Notice to Shareholders (Regarding the latest business progress and outlook)

Dear Shareholders,


In recent times, the uncertainty in both domestic and international financial markets has led to increased volatility in the stock market. 
 

Despite this, we would like to inform you that Celltrion's business operations and growth strategy are proceeding as planned, without disruption. In this regard, we would like to provide an update on some of the key aspects of our business. 


 

1. Our current revenue guidance is expected to be met without difficulty.

 

  • As announced on September 9, Celltrion has set revenue targets of 3.5 trillion KRW for 2024 and 5 trillion KRW for 2025.

     

  • As of the third quarter of this year, we have already achieved a cumulative revenue of 2.4936 trillion KRW, and we anticipate no challenges in surpassing our 3.5 trillion KRW target for 2024. Given this growth momentum, we are confident that our 2025 revenue target of 5 trillion KRW will also be achievable.

     

  • Globally, we are witnessing robust growth in bid wins and prescription performance across our established products, such as Remsima, as well as new offerings, Steqeyma(Stelara biosimilar) and Omlyclo(Xolair biosimilar). Notably, as of the fourth quarter, all foundational efforts to drive U.S. sales growth for Zymfentra have been successfully completed. This sets the stage for a significant acceleration in revenue growth, and we remain optimistic about our performance in the coming quarters

     

  •   Regarding the potential impact of the U.S. presidential election results on market stability, as previously mentioned, the anticipated policies of the newly inaugurated Trump 2.0 administration are expected to continue and build upon the previous Trump administration’s initiatives, such as drug price reduction measures and the America First Healthcare Plan. This policy direction is likely to create a favorable environment for the expansion of biosimilar prescriptions, which is a key area of focus for Celltrion’s business. 

     

  • Furthermore, the projected strengthening of the U.S. dollar, influenced by the administration’s "America First" policy, is expected to benefit Celltrion, given our strong reliance on export-driven revenue. Additionally, since our pharmaceutical products are exempt from tariffs under WTO regulations, we will not be impacted by potential tariff increases. As a result, if the Trump 2.0 administration takes office, we foresee a unique opportunity to focus on expanding our operations and improving performance, particularly in comparison to industries that may be more affected by policy shifts.
     

 

2. The groundwork for the CDMO business, poised to be a key growth driver, is advancing as planned. 

 

  • After announcing our plans for expanding our CDMO (Contract Development and Manufacturing Organization) business in September, we have been making rapid progress. We plan to establish a new CDMO subsidiary, fully owned by Celltrion, by the end of this year. The selection of sites and the scale and configuration of facilities are also progressing quickly. 

     

  • The project is advancing well, with the materialized business plan currently in its final review stage, and from next year, we will begin the design and construction of the plants and sales activities to lay the foundation for the CDMO business. 

 

 

3. We will focus on engaging with both domestic and international investors, beginning with the financial markets in Asia. 


From November 20th to the end of this year, Chairman Jung Jin Seo and other top management of Celltrion will visit key financial markets, such as Singapore and Hong Kong, to hold investor events. These events will be attended by global investors, and we will provide detailed explanations about our growth outlook, the potential of our CDMO business with detailed execution plans, our ongoing and upcoming innovative drug pipelines as our future growth drivers, and more.

 

  • In January next year, we will participate in the JP Morgan Healthcare Conference, the largest healthcare conference in the world, where we will present a more detailed roadmap of our innovative drug pipelines including two ADC candidates, CT-P70 and CT-P71, which have recently shown positive outcomes. Additionally, Celltrion plans to unveil an expanded lineup of innovative drugs at the conference, featuring a cocktail antibody drug combined with Celltrion’s immunology agent, as well as an orally administered antibody treatment aimed at IBD.

     

  • Celltrion will continue to actively engage in IR activities to ensure that the value of the company is well recognized by investors.

     

     

4. We are committed to prioritizing and enhancing shareholder value.

 

  • As part of our shareholder value enhancement policy, Celltrion has been actively buying back its own shares. We have completed three share buyback programs this year, and with the ongoing fourth buyback, we will repurchase approximately 1.82 million shares, worth about 335.1 billion KRW in total, by the end of this year.

 

  • In light of the recent escalation in domestic financial market uncertainty and to prevent excessive declines in our stock price, we are actively reviewing plans for additional share buybacks and are considering conducting share buybacks periodically until market conditions stabilize.

 

  • In addition to these efforts, we will continue to explore various shareholder-friendly policies to further enhance shareholder value and ensure that our management practices are aligned with the best interests of our shareholders.


     

 

We assure you that we will continue to make every effort to maintain open communication with our shareholders.

 Lastly, we would like to make one request to our valued shareholders.

 

We kindly ask shareholders who have entered into securities lending agreements regarding Celltrion shares to terminate these agreements.

 

Despite the ban on short selling, the current short position in Celltrion shares is approximately 300 billion KRW, and the securities lending balance remains high at approximately 1.268 trillion KRW. While this figure has decreased somewhat, it remains at a high level. An excessively high level of loaned shares poses the risk of being exploited against the company, especially during periods of stock price volatility.

 

By terminating these securities lending agreements, shareholders will directly contribute to the long-term growth and value enhancement of the company.

We deeply appreciate the continued support and interest of our shareholders. 
 

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News

Celltrion presents additional data from phase III randomized controlled trials to further support biosimilarity for CT-41 (biosimilar candidate of denosumab) and CT-P47 (biosimilar candidate of tocilizumab) at ACR Convergence 2024

78-Week results from Phase III randomized controlled trial (RCT) including switching data from reference denosumab to CT-P41 (biosimilar candidate of denosumab) demonstrate comparable efficacy and safety results; Results support the therapeutic equivalence of CT-P41 and reference denosumab in treating postmenopausal women with osteoporosis (PMO)[1] Data from the Phase III RCT showed comparable and sustained efficacy, safety and immunogenicity profile to the reference tocilizumab in patients with active moderate-to-severe rheumatoid arthritis (RA) over 1-year after single transition from Week 24[2] JERSEY CITY, N.J., Nov. 18, 2024 /PRNewswire/ -- Celltrion today presented additional data from a Phase III randomized controlled trial (RCT) for CT-P41, a biosimilar candidate referencing PROLIA®/XGEVA® (denosumab) in postmenopausal women with osteoporosis (PMO) and a Phase III RCT for CT-P47, a biosimilar candidate referencing ACTEMRA® (tocilizumab) in patients with moderate-to-severe active rheumatoid arthritis (RA) at the American College of Rheumatology (ACR) Convergence 2024 in Washington, D.C. The additional efficacy and safety results from Week 52 to Week 78 including switching data from reference denosumab to the CT-P41 (Treatment Period [TP] II) showed comparable and sustained efficacy results to reference denosumab in treating women with PMO after the single transition from reference denosumab to CT-P41. CT-P41 was well tolerated with a safety profile comparable to reference denosumab, and no notable safety issue was identified following the single transition compared with maintenance groups up to Week 78. The results further support the biosimilarity between CT-P41 and reference denosumab in treating women with PMO.[1] In addition, post-hoc impact analysis using data from the Phase III RCT was conducted to determine any correlation between immunogenicity and clinical outcomes in PMO between the treatment groups. According to the results, the impact of anti-drug antibody (ADA) on pharmacokinetics (PK), efficacy and safety and the treatment emergent adverse events (TEAE) incidences were comparable between the treatment groups in the ADA status groups.[3] Despite the high ADA incidence compared to the reference denosumab historical studies,[4] it can be suggested that ADA to CT-P41 and reference denosumab has no clinical impact considering the high sensitivity and specificity of the assay and further evaluation of immunogenicity impact. "We are excited to announce the additional evidence from the RCT that further supports the biosimilarity between CT-P41 and reference denosumab in treating PMO," said Hetal Patel, PharmD, MBA, Head of Medical Affairs at Celltrion USA. "These results further underline the capabilities of our dedicated biosimilar platform and anticipated diversification of our portfolio." Results of the single transition from the reference tocilizumab to CT-P47 from a Phase III RCT were also presented at the ACR. The 1-year results showed that CT-P47 had comparable and sustained efficacy, safety and immunogenicity profiles in patients with active moderate-to-severe rheumatoid arthritis (RA) compared to the reference tocilizumab even after switching. These data further support biosimilarity of CT-P47.[2] "Biosimilars offer cost savings and health gains for our patients and play an important role in treating rheumatic diseases," said Prof. Gerd-Rüdiger Burmester, MD, Professor of Medicine and Rheumatology, Senior Professor in the Department of Rheumatology and Clinical Immunology at Charité - Universitätsmedizin Berlin, Germany. "The RCT data of CT-P47 presented at ACR further establish the comparable safety and efficacy of biosimilars to their reference products." About CelltrionCelltrion is a leading biopharmaceutical company based in Incheon, South Korea that specializes in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. 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®. About Celltrion USACelltrion 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 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: www.celltrionusa.com. About CT-P41 (biosimilar candidate of denosumab)CT-P41 is a proposed biosimilar of reference denosumab, a fully human monoclonal antibody that binds the cytokine receptor activator of NF-κb ligand (RANKL). Based on data from the Phase III clinical trial designed to evaluate the efficacy, safety, and immunogenicity of CT-P41 compared to the reference denosumab, CT-P41 was filed for regulatory approval with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in November 2023 and March 2024, respectively. About CT-P47 (biosimilar candidate of tocilizumab)CT-P47, containing the active ingredient tocilizumab, is a recombinant humanized monoclonal antibody that acts as an interleukin 6 (IL-6) receptor antagonist. Based on data from the global Phase III clinical trial designed to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of CT-P47 compared to reference tocilizumab, CT-P47 was filed for regulatory approval with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in January and February 2024, respectively. FORWARD-LOOKING STATEMENTCertain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion Inc./Celltrion USA that may constitute forward-looking statements, under pertinent securities laws.These statements may be identified by words such as "prepares", "hopes to", "upcoming", "plans to", "aims to", "to be launched", "is preparing, "once gained", "could", "with the aim of", "may", "once identified", "will", "working towards", "is due", "become available", "has potential to", the negative of these words or such other variations thereon or comparable terminology.In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion Inc./Celltrion USA's management, of which many are beyond its control.Forward-looking statements are provided to allow potential investors the opportunity to understand management's beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them.Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or result expressed or implied by such forward-looking statements.Such Risks and uncertainties may include, among other things, uncertainties regarding the launch timing and commercial success of Celltrion in the United States; the uncertainties inherent in supply chain, manufacturing, research and development, and the possibility of unfavorable new clinical data and further analyses of existing clinical data as it relates to Celltrion products; intellectual property and/or litigation/settlement implications; decisions by the FDA impacting labeling, manufacturing processes, safety, promotion, and/or other matters that could affect the availability or commercial potential of Celltrion products; and uncertainties regarding access challenges for our biosimilar products where our product may not receive appropriate formulary access or remains in a disadvantaged position relative to competitive products; and competitive developments. A further description of risks and uncertainties can be found in Celltrion's Annual Report.Although forward-looking statements are based upon what management of Celltrion Inc./Celltrion USA believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Celltrion Inc./Celltrion USA undertakes no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements. TrademarksPROLIA® and XGEVA® are registered trademarks of Amgen Inc.ACTEMRA® is a registered trademark of Chugai Seiyaku Kabushiki Kaisha Corp., a member of the Roche Group.References[1] Jean-Yves Reginster et al., Efficacy and Safety Results of CT-P41 (Proposed Denosumab Biosimilar) Compared to Reference Denosumab in Postmenopausal Women with Osteoporosis: 78-Week Results from Phase 3 Randomized Controlled Trial. Oral Presentation (abstract no. 2563). Presented at ACR 2024[2] Gerd Burmester et al., Similar Efficacy, PK, Safety, and Immunogenicity of Tocilizumab Biosimilar (CT-P47) and Reference Tocilizumab in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: Week 52 Results from the Phase III Single Transition Study. Poster Presentation (abstract no. 0502). Presented at ACR 2024.[3] Jean-Yves Reginster et al., Impact of Immunogenicity on Clinical Outcomes in Postmenopausal Women with Osteoporosis: Results from a Randomized Controlled Phase 3 Study to Compare CT-P41 (Proposed Denosumab Biosimilar) and Reference Denosumab. Poster Presentation (abstract no. 2144). Presented at ACR 2024.[4] Denosumab U.S. Prescribing Information (2024)

2024
11
19
Celltrion Announces the Acquisition of iQone Healthcare Switzerland, Further Building Its Expertise and Foothold in Europe

Celltrion announces acquisition of iQone Healthcare Switzerland, accelerating direct commercialization of its biosimilars in the European regionThe acquisition strengthens Celltrion’s presence in Europe, driving growth and expanding access to its innovative biosimilar treatments November 15, 2024 08:30 AM INCHEON, South Korea - Celltrion (KRX:068270), a global biopharmaceutical leader, announced its acquisition of iQone Healthcare Switzerland, a specialty pharmaceutical company focused on distribution, sales, and marketing in Switzerland. The acquisition, expected to close by Q4, 2024, represents a significant milestone in Celltrion’s European expansion strategy. Upon completion, iQone Healthcare Switzerland will become a wholly owned subsidiary of Celltrion Healthcare Hungary Kft. The deal will also provide Celltrion access to in-licensing opportunities, further strengthening its pipeline of innovative therapies. Taehun Ha, Head of Europe and Vice President of Celltrion, Inc., emphasized the acquisition’s importance, stating, “This move represents a strategic shift in our growth strategy. While we have successfully built direct sales networks, we are now leveraging acquisitions to accelerate our European expansion. With a distribution network spanning more than 20 regions, we are well-positioned to compete in the increasingly competitive biosimilar market.” He added, “As a fully integrated company, Celltrion manages every stage of the value chain—from R&D and manufacturing to sales, marketing and distribution. This integration enables us to continue and expand our stable and growing supply of high-quality biosimilars, including in Switzerland, where we aim to further solidify our market presence and portfolio. It also underscores our commitment to leadership through local operational excellence and continuous innovation.” Laurent Massuyeau, founder and Executive Chairman of iQone Healthcare Switzerland, expressed his optimism, stating, “Our successful decade-long partnership with Celltrion has laid very strong foundations for this integration. By combining Celltrion’s portfolio expertise with our established commercial operation, this acquisition will drive growth and enhance access to essential biosimilar and innovative medicines in Switzerland. True to our values and with the support of the program “iQone for You”, an outstanding set of services directed to healthcare professionals and specially crafted for the Swiss market, we will continue to serve our customers with agility and efficiency and bring new therapeutic opportunities quickly to Switzerland." About CelltrionCelltrion is a leading biopharmaceutical company based in Incheon, South Korea that specialises in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. The company’s solutions include world-class monoclonal antibody biosimilars such as Remsima®, Truxima® and Herzuma®, providing broader patient access globally. Celltrion has also received U.S. FDA and EC approval for Vegzelma® and Yuflyma®, FDA approval for Zymfentra®, and EC approval for Remsima® SC, Omlyclo®, SteQeyma®. To learn more, please visit www.celltrion.com/en-us. About iQone Healthcare SwitzerlandiQone Healthcare, a Swiss-based specialty pharmaceutical company, is dedicated to the commercialization of biosimilars and innovative treatments for rare diseases. Its mission is to ensure that therapeutic advancements are accessible to Swiss patients in a timely manner, providing the care they need when they need it. Through its long-standing collaborations with several global pharmaceutical developers and manufacturers, iQone Healthcare provides a continually expanding selection of leading biosimilars and innovative products to healthcare professionals and institutions in Switzerland.iQone Healthcare has maintained a decade-long partnership with Celltrion as exclusive distribution partner for Switzerland, successfully marketing Celltrion product range, including Remsima®, Veblocema®, Truxima®, Herzuma®, Vegzelma®, and Yuflyma®. For more information, visit www.iqone-healthcare.com FORWARD-LOOKING STATEMENTCertain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion Inc. and its subsidiaries that may constitute forward-looking statements, under pertinent securities laws.These statements may be identified by words such as “prepares”, “hopes to”, “upcoming”, ”plans to”, “aims to”, “to be launched”, “is preparing, “once gained”, “could”, “with the aim of”, “may”, “once identified”, “will”, “working towards”, “is due”, “become available”, “has potential to”, the negative of these words or such other variations thereon or comparable terminology.In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion Inc. and its subsidiaries' management, of which many are beyond its control.Forward-looking statements are provided to allow potential investors the opportunity to understand management’s beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them.Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or result expressed or implied by such forward-looking statements.Although forward-looking statements contained in this presentation are based upon what management of Celltrion Inc. and its subsidiaries believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Celltrion Inc. and its subsidiaries undertake no obligation to update forward-looking statements if circumstances or management’s estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements.

2024
11
15
ZYMFENTRA® (infliximab-dyyb) coverage continues to increase through partnership with top 3 Pharmacy Benefit Managers (PBMs)

 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 - 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 USACelltrion 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: www.celltrionusa.com/. 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 InformationZYMFENTRA 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. MALIGNANCIESMalignancies, 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. CONTRAINDICATIONSZYMFENTRA 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 REACTIVATIONTNF 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. HEPATOTOXICITYHepatobiliary 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 FAILURECases 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 REACTIONCases 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 REACTIONSIn 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 REACTIONSIn 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 REACTIONSAgents 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 PRODUCTSSerious 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 PRODUCTSConsider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA. AUTOIMMUNITYTreatment 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 AGENTSPrior 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 REACTIONSIn 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.[1] Zymfentra Prescribing Information

2024
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Celltrion presents post hoc analysis of LIBERTY studies of ZYMFENTRA®  (infliximab-dyyb) at the American College of Gastroenterology 2024 Annual Scientific Meeting

Pivotal LIBERTY studies (LIBERTY-CD and LIBERTY-UC) previously demonstrated superior efficacy of subcutaneous (SC) infliximab over placebo for maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC)[1], [2]ZYMFENTRA® is the first and only FDA-approved subcutaneous infliximabLate-breaking post hoc analysis of the LIBERTY studies suggests no meaningful differences in efficacy and safety outcomes at week 54 and 102 weeks between monotherapy and combination therapy of SC infliximab with immunosuppressants[3] JERSEY CITY, N.J., Oct. 29, 2024 - Celltrion USA today announced a late-breaking post hoc analysis of the pivotal LIBERTY studies (LIBERTY-CD and LIBERTY-UC) of ZYMFENTRA® (infliximab-dyyb), during the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. The data demonstrate that clinical outcomes for patients treated with ZYMFENTRA monotherapy were comparable to those for patients on combination therapy with immunosuppressants (IS), suggesting that monotherapy could be a potential treatment option for patients with inflammatory bowel disease (IBD).[3] One-year data for the LIBERTY studies were originally published in the journal Gastroenterology.[4] ZYMFENTRA, the first and only FDA-approved subcutaneous infliximab, had previously shown superior efficacy over placebo for maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC) in the randomized LIBERTY-CD and LIBERTY-UC studies.[1], [2] The new post hoc analysis explored the impact of baseline IS use by comparing outcomes between monotherapy and combination therapy.[3] The analysis included 429 patients from the CD and UC cohorts across the LIBERTY studies (192 patients with CD [monotherapy, n=126; combination therapy, n=66] and 237 patients with UC [monotherapy, n=180; combination therapy, n=57]). In both studies, there were no meaningful differences in efficacy outcomes between monotherapy and combination therapy at Week 54 or Week 102, despite combination therapy generally showing higher mean trough levels of infliximab after Week 10. Additionally, the overall safety profile was comparable between monotherapy and combination therapy throughout the pooled maintenance and extension phase.[3] "The new data strengthens the case for ZYMFENTRA monotherapy as a potential treatment option for patients with Crohn's disease and ulcerative colitis," said Hetal Patel, PharmD MBA, Head of Medical Affairs at Celltrion USA. "At Celltrion, we are committed to offering therapies that help patients and healthcare providers make informed, personalized treatment decisions. These findings suggest that ZYMFENTRA could offer flexibility in treatment approaches, providing confidence in monotherapy as an alternative to combination therapy, while maintaining effective disease control." About Celltrion USACelltrion 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 new 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: www.celltrionusa.com. About ZYMFENTRA® (infliximab-dyyb)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) and 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 a self-injected form of infliximab and thus will be under patent protection for its dosage form by 2037 and for its route of administration by 2040. ZYMFENTRA® (infliximab-dyyb) U.S. Use and Important Safety InformationZYMFENTRA 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 INFECTIONSPatients 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. MALIGNANCIESMalignancies, 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. CONTRAINDICATIONSZYMFENTRA 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 REACTIVATIONTNF 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. HEPATOTOXICITYHepatobiliary 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 FAILURECases 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 REACTIONCases 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 REACTIONSIn 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 REACTIONSIn 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 REACTIONSAgents 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 PRODUCTSSerious 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 PRODUCTSConsider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA. AUTOIMMUNITYTreatment 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 AGENTSPrior 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 REACTIONSIn 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. References[1] Jean F. Colombel et al., Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn's disease: 2 years results of the LIBERTY-CD study. Poster (Su1762). Presented at DDW 2024.[2] Bruce E. Sands et al., Subcutaneous infliximab (CT-P13 SC) for ulcerative colitis: 2-year extension results of the LIBERTY-UC study. Poster (Su1779). Presented at DDW 2024.[3] Bruce E. Sands et al., Efficacy, Safety and Immunogenicity of Subcutaneous Infliximab (CT-P13 SC) Monotherapy  versus Combination Therapy with Immunosuppressants – A Post hoc Analysis of LIBERTY-CD and LIBERTY-UC Studies. Oral Presentation (abstract no. 44). Presented at ACG 2024.[4] Efficacy, safety and immunogenicity of subcutaneous infliximab (CT-P13 SC) monotherapy versus combination therapy with immunosuppressants – post hoc analysis of LIBERTY-CD and LIBERTY-UC study, Gastroenterology, Volume 166, Issue 3, Supplement, 2024, pages S11-S12, https://doi.org/10.1053/j.gastro.2023.11.051.

2024
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Celltrion presents 2-year post-hoc analysis findings for subcutaneous infliximab (CT-P13 SC), highlighting dose escalation as an option for managing loss of response in inflammatory bowel disease

A post-hoc analysis of the LIBERTY studies (LIBERTY-CD and LIBERTY-UC) show that dose escalation of subcutaneous (SC) infliximab (CT-P13 SC) in patients who initially respond but subsequently lose response demonstrates clinical efficacy over 102 weeks, with safety profiles remaining comparable between those with and without dose escalation1,2The findings highlight dose escalation in SC infliximab as a potential option for managing loss of response in inflammatory bowel disease (IBD), providing healthcare professionals with a more personalised approach to IBD care 1 October 15, 2024 08:30 AM INCHEON, South Korea-Celltrion today announced two-year results of subcutaneous infliximab (CT-P13 SC) dose escalation therapy at United European Gastroenterology (UEG) Week 2024 in Vienna. The post-hoc analysis from the LIBERTY-CD (Crohn’s disease) and LIBERTY-UC (ulcerative colitis) studies suggest that dose escalation of CT-P13 SC following intravenous (IV) induction in patients who initially respond but subsequently lose response, showed clinical efficacy over an extended period of 102 weeks. In the study, patients showed improvement in clinical remission at Week 102 [70.3% (26/37) in CD and 35.2% (25/71) in UC] or endoscopic response [40.5% (15/37) in CD] after dose escalation. Compared to the first dose escalation visit, patients who escalated the dose had a statistically significant reduction in mean modified Mayo score in UC (5.9 vs 2.1, P<0.0001) and mean CDAI score in CD (270.58 vs 76.31, P<0.0001) at Week 102. The 2-year data from the LIBERTY studies (LIBERTY-CD and LIBERTY-UC) suggest that dose escalation of subcutaneous infliximab is effective for patients who experience a loss of response after induction therapy, with comparable safety profiles. No new safety concerns were found after dose escalation in long term treatment. These findings indicate that dose escalation could be considered a potential option for managing loss of response in IBD.1,2 “Dose escalation has long been an option for individual optimisation of IBD patients, particularly in those who lose response after induction therapy with IV infliximab,” said Professor Stefan Schreiber, University Hospital Schleswig-Holstein, Department of Internal Medicine I, Kiel, Germany. “The post-hoc analysis indicates that dose escalation of CT-P13 SC is a possibility to restore efficacy and optimize outcome in those who initially responded to induction. Dose escalation in SC infliximab has a comparable safety profile and makes a valuable contribution to long-term management strategies for patients with moderately to severely active IBD.” “We are proud to share these important findings at UEGW, as they reinforce our commitment to advancing treatment options for patients with IBD,” said Mr. Kevin Byoung Seo Choi, Executive VP and head of the marketing division at Celltrion. “The updated SmPC in Crohn’s disease which notes that patients who initially responded to 5mg/kg but who lost response may regain response with dose escalation, along with the latest data, provide healthcare professionals with a personalised approach to IBD care, by addressing the complexities of managing this challenging condition.”3 About the subcutaneous (SC) formulation of CT-P13CT-P13 SC is the world’s first subcutaneous formulation of infliximab. A 120mg fixed dose of CT-P13 SC has been approved for use in 60 countries including the US, UK, EU, Canada, Brazil, Australia and Taiwan, in adults regardless of body weight. The SC formulation of infliximab has the potential to enhance treatment options by providing high consistency in drug exposure and a convenient method of administration.4,5 About CelltrionCelltrion is a leading biopharmaceutical company based in Incheon, South Korea that specialises in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. The company’s solutions include world-class monoclonal antibody biosimilars such as Remsima®, Truxima® and Herzuma®, providing broader patient access globally. Celltrion has also received U.S. FDA and EC approval for Vegzelma® and Yuflyma®, FDA approval for Zymfentra®, and EC approval for Remsima® SC, Omlyclo®, SteQeyma®. To learn more, please visit www.celltrion.com/en-us. FORWARD-LOOKING STATEMENTCertain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion Inc. and its subsidiaries that may constitute forward-looking statements, under pertinent securities laws.These statements may be identified by words such as “prepares”, “hopes to”, “upcoming”, ”plans to”, “aims to”, “to be launched”, “is preparing, “once gained”, “could”, “with the aim of”, “may”, “once identified”, “will”, “working towards”, “is due”, “become available”, “has potential to”, the negative of these words or such other variations thereon or comparable terminology.In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion Inc. and its subsidiaries' management, of which many are beyond its control.Forward-looking statements are provided to allow potential investors the opportunity to understand management’s beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them.Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or result expressed or implied by such forward-looking statements.Although forward-looking statements contained in this presentation are based upon what management of Celltrion Inc. and its subsidiaries believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Celltrion Inc. and its subsidiaries undertake no obligation to update forward-looking statements if circumstances or management’s estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements. References1 S. Schreiber et al., Two-year results of subcutaneous infliximab (CT-P13 SC) dose escalation therapy as an option for managing loss of response in inflammatory bowel disease – from LIBERTY-UC and LIBERTY-CD study. Oral presentation. Presented at UEGW 2024.2 Hanauer SB et al., Subcutaneous Infliximab (CT-P13) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY) Gastroenterology. 2024. https://www.gastrojournal.org/article/S0016-5085(24)04918-7/fulltext#%20. [Last accessed October 2024]3 European Medicines Agency. Subcutaneous and Intravenous Infliximab. Summary of product characteristics. 2024. https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf. [Last accessed October 2024]4 Schreiber S et al., Gastroenterology. 2021;160(7):2340-2353.5 Westhovens R et al., Rheumatology. 2021;60(5):2277-2287.

2024
10
15
Notice to Shareholders (Regarding the latest business progress and outlook)

Dear Shareholders,In recent times, the uncertainty in both domestic and international financial markets has led to increased volatility in the stock market.  Despite this, we would like to inform you that Celltrion's business operations and growth strategy are proceeding as planned, without disruption. In this regard, we would like to provide an update on some of the key aspects of our business.  1. Our current revenue guidance is expected to be met without difficulty. As announced on September 9, Celltrion has set revenue targets of 3.5 trillion KRW for 2024 and 5 trillion KRW for 2025. As of the third quarter of this year, we have already achieved a cumulative revenue of 2.4936 trillion KRW, and we anticipate no challenges in surpassing our 3.5 trillion KRW target for 2024. Given this growth momentum, we are confident that our 2025 revenue target of 5 trillion KRW will also be achievable. Globally, we are witnessing robust growth in bid wins and prescription performance across our established products, such as Remsima, as well as new offerings, Steqeyma(Stelara biosimilar) and Omlyclo(Xolair biosimilar). Notably, as of the fourth quarter, all foundational efforts to drive U.S. sales growth for Zymfentra have been successfully completed. This sets the stage for a significant acceleration in revenue growth, and we remain optimistic about our performance in the coming quarters   Regarding the potential impact of the U.S. presidential election results on market stability, as previously mentioned, the anticipated policies of the newly inaugurated Trump 2.0 administration are expected to continue and build upon the previous Trump administration’s initiatives, such as drug price reduction measures and the America First Healthcare Plan. This policy direction is likely to create a favorable environment for the expansion of biosimilar prescriptions, which is a key area of focus for Celltrion’s business.  Furthermore, the projected strengthening of the U.S. dollar, influenced by the administration’s "America First" policy, is expected to benefit Celltrion, given our strong reliance on export-driven revenue. Additionally, since our pharmaceutical products are exempt from tariffs under WTO regulations, we will not be impacted by potential tariff increases. As a result, if the Trump 2.0 administration takes office, we foresee a unique opportunity to focus on expanding our operations and improving performance, particularly in comparison to industries that may be more affected by policy shifts.  2. The groundwork for the CDMO business, poised to be a key growth driver, is advancing as planned.  After announcing our plans for expanding our CDMO (Contract Development and Manufacturing Organization) business in September, we have been making rapid progress. We plan to establish a new CDMO subsidiary, fully owned by Celltrion, by the end of this year. The selection of sites and the scale and configuration of facilities are also progressing quickly.  The project is advancing well, with the materialized business plan currently in its final review stage, and from next year, we will begin the design and construction of the plants and sales activities to lay the foundation for the CDMO business.   3. We will focus on engaging with both domestic and international investors, beginning with the financial markets in Asia. From November 20th to the end of this year, Chairman Jung Jin Seo and other top management of Celltrion will visit key financial markets, such as Singapore and Hong Kong, to hold investor events. These events will be attended by global investors, and we will provide detailed explanations about our growth outlook, the potential of our CDMO business with detailed execution plans, our ongoing and upcoming innovative drug pipelines as our future growth drivers, and more. In January next year, we will participate in the JP Morgan Healthcare Conference, the largest healthcare conference in the world, where we will present a more detailed roadmap of our innovative drug pipelines including two ADC candidates, CT-P70 and CT-P71, which have recently shown positive outcomes. Additionally, Celltrion plans to unveil an expanded lineup of innovative drugs at the conference, featuring a cocktail antibody drug combined with Celltrion’s immunology agent, as well as an orally administered antibody treatment aimed at IBD. Celltrion will continue to actively engage in IR activities to ensure that the value of the company is well recognized by investors.  4. We are committed to prioritizing and enhancing shareholder value. As part of our shareholder value enhancement policy, Celltrion has been actively buying back its own shares. We have completed three share buyback programs this year, and with the ongoing fourth buyback, we will repurchase approximately 1.82 million shares, worth about 335.1 billion KRW in total, by the end of this year. In light of the recent escalation in domestic financial market uncertainty and to prevent excessive declines in our stock price, we are actively reviewing plans for additional share buybacks and are considering conducting share buybacks periodically until market conditions stabilize. In addition to these efforts, we will continue to explore various shareholder-friendly policies to further enhance shareholder value and ensure that our management practices are aligned with the best interests of our shareholders.  We assure you that we will continue to make every effort to maintain open communication with our shareholders. Lastly, we would like to make one request to our valued shareholders. We kindly ask shareholders who have entered into securities lending agreements regarding Celltrion shares to terminate these agreements. Despite the ban on short selling, the current short position in Celltrion shares is approximately 300 billion KRW, and the securities lending balance remains high at approximately 1.268 trillion KRW. While this figure has decreased somewhat, it remains at a high level. An excessively high level of loaned shares poses the risk of being exploited against the company, especially during periods of stock price volatility. By terminating these securities lending agreements, shareholders will directly contribute to the long-term growth and value enhancement of the company.We deeply appreciate the continued support and interest of our shareholders.  

2024
11
16
Notice to Shareholders (Regarding the recent progress and business outlook)

In response to the growing interest and inquiries from our shareholders regarding the recent progress and our business outlook, we would like to provide updates focusing on the key points as outlined below.  First, we would like to provide an update on the status of Zymfentra prescription. Since the official U.S. launch of the new drug in the first quarter of 2024, we have been continuously working to expand PBM (Pharmacy Benefit Manager) coverage. As of now, we have successfully listed Zymfentra on the formularies of PBMs that cover approximately 80 percent of the market. Even considering that it is a newly launched drug, we have achieved coverage expansion at a relatively fast pace. However, for this to lead to actual patient prescriptions, insurers under the PBMs need to list Zymfentra. The listing process by insurers has been delayed by approximately 2 to 3 months compared to our original timeline. Nevertheless, the prescription volume of Zymfentra in the U.S. is currently increasing at a rapid pace, and shipments to wholesalers, which directly contribute to our revenue, are growing even faster. Also, online and TV advertisements for Zymfentra have been airing since October. Notably, the Youtube advertisement has garnered 1.5 million views in just two weeks, significantly outperforming the typical view counts for pharmaceutical ads. The customer traffic being directed to the Zymfentra website from the ad is rapidly increasing as well. We expect the impact of these advertisements to become more pronounced starting in November. As a result, we anticipate that both prescriptions and sales will accelerate further from this point onward. Given the overall situation, we anticipate achieving annual sales of 1 trillion KRW for Zymfentra by 2025 without significant challenges. We will provide a detailed explanation of the sales status, including shipments to wholesalers, as well as future outlooks, during the third-quarter earnings announcement. As previously announced, we are targeting 5 trillion KRW in total sales for 2025. We are currently finalizing detailed plans for each country and product. Given the expansion of our product portfolio and the growth in market share, we expect to achieve our targeted sales of 5 trillion KRW for 2025 without any difficulty.  Secondly, we would like to provide a brief account of profitability.  On December 28, 2023, with the merger of Celltrion, Inc., and Celltrion Healthcare, Celltrion acquired high-COGS inventories previously held by pre-merger Celltrion Healthcare. This has led to a temporary increase in Celltrion’s cost of sales this year.  Nevertheless, the proportion of high-cost inventories is continuously decreasing, as old inventories are being digested rapidly, driven by global prescription volume increases across all products and the production of new drug substances. Celltrion has been explaining to our investors and shareholders the increase in the COGS ratio is temporary and will recover to the normal level by the end of 2024. The ratio is improving as planned.  It should be noted that the COGS ratio improvement is done through normal operational activities regardless of yield improvements. Celltrion is continuously reducing costs through yield improvements and production internalization. These efforts will further accelerate the future COGS ratio improvement. During the first half of 2024, our operating profit margin temporarily declined due to increased amortization expenses related to intangible assets following the merger. However, the amortization of sales rights, which accounted for a significant portion of the expenses (amounting to 113.7 billion KRW), was completed in the first half of 2024. As a result, starting from the second half of 2024, we expect an improvement in our operating profit margin driven by improved COGS ratio and a significant reduction in amortization expenses for intangible assets.  Third, we would like to provide an update on our progress in entering the CDMO business. In September, we announced plans to expand our CDMO (Contract Development and Manufacturing Organization) business through public disclosure. The key focus of this plan is to secure a competitive edge over existing CDMO companies, fully leveraging Celltrion's expertise in antibody development and production with our higher productivity and lower expansion costs. We are currently advancing rapidly with detailed discussions on the business. Our plan is to establish a wholly-owned subsidiary of Celltrion by the end of the year, with full-scale facility expansion and commercial activities set to commence next year. Celltrion is committed to strengthening CDMO business to enhance our growth momentum, ultimately increasing shareholder value.  We are in the process of finalizing our Q3 2024 financial statements and will provide a more detailed explanation of our Q3 2024 results through public disclosure once completed.  We sincerely thank our shareholders for their continued interest in and support of Celltrion. 

2024
10
18
Notification Regarding Review Results of Merger Proposal

Dear Shareholders,   Celltrion has formed a special committee comprised of outside directors to examine whether to proceed with the merger. As part of this process, Celltrion conducted a ‘shareholder survey’, obtained an external evaluation from an accounting firm, and carried out an internal assessment with a global consulting firm.  In regard to this, we posted the notice ‘Collecting shareholder’s opinions to examine whether to proceed with the merger with Celltrion Pharm’ on our website on July 31, 2024, and conducted a shareholder survey on the potential merger from July 31 to August 12, 2024.  The results of the special committee's review, including opinions from shareholders and the decisions made by the Board of Directors, are as follows:  [Survey Results]                      Survey participation: 12,778 individuals (representing 2.5% of total shareholders), 104,431,289 shares (representing 50.6% of total issued shares).  Survey Results on the merger with Celltrion Pharm: In Favor (4.0%), Opposed (70.4%), Abstained (25.6%).       ※ As Chairman Jungjin Seo and Celltrion Holdings Co., Ltd., the major shareholders, had previously stated that          they would follow the majority opinion of shareholders after the survey ends to ensure a fair and objective survey          process, Chairman Jungjin Seo’s shares (8,268,563 shares) and Celltrion Holdings’ shares (47,644,470 shares)          were counted as opposed to the merger in the survey outcome.       ※ (Note) Survey results excluding the major shareholders: In Favor (8.7%), Opposed (36.2%), Abstained (55.1%).  [Special Committee Review Results] After conducting a comprehensive review of the shareholder survey regarding the merger, the necessity of pursuing the merger, and shareholder interests, it is deemed appropriate not to proceed with the merger at this time to protect the interests of both the company and its shareholders, despite acknowledging the potential synergies of merging with Celltrion Pharm. This decision is based on the company's commitment/policy to adequately reflect shareholder opinions and the financial burden associated with the appraisal rights. We recommended that the Board reevaluate the case once Celltrion and Celltrion Pharm can be appropriately valued.  [Board of Director Decision] Following a thorough discussion and consideration of the shareholder survey results and the special committee's review, the Board of Directors has decided not to proceed with the merger with Celltrion Pharm at this time. This decision takes into account the opposition from many shareholders and various other factors, despite the potential synergies from merging with Celltrion Pharm.Moving ahead, we will re-evaluate the merger proposal once a majority of shareholders from both companies approve the merger and when shareholder value increases for both companies. Currently, both companies will focus on their core businesses, aiming to create synergies and enhance corporate value.  Thank you.

2024
08
16
Latest Updates on Agreements with PBMs for Zymfentra

Celltrion recently informed our shareholders and analysts that we have successfully secured deals with two of the top three Pharmacy Benefit Managers (or PBMs) to include 'Zymfentra', the world's first and only subcutaneous infliximab, in their formulary. In addition, we are pleased to announce that on August 2 (EST), we successfully finalized a contract to list Zymfentra with the remaining one of the top three PBMs in the United States. As with the previous announcement, we ask for your understanding that we are unable to disclose the name of the PBM at this time due to contractual obligations. The US insurance market is divided into commercial and public insurance, and the three major PBMs handle formulary listing contracts for both types of insurance separately. Celltrion has completed formulary listing agreements for both commercial and public insurance with two of the top three PBMs, including ESI. For the remaining PBM, we have closed a deal for public insurance, leaving only the commercial insurance contract to be finalized through further negotiations. Within five months of its launch in March, Zymfentra has secured approximately 75% coverage across the entire U.S. insurance market. With this achievement, Celltrion has laid a strong foundation for the prescription growth of Zymfentra in the largest pharmaceutical market in the world.  While Celltrion is dedicated to expanding Zymfentra’s listing coverage, our focus goes beyond PBM contract closures; we are committed to turning this achievement into tangible sales.We extend our sincere gratitude for your unwavering support and confidence in Celltrion.

2024
08
05
Responses to Inquiries regarding the Inclusion of Zymfentra in PBM Formularies

Following the successful deal closure in April with Express Scripts, one of the top three PBMs, to list ‘Zymfentra’ on the formulary, Celltrion has received numerous inquiries from shareholders and analysts about the status of listing agreements with the other two PBMs.  We are pleased to announce that on July 30 , 2024(EST), we finalized a successful deal with another top-three PBM and wish to share this news preliminarily with our shareholders and analysts through our website.  While we are excited to share the details of this agreement, as provided below, we must adhere to contractual obligations, which prevent us from disclosing the name of the PBM at this time. Celltrion has signed a contract with Express Scripts to include Zymfentra, the world's first and only subcutaneous infliximab, in their formulary within two weeks of the product's launch in March. Following this agreement, we also secured a deal to list Zymfentra with another top three PBM as of July 30, 2024. In addition, Celltrion aims to sign an agreement shortly with the remaining top three PBM for the formulary inclusion of Zymfentra. This would allow Zymfentra to be listed on the formularies of all three major PBMs, which collectively cover about 80% of the US insurance market. Achieving this would provide a strong foundation for the prescription growth of Zymfentra in the largest pharmaceutical market in the world.  Our focus goes beyond PBM contract closures; we are committed to turning this achievement into actual sales. We will continue to keep you informed of related news through various channels.  We extend our sincere gratitude for your unwavering support and confidence in Celltrion.   

2024
08
01