Daniel J Cua’s research while affiliated with Janssen Research & Development, LLC and other places

IL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human mucosal-associated invariant T (MAIT), but not of conventional T cells. Protein and transcriptional profiling at the population and single cell level demonstrates that stimulation with IL-23 or the structurally related cytokine IL-12 drives distinct functional profiles, revealing a high level of plasticity of MAIT cells. IL-23, in particular, affects key molecules and pathways related to autoimmunity and cytotoxic functions. Integrated analysis of transcriptomes and chromatin accessibility, supported by CRISPR-Cas9 mediated deletion, shows that AP-1 transcription factors constitute a key regulatory node of the IL-23 pathway in MAIT cells. In conclusion, our findings indicate that MAIT cells are key mediators of IL-23 functions in immunity to infections and chronic inflammatory diseases.

Background Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralises interleukin 23 (IL-23) and binds to CD64, a receptor on cells that produce IL-23.1 The QUASAR Phase 2b/3 studies have demonstrated efficacy and safety in induction and maintenance phases.2,3 The cellular and molecular mechanism of action of GUS induction was also previously reported.4 Here, the molecular changes that occur with maintenance treatment are presented. Methods At maintenance baseline, clinical responders to GUS induction treatment (n=568) were randomized 1:1:1 to GUS SC 200mg q4w, GUS SC 100mg q8w, or placebo (PBO; GUS withdrawal). Molecular analysis of the randomised population was performed comparing maintenance baseline (M0) to Week 44 (M44). Transcriptional profiling of colonic biopsies from 396 patients was performed using RNA sequencing and gene modules were evaluated for differential expression. Serum proteins were evaluated from 430 patients using a targeted inflammation panel and differential protein abundance was assessed. Results Clinically, both GUS SC maintenance dose regimens were highly efficacious and achieved the primary endpoint of clinical remission and all major secondary endpoints at M44 compared with PBO.2 Molecular analysis demonstrated a further significant downregulation of key inflammatory gene modules from M0 to M44 (all false discovery rate [FDR]<0.05) from that previously observed during induction.4 Unique to maintenance, gene modules related to intestinal mesenchymal biology (pericytes, fibroblasts and endothelium) showed even greater changes in maintenance compared to induction. An upregulation of gene modules representing healthy epithelial biology (crypt, goblet cells, M-cells) was also observed at M44 (Figure 1). Importantly, patients who achieved clinical remission at M44 demonstrated the most significant changes and gene module expression levels at M44 approximated those observed in non-IBD healthy controls, consistent with the profile of healthy colonic tissue. Serum analysis showed continued reductions in inflammatory proteins (e.g. IL-17A, IL-8, FDR <0.05) and several chemokines from M0 to M44, including CCL11 that has been linked to mesenchymal biology. By M44, GUS withdrawal demonstrated a reversal in the anti-inflammatory effects achieved at the end of induction. Conclusion GUS maintenance therapy for UC mediated further improvements in the anti-inflammatory and pro-healing effects achieved during induction. Moreover, this work provides evidence supporting a role for mesenchymal biology in tissue remodeling during maintenance. Together, these data provide molecular evidence supporting the robust clinical benefit of GUS maintenance therapy. References 1.Atreya R, Abreu MT, Krueger JG, et al. P165 Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signaling. Journal of Crohn's and Colitis. 2024;18(Supplement_1):i470-i470. doi:10.1093/ecco-jcc/jjad212.0295 2.The Efficacy and Safety of Guselkumab as Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 QUASAR Maintenance Study. Gastroenterol Hepatol (N Y). Jul 2024;20(7 Suppl 6):8-9. 3.Peyrin-Biroulet L, Allegretti JR, Rubin DT, et al. Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study. Gastroenterology. Sep 1 2023;doi:10.1053/j.gastro.2023.08.038 4.Sridhar S, Hart A, Venkat S, et al. OP23 Guselkumab induction restores intestinal immune homeostasis and promotes epithelial repair in moderately to severely active Ulcerative Colitis. Journal of Crohn's and Colitis. 2024;18(Supplement_1):i41-i41. doi:10.1093/ecco-jcc/jjad212.0023

