CD64

Pictured: Facade of the FDA's building in Maryland/iStock, Grandbrothers The FDA on Thursday approved BeiGene’s PD-1 blocker tislelizumab—now to be marketed under the brand name Tevimbra—for the treatment of unresectable or metastatic esophageal squamous cell carcinoma. Thursday’s approval comes months after Novartis turned its back on tislelizumab, returning global rights to BeiGene. The companies signed a collaboration contract for tislelizumab in January 2021, but ran into several regulatory roadblocks. In January 2022, the FDA elected to defer its action on tislelizumab’s application in esophageal squamous cell carcinoma (ESCC) given delays in its inspection of the biotech’s facilities in China. According to BeiGene, Thursday’s regulatory victory represents Tevimbra’s first approval in the U.S. The therapy has been approved for 11 indications in China, where it is the leading PD-1 inhibitor. The company expects to launch Tevimbra in the U.S. in the second half of the year. BeiGene CMO of Solid Tumors Mark Lanasa in a statement said that with the approval, along with another pending application, “Tevimbra is poised to be a critical pillar of our solid tumor development program,” which currently includes more than 17 registration-enabling studies across various cancer indications. Per Tevimbra’s label, it can be used as a monotherapy for patients who had undergone prior systemic chemotherapy that did not include a PD-(L)1 blocker. The therapy does not have a boxed warning but comes with precautions against immune-mediated adverse events, infusion-related reactions and embryo-fetal toxicity. Tevimbra is a humanized monoclonal antibody that works by targeting and binding to the PD-1 protein, blocking it from interacting with Fc-gamma receptors found on macrophages. This mechanism of action allows Tevimbra to boost the immune system’s anti-cancer action and prevents tumor cells from evading the body’s immune detection. The FDA’s approval on Thursday is backed by data from the RATIONALE 302 study, which enrolled 512 patients and evaluated Tevimbra as a second-line treatment option. Its results showed that Tevimbra led to a statistically significant improvement in overall survival versus the investigator’s choice of chemotherapy. Tevimbra was also found to be safe overall. The most common adverse events included dysregulated levels of albumin, glucose, hemoglobin and lymphocytes, as well as anemia, fatigue and weight loss. BeiGene is also proposing Tislelizumab as a first-line treatment option for unresectable, recurrent locally advanced or metastatic ESCC, and for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. The FDA is currently reviewing these applications and is expected to release its decisions in July and December 2024, respectively. Tevimbra’s regulatory win follows the FDA’s approval last week of its BTK inhibitor Brukinsa (zanubrutinib), combined with Genentech’s Gazyva (obinutuzumab), for the treatment of relapsed or refractory follicular lymphoma. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Results from the global, Phase 3 RATIONALE 302 trial showed TEVIMBRA prolonged the survival of patients who received prior systemic treatment compared to chemotherapy Approval represents the first indication in the U.S. for TEVIMBRA BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BeiGene Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has approved TEVIMBRA® (tislelizumab-jsgr) as monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. TEVIMBRA will be available in the U.S. in the second half of 2024. “Today’s FDA approval of TEVIMBRA for patients with ESCC who have previously received chemotherapy, along with its ongoing review of our BLA for first-line ESCC patients, represents a significant step in our commitment to bringing this therapy to more patients around the world,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “As BeiGene’s first drug candidate produced through our immuno-oncology program and second approved medicine in the U.S., TEVIMBRA is poised to be a critical pillar of our solid tumor development program, which spans more than 17 registration-enabling clinical trials in more than 30 countries across regions globally.” The approval is based on the RATIONALE 302 trial, which met its primary endpoint in the intention-to-treat (ITT) population with a statistically significant and clinically meaningful survival benefit for TEVIMBRA compared with chemotherapy. In the ITT population, the median overall survival (OS) in the TEVIMBRA arm was 8.6 months (95% CI: 7.5, 10.4) compared to 6.3 months (95% CI: 5.3, 7.0) in the chemotherapy arm (p=0.0001; hazard ratio [HR]=0.70 [95% CI: 0.57, 0.85]). The safety pro TEVIMBRA was favorable over chemotherapy.i The most common (≥20%) adverse reactions for TEVIMBRA, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT and cough.i “Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, M.D., Associate Professor of Clinical Medicine, Section Chief Gastrointestinal Oncology, Division of Medical Oncology and Cancer Physician in Chief, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received TEVIMBRA saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.” Tislelizumab received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy in 2023 and a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) in February 2024 as a treatment for non-small cell lung cancer across three indications. The FDA is also reviewing Biologics License Applications (BLAs) for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC and patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The target action dates are July and December 2024, respectively. BeiGene has launched more than 17 potentially registration-enabling trials with TEVIMBRA, of which 11 Phase 3 randomized trials and four Phase 2 trials have already had positive readouts. Through these trials, TEVIMBRA has demonstrated its potential to deliver clinically meaningful improvements in survival benefits and quality of life for hundreds of thousands of cancer patients across a range of tumor types – in many cases, regardless of PD-(L)1 status – both as monotherapy and in combination with other regimens. More than 900,000 patients have been prescribed TEVIMBRA globally to date. About RATIONALE 302 RATIONALE 302 is a global, randomized, open-label, Phase 3 study (NCT03430843) designed to investigate the efficacy and safety of TEVIMBRA when compared with investigator’s choice of chemotherapy as a second-line treatment for patients with unresectable, locally advanced or metastatic ESCC. The study randomized 512 patients from 132 research sites in 11 countries in Europe, Asia and North America. About ESCC Globally, esophageal cancer (EC) is the sixth most common cause of cancer-related deaths, and ESCC is the most common histologic subtype, accounting for nearly 90% of ECs.ii An estimated 957,000 new EC cases are projected in 2040, an increase of nearly 60% from 2020, underscoring the need for additional effective treatments.ii EC is a rapidly fatal disease, and more than two-thirds of patients have advanced or metastatic disease at the time of diagnosis, with an expected five-year survival rate of less than 6% for those with distant metastases.iii About TEVIMBRA® (tislelizumab-jsgr) Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. U.S. Indication and Important Safety Information for TEVIMBRA (tislelizumab-jsgr) INDICATION TEVIMBRA (tislelizumab-jsgr), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. WARNINGS AND PRECAUTIONS Severe and Fatal Immune-Mediated Adverse Reactions TEVIMBRA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue TEVIMBRA depending on severity. In general, if TEVIMBRA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids. Immune-Mediated Pneumonitis TEVIMBRA can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.8% (75/1972) of patients receiving TEVIMBRA, including fatal (0.2%), Grade 4 (0.3%), Grade 3 (1.4%), and Grade 2 (1.7%) adverse reactions. Pneumonitis led to permanent discontinuation of TEVIMBRA in 35 (1.8%) patients and withholding of TEVIMBRA in 27 (1.4%) patients. Systemic corticosteroids were required in all patients with pneumonitis. Immune-mediated pneumonitis resolved in 47% of the 75 patients. Of the 27 patients in whom TEVIMBRA was withheld for pneumonitis, 18 reinitiated TEVIMBRA after symptom improvement; of these, 3 (17%) patients had recurrence of pneumonitis. Immune-Mediated Colitis TEVIMBRA can cause immune-mediated colitis, which can be fatal. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 0.9% (17/1972) of patients receiving TEVIMBRA, including Grade 3 (0.4%), and Grade 2 (0.5%) adverse reactions. Colitis led to permanent discontinuation of TEVIMBRA in 2 (0.1%) patients and withholding of TEVIMBRA in 10 (0.5%) patients. All 17 patients received systemic corticosteroids. Twelve (71%) of the 17 patients received high-dose systemic corticosteroids. Two (12%) of the 17 patients received immunosuppressive treatment. Immune-mediated colitis resolved in 88% of the 17 patients. Of the 10 patients in whom TEVIMBRA was withheld for colitis, 8 reinitiated TEVIMBRA after symptom improvement; of these, 1 (13%) patient had recurrence of colitis. Immune-Mediated Hepatitis TEVIMBRA can cause immune-mediated hepatitis, which can be fatal. Immune-mediated hepatitis occurred in 1.7% (34/1972) of patients receiving TEVIMBRA, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (1%), and Grade 2 (0.6%) adverse reactions. Immune-mediated hepatitis led to permanent discontinuation in 9 (0.5%) patients and withholding of TEVIMBRA in 20 (1%) patients. All patients received systemic corticosteroids. Twenty-nine (85%) of the 34 patients received high-dose systemic corticosteroids. One patient (2.9%) of the 34 patients received immunosuppressive treatment. Immune-mediated hepatitis resolved in 59% of the 34 patients. Of the 20 patients in whom TEVIMBRA was withheld for hepatitis, 12 reinitiated TEVIMBRA after symptom improvement; of these, 2 (17%) patients had recurrence of hepatitis. Immune-Mediated Endocrinopathies Adrenal Insufficiency TEVIMBRA can cause immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold TEVIMBRA depending on severity. Immune-mediated adrenal insufficiency occurred in 0.3% (6/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.2%) adverse reactions. Adrenal insufficiency did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 5 out of the 6 patients. All 6 patients received