Tubular Sweat Gland Adenomas

In the AdFIrst study, Biotest's fibrinogen concentrate (FC), BT524, met the primary endpoint, demonstrating its effectiveness in treating acquired fibrinogen deficiency (AFD) as equivalent to standard of care, while maintaining an excellent safety pro > Regulatory approval process in Europe and United States set to begin in Q4 2024. It would be the first FC approved for an AFD indication in the U.S. in a global market for AFD with an estimated potential of USD 800 million This milestone is part of Grifols’ robust innovation strategy, balancing internal and external investments to build a comprehensive and diversified portfolio BARCELONA, Spain, Feb. 14, 2024 (GLOBE NEWSWIRE) -- Grifols (MCE: GRF, MCE: GRF.P NASDAQ: GRFS), one of the world’s leading producers of plasma-derived medicines, today announced that Biotest’s positive topline results from AdFIrst, its phase 3 clinical trial of its fibrinogen concentrate (FC), BT524, advance this potential treatment for acquired fibrinogen deficiency (AFD), an underserved growth market. The FC from Biotest, a Grifols Group company, met the primary endpoint. It is as effective as standard of care in reducing intraoperative blood loss in patients with AFD, while also maintaining an excellent safety profile. “This successful clinical trial is a significant stride towards a potential therapy that could contribute to the care of patients who experience severe blood loss during major surgery,” said Jörg Schüttrumpf, Grifols Chief Scientific Innovation Officer. AFD, which typically occurs during surgical procedures when there’s insufficient fibrinogen to arrest bleeding, is commonly treated with cryoprecipitate (a plasma extract) or fresh frozen plasma, both containing fibrinogen. The drawback is that they also contain other proteins and elements that aren’t necessary, so large volumes are needed to ensure enough fibrinogen. Plus both need to be thawed in advance, time consuming when lives are at risk. FC, which is also used to treat AFD, is a precision medicine in which patients on the operating table immediately receive only what’s essential to curtail hemorrhaging. BT524 will likely enter regulatory authorization processes in Q4 2024 starting in Europe and the United States. It would be the first FC approved for an AFD indication in the U.S. in a global market with an estimated potential of USD 800 million. Fibrinogen, a plasma protein produced in the liver, plays a key role in stopping blood loss and in wound healing. Grifols’ experience with it to manage surgical bleeding includes the fibrinogen-based fibrin sealant the company launched five years ago. “The positive results for Biotest’s fibrinogen are an important milestone and strengthen a Grifols innovation strategy that’s diversified across plasma and non-plasma, balanced between internal and external investments, and includes both shorter- and longer-term development cycles,” said Victor Grifols Deu, Grifols Chief Operating Officer. Detailed results of the trial will be presented later this year. Biotest, a Grifols innovation driver The acquisition of Biotest has significantly reinforced Grifols’ access to plasma, as well as the company’s pipeline and sales presence. Furthermore, it has provided new scientific and industrial capabilities, enabling improved revenue growth and margin expansion through the introduction of innovative plasma proteins. The step forward in BT524’s development comes in the middle of two other Biotest innovations that also highlight this company’s increasing contributions to Grifols’ profitable growth. In late 2022, Biotest’s new immunoglobulin (Ig) Yimmugo® entered the European market and is awaiting authorization to become available in the U.S. Another Biotest protein, trimodulin – a polyvalent immunoglobulin with IgM, IgA and IgG – is in two phase 3 clinical trials evaluating its efficacy and safety in patients with either community-acquired pneumonia (CAP) or severe community-acquired pneumonia (sCAP). About Biotest’s AdFIrst trial The trial for Biotest’s fibrinogen concentrate (FC), BT524, is known as AdFIrst (Adjusted Fibrinogen Replacement Strategy) was a prospective, active-controlled, multicenter phase 3 trial investigating the efficacy and safety of BT524 in patients with acquired fibrinogen deficiency. Patients who had high blood loss during planned spinal or abdominal surgery were randomized 1:1 to treatment with BT524 or cryoprecipitate/fresh frozen plasma (FFP). To evaluate the efficacy of BT524, further blood loss was compared between both treatment options. Further information