IVX-241

Building on expertise in RSV prevention, acquisition will accelerate ambition to deliver portfolio of protective interventions to address high unmet needs in infectious diseases WILMINGTON, DE, USA I December 12, 2023 I AstraZeneca has entered into a definitive agreement to acquire Icosavax, Inc. (NASDAQ: ICVX), a US-based clinical-stage biopharmaceutical company focused on developing differentiated, high-potential vaccines using an innovative, protein virus-like particle (VLP) platform. The proposed acquisition will build on AstraZeneca’s expertise in respiratory syncytial virus (RSV), strengthening AstraZeneca’s Vaccines & Immune Therapies late-stage pipeline with Icosavax’s lead investigational vaccine candidate, IVX-A12. IVX-A12 is a potential first-in- class, Phase III-ready, combination protein VLP vaccine which targets both RSV and human metapneumovirus (hMPV), two leading causes of severe respiratory infection and hospitalisation in adults 60 years of age and older and those with chronic conditions such as cardiovascular, renal and respiratory disease. 1-3 There are currently no treatments or preventative therapies for hMPV and no combination vaccines for RSV. 4 IVX-A12 is the most advanced investigational vaccine targeting both RSV and hMPV and has a differentiated profile versus currently approved RSV vaccines. Phase II data demonstrate that IVX-A12 elicits robust immune responses against both RSV and hMPV one month after vaccination and reconfirm previous immunogenicity data seen in the Phase I trial. 5 As VLP vaccines mimic how naturally occurring viruses appear to the body’s immune system, they may offer potential benefits over non-VLP vaccines, including a stronger immune response, greater breadth of protection, greater durability requiring fewer boosters and, compared to the current adjuvanted RSV vaccine, a lower incidence of side effects. 6 Alongside Icosavax’s proprietary technology and leadership in protein design, the acquisition is expected to also bring their expertise and capabilities in protein virus-like particle science and development to AstraZeneca to support the progression of IVX-A12 and other differentiated VLP vaccines for high-burden respiratory infections. Iskra Reic, Executive Vice President, Vaccines & Immune Therapies, AstraZeneca, said: “This virus-like particle vaccine technology has the potential to transform prevention against severe infectious diseases, including RSV and hMPV. With the addition of Icosavax’s Phase III-ready lead asset to our late-stage pipeline, we will have a differentiated, advanced investigational vaccine, and a platform for further development of combination vaccines against respiratory viruses. This aligns with our strategy to deliver a portfolio of therapies to address high unmet needs in infectious diseases, and our ambition to protect the most vulnerable patients who have high risk of severe outcomes.” Adam Simpson, Chief Executive officer, Icosavax, said: “We are pleased to announce the proposed acquisition of Icosavax by AstraZeneca as we believe it offers the opportunity to accelerate, and expand access to, our potential first-in-class combination vaccine for older adults at risk of RSV and hMPV. We look forward to combining our skills and expertise in advancing the development of IVX-A12 with AstraZeneca’s decades of experience in RSV, resources, and capabilities in late-stage development.” Financial considerations Under the terms of the agreement, AstraZeneca, through a subsidiary, will initiate a tender offer to acquire all of Icosavax’s outstanding shares for a price of $15.00 per share in cash at closing, plus a non-tradable contingent value right for up to $5.00 per share in cash payable upon achievement of a specified regulatory milestone and a sales milestone. The upfront cash portion of the consideration represents a transaction value of approximately $0.8bn, a 43% premium to Icosavax’s closing market price on 11 th December 2023 and a 73% premium to the 60-day volume-weighted average price (VWAP) of $8.68 before this announcement. Combined, the upfront and maximum potential contingent value payments represent, if achieved, a transaction value of approximately $1.1bn, a 91% premium to Icosavax’s closing market price on 11 th December 2023 and a 130% premium to the 60-day VWAP. As part of the transaction, AstraZeneca will acquire the cash and marketable securities on Icosavax’s balance sheet, which totaled $229m as of 30 th September 2023. Notes Icosavax Icosavax is a biopharmaceutical company leveraging its innovative VLP platform technology to develop vaccines against infectious diseases, with an initial focus on life-threatening respiratory diseases and a vision for combination and pan-respiratory vaccines. Icosavax’s VLP platform incorporates antigen design capabilities and technology to enable multivalent, particle-based display of complex viral antigens, which it believes will induce broad, robust, and durable protection against the specific viruses targeted. Icosavax’s lead program is a combination vaccine candidate targeting respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). Its pipeline includes additional candidates that provide optionality as potential components of future combination and pan-respiratory vaccines, including influenza and SARS-CoV-2. Icosavax was formed in 2017 to advance the breakthrough VLP technology from the Institute for Protein Design at the University of Washington with the goal to discover, develop, and commercialize vaccines against infectious diseases. Icosavax is located in Seattle. RSV and hMPV in older adults RSV is a common, contagious virus that is a major cause of lower respiratory tract infection in adults. 7 Most adult RSV disease cases occur among older adults, with an estimated 60,000-160,000 hospitalisations and 6,000-10,000 deaths annually among US adults >65 years. 8 RSV infection can cause serious complications such as pneumonia or exacerbation of congestive heart failure, asthma, and chronic obstructive pulmonary disease. 7 hMPV causes disease very similar to RSV, including upper and lower respiratory tract infections that can be more severe in young children, older adults, and people with weakened immune systems. 4 Adults with hMPV infection may have viral pneumonia, worsening asthma, or COPD symptoms. 9 Data support similar morbidity and mortality for hMPV and RSV. 2 There are currently no treatment or prevention options for hMPV. 4 IVX-A12 IVX-A12 is a liquid, refrigerator-stable formulation comprised of IVX-121, Icosavax’s RSV prefusion F protein VLP vaccine candidate, and IVX-241, Icosavax’s hMPV prefusion F protein VLP vaccine candidate. In Icosavax’s Phase II trial, IVX-A12 showed robust immune responses across RSV and hMPV antibodies, reconfirming previous immunogenicity data seen in the smaller Phase I trial. The data are the first to demonstrate hMPV immune response in a Phase II combination vaccine trial. IVX-A12 was generally well-tolerated in the trial, with a safety profile similar to that seen in the Phase I trial. 5 IVX-A12 has been granted Fast Track Designation from the US Food and Drug Administration, a programme designed to facilitate the development and expedite the review of investigational drugs to treat serious conditions and fulfill an unmet medical need. 10 Icosavax VLP technology VLPs are a proven technology with multiple products on the market, including vaccines for human papillomavirus and hepatitis B. 6 While currently available vaccines utilise the few proteins that naturally fold into VLPs, 11 the Icosavax protein VLP platform builds on that success with intentionally designed VLPs to create highly differentiated vaccines. VLPs are designed to resemble the structure of viruses, with high-density, multivalent display of antigens. 6,11 This technology is believed to induce a stronger and more durable immune response versus traditional soluble antigens. 6,11 Transaction details The closing of the tender offer will be subject to certain conditions, including the tender of shares representing at least a majority of the total number of Icosavax’s outstanding shares, and other customary closing conditions and regulatory clearances. Upon the successful completion of the tender offer, AstraZeneca’s acquisition subsidiary will be merged with and into Icosavax and any remaining shares of common stock of Icosavax will be cancelled and converted into the right to receive the same merger consideration (including the contingent value right) per share payable in the tender offer. Subject to the satisfaction of the conditions in the merger agreement, the acquisition is expected to close in the first quarter of 2024. Important information about the tender offer The tender offer for the outstanding common stock of the Company has not yet commenced. This communication does not constitute a recommendation, an offer to purchase or a solicitation of an offer to sell the Company’s securities. An offer to purchase shares of the Company’s common stock will only be made pursuant to an Offer to Purchase and related tender offer materials. At the time the tender offer is commenced, AstraZeneca PLC (AstraZeneca), AstraZeneca Finance and Holdings Inc. and Isochrone Merger Sub Inc., a wholly owned indirect subsidiary of AstraZeneca, will file a Tender Offer Statement on Schedule TO with the Securities and Exchange Commission (the SEC) and thereafter the Company will file a Solicitation/Recommendation Statement on Schedule 14D-9 with the SEC with respect to the tender offer. The tender offer materials (including the Offer to Purchase, a related Letter of Transmittal and other tender offer documents) and the Solicitation/Recommendation Statement on Schedule 14D-9 will contain important information. The Company’s stockholders are urged to read these documents (including the Offer to Purchase and related Letter of Transmittal and certain other documents), and the Solicitation/Recommendation Statement, as may be amended from time to time, carefully when they become available because they will contain important information that they should consider before making any decision regarding tendering their shares of common stock. The tender offer materials and the Solicitation/Recommendation Statement will be made available for free at the SEC’s website at www.sec.gov . Copies of the documents filed with the SEC by AstraZeneca may be obtained at no charge on the investor relations page of AstraZeneca’s internet website at www.astrazeneca.com/investors . Copies of the documents filed with the SEC by Icosavax may be obtained at no charge under the “Investors” section of Icosavax’s internet website at www.Icosavax.com . 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 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca . References SOURCE: AstraZeneca

– IVX-A12 induced robust immune responses at Day 28 to both RSV and hMPV, and was generally well tolerated, consistent with prior IVX-A12 Phase 1 data – SEATTLE, Dec. 11, 2023 (GLOBE NEWSWIRE) -- Icosavax, Inc. (Nasdaq: ICVX), a biopharmaceutical company leveraging its innovative virus-like particle (VLP) platform technology to develop vaccines against infectious diseases, with an initial focus on life-threatening respiratory diseases and a vision of creating pan-respiratory vaccines for older adults, today announced positive topline interim results from its Phase 2 clinical trial of IVX-A12 against respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) in older adults. “We’re delighted to announce positive topline interim data from our Phase 2 trial of IVX-A12, our potential first-in-class combination vaccine candidate against RSV and hMPV,” said Adam Simpson, Chief Executive Officer of Icosavax. “We believe that IVX-A12 has the potential to address a significant unmet need and, as the furthest advanced RSV and hMPV combination vaccine in the clinic, to build on an emerging, large market opportunity.” IVX-A12 Phase 2 Trial Design The ongoing Phase 2 clinical trial of IVX-A12 is a randomized, observer-blinded, placebo-controlled, multi-center trial designed to evaluate the safety and immunogenicity of a single dose of RSV and hMPV combination VLP vaccine IVX-A12, with and without CSL Seqirus’ proprietary adjuvant MF59® (MF59). The trial enrolled 264 healthy older adults aged 60 to 85 years, of which 241 subjects were evaluable for immunogenicity. Subjects were administered a single dose of either IVX-A12 at the 300 µg combination dosage level (150 µg of RSV VLP (IVX-121) and 150 µg of hMPV VLP (IVX-241)), with or without MF59, or placebo. Topline Interim Results Topline interim safety and immunogenicity data from this trial were generally consistent with the previously reported Phase 1 data for IVX-A12. Safety: IVX-A12 was generally well-tolerated across both dosage groups. Solicited local and systemic adverse events (AEs) collected within seven days of vaccination were generally mild to moderate without severe events. No cases of fever were reported in any group. For unadjuvanted IVX-A12, the proportion of subjects experiencing any systemic AE within seven days was 32%, and similar to placebo (36%). The most common local and systemic AEs were injection site tenderness, injection site pain, and myalgia.There were no vaccine related serious adverse events (SAEs), clinical events or AEs of special interest (AESIs), or AEs leading to discontinuation. Immunogenicity: IVX-A12 induced robust immune responses against both RSV and hMPV at Day 28 across both formulations with and without adjuvant. For unadjuvanted IVX-A12: IVX-A12 induced geometric mean titers (GMTs) in RSV-A neutralizing antibody titers (nAbs) of approximately 12,200 IU/mL compared to approximately 2,000 IU/mL for placebo at Day 28. IVX-A12 induced GMTs in RSV-B nAbs of approximately 5,500 IU/mL compared to approximately 1,300 IU/mL for placebo at Day 28.IVX-A12 induced GMTs in hMPV-A nAbs of approximately 1,600 assay units/mL compared to approximately 400 assay units/mL for placebo at Day 28. IVX-A12 induced GMTs in hMPV-B nAbs of approximately 15,300 assay units/mL compared to approximately 6,700 assay units/mL for placebo at Day 28. No standardized international units exist in the field for hMPV. “The positive Phase 2 data announced today for IVX-A12 are very encouraging and mark another milestone in the field for RSV and hMPV vaccination in older adults, a vulnerable population with heightened risk of severe disease,” said Niranjan Kanesa-thasan, M.D., Chief Medical Officer of Icosavax. About Icosavax Icosavax is a biopharmaceutical company leveraging its innovative VLP platform technology to develop vaccines against infectious diseases, with an initial focus on life-threatening respiratory diseases and a vision for combination and pan-respiratory vaccines. Icosavax’s VLP platform incorporates antigen design capabilities and technology to enable multivalent, particle-based display of complex viral antigens, which it believes will induce broad, robust, and durable protection against the specific viruses targeted. Icosavax’s lead program is a combination vaccine candidate targeting respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). Its pipeline includes additional candidates that provide optionality as potential components of future combination and pan-respiratory vaccines, including influenza and SARS-CoV-2. Icosavax was formed in 2017 to advance the breakthrough VLP technology from the Institute for Protein Design at the University of Washington with the goal to discover, develop, and commercialize vaccines against infectious diseases. Icosavax is located in Seattle. For more information, visit www.icosavax.com. Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on the company’s current beliefs and expectations and include, but are not limited to: the company’s expectation regarding the opportunities for, and the prophylactic and commercial potential of, its vaccine candidates and technology platform and the potential for IVX-A12 to be a first-in-class combination vaccine candidate against RSV and hMPV. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in the company’s business, including, without limitation: the early stage of the company’s development efforts; the risk that results of a clinical trial at a particular time point may not predict final results and that an outcome may materially change as follow-up of subjects continues and following more comprehensive reviews of the data; the company’s approach to the development of vaccine candidates, including its development of a combination bivalent RSV/hMPV VLP vaccine candidate, which is a novel and unproven approach; potential delays in the development process including without limitation in the commencement, enrollment, conduct of, and receipt of data from, clinical trials; unexpected adverse side effects or inadequate immunogenicity or efficacy of the company’s vaccine candidates that may limit their development, regulatory approval, and/or commercialization; the company’s dependence on third parties in connection with manufacturing, research, and clinical testing; the risk that third party marketed RSV vaccines may make conducting clinical trials more difficult and costly and otherwise adversely affect the ability to successfully develop, obtain regulatory approval of and commercialize its vaccine candidates; the potential for challenges encountered in the manufacturing and scale up process; competing approaches and approved vaccines limiting the commercial value of the company’s vaccine candidates; regulatory developments in the United States and other countries; the company’s ability to fund its operating plans with its current cash, cash equivalents and investments; and other risks described in the company’s prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in the company’s quarterly report on Form 10-Q for the quarter ended September 30, 2023 and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Media Contact:Jessica Yingling, Ph.D.,Little Dog Communications Inc.jessica@litldog.com858.344.8091 Investor Contact:Laurence WattsGilmartin Group, LLClaurence@gilmartinir.com619.916.7620