systemic corticosteroids. Two (33%) of the 6 patients received high-dose systemic corticosteroids. Adrenal insufficiency resolved in 17% of the 6 patients. Hypophysitis TEVIMBRA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity. Hypophysitis/hypopituitarism occurred in 0.1% (1/1972) of patients receiving TEVIMBRA, including a Grade 2 (0.1%) adverse reaction. No TEVIMBRA treatment discontinuation or withholding was required. Thyroid Disorders TEVIMBRA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity. Thyroiditis: Immune-mediated thyroiditis occurred in 0.4% (7/1972) of patients receiving TEVIMBRA, including Grade 2 (0.3%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 1 (0.1%) patient. One (14%) of the 7 patients received systemic corticosteroids. Thyroiditis resolved in 29% of the 7 patients. Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 0.6% (12/1972) of patients receiving TEVIMBRA, including Grade 3 (0.1%), and Grade 2 (0.5%) adverse reactions. Hyperthyroidism led to the permanent discontinuation of TEVIMBRA in 1 (0.1%) patient and withholding of TEVIMBRA in 1 (0.1%) patient. One (8%) of the 12 patients received systemic corticosteroids. Hyperthyroidism resolved in 92% of the 12 patients. Hypothyroidism: Immune-mediated hypothyroidism occurred in 7% (132/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%) and Grade 2 (5%) adverse reactions. TEVIMBRA was not permanently discontinued in any patient, while treatment was withheld in 6 (0.3%) patients. Two (1.5%) of the 132 patients received systemic corticosteroids. All 132 patients received hormone replacement therapy. Hypothyroidism resolved in 27% of the 132 patients. The majority (86%) of patients with hypothyroidism required long-term thyroid hormone replacement. Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis Type 1 diabetes mellitus has been reported with PD-1/PD-L1 blocking antibodies. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity. Immune-Mediated Nephritis with Renal Dysfunction TEVIMBRA can cause immune-mediated nephritis, which can be fatal. Immune-mediated nephritis with renal dysfunction occurred in 0.4% (7/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.2%) adverse reactions. TEVIMBRA was permanently discontinued in 3 (0.2%) patients and treatment was withheld in 3 (0.2%) patients. All patients received systemic corticosteroids. Nephritis with renal dysfunction resolved in 57% of the 7 patients. Of the 3 patients in whom TEVIMBRA was withheld for nephritis, 2 reinitiated TEVIMBRA after symptom improvement and one patient had recurrence of nephritis. Immune-Mediated Dermatologic Adverse Reactions TEVIMBRA can cause immune-mediated rash or dermatitis. Cases of severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, some with fatal outcome. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue TEVIMBRA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.2% (24/1972) of patients receiving TEVIMBRA, including Grade 4 (0.2%), Grade 3 (0.4%), and Grade 2 (0.4%) adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of TEVIMBRA in 3 (0.2%) patients and withholding of TEVIMBRA in 9 (0.5%) patients. Twenty-three (96%) of the 24 patients received systemic corticosteroids. Immune-mediated skin reactions resolved in 58% of the 24 patients. Of the 9 patients in whom TEVIMBRA was withheld for dermatologic adverse reactions, 8 reinitiated TEVIMBRA after symptom improvement; of these, 2 (25%) patients had recurrence of immune-mediated rash. Other Immune-Mediated Adverse Reactions The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1972 patients who received TEVIMBRA: myositis, myocarditis, arthritis, polymyalgia rheumatica, and pericarditis. The following additional clinically significant immune-mediated adverse reactions have been reported with other PD-1/PD-L1 blocking antibodies, including severe or fatal cases. Cardiac/Vascular: Vasculitis Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy. Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.­­ Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis Musculoskeletal and Connective Tissue: Polymyositis, rhabdomyolysis and associated sequelae including renal failure Endocrine: Hypoparathyroidism Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection. Infusion-Related Reactions TEVIMBRA can cause severe or life-threatening infusion-related reactions. Infusion-related reactions occurred in 4.2% (83/1972) patients receiving TEVIMBRA, including Grade 3 or higher (0.3%) reactions. Monitor patients for signs and symptoms of infusion-related reactions. Slow the rate of infusion for mild (Grade 1) and interrupt the infusion for moderate (Grade 2) infusion-related reactions. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue TEVIMBRA. Complications of Allogeneic HSCT Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT. Embryo-Fetal Toxicity Based on its mechanism of action, TEVIMBRA can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TEVIMBRA and for 4 months after the last dose. ADVERSE REACTIONS Permanent discontinuation of TEVIMBRA due to an adverse reaction occurred in 19% of patients. Adverse reactions which resulted in permanent discontinuation in ≥ 1% of patients were hemorrhage, pneumonitis (including pneumonitis and immune-mediated pneumonitis), and pneumonia. Dosage interruptions of TEVIMBRA due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dosage interruptions in ≥ 2% of patients were pneumonia, pneumonitis, and fatigue. The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough. Please see full U.S. Prescribing Information including Medication Guide. About BeiGene BeiGene is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit and follow us on LinkedIn and X (formerly known as Twitter). Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding BeiGene’s ability to bring TEVIMBRA to more patients around the world; the future significance of TEVIMBRA in BeiGene’s solid tumor development program; the potential of TEVIMBRA to be an important treatment for ESCC; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law. To access BeiGene media resources, please visit our News & Media site. ___________________________ i Shen, L., Kato, K., Kim, S. B., Ajani, J. A., Zhao, K., He, Z., ... & Van Cutsem, E. (2022). Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): A randomized phase III study. Journal of Clinical Oncology. 40(26), 3065-3076. DOI: 10.1200/JCO.21.01926 ii Morgan E, et al. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022 Sep;163(3):649-658.e2. doi: 10.1053/j.gastro.2022.05.054. Epub 2022 Jun 4. PMID: 35671803. iii National Cancer Institute. Cancer stat facts: esophageal cancer. .

Submission is supported by data from the Phase 3 QUASAR program, which showed a significantly greater percentage of patients with moderately to severely active ulcerative colitis who received TREMFYA® achieved clinical remission at Week 44 compared with placebo SPRING HOUSE, Pa., March 11, 2024 /PRNewswire/ -- Johnson & Johnson today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of TREMFYA® (guselkumab) for treatment of adults with moderately to severely active ulcerative colitis (UC). The submission is based on results from the Phase 3 QUASAR program evaluating the efficacy and safety of TREMFYA® in the treatment of individuals living with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy, prior biologics and/or JAK inhibitors.1 The data show statistically significant and clinically meaningful improvements in symptoms, patient-reported outcomes such as fatigue and measures of disease activity including high bar endpoints such as endoscopic and histologic remission.2,3 The safety results were consistent with the known safety profile of TREMFYA® in approved indications.2,3,a "Despite advances in therapy, many people living with ulcerative colitis still experience inadequate response to or do not tolerate existing therapies," said David Lee, MD, PhD, Global Therapeutic Area Head Immunology. "TREMFYA has the potential to be a new treatment option for patients. We look forward to working with the FDA in review of this application and remain focused on developing new therapies for those living with chronic autoimmune conditions, such as ulcerative colitis, who are experiencing persistent and debilitating symptoms." TREMFYA® is a dual-acting IL-23i that blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23.4 IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases including UC.5 TREMFYA® was first approved in the U.S. in July 2017 for the treatment of adult patients with moderate-to-severe plaque psoriasis and was subsequently also approved for adults with active psoriatic arthritis in July, 2020.4 Clinical data from the Phase 3 QUASAR induction study through 12 weeks were presented at the 2023 Digestive Disease Week (DDW) Annual Meeting2 and results from the Phase 3 QUASAR maintenance study through 44 weeks will be presented at an upcoming medical meeting. Editor's Notes: a. TREMFYA® is not approved to treat UC. ABOUT THE QUASAR STUDY ( NCT04033445 ) QUASAR is a randomized, double-blind, placebo-controlled, parallel group, multicenter, seamless Phase 2b/3 program designed to evaluate the efficacy and safety of TREMFYA®, a selective IL-23 inhibitor, in adult patients with moderately to severely active ulcerative colitis who had an inadequate response or intolerance to conventional therapy (e.g., thiopurines or corticosteroids), prior biologics and/or JAK inhibitors (i.e., tumor necrosis factor-alpha antagonists, vedolizumab, or tofacitinib).1 QUASAR included a Phase 2b dose-ranging induction study, a confirmatory Phase 3 induction study, and a Phase 3 maintenance study. Efficacy, safety, pharmacokinetics, immunogenicity, and biomarkers are assessed at specified time points.1 ABOUT ULCERATIVE COLITIS Ulcerative colitis (UC) 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.6 It is the result of the immune system's overactive response.6 Symptoms vary, but may include loose and more urgent bowel movements, rectal bleeding or bloody stool, persistent diarrhea, abdominal pain, loss of appetite, weight loss and fatigue.6 ABOUT TREMFYA® (guselkumab) Developed by Johnson & Johnson, TREMFYA® is the first approved fully-human, dual-acting monoclonal antibody that blocks IL-23 by binding to the p19 subunit of IL-23 and binding to CD64, a receptor on cells that produce IL-23.4 IL-23 is an important driver of the pathogenesis of inflammatory diseases.5 Findings for dual acting are limited to in vitro studies that demonstrate guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model. The clinical significance of this finding is not known.7,8,9,10 TREMFYA® is approved in the U.S.,4 Canada,11 Japan12 and a number of other countries for the treatment of adults with moderate to severe plaque psoriasis (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 psoriatic arthritis ( PsA).4 It is also approved in the EU for the treatment of moderate to severe plaque PsO in adults who are candidates for systemic therapy and for the treatment of active PsA in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy.13 Johnson & Johnson maintains exclusive worldwide marketing rights to TREMFYA®. IMPORTANT SAFETY INFORMATION3 What is the most important information I should know about TREMFYA® (guselkumab)? TREMFYA® is a prescription medicine that may cause serious side effects, including: Serious Allergic Reactions. Stop using TREMFYA® and get emergency medical help right away if you develop any of the following symptoms of a serious allergic reaction: fainting, dizziness, feeling lightheaded (low blood pressure) swelling of your face, eyelids, lips, mouth, tongue or throat trouble breathing or throat tightness chest tightness skin rash, hives itching Infections. TREMFYA® may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with TREMFYA® and may treat you for TB before you begin treatment with TREMFYA® if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with TREMFYA®. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including: fever, sweats, or chills muscle aches weight loss cough warm, red, or painful skin or sores on your body different from your psoriasis diarrhea or stomach pain shortness of breath blood in your phlegm (mucus) burning when you urinate or urinating more often than normal Do not use TREMFYA® if you have had a serious allergic reaction to guselkumab or any of the ingredients in TREMFYA®. Before using TREMFYA®, tell your healthcare provider about all of your medical conditions, including if you: have any of the conditions or symptoms listed in the section "What is the most important information I should know about TREMFYA®?" have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You should avoid receiving live vaccines during treatment with TREMFYA®. are pregnant or plan to become pregnant. It is not known if TREMFYA® can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if TREMFYA® passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of TREMFYA®? TREMFYA® may cause serious side effects. See "What is the most important information I should know about TREMFYA®?" The most common side effects of TREMFYA® include: upper respiratory infections, headache, injection site reactions, joint pain (arthralgia), diarrhea, stomach flu (gastroenteritis), fungal skin infections, herpes simplex infections, and bronchitis. These are not all the possible side effects of TREMFYA®. Call your doctor for medical advice about side effects. Use TREMFYA® exactly as your healthcare provider tells you to use it. Please read the full Prescribing Information , including Medication Guide for TREMFYA®, and discuss any questions that you have with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1– 800– FDA– 1088. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. ABOUT JOHNSON & JOHNSON At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are a Johnson & Johnson companies. National Institutes of Health: Clinicaltrials.gov. A study of guselkumab in participants with moderately to severely active ulcerative colitis (QUASAR). Identifier: NCT04033445. Available at: . Accessed February 2024. 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. 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. US Food and Drug Administration. TREMFYA® Prescribing Information. Available at: . Accessed February 2024. 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. . Crohn's & Colitis Foundation. What is ulcerative colitis? Available at: . Accessed February 2024. Mehta H, et al. Differential Changes in inflammatory mononuclear phagocyte and T-Cell profiles within psoriatic skin during treatment with guselkumab vs. secukinumab. J Invest Dermatol 2021;141(7):1707-1718. Available at: . Accessed February 2024. Wang Y, et al. Monocytes/Macrophages play a pathogenic role in IL-23 mediated psoriasis-like skin inflammation. Sci Rep. 2019;9(1):5310. Available at: . Accessed February 2024. Matt P, et al. Up-regulation of CD64-expressing monocytes with impaired FcγR function reflects disease activity in polyarticular psoriatic arthritis. Scand J Rheumatol 2015; 44(6):464-473. Available at: . Accessed February 2024. McGonagle D, et al. Guselkumab, an IL-23p19 subunit–specific monoclonal antibody, binds CD64+ myeloid cells and potently neutralises IL-23 produced from the same cells. Presented at EULAR 2023, May 31-June 3. The Canadian Agency for Drugs & Technologies in Health. TREMFYA Prescribing Information. Available at: . Accessed February 2024. Japan Pharmaceuticals and Medical Devices Agency. Tremfya Report on the Deliberation Results. Available at: . Accessed February 2024. European Commission: Tremfya (guselkumab). Available at: . Accessed February 2024. SOURCE Johnson & Johnson