about the trial design can be found at (EudraCT number: 2017-001163-20). The trial met its primary endpoint, demonstrating that Fibrinogen concentrate (BT524) is non-inferior to standard of care (SOC), in reducing intraoperative blood loss in patients with acquired fibrinogen deficiency undergoing planned major spinal or abdominal surgery. Mean blood loss measured in the two treatment groups were 1,444 mL in the BT524 group versus 1,735 mL in the SOC group, resulting in a reduction of blood loss of 291 mL in patients treated with fibrinogen concentrate. About fibrinogen and fibrinogen deficiency Fibrinogen is a blood clotting factor that is produced in the liver. It plays a key role in primary haemostasis (stopping blood loss from bleeding wounds) and wound healing. In case of a lack or shortage of fibrinogen the blood's ability to clot is impaired, which leads to a much greater risk of bleeding and delayed haemostasis. The fibrinogen concentrate alternatives fresh frozen plasma (FFP) and cryoprecipitate contain variable amounts of fibrinogen and must be thawed prior to treatment. The defined amount of fibrinogen in the fibrinogen concentrate will allow a tailor-made, patient specific and highly effective therapy. About Grifols Grifols is a global healthcare company founded in Barcelona in 1909 committed to improving the health and well-being of people around the world. A leader in essential plasma-derived medicines and transfusion medicine, the company develops, produces and provides innovative healthcare services and solutions in more than 110 countries. Patient needs and Grifols’ ever-growing knowledge of many chronic, rare and prevalent conditions, at times life-threatening, drive the company’s innovation in both plasma and other biopharmaceuticals to enhance quality of life. Grifols is focused on treating conditions across a broad range of therapeutic areas: immunology, hepatology and intensive care, pulmonology, hematology, neurology and infectious diseases. A pioneer in the plasma industry, Grifols continues to grow its network of donation centers, the world’s largest with over 390 across North America, Europe, Africa and the Middle East and China. As a recognized leader in transfusion medicine, Grifols offers a comprehensive portfolio of solutions designed to enhance safety from donation to transfusion, in addition to clinical diagnostic technologies. It provides high-quality biological supplies for life-science research, clinical trials, and for manufacturing pharmaceutical and diagnostic products. The company also supplies tools, information and services that enable hospitals, pharmacies and healthcare professionals to efficiently deliver expert medical care. Grifols, with more than 24,000 employees in more than 30 countries and regions, is committed to a sustainable business model that sets the standard for continuous innovation, quality, safety and ethical leadership. In 2022, Grifols’ economic impact in its core countries of operation was EUR 9.6 billion. The company also generated 193,000 jobs, including indirect and induced. The company’s class A shares are listed on the Spanish Stock Exchange, where they are part of the Ibex-35 (MCE:GRF). Grifols non-voting class B shares are listed on the Mercado Continuo (MCE:GRF.P) and on the U.S. NASDAQ through ADRs (NASDAQ:GRFS). For more information, please visit . MEDIA CONTACT: Media Press Office media@grifols.com Tel. +34 93 571 00 02 INVESTORS: Investors Relations Department & Sustainability inversores@grifols.com - investors@grifols.com sostenibilidad@grifols.com - sustainability@grifols.com Tel. +34 93 571 02 21 LEGAL DISCLAIMER The facts and figures contained in this report that do not refer to historical data are “future projections and assumptions”. Words and expressions such as “believe”, “hope”, “anticipate”, “predict”, “expect”, “intend”, “should”, “will seek to achieve”, “it is estimated”, “future” and similar expressions, insofar as they relate to the Grifols group, are used to identify future projections and assumptions. These expressions reflect the assumptions, hypotheses, expectations and predictions of the management team at the time of writing this report, and these are subject to a number of factors that mean that the actual results may be materially different. The future results of the Grifols group could be affected by events relating to its own activities, such as a shortage of supplies of raw materials for the manufacture of its products, the appearance of competitor products on the market, or changes to the regulatory framework of the markets in which it operates, among others. At the date of compiling this report, the Grifols group has adopted the necessary measures to mitigate the potential impact of these events. Grifols, S.A. does not accept any obligation to publicly report, revise or update future projections or assumptions to adapt them to events or circumstances subsequent to the date of writing this report, except where expressly required by the applicable legislation. This document does not constitute an offer or invitation to buy or subscribe shares in accordance with the provisions of the following Spanish legislation: Royal Legislative Decree 4/2015, of 23 October, approving recast text of Securities Market Law; Royal Decree Law 5/2005, of 11 March and/or Royal Decree 1310/2005, of 4 November, and any regulations developing this legislation. In addition, this document does not constitute an offer of purchase, sale or exchange, or a request for an offer of purchase, sale or exchange of securities, or a request for any vote or approval in any other jurisdiction. The information included in this document has not been verified nor reviewed by the external auditors of the Grifols group.

Patient Reported Outcomes (PROs) based on a May 16, 2022 data cutoff in the QUILT 3.032 trial indicate stability of physical function and global health in patients who completed PRO questionnaires and reached month 24 on-study Overall, participants with complete responses (CRs) to combination therapy with the novel interleukin-15 (IL-15) superagonist N-803 and bacillus Calmette-Guerin (BCG) reported better physical function than those who did not achieve a CR at month 6 Stability of these PROs supports the safety and tolerability of the potential new treatment combination Taken together with the positive durable 71% response and 89.2% cystectomy avoidance rates in cohort A and a favorable safety pro the May 16, 2022 data cutoff, along with the available PROs, support a favorable risk-benefit ratio for N-803 plus BCG in this patient population The Food and Drug Administration (FDA) is currently reviewing the Biologics License Application (BLA) for N-803 plus BCG for the treatment of NMIBC CIS with a Prescription Drug User Fee Act (PDUFA) date of April 23, 2024 CULVER CITY, Calif.--(BUSINESS WIRE)-- ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, today announced that findings from Patient-Reported Outcomes (PROs) of participants in the phase 2/3 QUILT 3.032 study of N-803 plus BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) were published by the peer-reviewed journal Urology Practice. These PROs support the positive interim results from the study published in NEJM Evidence, wherein 71% of patients in cohort A with CIS with or without Ta/T1 disease achieved a complete response. The published PROs based on a May 16, 2022 data cutoff indicate that both physical function and global health as self-reported by QUILT 3.032 participants with BCG-unresponsive NMIBC CIS (cohort A) or papillary disease (cohort B), remained stable over the 2-year course of the study for patients who completed the PRO questionnaires and reached 24 months on-study. In addition, overall both cohort A and B participants who reached month 24 on-study and also completed an NMIBC-specific questionnaire focusing on the challenges of bladder cancer, also reported no decline of their health or urinary tract-related symptoms while in the study. Overall, participants who achieved a complete response with the novel combination therapy reported better physical function by month six of the study than those who did not achieve a complete response. “The self-reported stability of health and physical function over the course of the study by the participants reflect another aspect of safety and tolerability of this new combination therapy,” said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. “Taken together with the positive response rate in cohort A of over 70%, the persistence of responses and cystectomy avoidance, these QoL findings suggest a favorable risk-benefit ratio for this potential new therapeutic option for patients with BCG-unresponsive bladder cancer.” The finding of relative stability of global health and physical function during the course of the study is similar to that reported by others for BCG monotherapy, suggesting the novel combination is as tolerable as treatment with BCG alone. “Many current therapies for bladder cancer slow disease progression but can cause debilitating side effects,” said Principal Investigator Karim Chamie, M.D., Associate Professor of Urology at UCLA. “The data from the QUILT 3.032 Quality of Life study suggest that many patients not only have a durable response but also report no decline in physical function, which is very important for these patients.” QUILT 3.032 Study Details The ongoing phase 2/3 open-label multicenter registrational study QUILT 3.032 (NCT03022825) is evaluating the safety and efficacy of the investigational interleukin-15 superagonist N-803 (also known as Anktiva® and nogapendekin alfa inbakicept, NAI) in combination with a standard therapy for NMIBC, bacillus Calmette-Guerin (BCG), in patients who failed or in whom cancer returned after BCG monotherapy, and thus were diagnosed as BCG-unresponsive. The study comprises three cohorts, with cohort A enrolling patients with carcinoma in situ (CIS) with or without Ta/T1 disease and cohort B enrolling patients with high grade Ta/T1 papillary disease. Both cohorts A and B received combination N-803 plus BCG therapy. Cohort C patients, with CIS +/- Ta/T1 disease received N-803 monotherapy. The primary end point is the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival are secondary end points for cohort A. Cohort C was discontinued due to a low response rate with N-803 monotherapy, per study design. The FDA has accepted for review ImmunityBio’s resubmission of its biologics license application (BLA) for N-803 plus BCG for the treatment of BCG-unresponsive NMIBC CIS with or without Ta or T1 disease, and has set a user fee goal date (PDUFA date) of April 23, 2024. Bladder cancer is the 10th most-commonly diagnosed cancer, with approximately 80% of newly diagnosed cases being NMIBC. Intravesical (directly to the bladder) instillation of BCG after removal of cancer tissue from the lining of the bladder (transurethral resection of the bladder tumor; TURBT) is Standard-of-Care (SoC) for intermediate and high-risk NMIBC patients, but up to 40% of patients will fail BCG therapy and ~50% will relapse after an initial response and given a diagnosis of being BCG-unresponsive. Therapies approved by the FDA for this indication include pembrolizumab, nadofaragene, combined gemcitabine and docetaxel, and valrubicin. Radical cystectomy – surgical removal of the bladder - is also an option for these patients. QUILT 3.032 is being conducted to address the need for a safe, effective therapeutic option for BCG-unresponsive NMIBC patients that provides an opportunity for avoidance of radical cystectomy. N-803 is investigational. Safety and efficacy have not been established by any Health Authority or Agency, including the FDA. About ImmunityBio ImmunityBio is a vertically-integrated, clinical-stage biotechnology company developing next-generation therapies and vaccines that bolster the natural immune system to defeat cancers and infectious diseases. The Company’s range of immunotherapy and cell therapy platforms, alone and together, act to drive and sustain an immune response with the goal of creating durable and safe protection against disease. ImmunityBio is applying its science and platforms to treating cancers, including the development of potential cancer vaccines, as well as developing immunotherapies and cell therapies that ImmunityBio believes sharply reduce or eliminates the need for standard high-dose chemotherapy. These platforms and their associated product candidates are designed to be more effective, accessible, and easily administered than current standards of care in oncology and infectious diseases. For more information, please visit Immunitybio.com. Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements regarding data and results from ongoing clinical trials and potential implications therefrom, potential benefits to patients, potential treatment outcomes for patients, the regulatory review process and timing thereof, market and prevalence data, and ImmunityBio’s investigational agents as compared to other existing and potential treatment options, among others. While ImmunityBio believes the BLA resubmission addresses the issues identified in the FDA’s complete response letter, there is no guarantee that the FDA will ultimately agree that such issues have been successfully addressed and resolved. Statements in this press release that are not statements of historical fact are considered forward-looking statements, which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “goal,” “could,” “estimates,” “scheduled,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “indicate,” “projects,” “seeks,” “should,” “will,” “strategy,” and variations of such words or similar expressions. Statements of past performance, efforts, or results