Background Guselkumab (GUS) is a selective dual-acting IL-23p19 subunit inhibitor that potently neutralises interleukin 23 (IL-23) and binds to CD64, a receptor on cells that produce IL-23.1 GUS is now approved in the United States for treatment of moderately to severely active ulcerative colitis (UC). GUS has demonstrated efficacy in UC based on the results of the QUASAR Phase 2/3 programme.2,3 Mechanistic data from the Phase 2b induction study demonstrated a restoration of intestinal homeostasis and initiation of epithelial repair.4 These findings were confirmed in the larger Phase 3 QUASAR induction study presented here. Methods At induction baseline, 701 patients with moderately to severely active UC were randomized 3:2 to receive GUS 200mg IV induction or placebo (PBO) and clinical efficacy was assessed at Week 12 (WK12). Molecular analysis of the randomised population was performed comparing induction WK12 to baseline (WK0). Transcriptional profiling of colonic biopsies from 593 patients was performed with bulk RNA sequencing and gene modules were evaluated for differential expression. Serum proteomic profiling of 648 patients was conducted using a targeted O-Link Inflammation panel and differential protein abundance was assessed. Results Significantly higher proportions of patients treated with GUS 200mg IV achieved clinical remission, endoscopic improvement, histologic-endoscopic mucosal improvement (HEMI), and endoscopic remission at WK12 compared with PBO. GUS IV induction demonstrated significant downregulation of inflammatory transcriptional modules in colon tissue at WK12, representing Th17, plasma cell, neutrophil and inflammatory fibroblast biology, and an upregulation of healthy epithelium-related gene modules including goblet cells and healthy epithelium (all false discovery rate [FDR]<0.05). This response correlated with changes observed in the GUS 200mg IV arm of the Phase 2b induction study (r=0.97, p<0.0001). GUS treated patients who achieved HEMI at WK12 demonstrated the most robust changes in gene module expression at WK12 (p<0.0001), nearing non-IBD control levels. Inflammatory serum proteins were reduced as early as WK4, and continued to decline through WK12 (IFNγ, IL-17A, OSM, and IL-6, FDR<0.05). Changes in serum proteins were consistent with those observed in the GUS 200mg arm of the Phase 2b induction study (r=0.96, p<0.0001) (Figure 1). Conclusion Mechanistic observations in response to GUS 200mg IV induction were validated in the Phase 3 QUASAR induction study. These data demonstrate GUS IV induction reduced inflammatory biology towards normal while also increasing the healthy epithelium in patients who achieved HEMI at WK12. References 1. Atreya R, Abreu MT, Krueger JG, et al. P165 Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signaling. Journal of Crohn's and Colitis. 2024;18(Supplement_1):i470-i470. doi:10.1093/ecco-jcc/jjad212.0295 2. The Efficacy and Safety of Guselkumab as Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 QUASAR Maintenance Study. Gastroenterol Hepatol (N Y). Jul 2024;20(7 Suppl 6):8-9. 3. Peyrin-Biroulet L, Allegretti JR, Rubin DT, et al. Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study. Gastroenterology. Sep 1 2023;doi:10.1053/j.gastro.2023.08.038 4. Sridhar S, Hart A, Venkat S, et al. OP23 Guselkumab induction restores intestinal immune homeostasis and promotes epithelial repair in moderately to severely active Ulcerative Colitis. Journal of Crohn's and Colitis. 2024;18(Supplement_1):i41-i41. doi:10.1093/ecco-jcc/jjad212.0023

IL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human MAIT, but not of conventional T cells. Protein and transcriptional profiling at the population and single cell level demonstrates that stimulation with IL-23 or the structurally related cytokine IL-12 drives distinct functional profiles, revealing a high level of plasticity of MAIT cells. IL-23, in particular, affects key molecules and pathways related to autoimmunity and cytotoxic functions. Integrated analysis of transcriptomic and chromatin accessibility, supported by CRISPR/Cas9 mediated deletion, shows that AP-1 transcription factors constitute a key regulatory node of the IL-23 pathway in MAIT cells. In conclusion, our findings indicate that MAIT cells are key mediators of IL-23 functions in immunity to infections and chronic inflammatory diseases.

