University Hospital Heidelberg

Neurimmune today announced that three poster presentations related to ALXN2220 (formerly NI006) for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) will be presented by Neurimmune, our partners Alexion, AstraZeneca Rare Disease and our clinical investigators in Rochester, Minnesota at the XIX International Symposium on Amyloidosis, a scientific congress of the International Society of Amyloidosis (ISA). ALXN2220 is an investigational human monoclonal antibody designed to deplete amyloid deposits in ATTR-CM as add-on to standard of care.1,2 High-resolution live-cell imaging data presented will offer new insight into the underlying cellular mechanism of antibody-mediated amyloid removal with ALXN2220. Results will show the addition of ALXN2220 to ATTR patient-derived cardiac tissue triggered phagocytosis, including recruitment of macrophages to amyloid deposits, detachment, internalization and degradation of ATTR amyloid. An encore poster presentation will report results from the first-in-human study of ALXN2220. Initial treatment with ALXN2220 was well tolerated with a transient increase in C-reactive proteins, suggesting initial targeted immune activation and recruitment of phagocytic immune cells. Additionally, an encore poster presentation will describe the pharmacokinetic and pharmacodynamic (PK/PD) model used for the selection of the dose range, dose escalation, dosing interval and study duration. Presentation Details Title: ALXN2220: high-resolution live-cell imaging of antibody-mediated cardiac ATTR amyloid depletion Presenter: Aubin Michalon, Director Amyloidosis & Preclinical Development, Neurimmune Date: May 28, 2024 Poster ID: PBI (#226) Title: ALXN2220: targeted immune activation in patients undergoing antibody-mediated cardiac ATTR amyloid depletion Presenter: Fabian aus dem Siepen, University Hospital Heidelberg Date: May 29, 2024 Poster ID: PC116 (#227) Title: Prediction of cardiac ATTR depletion by NI006 using mechanistic PK/PD modeling Presenter: Aubin Michalon, Director Amyloidosis & Preclinical Development, Neurimmune Date: May 29, 2024 Poster ID: PC123 (#291) Amyloid transthyretin cardiomyopathy (ATTR-CM) is an underdiagnosed, systemic condition that leads to progressive heart failure and high rate of fatality within four years from diagnosis.3,4 Progressive ATTR amyloid depositions characterize the disease, causing heart failure and death. Despite recent advances and approved therapies, there remains significant unmet medical need in treating moderate to severe ATTR-CM, and amyloid depletion may constitute an important new mechanism to achieve further effectiveness. In 2022, Neurimmune entered into an exclusive global collaboration and license agreement with Alexion, AstraZeneca Rare Disease, for ALXN2220. Neurimmune is responsible for completion of the Phase 1b clinical study on behalf of Alexion, with Alexion incurring certain trial costs. Aside from the Phase 1b trial, Alexion is responsible for further clinical development, manufacturing, and commercialization of ALXN2220. In 2024, Alexion initiated the Phase 3 DepleTTR-CM clinical study to assess the efficacy and safety of ALXN2220 for the treatment of ATTR-CM. 1Garcia-Pavia et al., N Engl J Med 2023; 389(3):239. 2Michalon et al., Nat Commun 2021; 12(1):3142. 3 Lauppe RE, et al. Open Heart. 2021 Oct;8(2):e001755. 4 González-Duarte A, et al. Neurol Ther. 2020;9(1):135-149. Neurimmune is a biopharmaceutical company translating human immune memory into antibody therapeutics. Neurimmune develops drug candidates for CNS and related protein aggregation diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and ATTR cardiomyopathy. Neurimmune discovered NI101SQ, a human monoclonal antibody to deplete brain amyloid of patients with Alzheimer’s disease. With its Reverse Translational MedicineTM technology, Neurimmune discovered the anti-SOD1 antibody AP-101 for ALS and the anti-ATTR antibody NI006 for ATTR cardiomyopathy, programs being currently evaluated in clinical trials. John Capodanno (US) john.capodanno@dentonsglobaladvisors.com Martin Meier-Pfister (Switzerland) media@neurimmune.com

New clinical trial site opened in Italy for pectus excavatum and planned in Germany for bone reconstruction Company aims to expand EU market authorization from custom-made to off-the-shelf products and and to pursue market approval in the USA Leipzig, Germany, January 31, 2024 – BellaSeno GmbH, an ISO 13485-certified medtech company developing resorbable scaffolds using additive manufacturing technologies, today announced that additional, investigator-initiated clinical trials of its novel regenerative scaffolds for bone reconstruction and chest-wall defects (pectus excavatum) will be conducted in Germany and Italy, respectively. In 2023, BellaSeno had received market authorization for its custom-made, resorbable bone and pectus excavatum scaffolds in Europe. The clinical pectus excavatum trial in Italy will enroll a total of 10 patients, with 4 individuals having undergone surgery already. While initial clinical use cases in Australia demonstrated promisingoutcomes last year, this is the first time that a fully resorbable sternal prosthesis is being used in Europe. For each patient, the prosthesis was individually designed and 3D printed using polycaprolactone - a proven medical material in use for decades, e.g., for resorbable suture material. There will be a 2-year patient follow-up to assess the outcome of the operation. Following the publication of first clinical data by BellaSeno, a total of four European university hospitals have announced their plans to set up independent, investigator-initiated clinical trials to investigate further into this promising technology. Among the first sites, the Clinic for Trauma and Reconstructive Surgery at the University Hospital Heidelberg under the lead of Professor Dr. med. Gerhard Schmidmaier plans to initiate its IIT in Q1/2024, aiming to include up to 20 patients with a follow-up time of 2 years. "We are excited that several leading European university hospitals have decided to evaluate our scaffolds in independent clinical trials. This will help us obtain further clinical evidence on our proprietary approach of treating both soft and hard tissue defects," said Dr. Mohit Chhaya, Chief Executive Officer of BellaSeno. "The addition of real-world data will be beneficial for our planned market approval for off-the-shelf breast and bone reconstruction products in the USA and EU." “We look forward to learning more about the scientific background of BellaSeno's groundbreaking technology, especially how such a scaffold is being vascularized while it secures the position of the autologous bone graft in a large size defect,” said Professor Dr. med. Gerhard Schmidmaier, the primary investigator of the IIT in Heidelberg. “The initial results are promising, and as a team, we are committed to supporting these trials comprehensively. This technology has the potential to deliver a step change in the field of regenerative medicine, and we are eager to demonstrate the benefits it brings to patients with complex reconstructive needs.” BellaSeno´s MDR-certified manufacturing platform is designed to meet the requirements of medical scaffolds ranging from soft tissue to bone and enables the production of both custom-made and off-the-shelf sterile medical implants. ### About BellaSeno BellaSeno GmbH was founded in 2015 and is headquartered on the BioCity campus in Leipzig, Germany, with a subsidiary in Brisbane, Australia. The Company is developing novel resorbable soft tissue and bone reconstruction implants made by additive manufacturing (3D-printing) under ISO 13485 certification. The Company has received substantial financial support from private investors as well as from the Saxony Development Bank (SAB), the European Fund for Regional Development (EFRE), Germany´s Federal Ministry of Education and Research (BMBF) and the Australian government. The Company has been co-funded from tax resources based on the budget adopted by the members of Saxony State Parliament. Contact BellaSeno BellaSeno GmbH Dr. Mohit Chhaya mohit.chhaya@bellaseno.com Tel.: +49 176 2283 9583 Media Inquiries akampion Dr. Ludger Wess / Ines-Regina Buth Managing Partners info@akampion.com Tel. +49 40 88 16 59 64 Tel. +49 30 23 63 27 68

Results also presented during late-breaking session at ESC Heart Failure congress 2023 Neurimmune announced today that primary results of its Phase 1 proof-of-concept study of NI006, a recombinant human antibody to deplete amyloid deposits in ATTR cardiomyopathy, have been presented in Prague at Heart Failure 2023, a scientific congress of the European Society of Cardiology (ESC), and published in The New England Journal of Medicine. Amyloid transthyretin cardiomyopathy (ATTR-CM) is an underdiagnosed, systemic condition that leads to progressive heart failure and high rate of fatality within four years from diagnosis.1,2 Progressive ATTR amyloid depositions characterize the disease, causing heart failure and death. Despite recent advances and approved therapies, there remains significant unmet medical need in treating moderate to severe ATTR-CM, and amyloid depletion may constitute an important new mechanism to achieve further effectiveness. NI006 has been designed to target the pathology of ATTR-CM by enabling depletion of amyloid fibrils in the heart. This Phase 1 study investigated safety, tolerability, pharmacology, and efficacy at 12 months of NI006 treatment in ascending doses. Results indicate that the safety profile of NI006 is favorable up to the highest dose tested. No apparent dose-limiting