Fibrinogen, human–chmt (Grifols)

PRESS RELEASE Biotests’ positive fibrinogen phase III trial results published in The Lancet’s eClinicalMedicine The data will also be presented tomorrow as part of three abstracts at the currently ongoing International Society on Thrombosis and Haemostasis (ISTH) 2025 Congress The Phase III AdFIrst study met its primary endpoint demonstrating that Grifols fibrinogen concentrate, BT524, was non-inferior to standard of care for the treatment of bleeding in acquired fibrinogen deficiency (AFD) BT524 on track to launch in Europe later this year and, pending FDA approval, in the U.S. in early 2026 Dreieich, 23 June 2025. Biotest today announces that the positive Phase III study data on its fibrinogen concentrate, BT524, has been published in eClinicalMedicine, a peer-reviewed journal published by The Lancet Discovery Science Suite. The article1 highlights that the trial met its primary endpoint, demonstrating that treatment with BT524 is non-inferior to standard of care (SOC) with cryoprecipitate or fresh frozen plasma (FFP) in reducing clinically relevant intraoperative bleeding in patients with acquired fibrinogen deficiency (AFD) undergoing planned major spinal or abdominal surgery. Specifically, the adjusted mean of intraoperative blood loss was 1381 mL (95% confidence interval [CI] 1187–1574) in the BT524 group and 1660 mL (95% CI 1461–1860) in the FFP/cryoprecipitate group, resulting in a difference of blood loss of 279 mL between the study groups. BT524 demonstrated a positive safety profile and a statistically significant lower incidence of thromboembolic events (TEEs). Fibrinogen, a plasma protein produced in the liver, plays a key role in stopping blood loss and in wound healing. AFD is typically associated with major uncontrolled bleeding (such as during surgical procedures, trauma or postpartum hemorrhage). Low fibrinogen levels are insufficient to arrest bleeding and are commonly treated with fibrinogen sources such as cryoprecipitate. BT524 from Biotest was developed in collaboration with the Grifols Group. “The trial results, now featured in this prestigious clinical medicine journal, support the potential of BT524 to be considered for patients with clinically relevant uncontrolled bleeding,” said Dr. Jörg Schüttrumpf, CEO of Biotest AG. “We look forward to finalizing regulatory approval processes in Europe and the United States as soon as possible.” Niels Rahe-Meyer, M.D., Hannover Medical School, Germany, Department of Anesthesiology and Intensive Care Medicine, and main trial coordinator, added, “We look forward to sharing the results of the AdFIrst study more broadly with the medical community as part of the research publication and at ISTH. These data could represent a breakthrough in our understanding of hemorrhage management with fibrinogen.” Data from the study will be presented as part of three abstracts at the currently ongoing upcoming International Society on Thrombosis and Haemostais (ISTH) 2025 Congress in Washington, D.C., on June 21-25. Abstract details include: Abstract Number: PB1276 Title: Use of Fibrinogen Concentrate during Major Surgeries: Post-hoc Analysis of the Phase III AdFIrst Trial Presenter: Silke Aigner Session Date and Time: June 24, 10:50 – 11:10 a.m. (EDT) Abstract Number: PB1217 Title: Early Intra-operative Use of a Fibrinogen Concentrate in Patients Undergoing Major Abdominal Surgery Presenter: Ashok Roy Session Date and Time: June 24, 10:50 – 11:10 a.m. (EDT) Abstract Number: PB1219 Title: Efficacy and Safety of Fibrinogen Concentrate During Major Spinal Surgery: Phase III Randomized Trial Presenter: Maria José Colomina Session Date and Time: June 24, 13:45 – 14:45 p.m. (EDT) Previously AdFIrst data have been presented at congresses including the International Symposium on Intensive Care & Emergency Medicine (ISICEM); Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA); and the European Society of Anaesthesiology and Intensive Care (ESAIC). About AdFIrst trial The completed trial for Grifols’ fibrinogen concentrate (BT524), known as AdFIrst (Adjusted Fibrinogen Replacement Strategy), was a prospective, active-controlled, multicenter phase 3 non-inferiority trial investigating the efficacy and safety of BT524 in patients with acquired fibrinogen deficiency. Patients who had high blood loss during planned spinal or abdominal surgery were randomized 1:1 to treatment with BT524 or cryoprecipitate or fresh frozen plasma (FFP). To evaluate the efficacy of BT524, further blood loss was compared between both treatment options. The primary endpoint was intraoperative blood loss from the time of decision to treat until the end of surgery with a non-inferiority margin of 150 mL, assessed in the per-protocol analysis set (PPS). Safety was assessed in all patients who received at least one dose of trial drug. Further information about the trial design can be found at www.clinicaltrialsregister.eu (EudraCT number: 2017-001163-20) or ClinicalTrials.gov: NCT03444324. About fibrinogen and fibrinogen deficiency Fibrinogen is a blood clotting factor that is produced in the liver. It plays a key role in primary haemostasis (stopping blood loss from bleeding wounds) and wound healing. In case of a lack or shortage of fibrinogen the blood's ability to clot is impaired, which leads to a much greater risk of bleeding and delayed haemostasis. The fibrinogen concentrate alternatives fresh frozen plasma (FFP) and cryoprecipitate contain variable amounts of fibrinogen and must be thawed prior to treatment. The defined amount of fibrinogen in the fibrinogen concentrate will allow a tailor-made, patient specific and effective therapy. __________________________________________________________ 1) Rahe-Meyer N, et al. Efficacy and safety of human fibrinogen concentrate (BT524) in patients with major haemorrhage undergoing major orthopaedic or abdominal surgery (AdFIrst): a randomised, active-controlled, multicentre, partially blinded, phase 3 non-inferiority trial. eClinicalMedicine. 2025; 103264, https://doi.org/10.1016/j.eclinm.2025.103264. About Biotest Biotest is a provider of biological therapeutics derived from human plasma. With a value added chain that extends from pre-clinical and clinical development to worldwide sales, Biotest has specialised primarily in the areas of clinical immunology, haematology and intensive care medicine. Biotest develops and markets immunoglobulins, coagulation factors and albumin based on human blood plasma. These are used for diseases of the immune and haematopoietic systems. Biotest has more than 2,500 employees worldwide. Since May 2022, Biotest has been a part of the Grifols Group, based in Barcelona, Spain (www.grifols.com). Biotest AG will now also be publishing official press releases via X. You can find us at: https://twitter.com/BiotestAG IR contact Dr Monika Baumann (Buttkereit) Phone: +49-6103-801-4406 Mail: ir@biotest.com PR contact Miriam Oehme Mail: pr@biotest.com Biotest AG, Landsteinerstr. 5, 63303 Dreieich, Germany, www.biotest.com Ordinary shares: securities’ ID No. 522720; ISIN DE0005227201 Preference shares: securities’ ID No. 522723; ISIN DE0005227235 Listing: Open Market: Berlin, Düsseldorf, Hamburg/ Hanover, Munich, Stuttgart, Tradegate Disclaimer This document contains forward-looking statements on overall economic development as well as on the business, earnings, financial and assets position of Biotest AG and its subsidiaries. These statements are based on current plans, estimates, forecasts and expectations of the company and are thus subject to risks and elements of uncertainty that could result in significant deviation of actual developments from expected developments. The forward-looking statements are only valid at the time of publication. Biotest does not intend to update the forward-looking statements and assumes no obligation to do so.

PRESS RELEASE Important milestone for Biotest: Biologics License Application for Fibrinogen submitted to the US Food and Drug Administration (FDA) Biotest's fibrinogen aims to fulfill a high unmet medical need for additional fibrinogen to treat acquired fibrinogen deficiency US submission follows EU application for marketing authorization submitted in October 2024 Subject to FDA approval, new treatment would bring significant improvement in sales, EBIT and cash flow Dreieich, Germany, January 9, 2025. The Biologics License Application (BLA) for Biotest’s Fibrinogen has been submitted to the US Food and Drug Administration. Fibrinogen is the second product developed and manufactured by Biotest in Dreieich, Germany, for which a BLA has been submitted to the FDA. The new application covers both supplementation in patients with acquired fibrinogen deficiency and treatment and prophylaxis of acute bleeding episodes in all patients with congenital fibrinogen deficiency. The application is now under evaluation by the FDA, with a decision anticipated by the end of 2025. This submission follows Biotest's earlier application for marketing authorization in selected European markets filed in October 2024. “Clinical data demonstrates efficacy and safety of Biotest's Fibrinogen in various bleeding conditions,” said Dr. Christina Erb, Head of Scientific Operations and Innovation. “Fibrinogen deficiency can lead to uncontrolled blood loss potentially resulting in patient’s death. Biotest’s Fibrinogen can be stored at room temperature and is designed to be more convenient and faster to prepare than alternatives for the treatment of fibrinogen deficiency associated with severe blood loss. As such, it will provide an effective and safe option for the management of bleeding in patients with serious and potentially life-threatening conditions”. In many regions of the world, the use of cryoprecipitate or fresh frozen plasma as a fibrinogen substitute is the standard of care for the management of major surgical bleeding. However, these treatments contain not only fibrinogen, but also additional proteins and components that may exhibit undesired effects for the patient. In addition, they are not subject to the same rigorous pathogen safety protocols as Fibrinogen. Fibrinogen also offers the significant advantages of being readily available and allowing for faster administration, ensuring timely and targeted treatment. As a member of the Grifols Group, Biotest is committed to playing a leading role in expanding access to this therapy to a broader patient population. About Biotest’s Fibrinogen The newly developed manufacturing process for fibrinogen results in high-purity fibrinogen with a defined concentration, high level of viral safety and good solubility. About AdFIrst trial no. 995 The AdFIrst trial was a prospective, active-controlled, multicentre phase III trial investigating the efficacy and safety of Fibrinogen (BT524) in patients with acquired fibrinogen deficiency. Patients experiencing high blood loss during planned spinal or abdominal surgery were randomized 1:1 to treatment with Fibrinogen (BT524) or fresh frozen plasma (FFP)/cryoprecipitate. To evaluate the efficacy of BT524, blood loss was compared between the two treatment options. For more information on the trial design and outcomes, please visit www.clinicaltrialsregister.eu (EudraCT number: 2017-001163-20). Full trial results are expected to be published in a medical journal later in 2025. About fibrinogen and fibrinogen deficiency Fibrinogen is a blood clotting factor that is produced in the liver. It plays a key role in primary haemostasis (stopping blood loss from bleeding wounds) and wound healing. In case of a lack or shortage of fibrinogen blood's ability to clot is impaired which leads to a much greater risk of bleeding and delayed haemostasis. The Fibrinogen alternatives fresh frozen plasma (FFP) and cryoprecipitate contain variable amounts of fibrinogen and must be thawed prior to administration. The defined amount of fibrinogen in the fibrinogen developed by Biotest will allow a tailor-made, patient specific and highly effective treatment. About Biotest Biotest (www.biotest.com) is a provider of biological therapeutics derived from human plasma. With a value-added chain that extends from preclinical and clinical development to worldwide sales, Biotest has specialized primarily in the areas of clinical immunology, hematology, and intensive care medicine. Biotest develops and markets immunoglobulins, coagulation factors and albumin based on human blood plasma. These are used for diseases of the immune and hematopoietic systems. Biotest has more than 2,400 employees worldwide. The ordinary and preference shares of Biotest AG are listed in the Prime Standard on the German Stock Exchange. Since May 2022, Biotest has been a part of the Grifols Group, headquartered in Barcelona, Spain (www.grifols.com). IR contact Dr Monika Baumann (Buttkereit) Phone: +49-6103-801-4406 Mail: ir@biotest.com PR contact Dirk Neumüller Phone: +49-6103-801-269 Mail: pr@biotest.com Biotest AG, Landsteinerstr. 5, 63303 Dreieich, Germany, www.biotest.com Ordinary shares: securities’ ID No. 522720; ISIN DE0005227201 Preference shares: securities’ ID No. 522723; ISIN DE0005227235 Listing: Frankfurt (Prime Standard) Open Market: Berlin, Düsseldorf, Hamburg/ Hanover, Munich, Stuttgart, Tradegate Disclaimer This document contains forward-looking statements on overall economic development as well as on the business, earnings, financial and assets position of Biotest AG and its subsidiaries. These statements are based on current plans, estimates, forecasts and expectations of the company and are thus subject to risks and elements of uncertainty that could result in significant deviation of actual developments from expected developments. The forward-looking statements are only valid at the time of publication. Biotest does not intend to update the forward-looking statements and assumes no obligation to do so.