of our preclinical and clinical trials, about which inferences or assumptions may be made, can also be forward-looking statements and are not indicative of future performance or results. Forward-looking statements are neither forecasts, promises nor guarantees, and are based on the current beliefs of ImmunityBio’s management as well as assumptions made by and information currently available to ImmunityBio. Such information may be limited or incomplete, and ImmunityBio’s statements should not be read to indicate that it has conducted a thorough inquiry into, or review of, all potentially available relevant information. Such statements reflect the current views of ImmunityBio with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about ImmunityBio, including, without limitation, (i) the risks and uncertainties associated with the regulatory review process, (ii) whether or not the FDA will ultimately determine that the BLA resubmission and related actions successfully addresses and resolves the issues identified in the FDA’s complete response letter, (iii) uncertainties regarding the timeline of FDA review of the resubmitted BLA, (iv) any inability to successfully work with the FDA to find a satisfactory solution to address any concerns in a timely manner or at all during the review process for the BLA, including any inability to provide the FDA with data, analysis or other information sufficient to support an approval of the BLA, (v) the ability of ImmunityBio and its third party contract manufacturing organizations to adequately address the issues raised in the CRL, (vi) any potential facility re-inspections that may be required regarding ImmunityBio’s third party contract manufacturing organizations or otherwise and results therefrom, (vii) whether the FDA accepts the data and results as included in the BLA resubmission at levels consistent with the published results, or at all, (viii) the ability of ImmunityBio to continue its planned preclinical and clinical development of its development programs through itself and/or its investigators, and the timing and success of any such continued preclinical and clinical development and planned regulatory submissions, (xi) ImmunityBio’s ability to retain and hire key personnel, (ix) ImmunityBio’s ability to obtain additional financing to fund its operations and complete the development and commercialization of its various product candidates, (x) ImmunityBio’s ability to successfully commercialize its product candidates and uncertainties around regulatory reviews and approvals, (xi) ImmunityBio’s ability to scale its manufacturing and commercial supply operations for its product candidates and future approved products, and (xii) ImmunityBio’s ability to obtain, maintain, protect and enforce patent protection and other proprietary rights for its product candidates and technologies. More details about these and other risks that may impact ImmunityBio’s business are described under the heading “Risk Factors” in the Company’s Form 10-K filed with the U.S. Securities and Exchange Commission (“SEC”) on March 1, 2023 and the Company’s Form 10-Q filed with the SEC on November 9, 2023, and in subsequent filings made by ImmunityBio with the SEC, which are available on the SEC’s website at . ImmunityBio cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. ImmunityBio does not undertake any duty to update any forward-looking statement or other information in this press release, except to the extent required by law.

Data from Cohort 1 of the Phase 2 THOR-2 study showed oral erdafitinib reduced the risk of disease recurrence or death compared with intravesical standard-of-care chemotherapy MADRID, Oct. 21, 2023 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the Phase 2 randomized, open-label THOR-2 study evaluating BALVERSA® versus investigator choice of intravesical chemotherapy in patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) and select fibroblast growth factor receptor (FGFR) alterations which recurred after Bacillus Calmette-Guérin (BCG) therapy. Data from Cohort 1 of the study were featured today in a Proffered Paper Late-Breaking Session (Abstract #LBA102) at the European Society for Medical Oncology (ESMO) 2023 Congress taking place October 20-24 in Madrid, Spain, and simultaneously published in Annals of Oncology.1,2 Of the 73 patients included in Cohort 1, 49 were randomized to BALVERSA® and 24 were randomized to chemotherapy. Oral erdafitinib reduced the risk of recurrence of disease or death by 72 percent compared with intravesical chemotherapy in patients with high-risk