Infliximab

MoonLake Immunotherapeutics Reports Third Quarter 2024 Financial Results and Provides a Business Update Ended the third quarter with $493.9 million in cash, cash equivalents and short-term marketable debt securities, expected to support a roadmap rich in potential catalysts and a cash runway to the end of 2026Strong market performance of other IL-17 inhibitors in hidradenitis suppurativa (HS) and other inflammatory indications validating large market opportunity for sonelokimabPhase 3 clinical program in HS is progressing as per plan with primary endpoint readout anticipated as of mid-2025Preparations for Phase 3 clinical program in psoriatic arthritis (PsA) completed with patient enrollment expected to commence imminentlyAdditional Phase 2 programs, including trials in palmoplantar pustulosis (PPP) and axial spondyloarthritis (axSpA), and Phase 3 trial in adolescent HS, on track to commence around year-end ZUG, Switzerland, November 7, 2024 – MoonLake Immunotherapeutics (NASDAQ:MLTX) (“MoonLake” or the “Company”), a clinical-stage biotechnology company focused on creating next-level therapies for inflammatory diseases, today announced its financial results for the third quarter of 2024. During this period, MoonLake has made significant progress with the clinical development of its Nanobody® sonelokimab, which targets IL-17A and IL-17F dimers and are heavily implicated in the pathology of several Type 3 dermatological and rheumatological inflammatory conditions. Dr. Jorge Santos da Silva, Chief Executive Officer of MoonLake Immunotherapeutics, said: “MoonLake continued to make good clinical progress with sonelokimab in the third quarter across several large dermatology and rheumatology indications, with multiple Phase 3 and Phase 2 trials either underway or starting soon. The strong clinical data that we continue to build on suggests that the ability to inhibit all IL-17A and IL-17F containing dimers, together with the molecular advantages of our Nanobody®, translate into higher clinical responses for patients, and provide ample opportunity for differentiation of sonelokimab versus all competitors. We look forward to 2025 with multiple data catalysts, including the expected primary readout of our Phase 3 VELA program in HS as of mid-year.” Q3 highlights: Phase 3 HS program progressing well: clinical study sites across North America and Europe are actively enrolling patients into the identical VELA-1 and VELA-2 studies, to enable the anticipated primary endpoint readout as of mid-2025Preparations for the Phase 3 PsA program completed: imminent enrollment of first patients into the IZAR-1 study for bio-naïve* patients and into the IZAR-2 study for TNF-IR** patients, the first study including an IL-23 inhibitor as an active reference armPreparation for first ever dedicated clinical trial in adolescent HS on track: Phase 3 VELA TEEN clinical trial scheduled to commence around year-endPreparations for three additional Phase 2 trials advancing well: the LEDA trial in PPP and the S-OLARIS trial in axSpA anticipated to start around year-end, and the P-OLARIS trial in patients with seronegative spondylarthritis scheduled to start in early 2025Strong commercial performance of other IL-17 inhibitors in both HS and other inflammatory indications continues to outperform “street” expectations, leading to greater awareness and diagnosis, driving market growth and further validating the significant commercial opportunity for sonelokimab with its highly differentiated molecular characteristics (small Nanobody® size and both IL17A and IL-17F dimer binding) and potentially best in class clinical data to date * Patients without previous exposure to biologics ** Patients with an inadequate response to TNF inhibitors Third quarter 2024 financial results As of September 30, 2024, MoonLake held cash, cash equivalents and short-term marketable debt securities of $493.9 million. Research and development expenses for the quarter ended September 30, 2024, were $35.7 million, compared to $23.7 million in the previous quarter. The increase was primarily due to expenses pertaining to the ramp-up of the Phase 3 VELA program in HS and to prepare for the start of the new clinical trials in PsA, PPP and axSpA. General and administrative expenses for the quarter ended September 30, 2024 were $7.4 million, compared to the $6.9 million incurred in the previous quarter. The increase was primarily due to personnel-related costs to support organizational growth. Matthias Bodenstedt, Chief Financial Officer at MoonLake Immunotherapeutics, said: “MoonLake delivered a solid financial performance in Q3, with a strong cash position to at least the end of 2026. We continue to maintain a tight control of costs with a laser focus on value and delivery of our core company goals. We are incredibly fortunate to be custodians of sonelokimab which, as a pipeline-in-a-product across multiple large indications, could be worth over $8bn in sales by 2035 across the indications we are currently targeting. To optimally capture this opportunity, we continue to invest into our large clinical development programs (enrolling