Neurimmune Holding AG

Neurimmune today announced that long-term safety and efficacy data from the open-label extension of a Phase I trial related to ALXN2220 (formerly NI006) for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) will be presented in London at the ESC Congress 2024, a scientific congress of the European Society of Cardiology (ESC), on September 1, 17:48 UK time. Professor Peter van der Meer from the University Medical Centre Groningen, Netherlands, will present during the session for Advances in Amyloidosis. Presentation Details: Title: Long-term safety and efficacy of antibody ALXN2220 for depletion of cardiac amyloid transthyretin: Results of treatment beyond 12 months in the open-label extension of study NI006-101 Presenter: Peter van der Meer, MD, PhD, Cardiologist, University Medical Center Groningen (UMCG) Session: Advances in Amyloidosis Date: September 1, 2024 Time: 17:48 UK time Location: Science Box 1 Amyloid transthyretin cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure. Progressive ATTR amyloid depositions characterize the disease, leading to progressive heart failure and a high rate of fatality if left untreated. Despite recent advances in slowing disease progression, there is no treatment available to deplete cardiac ATTR amyloid and revert cardiac dysfunction. ALXN2220 is an investigational human monoclonal antibody designed to deplete amyloid deposits in ATTR-CM as add-on to standard of care.1,2 At the ESC Congress 2024, Neurimmune, Alexion, AstraZeneca Rare Disease and the clinical investigators will present new long-term safety, tolerability and efficacy data of ALXN2220 treatment beyond 12 months which was studied in a prolonged Open-Label Extension of the NI006-101 trial. Prof. Christoph Hock, Chief Medical Officer of Neurimmune, said: “The depletion of the cardiac ATTR amyloid deposits is a rational therapeutic target to revert disease pathology and restore organ function. Our data at ESC Congress 2024 underscores the commitment of Neurimmune and our partner Alexion to evaluate the safety and efficacy of longer-term ALXN2220 treatment to develop a best-in-class option for patients with ATTR-CM and to increase our understanding of the mechanisms underlying amyloid depletion.” 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 as 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. 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. With its Reverse Translational MedicineTM technology, Neurimmune discovered the brain amyloid depleter NI101SQ for Alzheimer’s disease, anti-SOD1 antibody AP-101 for ALS and the anti-ATTR antibody ALXN2220 (formerly 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

Ethris states that ETH47 can be a broadly protective antiviral candidate for respiratory diseases such as uncontrolled asthma. Credit: brizmaker via Shutterstock. German biotechnology company Ethris has announced initial positive Phase I data demonstrating the safety of its lead intranasal mRNA candidate ETH47. The data from the Phase I trial (ISRCTN15391202) shows that ETH47, when administered nasally, was safe and well tolerated, with no severe adverse events or drug-related adverse events of clinical relevance across all dose levels. A full data readout is expected in the third quarter of 2024. This follows an announcement from last week that Ethris secured $5m in funding from the Bill & Melinda Gates Foundation to support preparations for ETH47’s Phase IIa study including chemistry, manufacturing and controls (CMC) processes. In addition to this, on 18 June, Cipla announced that its wholly owned subsidiary, Cipla (EU), will invest an additional €3m ($3.2m) in Ethris, following a €15m investment back in 2022. ETH47 is a type III interferon (IFN)-encoding mRNA. The drug induces an innate immune defence response in the mucosa at virus entry sites. It can also inhibit viral replication, with Ethris stating the drug can be a broadly protective antiviral candidate for respiratory diseases. The German biotech company is using its Stabilised NanoParticle (SNaP) LNP platform to locally administer the drug to the lungs through inhalation or nasal spray. See Also: Osteoporosis market expected to reach $17.9bn across 7MM by 2033 The FDA awarded a record number of review designations to mRNA vaccines in 2023 The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) approved Ethris’s Phase I trial plan back in November 2023 for healthy participants. These initial positive results will support Ethris in its continued development towards human viral challenge studies, including a rhinovirus challenge study in mild asthmatics. Ethris has also highlighted uncontrolled asthma as a target indication for the drug. This is a condition where asthma symptoms persist or worsen despite treatment, indicating that the current management is not effectively controlling the symptoms. Asthmatics are more prone to viral infections due to dysregulation in interferon type III. ETH47 may boost mucosal immunity and correct low interferon levels, potentially improving treatment for uncontrolled asthma, according to the company. Ethris’ chief medical officer Thomas Langenickel said: “We look forward to sharing comprehensive Phase I data later this year as we continue evaluating ETH47 for the treatment of uncontrolled asthma. Furthermore, successful nasal delivery opens up mRNA therapeutics as a new potential modality to treat diseases of the respiratory tract.” Ethris teamed up with Neurimmune back in 2020 to develop mRNA-based, neutralising antibodies for a Covid-19 therapeutic formulated for inhalation.

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