resected papillary Ta/T1 NMIBC harboring FGFR mutations or fusions with recurrence after BCG treatment and who refused or were ineligible for radical cystectomy. With a median follow-up of 13.4 months at the data cutoff, median recurrence-free survival (RFS) was not met in patients who received BALVERSA® and was 11.6 months for patients who received chemotherapy (Hazard Ratio [HR]=0.28; 95 percent Confidence Interval [CI], 0.13-0.62; nominal p=0.0008). The six-month RFS in patients randomized to BALVERSA® was 96 percent compared to 73 percent in those assigned to chemotherapy. The 12-month RFS in patients assigned to BALVERSA® was 77 percent compared to 41 percent in patients who received chemotherapy. Grade 3 or 4 serious treatment-related adverse events (TRAEs) were observed in fifteen patients (31 percent) who received BALVERSA® and one patient (4 percent) randomized to chemotherapy. Fourteen patients (29 percent) assigned to BALVERSA® and zero patients who received intravesical chemotherapy had TRAEs that lead to discontinuation of treatment. Central serous retinopathy occurred in 19 patients (39 percent) who received BALVERSA® and resolved in 11 patients (58 percent). "Patients with NMIBC who experience disease recurrence after BCG treatment have limited treatment options, and those eligible patients with FGFR alterations who received erdafitinib in the THOR-2 trial had far fewer recurrences against patients treated by the current standard of care," said James W.F. Catto*, Ph.D., Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK and presenting author of the study. "Our findings underscore the importance of detecting certain genetic biomarkers to identify patients who may benefit from treatment with a targeted therapy like erdafitinib." "Janssen's ongoing development of BALVERSA reinforces our commitment to bringing targeted, precision medicines to patients with FGFR-driven bladder cancer," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "These results support the importance of testing for FGFR in early-stage bladder cancer and potential benefit with BALVERSA in patients with high-risk non-muscle-invasive bladder cancer where disease progression and poor outcomes are common." About THOR-2 THOR 2 (NCT04172675) is a Phase 2 randomized, open-label study evaluating BALVERSA® versus investigator choice of intravesical chemotherapy in participants with NMIBC who recurred after BCG therapy. Patients are categorized to one of three cohorts based on their disease presentation: patients with HR-NMIBC and a papillary tumour only, where early cancer cells are still confined within the innermost layer of the bladder lining (Cohort 1), patients with HR-NMIBC presenting as carcinoma in situ (CIS) with or without a concurrent papillary tumour (Cohort 2), or patients with intermediate-risk NMIBC presenting with papillary disease only (Cohort 3). Patients in Cohort 1 are randomized to receive either BALVERSA® or chemotherapy (mitomycin C or gemcitabine) in a 2:1 ratio and all patients in Cohorts 2 and 3 will receive BALVERSA®. The Cohort 1 primary endpoint is RFS; secondary endpoints include RFS at six- and 12-months, time to progression, overall survival, plasma concentration of BALVERSA® and number of patients with adverse events. The study consists of screening period, treatment phase, follow-up phase and long-term extension phase. About BALVERSA ® BALVERSA® (erdafitinib) is a once-daily, oral FGFR kinase inhibitor that received accelerated approval in 2019 for the treatment of adults with locally advanced or metastatic urothelial carcinoma (mUC) which has susceptible FGFR3 or FGFR2 genetic alterations and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Patients are selected for therapy based on an FDA-approved companion diagnostic for BALVERSA®. Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer is available at: In addition to the Phase 2 THOR-2 study, BALVERSA® is being studied in the Phase 3 THOR (NCT03390504) study comparing BALVERSA® in two cohorts; BALVERSA® versus standard of care chemotherapy (investigators choice of docetaxel or vinflunine) after at least one line of treatment including an anti-programmed death (ligand) 1 (PD-[L]1) agent (Cohort 1); and BALVERSA® compared to pembrolizumab after one prior treatment not containing an anti-PD-(L)1 agent (Cohort 2) in patients with metastatic or unresectable urothelial carcinoma, with selected FGFR genetic alterations, who showed disease progression during or after one or two prior lines of treatment.4,5 In August 2023, Janssen submitted a Supplemental New Drug Application to the U.S. Food and Drug Administration seeking the full approval of BALVERSA® based upon data from Cohort 1 Phase 3 THOR study. The Company also submitted a marketing authorization application to the European Medicines Agency in September 2023. In 2008, Janssen Pharmaceutica NV entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialize BALVERSA®. For more information, visit . About High-Risk Non-Muscle-Invasive Bladder Cancer High-risk non-muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer compared to low-risk NMIBC.6,7 HR-NMIBC makes up 15–44 percent of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS. Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.8,9 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.10 The high rates of recurrence and progression can pose significant morbidity and distress for these patients.9,11 BALVERSA® IMPORTANT SAFETY INFORMATION12 WARNINGS AND PRECAUTIONS Ocular Disorders – BALVERSA® can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) resulting in visual field defect. CSR/RPED was reported in 25% of patients treated with BALVERSA®, with a median time to first onset of 50 days. Grade 3 CSR/RPED, involving central field of vision, was reported in 3% of patients. CSR/RPED resolved in 13% of patients and was ongoing in 13% of patients at the study cutoff. CSR/RPED led to dose interruptions and reductions in 9% and 14% of patients, respectively, and 3% of patients discontinued BALVERSA®. Dry eye symptoms occurred in 28% of patients during treatment with BALVERSA® and were Grade 3 in 6% of patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed. Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms. Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography. Withhold BALVERSA® when CSR occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 in severity. For ocular adverse reactions, follow the dose modification guidelines [see Dosage and Administration (2.3)]. Hyperphosphatemia and Soft Tissue Mineralization – BALVERSA® can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification. Increases in phosphate levels are a pharmacodynamic effect of BALVERSA® [see Pharmacodynamics (12.2)]. Hyperphosphatemia was reported as an adverse reaction in 76% of patients treated with BALVERSA®. The median onset time for any grade event of hyperphosphatemia was 20 days (range: 8–116) after initiating BALVERSA®. Thirty-two percent of patients received phosphate binders during treatment with BALVERSA®. Cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification have been observed in 0.3% of patients treated with BALVERSA®. Monitor for hyperphosphatemia throughout treatment. In all patients, restrict phosphate intake to 600-800 mg daily. If serum phosphate is above 7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate level returns to <5.5 mg/dL. Withhold, dose reduce, or permanently discontinue BALVERSA® based on duration and severity of hyperphosphatemia [see Dosage and Administration (2.3), Table 2: Dose Modifications for Adverse Reactions]. Embryo-Fetal Toxicity – Based on the mechanism of action and findings in animal reproduction studies, BALVERSA® can cause fetal harm when administered to a pregnant woman. In a rat embryo-fetal toxicity study, erdafitinib was embryotoxic and teratogenic at exposures less than the human exposures at all doses studied. Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)]. Most common adverse reactions including laboratory abnormalities ≥20%: Phosphate increased (76%), stomatitis (56%), fatigue (54%), creatinine increased (52%), diarrhea (47%), dry mouth (45%), nail disorder (45%), alanine aminotransferase increased (41%), alkaline phosphatase increased (41%), sodium decreased (40%), decreased appetite (38%), albumin decreased (37%), dysgeusia (37%), hemoglobin decreased (35%), dry skin (34%), aspartate aminotransferase increased (30%), magnesium decreased (30%), dry eye (28%), alopecia (26%), palmar-plantar erythrodysesthesia syndrome (26%), constipation (28%), phosphate decreased (24%), abdominal pain (23%), calcium increased (22%), nausea (21%), and musculoskeletal pain (20%). The most common Grade 3 or greater adverse reactions (>1%) were stomatitis (9%), nail dystrophy*, palmar-plantar erythrodysesthesia syndrome (6%), paronychia (3%), nail disorder (10%), keratitis†, and hyperphosphatemia (1%). *Included within nail disorder. †Included within dry eye. An adverse reaction with a fatal outcome in 1% of patients was acute myocardial infarction. Serious adverse reactions occurred in 41% of patients, including eye disorders (10%). Permanent discontinuation