toxic effects or drug-related serious adverse reactions were observed. The pharmacokinetic profile was consistent with that of an IgG antibody, and no antidrug antibodies were detected. At doses of at least 10 mg per kilogram, cardiac amyloid deposition (detected by either scintigraphy or cardiac magnetic resonance imaging) was substantially reduced over a period of 12 months. Reductions were also seen in levels of biomarkers measuring cardiac stress and cardiomyocyte death, N-terminal pro-B-type natriuretic peptide and troponin T. “The depletion of the cardiac ATTR deposits is a rational therapeutic target to revert disease pathology and restore organ function”, said Dr. Pablo Garcia-Pavia from the Hospital Universitario Puerta de Hierro and CNIC in Madrid, Spain, and principal investigator of the study. “The results of this study are very promising and show initial evidence that NI006 acts as a depleter of cardiac amyloid load with potential to improve cardiac structure, function and outcomes in ATTR cardiomyopathy.” “ATTR cardiomyopathy is a rare but serious condition that is progressive, systemic and potentially fatal,” said Gianluca Pirozzi, SVP, Head of Development, Regulatory and Safety, Alexion. “These early results are encouraging, and we look forward to continuing to evaluate NI006 as a potential therapeutic option to address the high unmet medical need.” “We thank all patients, their families and investigators, study staff and collaborators for the participation in the NI006 first-in-human study”, said Prof. Christoph Hock, Chief Medical Officer of Neurimmune. “The NI006 results warrant further development of this drug candidate with the potential of reverting disease progression in ATTR amyloidosis.” In 2022, Neurimmune entered into an exclusive global collaboration and license agreement with Alexion, AstraZeneca’s Rare Disease group, for NI006. Neurimmune will continue to be responsible for completion of the current Phase 1 clinical trial on behalf of Alexion, and Alexion will pay certain trial costs. Following the Phase 1 trial, Alexion will be responsible for further clinical development, manufacturing, and commercialization. ClinicalTrials.gov number: NCT04360434. 1Lauppe RE, et al. Nationwide prevalence and characteristics of transthyretin amyloid cardiomyopathy in Sweden. Open Heart. 2021 Oct;8(2):e001755. doi: 10.1136/openhrt-2021-001755. 2González-Duarte A, et al. Impact of non-cardiac clinicopathologic characteristics on survival in transthyretin amyloid polyneuropathy. Neurol Ther. 2020;9(1):135-149. doi:10.1007/s40120-020-00183-7. N Engl J Med 2023; DOI: 10.1056/NEJMoa2303765 The authors’ affiliations are as follows: 1) Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, Madrid, Spain, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcon, Spain 2) University Hospital Heidelberg, Department of Cardiology, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany 3) Department of Cardiology, University of Rennes, CHU Rennes, INSERM, LTSI - UMR 1099, Rennes, France 4) CHU de Toulouse - Hôpital Rangueil, Service de Cardiologie, 1 Avenue du Pr. Jean Poulhès, 31059 Toulouse, France 5) Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands 6) Cardiovascular Center Darmstadt, Dieburger Straße 31c, 64287 Darmstadt, Germany 7) Alexion/AstraZeneca Rare Disease, 121 Seaport Blvd, Boston, MA 02210, USA 8) Neurimmune AG, Wagistrasse 18, 8952 Schlieren, Switzerland 9) Institute for Regenerative Medicine, University of Zurich, Wagistrasse 13, 8952 Schlieren, Switzerland 10) Center for Molecular Cardiology, University of Zurich, Wagistrasse 13, 8952 Schlieren, Switzerland 11) Cardiology Department and French National Reference Centre for Cardiac Amyloidosis, at Hôpitaux Universitaires Henri Mondor, AP-HP, and IMRB, INSERM, Université Paris Est Creteil, 94010 Créteil, France Neurimmune is a biopharmaceutical company translating human immune memory into antibody therapeutics. Neurimmune develops drug candidates for CNS and related protein aggregation diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, dementia with Lewy bodies and ATTR cardiomyopathy. Neurimmune discovered aducanumab, a human monoclonal antibody that removes amyloid beta from brains of patients with Alzheimer’s disease, and licensed it to Biogen. With its Reverse Translational MedicineTM technology, Neurimmune also discovered the anti-miSOD1 antibody AP-101 for ALS and the anti-ATTR antibody NI006 for ATTR cardiomyopathy, programs being currently evaluated in clinical trials. Neurimmune has three additional antibody programs in preclinical development and has recently expanded the spectrum of its treatment modalities by adding a small molecule program and programs involving vectorized expression of human antibody genes. Martin Meier-Pfister +41 43 244 8140 media@neurimmune.com