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Eli Lilly and Company, Ferring, Genentech/Roche, Gilead, Intercept, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Sanofi, and Takeda; and has been a shareholder for Iterative Scopes.
RP has been a consultant for Abbott, AbbVie, Abivax, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion Healthcare, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly and Company, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB; has received speakers fees from AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda; and has served on advisory boards for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Ventyx.