IL-23p19

— XENITH-UC, a Phase 2b study of XmAb942 in participants with ulcerative colitis, to begin in the second half of 2025 — — Single and multiple doses of XmAb942 are well tolerated and safety profile is consistent with the anti-TL1A drug class — — XmAb942 half-life supports a 12-week maintenance dosing interval in XENITH-UC — — Lead selection for XmAb TL1A x IL23p19 program on track for first-in-human study start in 2026 — — Management hosting webcast and conference call at 5:00 p.m. ET / 2:00 p.m. PT today — PASADENA, CA, USA I April 29, 2025 I Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and autoimmune diseases, today announced positive interim results from its first-in-human study of XmAb942, a high-potency, extended half-life, investigational anti-TL1A antibody in clinical development for patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). Interim results from the healthy volunteer dose-escalation study indicate that XmAb942 is well tolerated at single and multiple doses. Pharmacokinetic analysis of the single dose cohorts estimates a human half-life of greater than 71 days for XmAb942, which supports a 12-week dosing interval during maintenance treatment. Based on these positive interim results, Xencor is initiating the XENITH clinical program, advancing XmAb942 into a Phase 2b study in patients with moderate-to-severely active UC (XENITH-UC), with the expected study start in the second half of 2025. Lead selection for Xencor’s XmAb TL1A x IL23p19 bispecific antibody continues to advance. New in vitro studies show that several lead candidates match the target inhibition potency of commercial monospecific antibodies, but in a simple bispecific immunoglobulin G (IgG) format. Currently, these candidates are in final lead selection studies and manufacturing, in parallel, to prepare for the first-in-human study planned for 2026. “Our Phase 1 data for XmAb942 validate our design goals for a best-in-class anti-TL1A therapy, combining high potency with less frequent dosing to potentially improve clinical outcomes and convenience for patients living with inflammatory bowel disease,” said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. “We are excited to start our Phase 2b XENITH-UC trial later this year to efficiently support dose selection for pivotal studies, and we are poised to select our TL1A x IL23p19 bispecific lead candidate for an anticipated Phase 1 start in 2026. These and other milestones across our clinical portfolio are supported by our strong cash position.” Key Highlights From Phase 1 Study Interim Results The Phase 1 study of XmAb942 in healthy volunteers is a randomized, double-blind, placebo-controlled, dose-escalation trial, exploring intravenous (IV) and subcutaneous (SC) dose administration, at three escalating dose levels. The interim results reflect analyses with subjects in single dose cohorts (IV, n=24; SC, n=24) and in multiple dose cohorts (IV, n=16). XENITH-UC: Phase 2b Study in Ulcerative Colitis (UC) The Phase 2b study of XmAb942 in UC (XENITH-UC) will be a randomized, double-blind, placebo-controlled trial in patients with moderate-to-severely active UC, whose disease has progressed after at least one conventional or advanced therapy. XmAb942 will be administered intravenously during the 12-week induction period and subcutaneously every 12 weeks during the maintenance period. The primary endpoint of the study will be clinical remission based on the modified Mayo score at week 12. The study is designed to enroll approximately 220 patients across three induction dose levels and powered to enable Phase 3 dose selection. XENITH-UC is expected to start in the second half of 2025. Conference Call and Webcast Xencor will host a conference call and webcast today at 5:00 p.m. ET (2:00 p.m. PT) to review the interim results outlined in this news release. The live webcast of the conference call may be accessed through this link and through “Events & Presentations” in the Investors section of the Company’s website, located at investors.xencor.com . A recording will be available for at least 30 days. About XmAb942 XmAb942 is a high-potency, extended half-life, investigational anti-TL1A antibody in clinical development for patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The first generation of anti-TL1A antibodies, designed to block the interaction between the DR3 receptor and its ligand TL1A, have reduced disease activity in patients with UC and CD in multiple clinical studies. Interim results from a Phase 1 dose-escalation study in healthy volunteers indicate that XmAb942 is well tolerated at single and multiple doses. Pharmacokinetic analysis of the single dose cohorts estimates a human half-life of greater than 71 days for XmAb942, which supports a 12-week dosing interval during maintenance treatment. About Xencor Xencor is a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of patients with cancer and autoimmune diseases. More than 20 candidates engineered with Xencor’s XmAb® technology are in clinical development, and multiple XmAb medicines are marketed by partners. Xencor’s XmAb engineering technology enables small changes to a protein’s structure that result in new mechanisms of therapeutic action. For more information, please visit www.xencor.com . SOURCE: Xencor

The first a approved fully-human, dual-acting interleukin-23 (IL-23) inhibitor in moderately to severely active ulcerative colitis, 1,2,3,4,5 guselkumab showed statistically higher rates of endoscopic normalisation b at Week 44 compared with placebo. 2,6,7,8,9 Guselkumab is now approved for the treatment of ulcerative colitis in addition to existing indications of plaque psoriasis and psoriatic arthritis in the European Union. 2 BEERSE, Belgium I April 25, 2025 I Johnson & Johnson today announced that the European Commission (EC) has approved a Marketing Authorisation (MA) for TREMFYA ® (guselkumab) for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic treatment. 2 UC is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed. 10 Guselkumab is the first a approved fully-human, dual-acting IL-23p19 subunit inhibitor that blocks IL-23 and binds to CD64 c , a receptor on cells that produce IL-23. 1,2,3,4,5,11 IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases, d including UC. 11 “Treatment with guselkumab led to significant improvement in the chronic symptoms of ulcerative colitis with the capability of normalising the appearance of the intestinal lining,” said Laurent Peyrin-Biroulet, M.D., Ph.D., Head of the Inflammatory Bowel Disease (IBD) Unit at Nancy University Hospital in France and study investigator. “This approval represents a significant advancement in managing this chronic inflammatory disease.” The EC approval is supported by data from the QUASAR programme, which consists of the Phase 2b induction dose-ranging study and the Phase 3 induction and maintenance studies, evaluating the efficacy and safety of guselkumab in adult patients with moderately to severely active UC who had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic treatment. 2,6,7,8,9 Highlights from QUASAR showed: 2,7 The safety results were consistent with the known safety profile of guselkumab in approved indications for psoriasis (Pso) and psoriatic arthritis (PsA). 2 “There is significant need for new ulcerative colitis therapies that offer meaningful improvements in symptoms and the promise of remission – both overall clinical remission and visible healing of the colon through endoscopic normalisation,” 7,12 said Mark Graham, Senior Director, Therapeutic Area Lead, Immunology, J&J Innovative Medicine EMEA. “This approval builds on our sustained efforts to help improve the quality of life of patients, which can be significantly impacted from both a physical and mental health perspective. We look forward to seeing guselkumab continue to raise the bar of efficacy and become the new standard of care in the treatment of UC.” 7 For the treatment of UC, guselkumab is administered as a 200 mg induction dose intravenously at weeks 0, 4, and 8. 2 The recommended maintenance dosage is 100 mg administered by SC injection at week 16, and every 8 weeks (q8w) thereafter. Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w), may be considered. 2 This EC approval marks the third indication approved for guselkumab in the European Union (EU), 2 which builds on Johnson & Johnson’s nearly 30-year legacy of immunology innovation. Guselkumab first received approval in the EU in November 2017 for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy 1 and received subsequent approval in November 2020 for the treatment of active psoriatic arthritis in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy. 13 The EC is also currently reviewing the positive CHMP opinion to expand MA for guselkumab for the treatment of adult patients with moderately to severely active Crohn’s disease. The EC Decision is expected later this year. Editor’s Notes: a)   Guselkumab was the first IL-23 inhibitor to be approved in November 2017 for first-line treatment of moderate-to-severe plaque psoriasis. 1,2,3,4,5 b)   Also known as endoscopic remission. It is defined as a Mayo Endoscopic Subscore (MES) of 0. 2,14 c)   CD64+ cells are the predominant source of IL-23 in IBD. Cells not expressing CD64 may also contribute to IL-23 production but to a lesser extent. 15,16 d)   Based on in vitro studies in an inflammatory monocyte model. 15 e)   Clinical remission was defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy. 2,7 ABOUT THE QUASAR PROGRAMME ( EudraCT 2018-004002-25 ) 6 QUASAR is a randomised, double-blind, placebo-controlled, parallel group, multicentre, seamless Phase 2b/3 programme designed to evaluate the efficacy and safety of guselkumab, a selective IL-23 inhibitor, in adult patients with moderately to severely active ulcerative colitis who experienced an inadequate response or who demonstrate intolerance to conventional therapy (e.g., thiopurines or corticosteroids), other biologics and/or JAK inhibitors (i.e., tumor necrosis factor [TNF]-alpha antagonists, vedolizumab, and/or JAK inhibitors (tofacitinib)). 7 QUASAR includes a Phase 2b dose-ranging induction study, a confirmatory Phase 3 induction study, and a Phase 3 randomised withdrawal maintenance study, through a total of five years. 7,14 Efficacy, safety, pharmacokinetics, immunogenicity, and biomarkers are assessed at specified time points. 6 Full results are available in The Lancet . 7 ABOUT ULCERATIVE COLITIS Ulcerative colitis is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus. 10 It is the result of the immune system’s overactive response. 10 Symptoms vary but may typically include loose and more urgent bowel movements, rectal bleeding or bloody stool, persistent diarrhoea, abdominal pain, loss of appetite, weight loss, and fatigue. 17 Ulcerative colitis patients also have increased rates of depression. 18 ABOUT GUSELKUMAB Developed by Johnson & Johnson, guselkumab is the first approved fully-human, dual-acting IL-23p19 subunit inhibitor that blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23. 1,2,3,4.5,11 Findings for dual-acting are limited to in vitro studies and the clinical significance of this finding is not known. 15 Guselkumab is approved in the EU for the treatment of moderate to severe plaque psoriasis (Pso) in adults who are candidates for systemic therapy and for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying anti-rheumatic drug therapy. 2 It is also approved in the U.S, 19 Canada, 20 Japan 21 and a number of other countries for the treatment of adults with moderate-to-severe Pso who are candidates for injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light) and for the treatment of adult patients with active PsA. Johnson & Johnson maintains exclusive worldwide marketing rights to guselkumab. 1 European Medicines Agency. Tremfya (guselkumab): An overview of Tremfya and why it is authorized in the EU. Available at: https://www.ema.europa.eu/en/documents/overview/tremfya-epar-medicine-overview_en.pdf . Accessed April 2025. 2 J&J Data on file (RF-433976). European Medicines Agency. Updated TREMFYA Summary of Product Characteristics. Accessed April 2025. 3 EU SmPC: European Medicines Agency. Ilumetri Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/ilumetri-epar-product-information_en.pdf . Accessed April 2025. 4 EU SmPC: European Medicines Agency. Skyrizi Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/skyrizi-epar-product-information_en.pdf . Accessed April 2025. 5 Electronic Medicines Compendium. EU SmPC: European Medicines Agency. Omvoh Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/14882/smpc#gref . Accessed April 2025. 6 EU Clinical Trials Register: Clinicaltrialsregister.eu. A Phase 2b/3, randomised, double-blind, placebo-controlled, parallel-group, multicentre protocol to evaluate the efficacy and safety of guselkumab in participants with moderately to severely active ulcerative colitis (QUASAR). Identifier: 2018-004002-25. Available at: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-004002-25/SE/ . Accessed April 2025. 7 Rubin, D. et al. Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 3 Double-Blind, Randomised, Placebo-Controlled Induction and Maintenance Studies. The Lancet. December 2024. Available at: https://doi.org/10.1016/S0140-6736(24)01927-5. 8 Allegretti, J, et al. The efficacy and safety of guselkumab induction therapy in patients with moderately to severely active ulcerative colitis: Results from the Phase 3 QUASAR induction study. Presented at Digestive Disease Week, May 6-9. 9 Peyrin-Biroulet L, et al. Guselkumab in patients with moderately to severely active ulcerative colitis: QUASAR Phase 2b induction study. Gastroenterology. 2023 Dec;165(6):1443-1457. doi: 10.1053/j.gastro.2023.08.038. Epub 2023 Sep 1. PMID: 37659673. 10 Crohn’s & Colitis Foundation. What is ulcerative colitis? Available at: https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis . Accessed April 2025. . 11 Schinocca, C. et al. Role of the IL-23/IL-17 pathway in rheumatic diseases: an overview. Frontiers in immunology. 2021 Feb 22;12:321. Available at: https://doi.org/10.3389/fimmu.2021.637829. Accessed April 2025. 12 Turner D, Ricciuto A, Lewis A, et al; International Organization for the Study of IBD. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 2021; 160: 1570–83. 13 Johnson & Johnson Innovative Medicine. European Commission Approves Janssen’s TREMFYA®▼ (guselkumab), a First-in-Class Treatment for Active Psoriatic Arthritis (PsA). Available at: https://innovativemedicine.jnj.com/emea/european-commission-approves-janssens-tremfyarv-guselkumab-first-class-treatment-active-psoriatic . Accessed April 2025. 14 National Institutes of Health: ClinicalTrials.gov. A Phase 2b/3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Efficacy and Safety of Guselkumab in Participants with Moderately to Severely Active Ulcerative Colitis. Protocol CNTO1959UCO3001; Phase 2b/3 Amendment 3. Available at: https://cdn.clinicaltrials.gov/large-docs/45/NCT04033445/Prot_000.pdf . Accessed April 2025. 15 Atreya, R, et al. Guselkumab binding to CD64+ IL-23–producing myeloid cells enhances potency for neutralizing IL-23 signaling. J Crohns Colitis . 2024;18(suppl):S470. Accessed April 2025. 16 Kreuger JG, Eyerich K, Kuchroo VK. Il-23 past, present, and future: a roadmap to advancing IL-23 science and therapy. Front Immunol. 2024; 15:1331217. doi:10.3389/fimmu.2024.1331217. 17 NHS. Overview Ulcerative colitis. Available at: https://www.nhs.uk/conditions/ulcerative-colitis/ . Accessed April 2025. 18 Barberio, B. et al. Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis. The Lancet Gastroenterology & Hepatology. 2021 May;6(5):359-370. Available at: https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00014-5/abstract . 19 US Food and Drug Administration: Tremfya Product information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761061s009lbl.pdf . Accessed April 2025. 20 The Canadian Agency for Drugs & Technologies in Health. TREMFYA prescribing information. Available at: https://pdf.hres.ca/dpd_pm/00042101.pdf . Accessed April 2025. 21 Japan Pharmaceuticals and Medical Devices Agency. Tremfya report on the deliberation results. Available at: https://www.pmda.go.jp/files/000234741.pdf . Accessed April 2025. SOURCE: Johnson & Johnson

Johnson & Johnson (J&J) has announced that its dual-acting IL-23 inhibitor Tremfya (guselkumab) has been approved by the European Commission (EC) to treat adults with ulcerative colitis (UC). Patients eligible for the drug will have moderately to severely active cases of the disease and have had an inadequate response, lost response, or been intolerant to either conventional therapy or a biologic treatment. Over 2.5 million people in Europe are living with UC, one of the two main forms of inflammatory bowel disease (IBD). Patients can experience a range of unpredictable symptoms, including loose and more frequent bowel movements, bloody stools, abdominal pain and loss of appetite. Tremfya is designed to block IL-23, an important driver of the pathogenesis of inflammatory diseases, and is already approved in the EU to treat plaque psoriasis and psoriatic arthritis. For the treatment of UC, the drug is given as a 200mg induction dose intravenously at weeks zero, four and eight, followed by a recommended subcutaneous (SC) maintenance dose of 100mg at week 16 and then every eight weeks, or 200mg at week 12 and every four weeks thereafter for patients who do not show adequate therapeutic benefit to induction treatment. The EC’s latest decision follows a recent recommendation from the European Medicines Agency’s human medicines committee and was supported by results from the QUASAR programme, comprising a phase 2b induction dose-ranging study, and phase 3 induction and maintenance studies. In the maintenance trial, 45% of patients receiving a 100mg SC maintenance dose of Tremfya every eight weeks and 50% of those being treated with a 200mg SC dose of the drug every four weeks achieved the primary endpoint of clinical remission at week 44, compared to 19% of placebo-treated patients. Mark Graham, senior director, therapeutic area lead, immunology, J&J Innovative Medicine EMEA, said: “There is significant need for new UC therapies that offer meaningful improvements in symptoms and the promise of remission – both overall clinical remission and visible healing of the colon through endoscopic normalisation.” “We look forward to seeing [Tremfya] continue to raise the bar of efficacy and become the new standard of care in the treatment of UC,” he added. The EC is also reviewing a recommendation from the Committee for Medicinal Products for Human Use for Tremfya in Crohn’s disease, the other main form of IBD.