Introduction

Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that was efficacious in double-blind, placebo-controlled, treat-through trials in participants (pts) with moderately to severely active Crohn’s disease (CD) using IV induction and SC maintenance (GALAXI 2 & 3) or SC induction and maintenance (GRAVITI). Assessment of histologic disease activity is becoming increasingly important as a measure of treatment efficacy. Here we report histologic outcomes at Weeks (W) 12 & 48 from GRAVITI.

Aims & Methods

Pts were randomized 1:1:1 to GUS 400 mg SC every 4 weeks (q4w)→200 mg SC q4w, GUS 400 mg SC q4w→100 mg SC every 8 weeks (q8w), or placebo (PBO). Biopsies were obtained from the most affected area (or if no disease activity present, from normal-appearing mucosa) in 5 segments: terminal ileum, ascending colon, transverse colon, descending colon, and rectum. Histologic response, histologic remission, and the composite endpoints of histo-endoscopic response and histo-endoscopic remission were evaluated using Robarts Histopathology Index (RHI), Global Histologic Activity Score (GHAS), and Geboes scoring. Histologic response was assessed in pts with baseline histologic disease; histologic remission, histo-endoscopic response, and histo-endoscopic remission were assessed in the full analysis set (see definitions in table legend). Pts who met rescue criteria at W16 were considered non-responders at W48. Histologic endpoints in GRAVITI were exploratory and not controlled for multiple comparisons; p-values are nominal.

Results

Of the 347 pts in the full analysis set, 273 (78.7%) had baseline histologic disease per RHI score. SC induction with GUS (400 mg SC at W0, W4, & W8) resulted in greater rates of histologic response, histologic remission, histo-endoscopic response, and histo-endoscopic remission compared to placebo at W12 (Table). At W48, greater proportions of pts receiving GUS 100 mg SC q8w or GUS 200 mg SC q4w maintenance also achieved histologic response, histologic remission, histo-endoscopic response, and histo-endoscopic remission compared to PBO. Comparable outcomes were observed using GHAS or Geboes scoring criteria.

Conclusion

Compared to PBO, pts with moderately to severely active CD receiving SC induction and maintenance treatment with GUS achieved greater rates of histologic response, histologic remission, histo-endoscopic response, and histo-endoscopic remission through W48. These results support the use of histologic and composite histologic and endoscopic endpoints as a measure of CD activity, and the efficacy of SC guselkumab in CD.

Disclosure

GRD’H: consultancy activities for AbbVie, Agomab, Alimentiv, AstraZeneca, AMT, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom, Galapagos, GlaxoSmithKline, Gossamerbio, Immunic, Index, Johnson & Johnson, Kaleido, Origo, Pfizer, Polpharma, Procise Diagnostics, Prometheus Laboratories, Prometheus Biosciences, Progenity, and Protagonist Therapeutics Inc.; speaker’s bureau for AbbVie, Bristol Myers Squibb, Galapagos, Pfizer, and Takeda; and data monitoring board activities for AbbVie, AstraZeneca, Galapagos, and Seres Health.
ALH: lecturer and/or advisory board member for Bristol Myers Squibb, Celltrion, Falk, AbbVie, Johnson & Johnson, Takeda, Pfizer, Galapagos, MSD, and GSK.
RP: consulting fees from Abbivax, Abbott, AbbVie, Alimentiv (formerly Robarts), Amgen, AnaptsyBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Spyre Therapeutics, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, and UCB; speaker’s fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Johnson & Johnson, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; and participation in Advisory Boards for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.
FS: consultant, speaker, or researcher for AbbVie, Amgen, Celltrion, Ferring, Johnson & Johnson, Pfizer, Sandoz, and Takeda.
QC: steering committee adviser for Bristol Myers Squibb and Johnson & Johnson; research grants from Takeda and Johnson & Johnson.
SD: consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB and Vifor; and lecture fees from AbbVie, Amgen, Ferring, Gilead, Johnson & Johnson, Mylan, Pfizer and Takeda
TH: grant support from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, and Kissei Pharmaceutical Co. Ltd.; consulting fees from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Johnson & Johnson, Pfizer Inc., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, and Abivax; lecture fees from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Johnson & Johnson, Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., and Kissei Pharmaceutical Co. Ltd.
BES: consulting fees from AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mirador Therapeutics, 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, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics; consulting and speaking fees from Abivax; consulting and speaking fees and other support from Lilly; research grants, consulting and speaking fees and other support from Bristol Myers Squibb, Johnson & Johnson, Pfizer, and Takeda; and stock/stock options from Ventyx Biopharma.
MO, LS, PB, WvD, NT: employees and shareholders of Johnson & Johnson

Introduction

Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23.¹ In the Phase 3 QUASAR maintenance study (NCT04033445), both the GUS 100mg every 8 weeks (q8w) and 200mg q4w subcutaneous (SC) maintenance dose regimens were efficacious.² Here, we evaluated efficacy of these dose regimens in clinically relevant subgroups of participants (pts) with and without extensive ulcerative colitis (UC) disease or high inflammatory burden.

Aims & Methods

Clinical responders after 12 weeks of GUS intravenous (IV) induction were randomized 1:1:1 to GUS 100mg SC q8w, GUS 200mg SC q4w or placebo (PBO) (GUS withdrawal) at start of the maintenance study (M-0). Efficacy endpoints were analyzed at Week (W)44 in the primary analysis population of pts randomized and treated in the maintenance study who had a modified Mayo score of 5-9 at induction baseline (I-0). Subgroup analyses were conducted by (1) extent of UC disease (limited to left side of colon vs extensive) based on screening endoscopy and/or medical history at I-0 and (2) inflammatory burden based on serum C-reactive protein (CRP) levels (≤3 vs >3mg/L) at M-0.

Results

Of 568 pts in the primary analysis population, 257 (45.2%) had extensive UC disease at I-0 and 182 (32.0%) had serum CRP >3mg/L at M-0.
Proportions of pts achieving W44 clinical and histologic-endoscopic efficacy endpoints were greater with both GUS dose regimens vs PBO across subgroups (Table). For pts with extensive UC disease, the proportion of pts achieving clinical remission at W44 was numerically greater with GUS 200mg q4w (62.7%) relative to GUS 100mg q8w (49.4%) (PBO, 11.6%). For those with elevated CRP (>3mg/L) at M-0, clinical remission at W44 was achieved by 48.2% of GUS 200mg q4w vs 30.2% of GUS 100mg q8w pts (PBO, 14.3%). Proportions of pts achieving endoscopic improvement, histo-endoscopic improvement, endoscopic remission, and maintenance of clinical remission were also greater with GUS 200mg q4w in these subgroups. Among pts with disease limited to the left side of the colon or CRP ≤3mg/L at M-0, proportions of pts achieving these efficacy endpoints were similar with GUS 100mg q8w and GUS 200mg q4w.

Conclusion

For pts with moderately to severely active UC with extensive disease or high inflammatory burden, greater efficacy rates were observed with GUS 200mg SC q4w compared with GUS 100mg SC q8w.

References

1. Sachen KL et al. Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signaling. Front. Immunol. 2025;16:1532852.
2. Rubin DT et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49.

Disclosure

Study support: Johnson & Johnson.​
JRA: Abbvie, Bristol Myer Squibb, Ferring, Finch, Iterative Scopes, Johnson & Johnson, Merck, Pfizer, Roivant, Seres Therapeutics and Roivant Adiso
TH: AbbVie, Bristol Myers Squibb, Daiichi-Sankyo, EA Pharma Co, Ltd., JIMRO, Eli Lilly, Gilead Sciences, Johnson & Johnson, Kissei Pharmaceutical Co, Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc and Takeda Pharmaceutical Co., Ltd
BB: AbbVie, Alimentiv, Allergan, Amgen, AMT, Bausch Health, Bristol Myers Squibb, Business Intelligence, Celgene, Celltrion, Eupraxia Fresenius Kabi, Ferring, Genentech/Roche, Gilead, Iterative Scopes, GlaxoSmithKline, Jamp, Johnson & Johnson, Merck, Microbiome Insights, Mylan, Novartis, Organon, Pendopharm, Pfizer, Protagonist, Qu Biologic, Sandoz, Takeda, and Viatris
LPB: AbbVie, Abivax, Adacyte, Alimentiv, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Bristol Myers Squibb, Celltrion, Connect, Cytoki, Eli Lilly, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech/Roche, Gilead, Gossamer Bio, GlaxoSmithKline, HAC-Pharma, IAG, InDex, Inotrem, Johnson & Johnson, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM, ONO, OSE, Pandion, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Vectivbio, Ventyx, Viatris, Vifor, and Ysopia
MG, SY, NS, YM: Johnson & Johnson.
BES: AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Johnson & Johnson, Kaleido, Kallyope, Lilly, Merck, Microba, Mirador Therapeutics, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics
DTR: Abbvie, Altrubio, Apex, Avalo Therapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Johnson & Johnson, Lilly, Pfizer, Samsung Neurologica, and Takeda.
AD: Abivax, AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, CED Service GmbH, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Gilead, High5MD, Johnson & Johnson, Lilly, Materia Prima, MedToday, MSD, Pfizer, Pharmacosmos, Roche, Sandoz, Stada, Takeda, Thieme, Tillotts, UniMed Verlag and Vifor Pharma

Introduction

Total retocolectomy with ileal pouch anal anastomosis (IPAA) is the surgical procedure of choice for patients with ulcerative colitis (UC) refractory to clinical treatment and familial adenomatous polyposis (FAP) with many polyps in the rectum. Primary ileitis of the ileal pouch (IP) is one of the most common complications in UC, being rare in FAP. Previous studies have identified an increase in pro-inflammatory cytokines, as well as alterations in the apoptosis and macroautophagy pathways markers in the IP mucosa of UC patients, compared to those with FAP and normal distal ileum (controls). Since autophagy and apoptosis can be modulated by endoplasmic reticulum (ER) stress, we investigated this pathway in IP of UC compared to PAF and controls.

Aims & Methods

The aim was to evaluate the modulation of ER stress in the IP mucosa of UC and FAP patients who underwent IPAA, compared to controls. Thirty-two patients were included, ten in the UC group, twelve in FAP group and ten in the control group. Patients who had undergone ileostomy closure for less than one year and had clinical, histological, or endoscopic evidence of pouchitis were excluded. The patients underwent routine colonoscopy, and biopsies were performed from the IP. For the control group, biopsies were taken from the normal distal ileum. The local Ethics Committee approved the study. The biopsies were processed for RNA extraction and subsequent gene expression analysis using the quantitative PCR (qPCR) technique. The following transcripts were investigated: IRE1 (ERN), PERK (EIF2AK3), ATF6, GRP78 (HSPA5), GRP94 (HSP90B1), ATF3, STC2, DDIT3, DNAJC3, and CALR. Nonparametric tests were used for statistical analysis, with a significance level of p<0.05.

Results

The pouchitis disease activity index (PDAI) was applied to verify the absence of pouchitis, with all patients scoring lower than 7. There was no increase in the transcriptional level of the main ER stress pathway markers (ERE1, PERK, and ATF6) in the IP without pouchitis. However, there was a significantly lower expression of DDIT3 in the UC and FAP groups compared to the control (p≤0.05), which may suggest a deficiency in counterbalance the ER stress activation. On the other hand, concerning the UPR pathway markers, the levels of CALR and HSP90B1 were significantly higher in the IP of UC compared to the respective IP afferent loop (p≤0.05), supporting potential activation of the ER stress in the IP in the UC group. Additionally, the transcriptional level of ATF3 was significantly higher in the PAF group compared to the control (p≤0.05), which may indicate a counter-regulatory mechanism in response to tissue damage, which was not verified in the UC group.

Conclusion

Our findings demonstrated that markers of the unfolded protein response (UPR) signaling pathway, which is activated in response to ER stress, are modulated in the IP mucosa of UC patients, even in the absence of pouchitis. These results may explain the propensity to IP inflammation in UC patients. They may guide the identification of additional molecular pathways contributing to inflammation of the IP and the search for new therapeutic targets.

References

1. Negreiros LMV, Pascoal LB, Genaro LM, et al. Pouchitis: insight into the pathogenesis and clinical aspects. Am J Transl Res. 2022 Jul 15;14(7):4406-4425.
2. Rodrigues BL, Dotti I, Pascoal LB, et al. Endoplasmic Reticulum Stress in Colonic Mucosa of Ulcerative Colitis Patients Is Mediated by PERK and IRE1 Pathway Activation. Mediators Inflamm. 2022 Feb 9;2022:6049500.
3. Paiva NM, Pascoal LB, Negreiros LMV, et al. Ileal pouch of ulcerative colitis and familial adenomatous polyposis patients exhibit modulation of autophagy markers. Sci Rep. 2018 Feb 8;8(1):2619.
4. Qiao D, Zhang Z, Zhang Y, Chen Q, Chen Y, Tang Y, et al. Regulation of Endoplasmic Reticulum Stress-Autophagy: A Potential Therapeutic Target for Ulcerative Colitis. Front Pharmacol. 2021;Volume 12-2021.

Introduction

Tulisokibart, a TL1A monoclonal antibody, has demonstrated significantly higher rates of clinical remission and endoscopic and histologic improvements vs. placebo in participants with moderately to severely active ulcerative colitis (UC) in the ARTEMIS-UC clinical trial ¹. Although histologic remission has been associated with improved long-term outcomes in UC, histology is inconsistently performed and heterogeneously evaluated in routine clinical care as an assessment of remission depth.

Aims & Methods

This analysis of ARTEMIS-UC explores the correlation between changes in clinical, biomarker, endoscopic, and histologic endpoints following tulisokibart treatment over 50 weeks, potentially providing additional accessible indicators of treatment efficacy. ARTEMIS-UC enrolled two cohorts based on a genetic diagnostic test (Dx) for anti-TL1A treatment response: Cohort 1 (participants regardless of Dx results) and Cohort 2 (only Dx positive participants). We examined 15 relationships between five clinical, endoscopic, and biomarker endpoints and three histologic endpoints at Week 12 after induction (Cohort 1) and Week 50 (Cohorts 1 and 2) among induction responders continuing maintenance tulisokibart. Histologic endpoints included histologic improvement, histologic-endoscopic mucosal improvement (HEMI), and mucosal healing (Table) assessed in the Histology Analysis Set (HAS), i.e., participants who received ≥1 dose of study medication and had Geboes scores at both Baseline and Week 12. Clinical/endoscopic/biomarker endpoints included Modified Mayo Score for clinical remission, clinical response, endoscopic improvement, normalization of fecal calprotectin, and hsCRP normalization. The Phi correlation coefficient assessed pairwise correlations between clinical/endoscopic/biomarker and histologic endpoints.

Results

There were 65 and 34 tulisokibart participants included in the HAS population for the Week 12 and Week 50 analyses, respectively. The strongest correlations were the following: endoscopic improvement:HEMI, endoscopic improvement:mucosal healing, clinical remission:HEMI, and clinical remission:mucosal healing, all >0.8 at Week 12 (post-induction in Cohort 1) and >0.9 at Week 50 (post-maintenance dosing in Cohorts 1 and 2). Normalization of fecal calprotectin also demonstrated a strong correlation with histologic endpoints (>0.7) at Week 50 (Table).

Table: Correlation between Clinical and Histologic Endpoints

Conclusion

Strong correlations exist between clinical, endoscopic, and histologic endpoints after 12 weeks of induction therapy with tulisokibart, followed by 38 weeks of maintenance therapy in induction responders. These findings underscore the potential for clinical remission to reflect both endoscopic and histologic healing in UC patients, which may enhance patient management strategies and enable a more comprehensive understanding of treatment efficacy. Moreover, these findings indicate the potential of tulisokibart in achieving deep remission² in patients with ulcerative colitis.

References

1) Sands BE et al. N Engl J Med. 2024 ;391:1119-1129; 2) Lobatón T et al. United European Gastroenterol J. 2018;6:765-772.

Disclosure

The submitting author of an abstract is requested to declare any potential conflict of interest for all authors during the abstract submission. Moreover, the authors’ names (full first names, family names), gender and affiliation (places of work/institution, city, country) must be provided.
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Roche, Sanofi, Takeda, Tillotts Pharma; speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer
RWL discloses advisory board membership: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Takeda; research grant recipient: Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant, McKusker Charitable Foundation.
JL reports no financial competing interests
XH reports support from AbbVie, Abivax, Alphasigma, Arena, Cellgen, Gilead, Eli Lilly, Enterome, Janssen, InDex Pharmaceuticals, Pfizer, MSD, Roche, Salix, Sangamo, Takeda, and Theravance for clinical research; consulting fees from AbbVie, Abivax, Arena, Galapagos, Gilead, Janssen, Pfizer, Roche, Sangamo, Takeda, and Viatris; and lecture fees from AbbVie, Abivax, Amgen, Arena, Galapagos, Gilead, Fresenius-Kabi, Janssen, Pfizer, Roche, Sangamo, Takeda, and Mylan.
Brigid S. Boland: BSB has research grants from MSD, Mirador, Gilead as well as serves as a consultant for Abbvie, MSD, Celltrion.
JX, WZ, and MY are employees of MSD.