Background Combination induction therapy with guselkumab (GUS), an interleukin (IL)-23p19 subunit antagonist, and golimumab (GOL), a tumor necrosis factor (TNFα) antagonist, induced higher rates of clinical remission, endoscopic, and histologic outcomes than either monotherapy at Week (WK)12 in patients with ulcerative colitis (VEGA NCT03662542). Data through WK38 suggested the continued benefit of combination induction even after a transition to GUS monotherapy at WK12. Objectives To explore early molecular changes in colon tissue in a subset of patients at WK4 to define mechanistic contributions of each monotherapy and combination; these parameters were evaluated again at WK38 to assess potential carry-over of efficacy. Methods Colon biopsies were obtained at baseline (n=195), WK4 (n=42 substudy), and WK38 (n=172). Transcriptional profiles were generated with RNA sequencing (RNAseq). Gene correlation network analysis was applied in conjunction with publicly available single cell RNAseq data to define biologically relevant bulk and cell type-specific transcriptional modules associated with molecular features of disease. Gene set variation analysis (GSVA) was used to quantitatively assess changes in biologic modules with treatment. Results At WK4, combination induction (n=10) showed significant (p<0.05) decreases in molecular features compared to GUS (n=19) and GOL (n=13), including transcriptomic modules representing the IL-23 pathway, interferon response, and inflammatory epithelial and myeloid transcriptional states associated with endoscopic improvement at WK4 (Mayo endoscopy subscore of 0 or 1) (combination 5/11, GOL 1/13; GUS 2/19). Reduction (p<0.05) in inflammatory modules persisted through WK38 with combination vs monotherapy induction. Module changes between treatments at WK4 indicated a stronger correlation between GUS and combination (R=0.8; p=2.2e-16) than GOL and combination (R=0.52; p=4.1e-12), with processes associated with epithelial and stromal biology, and mucosal inflammation ( Figure 1 ). In contrast, the combination effect on specific neutrophil/myeloid biology at WK4 was more similar to GOL than GUS, supporting the early role of GOL in targeting innate inflammation. Conclusion Combination induction with GUS and GOL showed significant reductions in major inflammatory features of disease as early as WK4 which persisted through WK38 with GUS maintenance. Correlative analysis supports the role of GUS as the primary driver of tissue healing, with GOL further contributing to innate inflammatory activity, which demonstrate differential and complementary mechanisms of action of TNFα and IL-23p19 subunit blockade. REFERENCES: NIL • Download figure • Open in new tab • Download powerpoint Acknowledgements NIL Disclosure of Interests Dylan Richards Stock options in Johnson & Johnson, Employee of Janssen, Marion Vetter Stock options in Johnson & Johnson, Employee of Janssen, Matthew Germinaro Stock options in Johnson & Johnson, Employee of Janssen, Bram Verstockt Consultant fees from Abbvie, Alimentiv, Applied Strategic, Atheneum, BenevolentAI, Biora Therapeutics, Bristol Myers Squibb, Galapagos, Guidepont, Landos, Lily, Mylan, Inotrem, Ipsos, Janssen, Pfizer, Progenity, Sandoz, Santa Ana Bio, Sosei Heptares, Takeda, Tillots Pharma, and Viatris, Grant/research support from AbbVie, Biora Therapeutics, Landos, Pfizer, Sossei Heptares, and Takeda; speaker’s fees from Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Falk, Ferring, Galapagos, Janssen, Lily, MSD, Pfizer, R-Biopharm, Sandoz, Takeda, Tillots Pharma, Truvion, and Viatris, Raja Atreya Speakers for AbbVie, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Cellgene, Celltrion Healthcare, DrFalk Pharma, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Lilly, MSD Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche Pharma, Samsung Bioepis, Takeda Pharma, and Viatris, Consultant for AbbVie, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Cellgene, Celltrion Healthcare, DrFalk Pharma, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Lilly, MSD Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche Pharma, Samsung Bioepis, Takeda Pharma, and Viatris, Grant/research support from AbbVie, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Cellgene, Celltrion Healthcare, DrFalk Pharma, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Lilly, MSD Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche Pharma, Samsung Bioepis, Takeda Pharma, and Viatris, Julian Panes Payment for lectures including service on speakers bureaus from Abbott and Janssen, Consultant for Abbvie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech - Roche, GlaxoSmithKline, Janssen, Mirum, Morphic, Origo, Pandion, Pfizer, Progenity, Protagonist Therapeutics Inc., Revolo, Robarts, Takeda, Theravance, and Wassermann; Data Safety Monitoring Board or Advisory Board from Alimentive and Sanofi; Support for travel to meetings from Abbvie and Takeda during the conduct of the study, Grants from Abbvie and Pfizer; support for travel to meetings from Abbvie and Takeda during the conduct of the study, Bruce E. Sands Speaker’s fees from AbbVie, Abivax, Adiso Therapeutics, AgomAb, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead Sciences, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kalyope, 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 Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio, Stock options in Ventyx Biosciences, Consultant for AbbVie, Abivax, Adiso Therapeutics, AgomAb, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead Sciences, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kalyope, 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 Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio, Brian Feagan A member of the speakers bureau for Abbvie, Janssen, Takeda, and BI; payment for expert testimony from Morgan Lewis and Lenczner Slaght; support for attending meetings and/or travel from Abbvie, Janssen, Pfizer, Takeda, and BI, Stock options in Gossamer, Consultant fees from AbbVie, AbolerIS, AgomAB, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc, Arena, Avoro Capital Advisors, Atomwise, BioJamp, Biora, Boehringer-Ingelheim, Boxer, Celsius, Celgene/Bristol Myers Squibb, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GlaxoSmithKline, Hinge Bio, Hot Spot, Index, Imhotex, Immunic, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido, Landos, Leadiant, L.E.K. Consulting, LifeSci Capital, Lument AB, Millennium, MiroBio, Morphic, Mylan, OM Pharma, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd., Viatris, Ysios, Ysopia, and Zealand Pharma; Safety Monitoring Board or Advisory Board from AbbVie, Amgen, AMT, AnaptysBio, Axio, Boehringer-Ingelheim, Celgene/Bristol Myers Squibb, Ecor1Capital, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Index, Janssen, MiroBio, Morphic, Origo BioPharma, Pfizer, Progenity, Prometheus, RedX, Sanofi, Takeda, Tillotts, and Teva, Bradford McRae Stock options in Johnson & Johnson, Employee of Janssen, Daniel Cua Stock options in Johnson & Johnson, Employee of Janssen, Patrick Branigan Stock options in Johnson & Johnson, Employee of Janssen, Tom C. Freeman Stock options in Johnson & Johnson, Employee of Janssen

Background Selective inhibition of interleukin-23 (IL-23) through antagonism of the IL-23p19 subunit has demonstrated clinical efficacy in inflammatory bowel disease, but the mechanism of action (MoA) has not been fully defined. Objectives To provide a detailed evaluation of the cellular and molecular MoA of guselkumab (GUS), an IL-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) from the QUASAR Phase 2b induction study (NCT04033445). Methods Serum proteins were evaluated from 302 patients treated with intravenous GUS induction therapy or placebo (PBO) who had at least one paired sample at Weeks (WK) 0 and 4 or WK12. Matched colonic biopsies at WK0 and 12 were available for 255 patients. Transcriptional profiling was performed with bulk RNA sequencing (RNAseq). Transcriptional modules derived from public UC single cell RNAseq (scRNAseq) were evaluated with differential expression in the bulk RNAseq dataset. Flow cytometry and scRNAseq were performed on a subset of matched WK0 and WK12 cryopreserved biopsies from 60 patients. Results Both GUS induction doses were effective vs PBO in achieving key endpoints including clinical remission, endoscopic and histologic outcomes. GUS reduced serum IL-22, IFNγ and IL-17A (P<1e-05) as early as WK4, which further declined through WK12. Unsupervised analysis of tissue transcriptomic modules (n=69) revealed 57 that were significantly changed with GUS at WK12. The top 6 downregulated modules represented Th17 cell (IL-23 pathway), neutrophil, IFNγ signaling, plasma cell and inflammatory epithelial and fibroblast cell states, while modules associated with epithelial cell populations and metabolism were upregulated (all false discovery rate [FDR]<0.05). Fc-γ receptor (CD64) expression was increased at baseline in all patients and reduced at WK12. Flow cytometry demonstrated reductions of CD45+ lymphocyte and CD66+ granulocyte populations (P<0.01). Parallel scRNAseq showed a reduction of inflammatory monocytes and fibroblasts in GUS responders at WK12 while pro-healing indicators were observed at WK12 including an increase in EpCam+ cells, BEST4+ enterocytes, and ADAMDEC1+ fibroblasts (P<0.01). Module analysis indicated an increase in goblet cells (FDR<0.05) which play a role in barrier integrity. Conclusion GUS induction restored intestinal immune homeostasis in patients with UC who achieved key endpoints at WK12, demonstrated by resolution of inflammation associated with the IL-23 pathway and inflammatory myeloid, epithelial and fibroblast transcriptional states. GUS also promoted epithelial repair as evidenced by increases in epithelial cell population, consistent with endoscopic and histologic outcomes at WK12. REFERENCES NIL Acknowledgements NIL Disclosure of Interests Sunandini Sridhar Johnson & Johnson, Janssen, Amy Hart Johnson & Johnson, Janssen, Swati Venkat Johnson & Johnson, Janssen, Darren Ruane Johnson & Johnson, Janssen, Dan Horowitz Johnson & Johnson, Janssen, Tae Lee Johnson & Johnson, Janssen, Dawn Waterworth Johnson & Johnson, Janssen, Kuan-Hsiang G. Huang Johnson & Johnson, Janssen, Matthew Germinaro Johnson & Johnson, Janssen, Marion Vetter Johnson & Johnson, Janssen, Daniel Cua Johnson & Johnson, Janssen, Tom C. Freeman Johnson & Johnson, Janssen, Christopher Sisk Johnson & Johnson, Janssen, Bradford McRae Johnson & Johnson, Janssen, Bram Verstockt Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Falk, Ferring, Galapagos, Janssen, Lily, MSD, Pfizer, R-Biopharm, Sandoz, Takeda, Tillots Pharma, Truvion, and Viatris, Abbvie, Alimentiv, Applied Strategic, Atheneum, BenevolentAI, Biora Therapeutics, Bristol Myers Squibb, Galapagos, Guidepont, Landos, Lily, Mylan, Inotrem, Ipsos, Janssen, Pfizer, Progenity, Sandoz, Santa Ana Bio, Sosei Heptares, Takeda, Tillots Pharma, and Viatris, AbbVie, Biora Therapeutics, Landos, Pfizer, Sossei Heptares and Takeda, David T. Rubin AbbVie, Altrubio, Allergan, Arena, Aslan, Athos, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corp/Syneos, Connect, GalenPharma/Atlantica, Genentech/Roche, InDex, Ironwood, Iterative Scopes, Janssen, Eli Lilly, Pfizer, Prometheus, Reistone, Takeda, and Techlab; co-founder of Cornerstones Health, Takeda, Bruce E. Sands AbbVie, Abivax, Adiso Therapeutics, AgomAb, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead Sciences, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kalyope, 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 Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio;, Ventyx Biosciences, AbbVie, Abivax, Adiso Therapeutics, AgomAb, Alimentiv, Amgen, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Gilead Sciences, Genentech, Glaxo SmithKline, Gossamer Bio, HMP Acquisition, Imhotex, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kalyope, 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 Operating Company, Takeda, Target RWE, Theravance Biopharma R&D, TLL Pharmaceutical, USWM Enterprises, Ventyx Biosciences, and Viela Bio;, Patrick Branigan Johnson & Johnson, Janssen.