Cilgavimab/Tixagevimab

New in vitro neutralization data show continued, consistent neutralizing activity of PEMGARDA™ (pemivibart) against XEC Centers for Disease Control reports XEC and KP.3.1.1 (previously disclosed as susceptible to PEMGARDA) together constitute the majority of national SARS-CoV-2 variantsXEC data underscore continued pemivibart activity in the face of virus evolution including recently emerging types of structural changes to spike N-terminal domainData submitted to FDA, with timely update to PEMGARDA™ Fact Sheet for Healthcare Providers anticipatedContinued consistent activity for almost three years, with no meaningful change to pemivibart neutralization activity anticipated for the foreseeable future if the epitope pemivibart targets remains structurally intact, as it has since Omicron BA.1 WALTHAM, Mass., Jan. 10, 2025 (GLOBE NEWSWIRE) -- Invivyd, Inc. (Nasdaq: IVVD), a biopharmaceutical company devoted to delivering protection from serious viral infectious diseases, today announced that new in vitro neutralization data show continued neutralizing activity of PEMGARDA™ (pemivibart) and pipeline candidate VYD2311 against dominant SARS-CoV-2 variant XEC. As anticipated based on the structural biology of pemivibart and VYD2311, the data are largely consistent with those previously reported for KP.3.1.1. The Centers for Disease Control (CDC) estimates that XEC and KP.3.1.1 accounted for an aggregate 69% of U.S. circulating variants of SARS-CoV-2 for the two weeks ended December 21, 2024. Invivyd generated these new data as part of its ongoing industrial virology effort, which leverages a consistent, high-quality, independent, third-party pseudoviral system that routinely tests authentic Invivyd-produced pemivibart and is supported by extensive structure-based and proprietary analytics. Invivyd has demonstrated positive PEMGARDA neutralization activity against over 75% of currently circulating U.S. variants, and all prior variants, tested to date. Further, the company estimates that every clinical variant reported in the CDC COVID Tracker since the Omicron BA.1 lineage has been susceptible to pemivibart even if untested due to the consistent structural integrity of the pemivibart epitope. Therefore, Invivyd does not anticipate any meaningful change to pemivibart neutralization activity, aside from expected normal quantitative variation in assay output, for the foreseeable future if the epitope pemivibart targets remains structurally intact, as it has since Omicron BA.1. “We designed pemivibart and our pipeline molecules to resist the effects of evolution,” said Robert Allen, Ph.D., Chief Scientific Officer. “Pemivibart has now demonstrated antiviral activity in neutralization assays representing thirty-nine distinct SARS-CoV-2 variants across almost three years of rapid virus evolution. The ongoing pemivibart activity, with minimal quantitative change in neutralization activity, especially as compared to predecessor medicines such as Evusheld™ (tixagavimab/cilgavimab), is incredibly reassuring and validating of our fundamental R&D engine and potentiates our ability to successfully drug this target for long periods of time despite evolutionary pressure.” “Invivyd has worked to construct what we believe is the world’s most advanced and capable antibody discovery and virology platform designed to provide best-in-class molecules and virologic assessment,” noted Marc Elia, Chairman of Invivyd Board of Directors. “Therefore, we are pleased but not surprised by today’s robust data that confirm ongoing PEMGARDA™ (pemivibart) neutralizing activity against key current circulating viral lineages.” “Amidst the continual mutations that characterize SARS-CoV-2, proactively monitoring viral evolution as Invivyd is doing is a necessity in order to continuously test PEMGARDA against emerging variants of SARS-CoV- 2,” noted Amesh Adalja, MD, FIDSA, FACP, FACEP, Senior Scholar, Johns Hopkins Center for Health Security. “It is reassuring that PEMGARDA continues to show neutralizing activity against XEC, the current dominant circulating variant in the U.S. As we see COVID-19 numbers continue to rise through the respiratory season, PEMGARDA offers a valuable tool for certain moderately to severely immunocompromised patients who need options.” Data showing continued in vitro neutralizing activity of PEMGARDA™ (pemivibart) against XEC have been submitted to the U.S. Food and Drug Administration (FDA), with a timely update to the PEMGARDA Fact Sheet for Healthcare Providers anticipated. About PEMGARDAPEMGARDA™ (pemivibart) is a half-life extended investigational monoclonal antibody (mAb). PEMGARDA was engineered from adintrevimab, Invivyd’s investigational mAb that has a robust safety data package and provided evidence of clinical efficacy in a global Phase 2/3 clinical trial for the prevention and treatment of COVID-19. PEMGARDA has demonstrated in vitro neutralizing activity against major SARS-CoV-2 variants, including JN.1, KP.3.1.1 and XEC. PEMGARDA targets the SARS-CoV-2 spike protein receptor binding domain (RBD), thereby inhibiting virus attachment to the human ACE2 receptor on host cells. PEMGARDA (pemivibart) injection (4500 mg), for intravenous use is an investigational mAb that has not been approved, but has been authorized for emergency use by the U.S. FDA under an EUA for the pre-exposure prophylaxis (prevention) of COVID-19 in adults and adolescents (12 years of age and older weighing at least 40 kg) who have moderate-to-severe immune compromise due to certain medical conditions or receipt of certain immunosuppressive medications or treatments and are unlikely to mount an adequate immune response to COVID-19 vaccination. Recipients should not be currently infected with or have had a known recent exposure to an individual infected with SARS-CoV-2. PEMGARDA is not authorized for use for treatment of COVID-19 or post-exposure prophylaxis of COVID-19. Pre-exposure prophylaxis with PEMGARDA is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended. Individuals for whom COVID-19 vaccination is recommended, including individuals with moderate-to-severe immune compromise who may derive benefit from COVID-19 vaccinations, should receive COVID-19 vaccination. In individuals who have recently received a COVID-19 vaccine, PEMGARDA should be administered at least 2 weeks after vaccination. Anaphylaxis has been observed with PEMGARDA and the PEMGARDA Fact Sheet for Healthcare Providers includes a boxed warning for anaphylaxis. The most common adverse events (all grades, incidence ≥2%) observed in participants who have moderate-to-severe immune compromise treated with PEMGARDA included systemic and local infusion-related or hypersensitivity reactions, upper respiratory tract infection, viral infection, influenza-like illness, fatigue, headache, and nausea. For additional information, please see the PEMGARDA full product Fact Sheet for Healthcare Providers, including important safety information and boxed warning. To support the EUA for PEMGARDA, an immunobridging approach was used to determine if PEMGARDA may be effective for pre-exposure prophylaxis of COVID-19. Immunobridging is based on the serum virus neutralizing titer-efficacy relationships identified with other neutralizing human mAbs against SARS-CoV-2. This includes adintrevimab, the parent mAb of pemivibart, and other mAbs that were previously authorized for EUA. There are limitations of the data supporting the benefits of PEMGARDA. Evidence of clinical efficacy for other neutralizing human mAbs against SARS-CoV-2 was based on different populations and SARS-CoV-2 variants that are no longer circulating. Further, the variability associated with cell-based EC50 value determinations, along with limitations related to pharmacokinetic data and efficacy estimates for the mAbs in prior clinical trials, impact the ability to precisely estimate protective titer ranges. Additionally, certain SARS-CoV-2 viral variants may emerge that have substantially reduced susceptibility to PEMGARDA, and PEMGARDA may not be effective at preventing COVID-19 caused by these SARS-CoV-2 viral variants. The emergency use of PEMGARDA is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner. PEMGARDA is authorized for use only when the combined national frequency of variants with substantially reduced susceptibility to PEMGARDA is less than or equal to 90%, based on available information including variant susceptibility to PEMGARDA and national variant frequencies. About VYD2311 VYD2311 is a novel monoclonal antibody (mAb) candidate being developed for COVID-19 to continue to address the urgent need for new therapeutic options for vulnerable populations, including immunocompromised people. VYD2311 was engineered from adintrevimab, Invivyd’s investigational mAb that has a robust safety data package and demonstrated clinically meaningful results in global Phase 3 clinical trials for both the prevention and treatment of COVID-19. The pharmacokinetic profile of VYD2311 may offer the ability to deliver clinically meaningful titer levels through more patient-friendly means such as an intramuscular route of administration. About InvivydInvivyd, Inc. (Nasdaq: IVVD) is a biopharmaceutical company devoted to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2. The company’s proprietary INVYMAB™ platform approach combines state-of-the-art viral surveillance and predictive modeling with advanced antibody engineering. INVYMAB is designed to facilitate the rapid, serial generation of new monoclonal antibodies (mAbs) to address evolving viral threats. In March 2024, Invivyd received emergency use authorization (EUA) from the U.S. FDA for its first mAb in a planned series of innovative antibody candidates. Visit https://invivyd.com/ to learn more. Trademarks are the property of their respective owners. Cautionary Note Regarding Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “could,” “expects,” “estimates,” “intends,” “potential,” “projects,” and “future” or similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements include statements concerning, among other things, the company’s ongoing research and development activities, as well as future potential research and development efforts; the company’s ongoing industrial virology effort, which leverages a consistent, high-quality, independent, third-party pseudoviral system that routinely tests authentic Invivyd-produced pemivibart and is supported by extensive structure-based analytics and proprietary analytics; the ongoing in vitro neutralizing activity of PEMGARDA against major SARS-CoV-2 variants; anticipated timely updates to the PEMGARDA Fact Sheet for Healthcare Providers; the company’s expectations regarding the neutralization activity of pemivibart for the foreseeable future; the design of pemivibart and the company’s pipeline molecules to resist the effects of evolution; the company’s beliefs regarding the potential of its fundamental R&D engine and ability to successfully drug its target for long periods of time despite evolutionary pressure; the company’s beliefs regarding its antibody discovery and virology platform and its potential to provide best-in-class molecules and virologic assessment; the potential of PEMGARDA as a mAb for pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and adolescents who have moderate-to-severe immune compromise; the potential ability of VYD2311 to deliver clinically meaningful titer levels through more patient-friendly means such as an intramuscular route of administration; the company’s devotion to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2; the design of the company’s INVYMAB platform approach to facilitate the rapid, serial generation of new mAbs to address evolving viral threats; and other statements that are not historical fact. The company may not actually achieve the plans, intentions or expectations disclosed in the company’s forward-looking statements and you should not place undue reliance on the company’s forward-looking statements. These forward-looking statements involve risks and uncertainties that could cause the company’s actual results to differ materially from the results described in or implied by the forward-looking statements, including, without limitation: the timing and progress of the company’s discovery, preclinical and clinical development activities; the risk that results of nonclinical studies or clinical trials may not be predictive of future results, and interim data are subject to further analysis; unexpected safety or efficacy data observed during preclinical studies or clinical trials; the predictability of clinical success of the company’s product candidates based on neutralizing activity in nonclinical studies; potential variability in neutralizing activity of product candidates tested in different assays, such as pseudovirus assays and authentic assays; the company’s reliance on third parties with respect to virus assay creation and product candidate testing and with respect to its clinical trials; variability of results in models and methods used to predict activity against SARS-CoV-2 variants; whether the epitope that pemivibart targets remains structurally intact; whether pemivibart, VYD2311 or any other product candidate is able to demonstrate and sustain neutralizing activity against major SARS-CoV-2 variants, particularly in the face of viral evolution; how long the EUA granted by the FDA for PEMGARDA will remain in effect and whether the EUA is revised or revoked by the FDA; the company’s ability to maintain and expand sales, marketing and distribution capabilities to successfully commercialize PEMGARDA; uncertainties related to the regulatory authorization or approval process, and available development and regulatory pathways for authorization or approval of the company’s product candidates; the ability to maintain a continued acceptable safety, tolerability and efficacy profile of any product candidate following regulatory authorization or approval; changes in the regulatory environment; changes in expected or existing competition; the complexities of manufacturing mAb therapies; the company’s ability to leverage its INVYMAB platform approach to facilitate the rapid, serial generation of new mAbs to address evolving viral threats; the company’s ability to continue as a going concern; and whether the company has adequate funding to meet future operating expenses and capital expenditure requirements. Other factors that may cause the company’s actual results to differ materially from those expressed or implied in the forward-looking statements in this press release are described under the heading “Risk Factors” in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, each filed with the Securities and Exchange Commission (SEC), and in the company’s other filings with the SEC, and in its future reports to be filed with the SEC and available at www.sec.gov. Forward-looking statements contained in this press release are made as of this date, and Invivyd undertakes no duty to update such information whether as a result of new information, future events or otherwise, except as required under applicable law. This press release contains hyperlinks to information that is not deemed to be incorporated by reference in this press release. Contacts:Media Relations(781) 208-0160media@invivyd.com Investor Relations(781) 208-0160investors@invivyd.com

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