SARS-CoV-2 S protein

Head-to-head data, presented at OPTIONS XII for the Control of Influenza Conference, demonstrates advantage of sa-mRNA over conventional mRNA in duration of immune response; Results highlight CSL and Arcturus Therapeutics’ commitment to advancing COVID-19 vaccine innovation to protect public health. WALTHAM, Mass. and SAN DIEGO , Sept. 30, 2024 /PRNewswire/ -- Global biotechnology leader CSL (ASX:CSL; USOTC:CSLLY) and self-amplifying messenger RNA (sa-mRNA) pioneer Arcturus Therapeutics (Nasdaq: ARCT) today announced the results of a head-to-head study demonstrating that self-amplifying (sa-mRNA) COVID-19 vaccine maintained superior immunogenicity compared to the conventional mRNA vaccine Comirnaty ® for up to one year against Wuhan-Hu-1, Omicron BA.4-5 and certain other variants, and at one-sixth the dose of the comparator (5 μg vs 30 μg, respectively). The data, presented as a poster at the OPTIONS XII for the Control of Influenza conference, highlights 12-month follow-up analysis of the Phase 3 trial conducted in Japan by Meiji Seika Pharma, evaluating a booster dose of ARCT-154, showing that the vaccine elicited superior immunogenicity and antibody persistence over Comirnaty ® for up to 12 months postvaccination, against multiple SARS-CoV-2 strains and in both younger and older adult age groups. “The 12-month results from the ARCT-154 study continue to establish the durability of immune response from this self-amplifying mRNA vaccine and reinforce the ability of this vaccine to provide protection against COVID-19 at lower doses compared to conventional mRNA vaccines,” said Jonathan Edelman , M.D., Senior Vice President, Vaccines Innovation Unit, CSL. “We are proud to showcase at the 2024 OPTIONS conference with these important data about the first sa-mRNA COVID-19 vaccine now approved in Japan .” Additional data presented by CSL and Arcturus finds that the bivalent formula, ARCT-2301, developed on the same platform as ARCT-154, induces superior immunogenicity over conventional bivalent mRNA vaccine Comirnaty ® that persists against key variants up to six months postvaccination. “The recent surge in COVID-19 infections and the emerging new variants illustrate the critical need for vaccines that provide a longer duration of protection compared to conventional mRNA vaccines,” said Igor Smolenov, M.D., Ph.D. Chief Development Officer of Arcturus Therapeutics. “These compelling new studies reaffirm that these sa-mRNA vaccines have the potential to offer potent protection against COVID-19.” The COVID-19 vaccine from this sa-mRNA platform targeted against the JN.1 variant is approved in Japan for immunization against COVID-19 in adults 18 years and older and is being sold under the trade name KOSTAIVE ® . ARCT-154 12-month Study Design and Results The randomized, double-blind, active-controlled Phase 3 study was conducted at 11 clinical sites in Japan. The study enrolled 828 adults who had previously been fully immunized with three doses of mRNA vaccine(s). Participants were randomized equally to receive a booster dose of either ARCT-154 or Comirnaty ® . Immune responses were measured as neutralizing antibodies against the Wuhan-Hu-1 and Omicron BA.4-5 strains in sera obtained at Day 1 before booster vaccination, and Days 29, 91, 181, and 361 after vaccination of participants who were seronegative for SARS-CoV-2 nucleocapsid protein (N-protein), considered to be an indicator of recent COVID-19 infection. At the same timepoints neutralizing antibodies against Delta, Omicron BA.2, Omicron BA.2.86, and Omicron XBB.1.5.6 variants were measured in subsets of participants (~30 per group). Responses are expressed as group geometric mean titers (GMT) with 95% confidence intervals, and geometric mean titer ratio (GMTR) between the two vaccine groups at each timepoint. At Day 29, neutralizing antibodies (GMTs unadjusted) against the Wuhan-Hu-1 strain in ARCT-154 recipients (n = 378) were superior to those in the Comirnaty ® group (n = 374): GMT = 5390 (95% CI: 4899–5931) vs. 3738 (3442–4060), a GMT ratio of 1.44 (1.27–1.64). This advantage persisted through all time points. At Day 361 (unadjusted) GMTs were 3396 (3019–3821) and 1771 (1532–2047) in ARCT-154 (n = 272) and Comirnaty ® (n = 266) groups, a GMT ratio of 1.92 (1.59–2.31). Differences were also observed in responses against Omicron BA.4-5, with GMT ratios of 1.31 (1.07–1.59) at Day 29 and 1.89 (1.42– 2.50) at Day 361. A subset of subjects who were seronegative for N-protein displayed similar differences in immune responses between ARCT-154 and Comirnaty ® against the Delta, Omicron BA.2, BA.2.86, and XBB.1.5.6 variants at Day 361. The GMT ratios were 1.88 (0.79–4.49) against Delta, 2.34 (1.06–5.17) against Omicron BA.2, 2.51 (1.00–6.31) against Omicron BA.2.86 and 2.81 (1.09–7.28) against Omicron XBB.1.5.6. Bivalent 6-month Study Design and Results In this randomized, multicenter, Phase 3, observer-blind, active-controlled trial in Japan , fully-immunized (3‒5 doses of mRNA vaccine) adults were randomized 1:1 to receive a booster dose of ARCT-2301 or Comirnaty ® Original/BA.4-5. The primary objective was to demonstrate non-inferiority of the immunogenicity of ARCT-2301 vs. Comirnaty ® Original/BA.4-5 at Day 29 as neutralizing antibody GMT and seroresponse rates (SRR) against Omicron BA.4-5. Key secondary outcomes included titers of neutralizing antibodies against Wuhan-Hu-1 and Omicron XBB.1.5. Between September and November 2023 , 930 men and women (19‒80 years) with at least three prior mRNA COVID-19 vaccinations were enrolled at nine medical centers in Japan and administered ARCT-2301 (n = 465) or Comirnaty ® Original/BA.4-5 (n = 465) boosters. At Day 29 ARCT-2301 (n = 398) induced superior neutralizing antibody responses vs. Comirnaty ® (n = 405) against Omicron BA.4-5 (GMT ratio 1•49 [95% CI: 1.26–1.76], SRR difference 7.2% [95% CI: 0.6–13.7]), and against Wuhan-Hu-1 (GMT ratio 1.45 [1.28–1.63], SRR difference 12.5% [5.9–19.0]). The difference persisted through six months with GMT ratios of 2.17 (95% CI: 1.75-2.69) and 1.98 (95% CI: 1.69-2.31), respectively. Antibody responses against Omicron XBB.1.5 were also higher after ARCT-2301 vs. Comirnaty ® (GMT ratio 1.63 [1.36–1.94], SRR difference 16.7% [10.1–23.2]). About sa-mRNA mRNA vaccines help protect against infectious diseases by providing a blueprint for cells in the body to make a protein to help our immune systems recognize and fight the disease. Unlike standard mRNA vaccines, self-amplifying mRNA vaccines instruct the body to make more mRNA and protein to boost the immune response. About CSL CSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat hemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses: CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 32,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on Twitter.com/CSL . For more information about CSL, visit . About Arcturus Founded in 2013 and based in San Diego, California , Arcturus Therapeutics Holdings Inc. (Nasdaq: ARCT) is a global mRNA medicines and vaccines company with enabling technologies: (i) LUNAR® lipid-mediated delivery, (ii) STARR® mRNA Technology (sa-mRNA) and (iii) mRNA drug substance along with drug product manufacturing expertise. Arcturus developed KOSTAIVE ® , the first self-amplifying messenger RNA (sa-mRNA) COVID vaccine in the world to be approved. Arcturus has an ongoing global collaboration for innovative mRNA vaccines with CSL Seqirus, and a joint venture in Japan, ARCALIS, focused on the manufacture of mRNA vaccines and therapeutics. Arcturus’ pipeline includes RNA therapeutic candidates to potentially treat ornithine transcarbamylase (OTC) deficiency and cystic fibrosis (CF), along with its partnered mRNA vaccine programs for SARS-CoV-2 (COVID-19) and influenza. Arcturus’ versatile RNA therapeutics platforms can be applied toward multiple types of nucleic acid medicines including messenger RNA, small interfering RNA, circular RNA, antisense RNA, self-amplifying RNA, DNA, and gene editing therapeutics. Arcturus’ technologies are covered by its extensive patent portfolio (over 400 patents and patent applications in the U.S., Europe, Japan, China, and other countries). For more information, visit . In addition, please connect with us on Twitter and LinkedIn . Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact included in this press release, are forward-looking statements, including those regarding strategy, future operations, the likelihood that KOSTAIVE will provide a longer duration of protection, the likelihood and timing of future approvals of KOSTAIVE anywhere in the world including Europe , the plans to submit additional regulatory filings and timing thereof, that preclinical or clinical data will be predictive of future clinical results, and the impact of general business and economic conditions. Arcturus may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in any forward-looking statements such as the foregoing and you should not place undue reliance on such forward-looking statements. These statements are only current predictions or expectations, and are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels of activity, performance or achievements to be materially different from those anticipated by the forward-looking statements, including those discussed under the heading “Risk Factors” in Arcturus’ most recent Annual Report on Form 10-K, and in subsequent filings with, or submissions to, the SEC, which are available on the SEC’s website at . Except as otherwise required by law, Arcturus disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. CSL Media Contacts: Sue Thorn Mobile: 617 799 3151 Email: sue.thorn@cslbehring.com Australia : Jimmy Baker Mobile: +61 450 909 211 Email: Jimmy.Baker@csl.com.au Asia Pacific : Hamish Walsh +61 422 424 338 Email: hamish.walsh@seqirus.com Arcturus Media Contact: Neda Safarzadeh VP, Head of IR/PR/Marketing Email: IR@arcturusrx.com View original content to download multimedia: SOURCE CSL

Submission based on positive SUPERNOVA Phase III trial data which demonstrated a statistically significant reduction in the incidence of COVID‑19 in an immunocompromised patient population LONDON, UK I July 01, 2024 I AstraZeneca’s Marketing Authorisation Application (MAA) for sipavibart has been accepted under an accelerated assessment procedure by the European Medicines Agency (EMA), for the pre-exposure prophylaxis (prevention) of COVID-19 in immunocompromised patients. Sipavibart is an investigational long-acting antibody designed to provide COVID-19 protection for immunocompromised patients who often do not respond adequately to vaccination alone and remain at high risk of serious outcomes from COVID-19. The EMA’s Committee for Medicinal Products for Human Use (CHMP) granted sipavibart accelerated assessment as it was deemed of major interest for public health and therapeutic innovation. Accelerated assessment aims to reduce the timeframe for the CHMP to review a MAA compared to the standard procedure. The MAA is based on positive results from the SUPERNOVA Phase III trial which demonstrated sipavibart’s safety and efficacy in preventing symptomatic COVID-19 in immunocompromised patients, compared to control, in a variant landscape in which COVID-19 cases captured over the course of the trial were caused by several different SARS-CoV-2 variants. 1 SUPERNOVA is the only Phase III trial that provides efficacy data for COVID-19 pre-exposure prophylaxis exclusively in immunocompromised patients. 2 Prof. Paul Loubet, M.D., Ph.D., MPH, Professor of infectious diseases, University of Montpellier, head of the Infectious and Tropical Diseases department, Nîmes University Hospital, France, and SUPERNOVA trial investigator, said: “The disease burden of COVID-19 remains high for immunocompromised patients who are disproportionately impacted compared to the general population, despite vaccination. With cases expected to rise in the winter months, adding more pressure to stretched healthcare systems, sipavibart has the potential to be an important option for immunocompromised patients who remain at risk, and it has demonstrated COVID-19 protection in a mixed variant environment.” Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: “Immunocompromised patients currently have no options for COVID-19 protection in Europe beyond vaccination, which often is not sufficient to protect them against serious COVID-19 outcomes. We are pleased that the EMA has accepted this regulatory submission with an accelerated assessment procedure and will work to bring sipavibart to these highly vulnerable patients.” Data from the SUPERNOVA trial will be presented at a forthcoming medical meeting. In addition to the EMA, AstraZeneca is in dialogue with other regulatory authorities on potential authorisation or approval pathways for sipavibart. Notes COVID-19 and the continued unmet need in the immunocompromised population Despite the World Health Organization declaring an end to the pandemic a year ago, COVID-19 remains a significant problem for immunocompromised patients today and severe COVID-19 outcomes can fluctuate significantly throughout the year. People who are immunocompromised including blood cancer patients, those who have organ transplants, those with end-stage renal disease requiring dialysis and those taking immunosuppressive medications typically have an insufficient immune response to COVID-19 vaccination, leaving them at high risk of severe outcomes from COVID-19, even when fully vaccinated. 3-8 Findings from INFORM , a large real-world evidence study, reinforce the ongoing, significant and disproportionate burden of COVID-19 for the immunocompromised compared to the general population. Despite accounting for up to 4% of the INFORM study population, about 25% of COVID-19 hospitalisations, ICU admissions and deaths are borne by immunocompromised patients, even after multiple doses of COVID-19 vaccines. 3 SUPERNOVA SUPERNOVA is a large Phase III, global, randomised, double-blind, placebo-controlled trial assessing the safety and efficacy of sipavibart compared to control (tixagevimab/cilgavimab or placebo) for the prevention of COVID-19, providing the only COVID-19 efficacy data in immunocompromised patients. 2 Positive high-level results from SUPERNOVA showed that sipavibart demonstrated a statistically significant reduction in the incidence of symptomatic COVID‑19 compared to control (tixagevimab/cilgavimab or placebo) in an immunocompromised patient population. 1 The trial met both dual primary endpoints; relative risk reduction of symptomatic COVID-19 caused by any SARS-CoV-2 variant and the relative risk reduction of infections caused by SARS-CoV-2 variants not containing the F456L mutation. 1 SUPERNOVA demonstrated the potential benefit of sipavibart in an evolving variant landscape in which COVID-19 cases captured over the course of the trial were caused by several different SARS-CoV-2 variants. 1 All participants in the trial had an immunocompromising condition and/or were on immunosuppressive treatments, which put them at risk to mount an inadequate immune response to vaccination and at high risk of developing severe COVID-19. Participants enrolled in the study included patients with conditions such as hematologic malignancies, solid organ transplant recipients, hematopoietic stem cell transplants, end stage kidney disease/dialysis, and being within one year of receipt of B cell depleting therapy. 1,2 Sipavibart was generally well-tolerated in the trial and preliminary analyses show adverse events were balanced between the control and sipavibart arms. 1 Sipavibart Sipavibart (formerly AZD3152) is an investigational long-acting monoclonal antibody (LAAB) against COVID-19. Sipavibart was designed to provide broad and potent coverage across Omicron and ancestral viral variants by neutralising spike protein interaction with the host receptor ACE2. 9 Sipavibart was derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. Sipavibart has been engineered using the same antibody scaffold as Evusheld and was optimised with the same half-life extension and reduced Fc effector function and complement C1q binding platform. 9 The reduced Fc effector function aims to minimise the risk of antibody-dependent enhancement of disease – a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease. Sipavibart was licensed by AstraZeneca in May 2022 from RQ Biotechnology . AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca . References 1. AstraZeneca. (16 May 2024). SUPERNOVA Phase III trial of sipavibart long-acting antibody met primary endpoints in preventing COVID-19 in immunocompromised patient population [Press Release]. Las Accessed June 2024 https://www.astrazeneca.com/media-centre/press-releases/2024/supernova-trial-met-covid-19-prevention-endpoint.html . 2. Clinialtrials.gov. Last Accessed June 2024 https://clinicaltrials.gov/study/NCT05648110?term=AZD3152&rank=3 3. Evans RA et al. Impact of COVID-19 on Immunocompromised Populations during the Omicron Era: Insights from the Observational Population-Based INFORM Study. The Lancet Regional Health – Europe . 2023;0(0):100747. doi:10.1016/J.LANEPE.2023.100747 4. Dube S. Continued Increased Risk of COVID-19 Hospitalisation and Death in Immunocompromised Individuals Despite Receipt of ≥4 Vaccine Doses: Updated 2023 Results from INFORM, a Retrospective Health Database Study in England. Poster P0409 at ECCMID 2024. 5. Turtle L. Individuals with Multiple Sclerosis Are at High Risk for COVID-19 Hospitalisation and Death Despite High Rates of Vaccination: Results from the England INFORM Study. Oral Presentation at ECCMID 2024. 6. Meeraus W. High Prevalence of Immunocompromising Conditions Among Patients with Severe Acute Respiratory Infection, Including SARS-CoV-2: Results from a Multicentre, Test-Negative Case Control Study. Abstract #01796 at ECCMID 2024. 7. Meeraus W. Immunocompromise, Cancer and Other Comorbidities in Patients with Severe Acute Respiratory Infection Testing Positive Versus Negative for SARS-CoV-2: A Post Hoc Analysis of COVIDRIVE Data from May 2021 to May 2023. Abstract #01800 at ECCMID 2024. 8. Ketkar A et al. Assessing the Risk and Costs of COVID-19 in Immunocompromised Populations in a Large United States Commercial Insurance Health Plan: The EPOCH-US Study. Curr Med Res Opin. 2023 . 39 (8):1103-1118. 9. Francica JR, Cai Y, Diallo S, et al. 1355. The SARS-CoV-2 Monoclonal Antibody AZD3152 Potently Neutralizes Historical and Emerging Variants and is Being Developed for the Prevention and Treatment of COVID-19 in High-risk Individuals . Open Forum Infect Dis . 2023 Nov 27;10(Suppl 2):ofad500.1192. doi: 10.1093/ofid/ofad500.1192. SOURCE: AstraZeneca

Developed to provide protection for millions of immunocompromised and elderly individuals who are most vulnerable to COVID-19 GHENT, Belgium, June 04, 2024 (GLOBE NEWSWIRE) -- ExeVir Bio, a biotech company developing robust heavy chain-only antibody therapies for broad protection against infectious diseases, today announced new data demonstrating that its antibodies are exceptionally potent in neutralizing the SARS-CoV-2 variant JN.1, the parental strain of the currently most dominantly circulating variants worldwide. ExeVir's COVID-19 program focuses on addressing the high unmet medical need to protect and treat immunocompromised and elderly individuals that account for respectively 4% and 10% of the global population. Despite the availability of effective vaccines, the immunocompromised and elderly remain at a higher risk for severe COVID-19 as they are often not able to elicit an adequate immune response to vaccination and therefore would strongly benefit from additional protection in the form of antibody therapeutics. ExeVir’s variant-proof lead clinical candidate XVR013m is a heavy chain-only antibody that targets a unique membrane-proximal epitope in the S2 subunit of the spike protein. This binding region remains completely unmutated across all variants of concern, variants of interest and variants under monitoring that have circulated to date. XVR013m demonstrates exceptional neutralization potency against JN.1, the parental strain of the currently most dominantly circulating variants worldwide, with an IC50 of 2.8 ng/mL in a pseudovirus neutralization assay, unchanged compared to all previously tested variants. The activity against new circulating variants under monitoring is continually being tested. ExeVir is currently gearing up to start the clinical development of the variant-proof XVR013m in 2025 as a solution for the prevention of COVID-19 in the target populations of immunocompromised and elderly individuals. Jeanne Bolger, interim CEO of ExeVir, said: “COVID-19 is here to stay and is still the most important respiratory infectious disease causing substantially more hospitalizations and deaths compared to influenza and RSV. Today, no real seasonality is observed for COVID-19, in sharp contrast to influenza and RSV. Our antibody XVR013m is differentiated by targeting a unique and highly conserved epitope in the S2 subunit of the SARS-CoV-2 spike protein that makes it virtually variant-proof.” Viki Bockstal, CSO of ExeVir, said: “XVR013m not only demonstrates exceptional virus neutralization potency against all variants tested to date, it is also anticipated to maintain its activity against future variants because of the unique nature of the epitope. There is still a strong and urgent medical need for novel antibodies that work against both the newest as well as future SARS-CoV-2 variants, and these new data again demonstrate that XVR013m has the potential to become a durable therapeutic solution to protect the most vulnerable patients from this serious infectious disease.” References 1. Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study, Evans et al, The Lancet, 2023. . 2. World population above 65 years old: Population ages 65 and above, total | Data (worldbank.org) For more information contact: ExeVir Bio Veronique Vandevoorde vvandevoorde@exevir.com Scius Communications (for media) Katja Stout +44 778 943 5990 katja@sciuscommunications.com Daniel Gooch +44 774 787 5479 daniel@sciuscommunications.com About ExeVir Bio ExeVir Bio is a clinical stage biotechnology company developing heavy-chain only antibody therapies focusing on infectious diseases. The company is harnessing its llama-derived antibody (VHH) technology platform to generate multi-specific antibodies for prophylaxis and treatment of infectious diseases. ExeVir’s initial focus is on prevention of COVID-19 for the immunocompromised patient population, including active chemotherapy, immunosuppressive drugs, solid organ transplantation, hematological malignancies, AIDS patients, and for the elderly, where there remains a high unmet need due to the limitations of current vaccines and therapeutic approaches. ExeVir has demonstrated it can progress its candidates from research to the clinic in under one year, execute on Phase 1a and Phase 1b studies, and conduct scale-up manufacturing. Leveraging this extensive experience, its XVR013m asset is being developed to start a First in Human clinical trial in 2025. VHHs are smaller in size than whole antibodies, giving them access to hidden epitopes that traditional monoclonal antibodies are unable to reach with potential for deeper tissue penetration and simpler, more cost-effective manufacturing. VHHs can be linked together like building blocks into single multispecific molecules to tackle different epitopes or act through different mechanisms of actions at once, to address the “arms race” in more complex and co-evolving infectious diseases. ExeVir is a spin out of VIB, the leading Belgium-based life sciences research institute. It is backed by strong investors including Fund+, which led the series A of EUR 42 million, together with an international consortium including UCB Ventures, SFPIM, V-Bio Ventures, VIB, Wallonie Entreprendre, Noshaq, Vives IUF and SambrInvest. ExeVir has received support from VLAIO, the SPW-Recherche and the European Union, leading to a total of EUR 18 million in non-dilutive funding. In 2023, ExeVir secured an option for EUR 25 million venture debt financing from the European Investment Bank. Find out more on ExeVir’s LinkedIn or on ExeVir’s website