due to an adverse reaction occurred in 13% of patients. The most frequent reasons for permanent discontinuation included eye disorders (6%). Dosage interruptions occurred in 68% of patients. The most frequent adverse reactions requiring dosage interruption included hyperphosphatemia (24%), stomatitis (17%), eye disorders (17%), and palmar-plantar erythrodysesthesia syndrome (8%). Dose reductions occurred in 53% of patients. The most frequent adverse reactions for dose reductions included eye disorders (23%), stomatitis (15%), hyperphosphatemia (7%), palmar-plantar erythrodysesthesia syndrome (7%), paronychia (7%), and nail dystrophy (6%). Drug Interactions Moderate CYP2C9 or strong CYP3A4 Inhibitors: Consider alternative agents or monitor closely for adverse reactions. (7.1) Strong CYP2C9 or CYP3A4 inducers: Avoid concomitant use with BALVERSA®. (7.1) Moderate CYP2C9 or CYP3A4 inducers: Increase BALVERSA® dose up to 9 mg. (7.1) Serum phosphate level-altering agents: Avoid concomitant use with agents that can alter serum phosphate levels before the initial dose modification period. (2.3, 7.1) CYP3A4 substrates: Avoid concomitant use with sensitive CYP3A4 substrates with narrow therapeutic indices. (7.2) OCT2 substrates: Consider alternative agents or consider reducing the dose of OCT2 substrates based on tolerability. (7.2) P-gp substrates: Separate BALVERSA® administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic indices. (7.2) Use in Specific Populations Lactation – Because of the potential for serious adverse reactions from erdafitinib in a breastfed child, advise lactating women not to breastfeed during treatment with BALVERSA® and for one month following the last dose. Please see the full Prescribing Information for BALVERSA®. About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Oncology, Immunology, Neuroscience, Cardiovascular, Pulmonary Hypertension, and Retina. Learn more at . Follow us at @JNJInnovMed and @JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc. are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of BALVERSA® (erdafitinib). 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; competition, including technological advances, new products and patents attained by competitors; challenges to patents; 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 January 1, 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. *Dr. Catto has not been paid for any media work. ____________________ 1 Catto J, et al. THOR-2 Cohort 1: Results of Erdafitinib (Erda) vs Intravesical Chemotherapy (Chemo) in Patients (Pts) With High-Risk Non–Muscle-Invasive Bladder Cancer (HR NMIBC) With Select Fibroblast Growth Factor Receptor Alterations (FGFRalt) Who Received Prior Bacillus Calmette-Guérin (BCG) Treatment. 2023 European Society for Medical Oncology Congress. Presented at the 2023 European Society for Medical Oncology Congress. 2 Catto J, et al. Erdafitinib in BCG-treated high-risk non-muscle invasive bladder cancer. Annals of Oncology. Published online: October 20, 2023. Available at: (23)04015-2/fulltext 3 U.S. Food & Drug Administration. FDA grants accelerated approval to erdafitinib for metastatic urothelial carcinoma. Available at: . Accessed September 2021. 4 Clincialtrials.gov. A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations. . Accessed May 2023. 5 ASCO Publications. Phase 3 THOR study: Results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt). Available at: 6 Grab-Heyne K, et al. Intermediate and high-risk non-muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs. Front Oncol. 2023;13:1170124. 7 Lieblich A, et al. The management of non-muscle-invasive bladder cancer: A comparison of European and UK guidelines. J Clin Urol. 2018;11(2):144-148. 8 Claps F, et al. BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer: Current Treatment Landscape and Novel Emerging Molecular Targets. Int J Mol Sci. 2023;24(16):12596. 9 Brooks NA, O'Donnell MA. Treatment options in non-muscle-invasive bladder cancer after BCG failure. Indian J Urol. 2015;31(4):312-319. doi:10.4103/0970-1591.166475. 10 Guancial EA, et al. Bladder cancer in the elderly patient: challenges and solutions. Clin Interv Aging. 2015; 10:939–949. 11 Chamie K, et al. Recurrence of high-risk bladder cancer: A population-based analysis. Cancer. 2013. 119(17):3219–3227. 12 BALVERSA Prescribing Information. Media Contacts: Suzanne Frost +1 416-317-0304 Brian Kenney +1 215-620-0111 Investor Relations: Raychel Kruper [email protected] U.S. Medical Inquiries: +1 800-526-7736 SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson