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TEANECK, N.J., Dec. 5, 2023 /PRNewswire/ -- GC Biopharma USA announced that a manuscript describing its landmark CEX technology, which removes FXIa from its 10% intravenous immunoglobulin (IVIG) preparation (GC5107), was published in Frontiers in Cardiovascular Medicine. The presence of residual activated coagulation factor XI (FXIa) in IVIG products was identified as the root cause of a small number of thromboembolic events (TEEs) in patients who received IVIG therapy1 Immunoglobulin (IG) therapy is a mainstay of treatment for patients with primary immunodeficiencies and autoimmune disorders. Numerous licensed IG products formulated for intravenous (IV) or subcutaneous administration are available. While all human IG is manufactured from pooled plasma using variations on the Cohn-Oncley cold ethanol fractionation process, differences in starting material, downstream purification steps, and added stabilizers result in final products that differ in composition in ways that may be very important to individual patients. Published reports of a small number of TEEs occurring in patients who received high doses of IVIG in the 1990s were attributed to an increase in blood viscosity following infusion or to patient-related factors such as heart disease, renal insufficiency, or prolonged immobilization. Subsequent investigations identified FXIa as a contaminant in some commercial IG preparations. In 2010, an unexpected increase in TEEs associated with using an IVIG product resulted in its temporary removal from the market; residual FXIa was subsequently confirmed to be the root cause2. GC Biopharma USA's rigorous studies have confirmed that a novel 10% IVIG manufacturing process, including CEX chromatography, is a reliable means of removing FXIa from the final preparation. After extensive rounds of testing, including a spiking study to evaluate the capacity of the process to remove high levels of the FXIa protein, the authors have demonstrated that CEX chromatography removes more than 99% of FXIa protein and reduces FXIa activity to below detection limits, even in samples containing 158x greater FXIa levels than that of normal samples. Dr. Jae UK Jeong, Head of R&D, stated, "We are proud to have a world-class team at GC Biopharma focused on developing robust proprietary manufacturing processes for IVIG focused on safety and improved patient outcomes." It is hoped that this novel proprietary manufacturing process will further support the product's safety—especially for high-risk patients who require IVIG. Link to Report–Cation Exchange Chromatography Removes FXIa from a 10% Intravenous Immunoglobulin Preparation About GC5107 GC5107 is a liquid solution containing 10% immunoglobulin G (100 mg/mL) for intravenous infusion, manufactured from pooled human plasma from US donors. The manufacturing process includes three steps to reduce the risk of virus transmission. These include fractionation, solvent/detergent (S/D) treatment, and nanofiltration. About Thrombotic Embolic Events (TEE's) Thrombotic events (TEs) are rare, but often, serious adverse events may occur after administering immune globulin (IG) products.2 FXIa was identified as the major biochemical root cause for the increased procoagulant potential and excluded numerous other factors. This underlines the principal importance of FXIa as an inducing factor of thromboembolic events. The clear-cut correlation of enhanced FXIa levels with an overall elevated procoagulant potential can obviously lead to thrombosis, probably dependent on the individual risk factors, which deserve further investigation.1 As early as 2000, Wolberg and colleagues suggested FXIa in different IVIG brands as a potential reason for an enhanced thrombotic risk during or after IVIG administration.3 About GC Biopharma GC Biopharma (formerly known as Green Cross Corporation) is a biopharmaceutical company that delivers lifesaving and life-sustaining protein therapeutics and vaccines. Headquartered in Yongin, South Korea, GC Biopharma is a leading global plasma protein and vaccine product manufacturer dedicated to quality healthcare solutions for over half a century. About GC Biopharma USA, Inc. GC Biopharma USA, Inc., headquartered in Teaneck, NJ, established its sales, marketing, and business operations in 2018 to serve customers and patients throughout the US. Our foundation is built on the expertise of our parent company, GC Biopharma, a leading biopharmaceutical company delivering plasma therapies and vaccines worldwide. With GC Biopharma USA, Inc., GC Biopharma will further extend its footprint, bringing its expertise and legacy to the United States. This press release may contain forward-looking statements that express GC Biopharma USA management's current beliefs and expectations. Such statements do not represent any guarantee of future performance by GC Biopharma USA or its management and involve known and unknown risks, uncertainties, and other factors. GC Biopharma USA undertakes no obligation to update or revise any forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rules. Roemisch JR, Kaar W, Zoechling A, Kannicht C, Putz M, Kohla G, et al. Identification of activated FXI as the major biochemical root cause in IVIG batches associated with thromboembolic events. Analytical and experimental approaches resulting in corrective and preventive measures implemented into the Octagam manufacturing process. WebmedCentral Immunother. (2011) 2(6):WMC002002. doi: 10.9754/journal.wmc.2011.002002 Daniel GW, Menis M, Sridhar G, Scott D, Wallace AE, Ovanesov MV, et al. Immune globulins and thrombotic adverse events as recorded in a large administrative database in 2008 through 2010. Transfusion (2012) 52(10):2113–21. doi:10.1111/j.1537-2995.2012. 03589.x Wolberg AS, Kon RH, Monroe DM, Hoffman M: Coagulation Factor XI is a contaminant in intravenous immunoglobulin preparations. American Journal of Hematology 2000; 65: 30 34.

Independent Data Monitoring Committee (IDMC) recommends stopping the OCEANIC-AF study due to an inferior efficacy of asundexian versus the control arm OCEANIC-AF is one trial which evaluates asundexian versus apixaban in patients with atrial fibrillation at risk for stroke within the overall OCEANIC phase III program IDMC recommends continuing the OCEANIC-STROKE phase III as planned BERLIN, Germany I November 19, 2023 I OCEANIC-AF, a phase III study investigating asundexian compared to apixaban (a direct oral anticoagulant) in patients with atrial fibrillation at risk for stroke is being stopped early. This decision is based on the recommendation of the study’s Independent Data Monitoring Committee (IDMC) as part of ongoing surveillance which showed an inferior efficacy of asundexian versus the control arm. Bayer will further analyze the data to understand the outcome and publish the data. Available safety data are consistent with previously reported safety profiles of asundexian. The IDMC recommends continuing the OCEANIC-STROKE phase III study as planned. Appropriate measures will be taken to close the OCEANIC-AF study and patients will be contacted by their treating physicians/investigators to discuss next steps. “Although the results from this analysis do not support the continuation of the OCEANIC-AF study, we will continue investigating asundexian in the OCEANIC-STROKE study and are currently reevaluating other indications in patients in need of antithrombotic treatment,” said Dr. Christian Rommel, Member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Global Head of Research and Development. Other evidence suggests the benefit of anticoagulation therapy on top of standard of care in the population of the OCEANIC-STROKE study which lacks adequate treatment options. Asundexian is an investigational agent and has not been approved by any health authority for use in any country, for any indication. About the OCEANIC Program The OCEANIC clinical trial program is designed to evaluate the use of asundexian, as an oral FXIa inhibitor, in patients with atrial fibrillation (AF) at risk of stroke and in patients following acute non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA), aiming to improve the benefit-risk profile when compared to standard of care. The program consists of three large multinational studies, OCEANIC-AF, OCEANIC-STROKE and OCEANIC-AFINA. Patient recruitment for OCEANIC-AFINA has not yet started. About OCEANIC-AF, OCEANIC-STROKE and OCEANIC-AFINA OCEANIC-AF is a multicenter, international, randomized, active comparator-controlled, double-blind, double-dummy, parallel-group, 2-arm Phase III study investigating asundexian compared to apixaban (a non-vitamin K antagonist oral anticoagulant) in patients with atrial fibrillation at risk for stroke to determine the safety and efficacy of asundexian on prevention of stroke and systemic embolism. OCEANIC-STROKE is a multicenter, international, randomized, placebo-controlled, double-blind, parallel group and event-driven Phase III study investigating the efficacy and safety of asundexian for prevention of ischemic stroke compared to placebo on top of standard-of-care antiplatelet therapy in patients after an acute non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) / mini-stroke. OCEANIC-AFINA is a multicenter, international, randomized, placebo-controlled, double-blind, parallel-group, 2-arm Phase III study comparing the use of asundexian with placebo in patients with atrial fibrillation (AF) (≥65 years of age) at high risk for stroke or systemic embolism who are deemed ineligible for OAC treatment. OCEANIC-AFINA is not yet recruiting patients; Bayer will now reevaluate the study design in light of the OCEANIC-AF decision. About FXIa inhibitors and Asundexian Factor XI is a protein in the blood which is converted into its active enzyme form (Factor XIa) as part of the blood coagulation cascade. FXIa inhibition specifically targets the FXIa protein involved in pathological thrombus formation, while leaving hemostasis intact. Asundexian, as an oral direct, potent inhibitor of activated coagulation factor XI (FXIa), acts selectively on the coagulation cascade, thereby offering the potential to prevent events like stroke without a corresponding increase in bleeding risk associated with the current standard of care (SoC). Asundexian is currently being evaluated as a potential treatment option in thrombosis prevention and could represent a new approach in antithrombotic treatment. Asundexian is a once-daily, oral investigational agent and has not been approved by any health authority for use in any country, for any indication. About Atrial Fibrillation AF is one of the most common sustained cardiac rhythm disorders (arrhythmias). It results from rapid, disorganized electrical signals in the upper chambers (atria) of the heart, causing them to quiver and contract quickly and irregularly. As a result, the atria do not empty completely, and blood does not flow properly, causing blood clots to form. These blood clots can break loose and travel to the brain, resulting in a stroke. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com . Find more information at https://pharma.bayer.com Follow us on Facebook: http://www.facebook.com/bayer Follow us on Twitter: @BayerPharma SOURCE: Bayer

New study includes patients aged ≥65 years with atrial fibrillation (AF) at high risk for ischemic stroke or systemic embolism who are deemed ineligible for oral anticoagulant (OAC) treatment due to increased risk of bleeding OCEANIC-AFINA, the latest Phase III study in the OCEANIC clinical trial program, will investigate asundexian in this specific patient group OCEANIC-AFINA complements the ongoing OCEANIC-AF study, further expanding Bayer’s landmark clinical trial program with asundexian, enrolling nearly 30,000 patients in over 40 countries Asundexian is being evaluated as a potential improved treatment option in stroke prevention and could be part of an entirely new class of treatment options in thrombosis management WHIPPANY, N.J.--(BUSINESS WIRE)-- Bayer today announced it expanded its Phase III OCEANIC clinical development program for the investigational drug asundexian (BAY2433334) by initiating a third clinical study, OCEANIC-AFINA. OCEANIC AFINA is a Phase III study investigating asundexian as a potential treatment option in patients (≥65 years of age) with atrial fibrillation (AF) at high risk for stroke or systemic embolism who are deemed ineligible for oral anticoagulation (OAC) treatment due to an increased risk of bleeding. OCEANIC-AFINA complements OCEANIC-AF, an ongoing Phase III study investigating the efficacy and safety of asundexian for the prevention of stroke or systemic embolism in people with AF. Together, the results from OCEANIC-AFINA and OCEANIC-AF aim to provide robust evidence for the efficacy and safety of asundexian across a broad range of patients with AF, including those who are at high risk for both ischemic stroke or systemic embolism and major bleeding events. Studies show that 1 in 3 patients with AF are undertreated or untreated with oral anticoagulants, 1,2 leading to a substantial unmet need for an effective therapy that does not further increase the risk of bleeding during treatment. Elderly patients with AF at high risk for bleeding and patients with AF and end-stage kidney disease (ESKD) on hemodialysis are often treated with a lower dose than recommended by guidelines.3 Further, those who discontinue OACs are at increased risk of experiencing a subsequent ischemic stroke.4 Inhibiting FXIa with asundexian might be able to tackle this unmet need, as it could provide protection from thrombotic events without a corresponding increase in bleeding risk. “The promising clinical results we have seen so far indicate that asundexian could mark a new option for antithrombotic treatment for a broader range of patients”, said Dr. Christian Rommel, Member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Global Head of Research and Development. “It is our vision to support patients with atrial fibrillation, including those, that up to now were deemed as not eligible for treatment with OACs. We aim to offer them a new therapy option to help physicians confidently prescribe antithrombotic treatment to protect their patients. With OCEANIC-AFINA we will evaluate asundexian in a vulnerable untreated patient population.” “For physicians, there are challenging clinical decisions we have to make when considering treatment options for atrial fibrillation patients who are at high bleeding risk, and not suitable for currently available oral anticoagulants”, said Dr. Roxana Mehran, Professor of Medicine and Director of Interventional Cardiovascular Research and Clinical Trials at Icahn School at Mount Sinai. “These patients are often overlooked and excluded from clinical trials, so it is gratifying to see Bayer’s announcement of this study.” OCEANIC-AFINA is a multicenter, international, randomized, placebo-controlled, double-blind, parallel-group, 2-arm Phase III study comparing the use of asundexian with placebo in patients (≥65 years of age) with AF at high risk for stroke or systemic embolism who are deemed ineligible to receive treatment with OACs. The primary efficacy objective of OCEANIC-AFINA is to compare the time to first occurrence of ischemic stroke or systemic embolism between AF patients treated with asundexian or placebo. The primary safety objective is to describe the time to first occurrence of ISTH (International Society on Thrombosis and Hemostasis) major bleeding in participants receiving asundexian and placebo.5 The study is expected to enroll nearly 2,000 patients with AF. Asundexian is an investigational agent and has not been approved by any health authority for use in any country, for any indication. It is currently being evaluated as a potential once-daily oral Factor XIa (FXIa) inhibitor for prevention of thromboembolic events, reducing pathological clot formation while allowing hemostasis to form clots to stop the bleeding. About the OCEANIC Program The OCEANIC clinical trial program is designed to evaluate the use of asundexian, as an oral FXIa inhibitor, in patients with atrial fibrillation (AF) at risk of stroke and in patients following acute non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA), aiming to improve the benefit-risk pro compared to standard of care. The program started with two large multinational studies, OCEANIC-AF and OCEANIC-STROKE, and is one of the largest clinical trial programs Bayer has undertaken, expecting to enroll nearly 30,000 patients in over 40 countries. The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for asundexian as a potential treatment to prevent stroke and systemic embolism in people with atrial fibrillation (AF) as well as for the prevention of stroke in patients after an acute non-cardioembolic ischemic stroke. About OCEANIC-AF, OCEANIC-STROKE and OCEANIC-AFINA OCEANIC-AF is a multicenter, international, randomized, active comparator-controlled, double-blind, double-dummy, parallel-group, 2-arm Phase III study investigating asundexian compared to apixaban (a non-vitamin K antagonist oral anticoagulant) in patients with atrial fibrillation at risk for stroke to determine the safety and efficacy of asundexian on prevention of stroke and systemic embolism. OCEANIC-STROKE is a multicenter, international, randomized, placebo-controlled, double-blind, parallel group and event-driven Phase III study investigating the efficacy and safety of asundexian for prevention of ischemic stroke compared to placebo on top of standard-of-care antiplatelet therapy in patients after an acute non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) / mini-stroke. OCEANIC-AFINA is a multicenter, international, randomized, placebo-controlled, double-blind, parallel-group, 2-arm Phase III study comparing the use of asundexian with placebo in patients with atrial fibrillation (AF) (≥65 years of age) at high risk for stroke or systemic embolism who are deemed ineligible for OAC treatment. About FXIa inhibitors and Asundexian Factor XI is a protein in the blood which is converted into its active enzyme form (Factor XIa) as part of the blood coagulation cascade. FXIa inhibition specifically targets the FXIa protein involved in pathological thrombus formation, while leaving hemostasis intact. Asundexian, as an oral direct, potent inhibitor of activated coagulation factor XI (FXIa), acts selectively on the coagulation cascade, thereby offering the potential to prevent events like stroke without a corresponding increase in bleeding risk associated with the current standard of care (SoC). Asundexian is currently being evaluated as a potential treatment option in thrombosis prevention and could represent a new approach in antithrombotic treatment. Asundexian is a once-daily, oral investigational agent and has not been approved by any health authority for use in any country, for any indication. About Atrial Fibrillation AF is one of the most common sustained cardiac rhythm disorders (arrhythmias). It results from rapid, disorganized electrical signals in the upper chambers (atria) of the heart, causing them to quiver and contract quickly and irregularly. As a result, the atria do not empty completely, and blood does not flow properly, causing blood clots to form. These blood clots can break loose and travel to the brain, resulting in a stroke.6 About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to . Find more information at Follow us on Facebook: Follow us on Twitter: @BayerPharma Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References Steinberg BA, Gao H, Shrader P, Pieper K, Thomas L, Camm AJ, Ezekowitz MD, Fonarow GC, Gersh BJ, Goldhaber S, Haas S. International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries. American heart journal. 2017 Dec 1;194:132-40. Steinberg BA, Shrader P, Pieper K, Thomas L, Allen LA, Ansell J, Chan PS, Ezekowitz MD, Fonarow GC, Freeman JV, Gersh BJ. Frequency and Outcomes of Reduced Dose Non–Vita-min K Antagonist Anticoagulants: Results From ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II). Journal of the American Heart Association. 2018 Feb 16;7(4):e007633. Al-Khatib, S. Pokorney, S. et al. (2020). Underuse of Oral Anticoagulants in Privately Insured Patients with Atrial Fibrillation: A Population Being Targeted by t. Am Heart J. (229), pp.110-117. García Rodríguez, L. et al. (2021). Discontinuation of oral anticoagulation in atrial fibrillation and risk of ischaemic stroke. Heart BMJ. (107), pp.542-548. Bayer AG. OCEANIC-AFINA Study Concept. Data on file. 2023 NHS choices. Atrial fibrillation complications. Available at: . Accessed: November 2023