over 2,500 patients globally) whilst ramping up preparations for regulatory filings, and other pre-commercial activities.” Upcoming investor and medical conferences: American College of Rheumatology (ACR) Conference, November 14-19 Washington DC, USJefferies London Healthcare Conference, November 19-21, 2024, London, UKCiti’s 19th Annual BioPharma Conference, December 3-5, Miami, USJP Morgan Annual Healthcare Conference, January 13-16, San Francisco, US14th Conference of the European Hidradenitis Suppurativa Foundation e.V., Vilnius, Lithuania, February 12-14American Academy of Dermatology 2025 Annual Meeting, 7-11 March, Orlando, Florida -Ends- About MoonLake Immunotherapeutics MoonLake Immunotherapeutics is a clinical-stage biopharmaceutical company unlocking the potential of sonelokimab, a novel investigational Nanobody® for the treatment of inflammatory disease, to revolutionize outcomes for patients. Sonelokimab inhibits IL-17A and IL-17F by inhibiting the IL-17A/A, IL-17A/F, and IL17F/F dimers that drive inflammation. The company’s focus is on inflammatory diseases with a major unmet need, including hidradenitis suppurativa and psoriatic arthritis – conditions affecting millions of people worldwide with a large need for improved treatment options. MoonLake was founded in 2021 and is headquartered in Zug, Switzerland. Further information is available at www.moonlaketx.com. About Sonelokimab Sonelokimab (M1095) is an investigational ~40 kDa humanized Nanobody® consisting of three VHH domains covalently linked by flexible glycine-serine spacers. With two domains, sonelokimab selectively binds with high affinity to IL-17A and IL-17F, thereby inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers. A third central domain binds to human albumin, facilitating further enrichment of sonelokimab at sites of inflammatory edema. Sonelokimab is being assessed in two lead indications, HS and PSA, and MoonLake is pursuing other indications in dermatology and rheumatology. For HS, sonelokimab is being assessed in the Phase 3 trials, VELA-1 and VELA-2, following the successful outcome of MoonLake’s end-of-Phase 2 interactions with the FDA and as well as positive feedback from its interactions with the EMA announced in February 2024. In June 2023, topline results of the MIRA trial (NCT05322473) at 12 weeks showed that the trial met its primary endpoint, the Hidradenitis Suppurativa Clinical Response (HiSCR)75, which is a higher measure of clinical response versus the HiSCR50 measure used in other clinical trials, setting a landmark milestone. In October 2023, the full dataset from the MIRA trial at 24 weeks showed that maintenance treatment with sonelokimab led to further improvements in HiSCR75 response rates and other high threshold clinical and patient relevant outcomes. The safety profile of sonelokimab in the MIRA trial was consistent with previous trials with no new safety signals detected. For PsA, sonelokimab is being assessed in the Phase 3 trials, IZAR-1 and IZAR-2, following the announcement in March 2024 of the full dataset from the global Phase 2 ARGO trial (M1095-PSA-201) evaluating the efficacy and safety of the Nanobody® sonelokimab over 24 weeks in patients with active PsA. Significant improvements were observed across all key outcomes, including up to 61% of patients treated with sonelokimab achieving an American College of Rheumatology (ACR) 50 response and Minimal Disease Activity (MDA) at week 24. This followed the positive top-line results in November 2023, where the trial met its primary endpoint with a statistically significant greater proportion of patients treated with either sonelokimab 60mg or 120mg (with induction) achieving ACR50 response compared to those on placebo at week 12. All key secondary endpoints in the trial were met for the 60mg and 120mg doses with induction. The safety profile of sonelokimab in the ARGO trial was consistent with previous trials with no new safety signals detected. A Phase 2 trial is expected to be initiated in 2024 for palmo-plantar pustulosis (PPP), a debilitating inflammatory skin condition affecting a significant number of patients. In addition, in 2024, a Phase 3 trial is expected to be initiated in adolescent HS, a condition that typically manifests at this early stage of a patient’s life, and the period in which irreversible damage and inflammatory remission is most critical. Sonelokimab also is also planned to be assessed for seronegative spondyloarthritis with a Phase 2 trial in radiographic and non-radiographic axial spondyloarthritis (axSpA) expected to start by end of 2024, and a Phase 2 trial in axSpA with PsA in 2025. The trials are expected to feature an innovative design complementing traditional clinical outcomes with modern imaging techniques. Sonelokimab has also been assessed in a randomized, placebo-controlled third party Phase 2b trial (NCT03384745) in 313 patients with moderate-to-severe plaque-type psoriasis. High threshold clinical responses (Investigator’s Global Assessment Score 0 or 1, and Psoriasis Area and Severity Index 90/100) were observed in patients with moderate-to-severe plaque-type psoriasis. Sonelokimab was generally well tolerated, with a safety profile similar to the active control, secukinumab (Papp KA, et al. Lancet. 2021; 397:1564-1575). In an earlier third party Phase 1 trial in patients with moderate-to-severe plaque-type psoriasis, sonelokimab has been shown to decrease (to normal skin levels) the cutaneous gene expression of pro-inflammatory cytokines and chemokines (Svecova D. J Am Acad Dermatol. 2019;81:196–203). About Nanobodies® Nanobodies® represent a new generation of antibody-derived targeted therapies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies (VHH). Nanobodies® have a number of potential advantages over traditional antibodies, including their small size, enhanced tissue penetration, resistance to temperature changes, ease of manufacturing, and their ability to be designed into multivalent therapeutic molecules with bespoke target combinations. The terms Nanobody® and Nanobodies® are trademarks of Ablynx, a Sanofi company. About the VELA program The VELA program is expected to enroll 800 patients across two similarly designed Phase 3 trials (VELA-1 and VELA-2) with the aim to evaluate the efficacy and safety of the Nanobody® sonelokimab, administered subcutaneously, in adult patients with active moderate-to-severe hidradenitis suppurativa. Similar to the design of the landmark Phase 2 MIRA trial, the primary endpoint of the program is the percentage of participants achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75), defined as a ≥75% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline. The trial will also evaluate a number of secondary endpoints, including the proportion of patients achieving Hidradenitis Suppurative Clinical Response (HiSCR50), the change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4), the proportion of patients achieving a Dermatology Life Quality Index (DLQI) total score of ≤5, and the proportion of patients achieving at least 30% reduction from baseline in Numerical Rating Scale (NRS30) in the Patient’s Global Assessment of Skin Pain (PGA Skin Pain). Further details are available under NCT06411379 and NCT06411899 at www.clinicaltrials.gov. About IZAR IZAR-1 (NCT06641076) and IZAR-2 (NCT06641089) are global, randomized, double-blind, placebo-controlled Phase 3 trials designed to evaluate the efficacy and safety of sonelokimab compared with placebo in a total of approximately 1,500 adults with active PsA, with a primary endpoint of superiority to placebo in ACR 50 response at Week 16. IZAR-1 will enroll biologic-naïve patients and include an evaluation of radiographic progression, while IZAR-2 will enroll patients with an inadequate response to tumor necrosis factor-α inhibitors (TNF-IR) — reflecting patients commonly seen in clinical practice — and will be the first PsA trial to include a risankizumab active reference arm. Both trials will also assess a range of secondary endpoints reflecting the multiple disease manifestations characteristic of PsA. These include skin and nail outcomes, multidomain outcomes, and patient-reported outcome measures such as pain and quality of life assessments. About Hidradenitis Suppurativa Hidradenitis suppurativa is a severely debilitating chronic skin condition resulting in irreversible tissue destruction. HS manifests as painful inflammatory skin lesions, typically around the armpits, groin, and buttocks. Over time, uncontrolled and inadequately treated inflammation can result in irreversible tissue destruction and scarring. The disease affects 0.05–4.1% of the global population, with three times more females affected than males. Real-world data in the US indicates that at least 2 million unique patients have been diagnosed with and treated for HS between 2016 and 2023 alone, highlighting a significant unmet need and impact on healthcare systems, and a market opportunity exceeding $10bn by 2035. Onset typically occurs in early adulthood and HS has a profound negative impact on quality of life, with a higher morbidity than other dermatologic conditions. There is increasing scientific evidence to support IL-17A- and IL-17-mediated inflammation as a key driver of the pathogenesis of HS, with other identified risk factors including genetics, cigarette smoking, and obesity. About Psoriatic Arthritis Psoriatic arthritis (PsA) is a chronic, progressive and complex inflammatory disease that manifests across multiple domains, leading to substantial functional impairment and decreased quality of life. The clinical features of PsA are diverse, comprising both musculoskeletal (peripheral arthritis, spondylitis, dactylitis, and enthesitis) and non-musculoskeletal (skin and nail disease) domains. PsA occurs in up to 30% of patients with psoriasis, most commonly those aged between 30 and 60 years. Although the exact mechanism of disease is not fully understood, evidence suggests that activation of the IL-17 pathway plays an important role in the disease pathophysiology. Cautionary Statement Regarding Forward Looking Statements This press release contains certain “forward-looking statements” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements include, but are not limited to, statements regarding MoonLake’s expectations, hopes, beliefs, intentions or strategies regarding the future including, without limitation, statements regarding: plans for and timing of clinical trials, including initiation of Phase 3 VELA TEEN trial of sonelokimab in adolescents with HS, commencement of clinical trials of sonelokimab in PPP, axSpA and seronegative spondylarthritis, topline results of the Phase 3 VELA program of sonelokimab in HS and enrollment of first patents into Phase 3 IZAR-1 and IZAR-2 trials, the efficacy and safety of sonelokimab for the treatment of HS, PsA, PPP, axSpA and seronegative spondylarthritis, including in comparison to existing standards or care or other competing therapies, clinical trials and research and development programs and the anticipated timing of the results from those studies and trials, potential market opportunities for sonelokimab and our anticipated cash usage and the period of time we anticipate such cash to be available. In addition, any statements that refer to projections, forecasts, or other characterizations of future events or circumstances, including any underlying assumptions, are forward- looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that statement is not forward looking. Forward-looking statements are based on current expectations and assumptions that, while considered reasonable by MoonLake and its management, as the case may be, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with MoonLake’s business in general and limited operating history, difficulty enrolling patients in clinical trials, state and federal healthcare reform measures that could result in reduced demand for MoonLake’s product candidates and reliance on third parties to conduct and support its preclinical studies and clinical trials and the other risks described in or incorporated by reference into MoonLake’s Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent filings with the Securities and Exchange Commission. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. MoonLake does not undertake or accept any duty to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or in the events, conditions or circumstances on which any such statement is based. CONTACT MoonLake Immunotherapeutics Investors Carla Bretes, Director IR & BD ir@moonlaketx.com MoonLake Immunotherapeutics Media Patricia Sousa, Director Corporate Affairs media@moonlaketx.com ICR Healthcare Mary-Jane Elliott, Ashley Tapp, Namrata Taak Tel: +44 (0) 20 3709 5700 MoonLake@ICRHealthcare.com MOONLAKE IMMUNOTHERAPEUTICSCONDENSED CONSOLIDATED BALANCE SHEETS (Amounts in USD, except share data) September 30, 2024 (Unaudited) December 31.2023Current assets Cash and cash equivalents $ 375,656,291 $ 451,169,337Short-term marketable debt securities 118,268,400 59,838,900Other receivables 2,407,062 1,056,862Prepaid expenses - current 15,984,425 2,102,203Total current assets 512,316,178 514,167,302 Non-current assets Operating lease right-of-use assets 3,251,197 3,628,480Property and equipment, net 581,378 320,865Prepaid expenses - non-current 2,064,575 8,423,468Total non-current assets 5,897,150 12,372,813Total assets $ 518,213,328 $ 526,540,115 Current liabilities Trade and other payables $ 10,710,603 $ 1,837,684 Short-term portion of operating lease liabilities 1,444,893 1,197,876Accrued expenses and other current liabilities 7,925,524 6,930,120Total current liabilities 20,081,020 9,965,680 Non-current liabilities Long-term portion of operating lease liabilities 1,935,709 2,499,990Pension liability 694,959 583,426Total non-current liabilities 2,630,668 3,083,416Total liabilities 22,711,688 13,049,096Commitments and contingencies (Note 15) Equity Class A Ordinary Shares: $0.0001 par value; 500,000,000 shares authorized; 63,046,025 shares issued and outstanding as of September 30, 2024; 60,466,453 shares issued and outstanding as of December 31, 2023 6,305 6,047Class C Ordinary Shares: $0.0001 par value; 100,000,000 shares authorized; 841,269 shares issued and outstanding as of September 30, 2024; 2,505,476 shares issued and outstanding as of December 31, 2023 84 251Additional paid-in capital 675,343,443 609,969,236Accumulated deficit (189,988,477) (116,657,472)Accumulated other comprehensive income 2,833,970 2,357,621Total shareholders’ equity 488,195,325 495,675,683Noncontrolling interests 7,306,315 17,815,336Total equity 495,501,640 513,491,019Total liabilities and equity $ 518,213,328 $ 526,540,115 MOONLAKE IMMUNOTHERAPEUTICSCONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS(Unaudited) (Amounts in USD, except share and per share data) For the Three Months Period Ended September 30, June 30, 2024 2024Operating expenses Research and development $ (35,735,514) $ (23,662,147)General and administrative (7,376,495) (6,916,054)Total operating expenses (43,112,009) (30,578,201)Operating loss (43,112,009) (30,578,201) Other income, net 7,089,691 5,898,148Loss before income tax (36,022,318) (24,680,053) Income tax expense (92,106) (78,701)Net loss $ (36,114,424) $ (24,758,754)Of which: net loss attributable to controlling interests shareholders (35,390,337) (24,267,012)Of which: net loss attributable to noncontrolling interests shareholders (724,087) (491,742) Net unrealized gain (loss) on marketable securities and short term investments (325,510) 652,097Actuarial gain (loss) on employee benefit plans (115,629) (76,479)Other comprehensive income (loss) (441,139) 575,618Comprehensive loss $ (36,555,563) $ (24,183,136)Comprehensive loss attributable to controlling interests shareholders (35,822,526) (23,703,201Comprehensive loss attributable to noncontrolling interests (733,037) (479,935) Weighted-average number of Class A Ordinary Shares, basic and diluted 62,896,782 62,874,637Basic and diluted net loss per share attributable to controlling interests shareholders $ (0.56) $ (0.39)

Celltrion USA has expanded access to ZYMFENTRA ® (infliximab-dyyb), the first and only FDA-approved subcutaneous (SC) infliximab, to a significant share of the U.S. market The availability of ZYMFENTRA will support greater patient access and choice while helping to drive greater affordability to patients and health care systems JERSEY CITY, N.J., Oct. 31, 2024 /PRNewswire/ -- Celltrion USA announced today that, through continued partnership with key PBMs and health plans, the company has expanded access to ZYMFENTRA ® (infliximab-dyyb), the first and only U.S. Food and Drug Administration (FDA)-approved subcutaneous infliximab. With these partnerships Celltrion has now secured comprehensive access across the US health care system. ZYMFENTRA has attained access to a significant share of the U.S. market, providing an increase in availability to patients and prescribers. This achievement reflects unmet needs of patients, providers and payers, as well as Celltrion USA's ability to deliver on our strong heritage of supply, manufacturing and commitment to biologics. "Our extensive engagement with PBMs and health plans from the outset have led to the comprehensive expanded access for ZYMFENTRA in a short time frame," said Thomas Nusbickel, Celltrion USA Chief Commercial Officer (CCO). "This achievement underscores ZYMFENTRA's unique and innovative therapeutic advantages, and we look forward to expanding our outreach to deliver its treatment benefits to as many patients in the U.S. as possible." ZYMFENTRA was approved by the FDA in October 2023 through the Biologics License Application (BLA) under the 351 (a) pathway of the Public Health Service Act (a "stand-alone" BLA). ZYMFENTRA is the first FDA-approved subcutaneous infliximab for the treatment of moderately to severely active ulcerative colitis and moderately to severely active Crohn's disease. About Celltrion USA Celltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion currently has five biosimilars approved by the U.S. FDA: INFLECTRA® (infliximab-dyyb), TRUXIMA® (rituximab-abbs), HERZUMA® (trastuzumab-pkrb), VEGZELMA® (bevacizumab-adcd), and YUFLYMA®(adalimumab-aaty) as well as a novel biologic ZYMFENTRA®. Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence, and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. For more information, please visit: . About ZYMFENTRA® (infliximab-dyyb) [1] ZYMFENTRA is a prescription medicine used as an injection under the skin (subcutaneous injection) by adults for the maintenance treatment of: moderately to severely active ulcerative colitis following treatment with an infliximab product given by intravenous infusion (IV), moderately to severely active Crohn's disease following treatment with an infliximab product given by intravenous infusion (IV). ZYMFENTRA blocks the action of tumor necrosis factor-alpha (TNF-alpha), a protein that can be overproduced in response to certain diseases and cause the immune system to attack normal, healthy parts of the body. ZYMFENTRA® (infliximab-dyyb) was approved by the FDA through the Biologics License Application (BLA) under the 351 (a) pathway of the Public Health Service Act (a "stand-alone" BLA). ZYMFENTRA is considered a new biologic with a first-approved subcutaneous administration form and thus will be under patent protection for its dosage form by 2037 and for its route of administration by 2040. Indication and Important Safety Information ZYMFENTRA is a prescription medicine indicated in adults for maintenance treatment of: Moderately to severely active Crohn's disease following treatment with an infliximab product administered intravenously. Moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously. It is not known if ZYMFENTRA is safe and effective in children under 18 years of age. What is the most important information I should know about ZYMFENTRA? SERIOUS INFECTIONS Patients treated with ZYMFENTRA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with ZYMFENTRA. Treatment for latent infection should be initiated prior to treatment with ZYMFENTRA. Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness. Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. The risks and benefits of treatment with ZYMFENTRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with ZYMFENTRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Risk of infection may be higher in patients greater than 65 years of age, patients with comorbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab included arthritis bacterial, pneumonia, and urinary tract infection. MALIGNANCIES Malignancies, some fatal, have been reported in children, adolescents, and young adults treated with TNF blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants. Post-marketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis, and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with ZYMFENTRA, especially in these patient types. In clinical trials of all TNF blockers, more cases of malignancies were observed compared with controls and the expected rate in the general population. In clinical trials of some TNF blockers, including infliximab products, more cases of other malignancies were observed compared with controls. As the potential role of TNF blocker therapy in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. CONTRAINDICATIONS ZYMFENTRA is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients of ZYMFENTRA or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness). HEPATITIS B VIRUS REACTIVATION TNF blockers, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating ZYMFENTRA. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing ZYMFENTRA for patients identified as carriers of HBV, and monitor closely for active HBV infection during and following termination of therapy with ZYMFENTRA. Discontinue ZYMFENTRA in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of ZYMFENTRA, and monitor patients closely. HEPATOTOXICITY Hepatobiliary disorders, including acute liver failure, jaundice abnormal hepatic function, hepatic steatosis, hepatitis, hepatotoxicity, hyperbilirubinemia, and non-alcoholic fatty liver, have been reported in patients receiving infliximab products post-marketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, ZYMFENTRA should be discontinued, and a thorough investigation of the abnormality should be undertaken. CONGESTIVE HEART FAILURE Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Some cases had a fatal outcome. In several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. ZYMFENTRA has not been studied in patients with a history of CHF and ZYMFENTRA should be used with caution in patients with CHF. HEMATOLOGIC REACTION Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to infliximab-product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of ZYMFENTRA in patients who develop significant hematologic abnormalities. HYPERSENSITIVITY AND OTHER ADMINISTRATION REACTIONS In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylaxis, hypotension, and serum sickness) have been reported following administration of infliximab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. INJECTION SITE REACTIONS In clinical studies, localized injection-site reactions were reported following administration of ZYMFENTRA. If a clinically significant injection-site reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA. NEUROLOGIC REACTIONS Agents that inhibit TNF have been associated with central nervous system (CNS) manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering ZYMFENTRA in patients with these disorders and consider discontinuation if these disorders develop. RISK OF INFECTION WITH CONCURRENT ADMINISTRATION OF OTHER BIOLOGICS PRODUCTS Serious infections and neutropenia have been reported with concurrent use of ZYMFENTRA with other immunosuppressive biological products. The concurrent use of ZYMFENTRA with other immunosuppressive biological products used to treat UC and CD may increase the risk of infection and is not recommended. RISK OF ADDITIVE IMMUNOSUPPRESSIVE EFFECTS FROM PRIOR BIOLOGICAL PRODUCTS Consider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA. AUTOIMMUNITY Treatment with TNF blockers may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue ZYMFENTRA treatment if symptoms of a lupus-like syndrome develop. VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS Prior to initiating ZYMFENTRA, update vaccinations in accordance with current vaccination guidelines. Live vaccines or therapeutic infectious agents should not be given with ZYMFENTRA due to the possibility of clinical infections, including disseminated infections. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to ZYMFENTRA. ADVERSE REACTIONS In clinical trials with ZYMFENTRA, the most common adverse reactions occurring in ≥3% of ZYMFENTRA -treated patients included site reactions, COVID-19, anemia, arthralgia, infection site reaction, increased alanine aminotransferase and abdominal pain for UC, and COVID-19, headache, upper respiratory tract infection, injection site reaction, diarrhea, increased blood creatine phosphokinase, arthralgia, increased alanine aminotransferase, hypertension, urinary tract infection, neutropenia, dizziness and leukopenia for CD. Please click for Full U.S. Prescribing Information. Globally, prescribing information varies; refer to the individual country product label for complete information. For further information please contact: Celltrion Global PR Team [email protected] SOURCE Celltrion USA WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED