Chorioretinitis

97% reduction in treatment burden at nine months after treatment with ABBV-RGX-314 Data consistent with that from multiple previous studies demonstrating favorable safety and efficacy profile Well tolerated with zero cases of intraocular inflammation in a setting of no prophylactic steroids Data highlight the potential of ABBV-RGX-314 to treat both eyes in wet AMD ROCKVILLE, Md., Oct. 21, 2024 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced positive data from the Phase II fellow eye sub-study evaluating the subretinal delivery of ABBV-RGX-314 in patients with bilateral wet age-related macular degeneration (wet AMD). The new data were presented at the American Academy of Ophthalmology (AAO) meeting by Arshad Khanani, M.D., M.A., FASRS, Director of Clinical Research at Sierra Eye Associates, Reno, NV. "The results presented at AAO from the Phase II sub-study, the first to evaluate a gene therapy in fellow eyes for wet AMD, demonstrate that ABBV-RGX-314 could be a treatment for patients with bilateral disease and add to the already-robust data demonstrating ABBV-RGX-314's potential to impact the treatment paradigm for patients with wet AMD," said Curran Simpson, President and Chief Executive Officer of REGENXBIO. "With more treated patients and the longest-term data of any gene therapy program for wet AMD, REGENXBIO, with our partner AbbVie, are well-positioned to bring the first gene therapy to market with the hope of preserving long-term vision for millions of patients globally with wet AMD." "The majority of our patients with wet AMD eventually have bilateral disease and face a substantial treatment burden with frequent lifelong injections in both eyes. This leads to suboptimal real-world vision outcomes with current standard of care," said Dr. Khanani. "The fellow eye dosing data with ABBV-RGX-314 is a milestone for the field of gene therapy for common retinal diseases, as this is the first time we have performed bilateral treatment for wet AMD patients. These results, combined with the durable treatment effect up to four years shown in long-term follow up, highlight the potential of ABBV-RGX-314 as a one-time effective treatment option for patients with wet AMD." Data and Safety Summary The fellow eye sub-study was designed to evaluate the safety and efficacy of a single dose (1.3x1011 GC/eye) of ABBV-RGX-314 using subretinal delivery in the fellow eye of previously treated patients. The second eye was treated with ABBV-RGX-314 approximately one year or more after administration of ABBV-RGX-314 in the first eye. This dose is being evaluated in the ongoing pivotal trials of ABBV-RGX-314 and is similar to one of the doses evaluated in the Phase I/IIa trial, which demonstrated durable treatment effect up to four years in a long-term follow up study. The fellow eye sub-study data at nine months includes nine patients who received ABBV-RGX-314 using subretinal delivery in the Phase I/IIa or bridging studies and elected to receive treatment in their second eye. Prior to ABBV-RGX-314 administration, these patients had a high treatment burden in the fellow eye and had received an average of nine anti-VEGF injections in the year prior to entering the study, including anti-VEGF injections intended to be longer-lasting treatments. At nine months post-administration of ABBV-RGX-314, key findings from the Phase II fellow eye sub-study include: 97% reduction in annualized anti-VEGF treatment burden 100% of patients required either zero or one supplemental injection 78% of patients were completely injection-free Additionally, patients demonstrated sustained best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at nine months. ABBV-RGX-314 produced similar levels of aqueous protein in both treated eyes. As of September 11, 2024, ABBV-RGX-314 was well tolerated in the treated fellow eye with no drug related serious adverse events. No cases of intraocular inflammation, chorioretinitis, vasculitis, occlusion or hypotony were observed. No prophylactic steroids were used in this trial, other than those typically used in vitrectomy surgery. Common adverse events included mild retinal pigmentary changes occurring in periphery and post-operative conjunctival hemorrhage, which all resolved within days to weeks. Data presented is available on the "Publications" section of the REGENXBIO website at . About ABBV-RGX-314 ABBV-RGX-314, being developed in collaboration with AbbVie, is being investigated as a potential one-time treatment for wet AMD, diabetic retinopathy, and other chronic retinal conditions. ABBV-RGX-314 consists of the NAV® AAV8 vector, which encodes an antibody fragment designed to inhibit vascular endothelial growth factor (VEGF). ABBV-RGX-314 is believed to inhibit the VEGF pathway by which new, leaky blood vessels grow and contribute to the accumulation of fluid in the retina. REGENXBIO is advancing research in two separate routes of administration of ABBV-RGX-314 to the eye, through a standardized subretinal delivery procedure as well as delivery to the suprachoroidal space. REGENXBIO has licensed certain exclusive rights to the SCS Microinjector® from Clearside Biomedical, Inc. to deliver gene therapy treatments to the suprachoroidal space of the eye. About Wet AMD Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long frequent, repeated intraocular injections to maintain efficacy. Due to the burden of treatment, it is difficult for patients to adhere to frequent injections, which can lead to a decline in vision over time. ABOUT REGENXBIO Inc. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for retinal and rare diseases, including ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, RGX-202 for the treatment of Duchenne and RGX-121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO's AAV Therapeutic platform, including Novartis' ZOLGENSMA for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit . FORWARD-LOOKING STATEMENTS This press release includes "forward-looking statements," within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements express a belief, expectation or intention and are generally accompanied by words that convey projected future events or outcomes such as "believe," "may," "will," "estimate," "continue," "anticipate," "assume," "design," "intend," "expect," "could," "plan," "potential," "predict," "seek," "should," "would" or by variations of such words or by similar expressions. The forward-looking statements include statements relating to, among other things, REGENXBIO's future operations and clinical trials. REGENXBIO has based these forward-looking statements on its current expectations and assumptions and analyses made by REGENXBIO in light of its experience and its perception of historical trends, current conditions and expected future developments, as well as other factors REGENXBIO believes are appropriate under the circumstances. However, whether actual results and developments will conform with REGENXBIO's expectations and predictions is subject to a number of risks and uncertainties, including the timing of enrollment, commencement and completion and the success of clinical trials conducted by REGENXBIO, its licensees and its partners, the timing of commencement and completion and the success of preclinical studies conducted by REGENXBIO and its development partners, the timely development and launch of new products, the ability to obtain and maintain regulatory approval of product candidates, the ability to obtain and maintain intellectual property protection for product candidates and technology, trends and challenges in the business and markets in which REGENXBIO operates, the size and growth of potential markets for product candidates and the ability to serve those markets, the rate and degree of acceptance of product candidates, and other factors, many of which are beyond the control of REGENXBIO. Refer to the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of REGENXBIO's Annual Report on Form 10-K for the year ended December 31, 2023, and comparable "risk factors" sections of REGENXBIO's Quarterly Reports on Form 10-Q and other filings, which have been filed with the U.S. Securities and Exchange Commission (SEC) and are available on the SEC's website at . All of the forward-looking statements made in this press release are expressly qualified by the cautionary statements contained or referred to herein. The actual results or developments anticipated may not be realized or, even if substantially realized, they may not have the expected consequences to or effects on REGENXBIO or its businesses or operations. Such statements are not guarantees of future performance and actual results or developments may differ materially from those projected in the forward-looking statements. Readers are cautioned not to rely too heavily on the forward-looking statements contained in this press release. These forward-looking statements speak only as of the date of this press release. Except as required by law, REGENXBIO does not undertake any obligation, and specifically declines any obligation, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Zolgensma® is a registered trademark of Novartis Gene Therapies. SCS Microinjector® is a trademark of Clearside Biomedical, Inc. All other trademarks referenced herein are registered trademarks of REGENXBIO. CONTACT: Dana Cormack Corporate Communications [email protected] George E. MacDougall Investor Relations [email protected] SOURCE REGENXBIO Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

– Findings from nine human factors studies, assessing design and user interface, suggest SelfJect functions as an effective delivery device when used as intended1 – – The SelfJect delivery device received the Arthritis Foundation's Ease of Use certification – DUBLIN, Sept. 17, 2024 /PRNewswire/ -- Mallinckrodt plc, a global specialty pharmaceutical company, today announced the publication of findings from seven formative and two validation human factors studies of recently launched Acthar Gel (repository corticotropin injection) Single-Dose Pre-filled SelfJect™ Injector ("SelfJect").2 The manuscript, describing the formative and human factor outcomes, was recently published online in Expert Opinion on Drug Delivery. Approved by the U.S. Food and Drug Administration (FDA) in February of 2024, SelfJect also received the Arthritis Foundation's Ease of Use® certification. This certification recognizes SelfJect for its easy-to-use design, based on testing by an independent third party. Acthar Gel is a naturally sourced complex mixture of adrenocorticotropic hormone (ACTH) analogs and other pituitary peptides.2 Acthar Gel is approved by the FDA for the treatment of several autoimmune disorders and medical conditions known to cause inflammation.2 SelfJect is available in 40 USP units/0.5 mL and 80 USP units/1.0 mL injectors and must be administered by people 18 years of age or older. SelfJect is not to be used for the treatment of infantile spasms. Please see Indications and Important Safety Information for Acthar Gel below. "We're proud of the extensive research and testing conducted to develop SelfJect, including these human factors studies which were critical to our application for FDA approval," said Lisa French, Executive Vice President & Chief Commercial Officer. "These results, and the Arthritis Foundation's Ease of Use certification, are a testament to our commitment to modernize Acthar Gel for our patient community. In keeping with our mission of listening for needs, SelfJect provides an administration option designed to better support patients, caregivers, and medical professionals in managing appropriate conditions." Arthritis Foundation President and CEO Steven Taylor said, "Ease of Use products and packaging are designed to help people with arthritis and those with physical limitations by making everyday tasks easier. We're excited to partner with companies like Mallinckrodt that understand the importance of developing products and packages with the needs of patients at the forefront." About the Studies Human factors studies were conducted utilizing SelfJect to assess the design of the injection device and its user interface, as well as mitigate potential use-related hazards, through observation of participants using the device and participant feedback.1 The published research includes results from nine studies, including seven formative studies, a validation study (with four prior pilot validation studies), and a supplemental validation study with participants including lay users, patients, caregivers, and healthcare providers.1 The formative studies tested and developed various components such as packaging and instructional material, whereas the validation study evaluated administration of the device with the intended-to-market user interface and representative users in representative simulated-use environments.1 Four pilot studies then generated additional protocol recommendations for the validation study.1 In the 160-participant validation study, 91% (n=146) of participants successfully administered their first injection, with 98% (n=156) cumulative success after the second trial.1 Use errors were rare with simulated-use (6.9% [n=194] of all evaluated tasks) and knowledge-based (1.6% [n=56] of all evaluated tasks) testing. The most common use errors were related to not appropriately warming the product before administration.1 Limitations of the studies include1: The controlled study setting may not have accurately replicated real-world complexities that play a role in the administration of Acthar Gel via SelfJect, potentially altering the number of study use errors and deviation. Injections were performed with placebo gel into an injection pad and not a patient. The feedback that a user receives when injecting into skin versus a surrogate injection pad may influence use behavior. A more realistic delivery container could have been used to cue the participant that this product would arrive cold and would need to be stored appropriately. Participant selection bias, reliance on self-reported and qualitative data, and small sample sizes in the formative and pilot studies may have impacted results. If a customer is interested in learning more about SelfJect, they can reach out to their local representative or visit ActharHCP.com. INDICATIONS Acthar Gel is indicated for: Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age Treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: keratitis, iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation Symptomatic sarcoidosis Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus Treatment during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis (polymyositis) Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy); ankylosing spondylitis IMPORTANT SAFETY INFORMATION Contraindications Acthar is contraindicated: For intravenous administration In infants under 2 years of age who have suspected congenital infections With concomitant administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of Acthar In patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, or sensitivity to proteins of porcine origin Warnings and Precautions The adverse effects of Acthar are related primarily to its steroidogenic effects Acthar may increase susceptibility to new infection or reactivation of latent infections Suppression of the hypothalamic-pituitary-adrenal (HPA) axis may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by tapering of the dose when discontinuing treatment. During recovery of the adrenal gland patients should be protected from the stress (e.g., trauma or surgery) by the use of corticosteroids. Monitor patients for effects of HPA axis suppression after stopping treatment Cushing's syndrome may occur during therapy but generally resolves after therapy is stopped. Monitor patients for signs and symptoms Acthar can cause elevation of blood pressure, salt and water retention, and hypokalemia. Monitor blood pressure and sodium and potassium levels Acthar often acts by masking symptoms of other diseases/disorders. Monitor patients carefully during and for a period following discontinuation of therapy Acthar can cause gastrointestinal (GI) bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain GI disorders. Monitor for signs of perforation and bleeding Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression to psychosis. Existing conditions may be aggravated Patients with comorbid disease may have that disease worsened. Caution should be used when prescribing Acthar in patients with diabetes and myasthenia gravis Prolonged use of Acthar may produce cataracts, glaucoma, and secondary ocular infections. Monitor for signs and symptoms Acthar is immunogenic and prolonged administration of Acthar may increase the risk of hypersensitivity reactions. Cases of anaphylaxis have been reported in the postmarketing setting. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH and Acthar activity There may be an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver Long-term use may have negative effects on growth and physical development in children. Monitor pediatric patients Decrease in bone density may occur. Bone density should be monitored in patients on long-term therapy Adverse Reactions Commonly reported postmarketing adverse reactions for Acthar include injection site reaction, asthenic conditions (including fatigue, malaise, asthenia, and lethargy), fluid retention (including peripheral swelling), insomnia, headache, and blood glucose increased The most common adverse reactions for the treatment of infantile spasms (IS) are increased risk of infections, convulsions, hypertension, irritability, and pyrexia. Some patients with IS progress to other forms of seizures; IS sometimes masks these seizures, which may become visible once the clinical spasms from IS resolve Pregnancy Acthar may cause fetal harm when administered to a pregnant woman Please see full Prescribing Information for additional Important Safety Information. ABOUT MALLINCKRODT Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company's Specialty Brands reportable segment's areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit . CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS This release contains forward-looking statements, including with regard to Acthar Gel (repository corticotropin injection), the Acthar Gel Single-Dose Pre-filled SelfJect™ Injector, the potential of these products to improve health and treatment outcomes, their potential impact on patients and the availability of Acthar Gel Single-Dose Pre-filled SelfJect Injector in the U.S. in the future. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: the effects of Mallinckrodt's recent emergence from bankruptcy; satisfaction of, and compliance with, regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; changes in market demand; issues with product quality, manufacturing or supply, or patient safety issues or adverse side effects or adverse reactions associated with Acthar Gel and Acthar Gel Single-Dose Pre-filled SelfJect Injector; and other risks identified and described in more detail in the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Mallinckrodt's most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law. CONTACT Media Inquiries Green Room Communications 908-577-4531 [email protected] Investor Relations Derek Belz Vice President, Investor Relations 314-654-3950 [email protected] Mallinckrodt, the "M" brand mark, SelfJect, and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ©2024 Mallinckrodt. US-2400718 09/24 References 1 Linnane A, Lau M, Miranda P, Elliott S. Formative and Validation Human Factors Studies of a New Disposable Prefilled Injection Device for Subcutaneous Delivery of Acthar Gel (Repository Corticotropin Injection). Expert Opinion on Drug Delivery. 2024. . 2 Acthar® Gel (repository corticotropin injection) [prescribing information]. Bridgewater, NJ: Mallinckrodt ARD LLC. SOURCE Mallinckrodt plc WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Focuses on ten product approvals through 2027 Expects to submit next-generation COVID vaccine for approval in 2024 Expects to submit flu/COVID combination vaccine for approval in 2024 Announces positive Phase 3 results for its RSV vaccine for high-risk adults aged 18 to 59; expects to submit sBLA for U.S. approval in 2024 Announces positive Phase 3 results for its standalone flu vaccine for adults aged 65 and older relative to high-dose licensed comparator Announces norovirus vaccine advances into Phase 3 study, bringing the total of non-respiratory pivotal stage programs to five, across oncology, rare diseases and first-in-class vaccines Implements portfolio prioritization and cost efficiencies to reduce R&D expense by $1.1 billion, from $4.8 billion in 2024E to $3.6-3.8 billion in 2027 Updates and extends financial framework through 2028 CAMBRIDGE, MA, USA I September 12, 2024 I Moderna, Inc. (NASDAQ:MRNA) today announced program and financial updates demonstrating progress and strategic prioritization of its mRNA pipeline at its annual R&D Day event. The updates include data readouts in the Company’s respiratory vaccine portfolio and a revised financial framework. “Moderna now has five respiratory vaccines with positive Phase 3 results and expects to submit three for approval this year. In addition, we have five non-respiratory products in pivotal studies across cancer, rare diseases and latent vaccines with potential for approval by 2027. Our demonstrated probability of success in R&D has been higher than industry standards at every stage of development,” said Stéphane Bancel, CEO of Moderna. “The size of our late-stage pipeline combined with the challenge of launching products means we must now focus on delivering these 10 products to patients, slow down the pace of new R&D investment, and build our commercial business.” Research and Development Strategy Over the past three years, Moderna’s robust pipeline has achieved milestones across multiple late-stage clinical trials, and its early-stage portfolio has produced proof-of-concept data with multiple candidates ready for pivotal studies. Moderna’s rate of success in research and development has been higher than the traditional biopharmaceutical industry. The Company’s combined probability of success across its mid- and late-stage pipeline is approximately 66% compared to the industry average of approximately 19%.[1] Moderna’s broad clinical success and recent commercial challenges necessitate a more selective and paced approach to its research and development investment. Through portfolio prioritization and cost efficiencies, the Company expects to reduce annual research and development expense by approximately $1.1 billion starting in 2027. During this time, Moderna will expand its commercial portfolio into oncology, rare diseases, and first-in-class non-respiratory vaccines. The Company expects this strategy to yield 10 product approvals over the next three years. Specifically, in 2021-2023, Moderna invested proceeds from its pandemic-era vaccine sales into building a diverse pipeline and established the market for its COVID-19 vaccine, Spikevax®. In 2023-2026, the Company is establishing a portfolio of five commercial respiratory vaccines that address viruses with the greatest burden of disease. Its RSV vaccine mRESVIA® was approved this year, and its investigational next-generation COVID-19 vaccine, combination flu/COVID vaccine, and RSV vaccine for high-risk younger adults, are moving toward regulatory submissions in 2024. Looking ahead to 2026-2028, Moderna will expand its commercial portfolio with first-in-class vaccines and therapeutics to address non-respiratory diseases, including cytomegalovirus, norovirus, propionic acidemia, methylmalonic acidemia, and melanoma. Updates from Moderna’s late-stage portfolio and approved vaccines include: Respiratory Virus Vaccines COVID-19 According to the U.S. Centers for Disease Control and Prevention, COVID-19 causes three times more hospitalizations than flu in people aged 65 years and older.[2] Additionally, more than 95% of adults hospitalized in 2023-2024 due to COVID-19 had no record of receiving the latest vaccine.[3] People who are hospitalized may experience a significant impact on their quality of life, including loss of muscle mass, decline in daily activity, risk of hospital readmission and death. Additionally, Long COVID data also suggest even traditionally low-risk groups should be vaccinated.[4] More than 200 symptoms of Long COVID have been reported, such as anxiety, brain fog and extreme fatigue, and Long COVID can impact many different parts of the body, including the brain, heart and lungs. Moderna continues to address the needs of the endemic COVID-19 market by supporting public health efforts to drive vaccination coverage rates to reduce the substantial burden of COVID-19 as well as by advancing next-generation vaccines. The Company’s mRNA platform produced variant-matched vaccines on an accelerated time horizon to help ensure the availability of Spikevax targeting the two selected strains this season. The updated Spikevax formulas have been approved or authorized in multiple regions including the U.S., Taiwan, Japan, the UK, Switzerland, the United Arab Emirates, South Korea and Israel. Positive results from the NEXTCove Phase 3 trial in participants aged 12 years and older showed that Moderna’s next-generation COVID-19 vaccine, mRNA-1283 , demonstrated non-inferior relative vaccine efficacy (rVE) compared to Spikevax, with a positive point estimate of 9.3% (99.4% CI: -6.6, 22.8). rVE was highest at 13.5% (95% CI: -7.7, 30.6) in participants aged 65 years and older. mRNA-1283, which is designed to have enhanced stability in refrigerated conditions and will be packaged in pre-filled syringes, paves the way for a combination vaccine against flu and COVID-19, enhancing the Company’s overall respiratory portfolio. The Company expects to file for approval in 2024 and intends to use a Priority Review Voucher. Respiratory Syncytial Virus (RSV) In addition to acute mortality and morbidity, RSV infection is associated with long-term sequelae such as exacerbation of chronic obstructive pulmonary disease in older adults. In the U.S., each year there are up to 160,000 hospitalizations and 10,000 deaths in adults 65 years and older due to RSV.[5] Across high-income countries in 2019, RSV caused an estimated 5.2 million cases, 470,000 hospitalizations and 33,000 in-hospital deaths in adults 60 years and older.[6] In the younger adult population, potential risk factors such as chronic obstructive pulmonary disease (COPD), asthma, diabetes and obesity may cause an increased risk for RSV disease. Moderna’s RSV vaccine, mRESVIA (mRNA-1345) , has been approved for adults aged 60 years and older in the U.S. and EU. mRNA-1345 is in an ongoing Phase 3 study (P303) designed to test immunogenicity and safety in high-risk adults 18 to 59 years of age. In the trial, mRNA-1345 met all primary immunogenicity endpoints and the 50 µg dose, which is the same for the currently approved mRESVIA vaccine for adults 60 years and above, was well tolerated with no safety concerns identified. The Company intends to file a supplemental Biologics License Application (sBLA) for U.S. approval in 2024 to extend the indicated age range of mRNA-1345 to high-risk adults 18 to 59 years old, and intends to use a Priority Review Voucher. Influenza (Flu) Worldwide, there are 3-5 million severe cases of flu and 290,000-650,000 flu-related respiratory deaths annually.[7] Two main types of influenza viruses (A and B) cause seasonal flu epidemics, and the influenza A viruses lead to most flu-related hospitalization in older adults. Moderna has several seasonal influenza vaccine candidates in clinical development. The Company’s investigational seasonal flu vaccine, mRNA-1010 , demonstrated consistently acceptable safety and tolerability across three Phase 3 trials. In the most recent Phase 3 trial (P303), which was designed to test the immunogenicity and safety of an optimized vaccine composition, mRNA-1010 met all immunogenicity primary endpoints, demonstrating higher antibody titers compared to a licensed standard-dose flu vaccine (Fluarix®). In an older adult extension study of P303, mRNA-1010 met all primary immunogenicity endpoints-including superiority for all strains-compared to a licensed enhanced flu vaccine (Fluzone HD®) and showed an acceptable reactogenicity profile. Moderna is no longer pursuing an accelerated approval pathway for the regulatory submission of its standalone flu vaccine, mRNA-1010, to focus its resources on the submission of a potentially more impactful flu/COVID combination vaccine, mRNA-1083, this year. The Company plans to start a confirmatory vaccine efficacy study for mRNA-1010 in 2024, funded by previously announced project financing through Blackstone Life Sciences. Combination Respiratory Vaccines Currently, flu and COVID-19 are responsible for thousands of hospitalizations and hundreds of deaths each week in the U.S. To address the burden of these respiratory diseases, the Company’s combination vaccine candidates are designed for increased uptake, higher compliance, consumer convenience and benefits to healthcare systems. As announced in June, the Phase 3 study of the Company’s investigational combination vaccine against flu and COVID-19, mRNA-1083 , met its primary endpoints and elicited higher immune responses against influenza virus and SARS-CoV-2 than licensed flu and COVID vaccines in adults 50 years and older, including an enhanced flu vaccine in adults 65 years and older.mRNA-1083 also showed an acceptable safety and reactogenicity profile compared to co-administered flu and COVID-19 vaccines. The Company expects to file for approval in 2024 and intends to use a Priority Review Voucher. Latent and Other Virus Vaccines Cytomegalovirus (CMV) CMV, a latent virus, is the most common infectious cause of birth defects in the U.S. and is responsible for several billion dollars in annual healthcare costs. One in 200 babies in the U.S. are born with a congenital CMV infection, and of those affected, one in five will have severe, life-altering health problems. Possible short- and long-term sequelae of CMV infection include microcephaly, chorioretinitis, seizures, sensorineural hearing loss, cognitive impairment and cerebral palsy. CMVictory is a pivotal Phase 3 trial evaluating mRNA-1647 against primary CMV infection in women 16 to 40 years of age. The trial is accruing cases, and a Data Safety Monitoring Board (DSMB) will evaluate vaccine efficacy from the interim analysis when the trial has accrued 81 confirmed cases. The Company expects a vaccine efficacy readout as early as the end of 2024. Norovirus Enteric viruses, including norovirus, are a leading cause of diarrheal diseases, resulting in significant morbidity and mortality worldwide, particularly among young children and older adults. Norovirus is highly contagious and a leading cause of diarrheal disease globally, associated with 18% of all acute gastroenteritis (AGE),[8] resulting in approximately 200,000 deaths per year and substantial healthcare costs.[9] Given the wide diversity of norovirus genotypes, a broadly effective norovirus vaccine will require a multivalent vaccine design.[10] A Phase 1 trial designed to evaluate the safety, reactogenicity and immunogenicity of a trivalent norovirus vaccinecandidate, mRNA-1403 , in participants 18 to 49 years of age and 60 to 80 years of age in the U.S. is ongoing. An interim analysis showed that a single dose of mRNA-1403 elicited a robust immune response across all dose levels evaluated with a clinically acceptable reactogenicity and safety profile. Additionally, robust histo-blood group antigen (HBGA) blocking antibody titers were observed against vaccine-matched norovirus genogroup I and II selected strains across all dose levels evaluated. Similar mRNA-1403-induced HBGA-blocking antibody titers were observed in younger adult and older adult age groups. The Company plans to initiate a pivotal Phase 3 trial imminently. Oncology Therapeutics The Company’s oncology portfolio includes the individualized neoantigen therapy (INT) being developed in partnership with Merck. Earlier this year, Moderna and Merck initiated three new randomized clinical studies in additional tumor types, including a Phase 2 adjuvant treatment in patients with renal cell carcinoma, or kidney cancer; a Phase 2 adjuvant treatment in patients with high-risk muscle-invasive bladder cancer; and a Phase 2/3 neoadjuvant and adjuvant treatment in patients with cutaneous squamous cell carcinoma, the second most common form of skin cancer. Moderna’s global clinical trial footprint for INT has grown to more than 45 countries. The Phase 3 clinical trial for adjuvant melanoma, mRNA-4157 , is substantially enrolled and has closed screening to new patients in many countries. Moderna and its partner Merck have had preliminary discussions with regulators on approval based on the Phase 2 results. While discussions are ongoing, initial feedback from FDA has not been supportive of accelerated approval based on the current data. The Company and its partner Merck will continue engaging with regulators on the program, and remain focused on executing the Phase 3 trial. Rare Disease Therapeutics In the prioritized portfolio, the Company’s rare disease candidates include therapies targeting two organic acidemias caused by deficient metabolic enzymes, methylmalonic acidemia (MMA) and propionic acidemia (PA), both of which are characterized by metabolic decompensation events (MDEs) that can lead to severe and life-threatening symptoms such as vomiting, lethargy, seizures and coma. Methylmalonic acidemia (MMA) therapeutic In an ongoing Phase 1/2 study designed to evaluate safety and pharmacology in trial participants with MMA , mRNA-3705 was generally well-tolerated to date with no discontinuations due to safety and no events meeting protocol-defined dose-limiting toxicity criteria. Initial data is encouraging, withreductions in methylmalonic acid and other pathway biomarkers in participants, particularly at doses of at least 0.4 mg/kg Q2W. Early results suggest potential decreases in annualized rates of MMA-related hospitalizations and MDEs compared to pre-treatment rates. Moderna is working to identify an optimal dose and continues to engage with the U.S. FDA, via the START Program , and other global regulators. The Company is on track to begin generating pivotal study data by the end of 2024. Propionic acidemia (PA) therapeutic In an ongoing Phase 1/2 study designed to evaluate safety and pharmacology in trial participants with PA, mRNA-3927 was generally well-tolerated to date with no events meeting protocol-defined dose-limiting toxicity criteria. Early results suggest potential decreases in annualized MDE frequency compared to pre-treatment, and the majority of patients have elected to continue on the open label extension study. The Company is on track to begin generating pivotal study data by the end of 2024. Programs Discontinued Based on the Company’s strategic prioritization, five programs in its pipeline are discontinued: Financial Updates Moderna expects its commercial respiratory franchise to be profitable in 2024 and beyond. In addition, the Company is updating its projected 2024 research and development expenses to approximately $4.8 billion, primarily driven by the purchase of a Priority Review Voucher, and selling, general and administrative expenses to approximately $1.2 billion. Moderna is also reducing its expected research and development investment for 2025-2028 by approximately 20%, from $20 billion for the period to $16 billion through prioritization. The Company aims to complete the majority of its respiratory investments by 2026. It is increasing research and development investments in oncology, and pacing its investments in latent and other vaccines and in rare disease therapeutics. The Company is introducing an updated financial framework for 2025 and 2026-2028. Revenue: The Company expects 2025 revenue of $2.5 billion to $3.5 billion. For 2026-2028 the Company expects a compounded annual growth rate of more than 25% or more, driven by new product launches. Cost of Sales: Cost of sales is expected to be in the range of 35% to 45% in 2025. For 2026-2028, the Company expects cost of sales to decrease as a percentage of sales with increasing revenue. Research and Development Expenses: Full-year 2025 research and development expenses are anticipated to be $4.2 billion to $4.5 billion. In the 2026-2028 period, research and development expenses are expected to be approximately $11.5 billion on a cumulative basis. Selling, General and Administrative Expenses: Selling, general and administrative expenses for 2025 are projected to be $1.0 billion to $1.2 billion. For 2026-2028, selling expenses are expected to increase incrementally as new products are brought to market, while general and administrative expenses are expected to remain flat. Income Taxes: The Company continues to expect its full-year 2025 tax expense to be negligible. Tax will also be negligible for the 2026-2028 period. Capital Expenditures: Capital expenditures for 2025 are expected to be approximately $0.3 billion. For 2026-2028, capital expenditures are expected to be flat to down from 2025 levels. Cash and Investments: Year-end cash and investments for 2025 are projected to be approximately $6 billion. Moderna plans to break even on an operating cash cost basis (which excludes stock-based compensation, depreciation and amortization expense) with $6 billion in revenue. The Company expects to achieve this in 2028. The Company has sufficient capital to fund its plans until achieving break even on a cash cost basis without raising additional equity. About Moderna Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the Company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines. Moderna’s mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. INDICATION (U.S.) SPIKEVAX (COVID-19 Vaccine, mRNA) is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older. IMPORTANT SAFETY INFORMATION FOR SPIKEVAX INDICATION (U.S.) mRESVIA (Respiratory Syncytial Virus Vaccine) is a vaccine indicated for active immunization for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in adults 60 years of age and older. IMPORTANT SAFETY INFORMATION FOR MRESVIA Spikevax® and mRESVIA® are registered trademarks of Moderna. Fluarix® is a registered trademark of GSK. Fluzone® is a registered trademark of Sanofi Pasteur. [1] Statistics for Moderna based upon internal data from 10 Phase 2 trials, and six Phase 3 trials. Data reported as of September 12, 2024. Industry statistics derived from Phase 2 and 3 study data from Wong et al., Biostatistics (2019) 20, 2, pp 273-286. [2] https://www.cdc.gov/resp-net/dashboard/index.html. Data last updated as of September 6, 2024 for 2023-2024 season. [3] https://www.cdc.gov/respiratory-viruses/risk-factors/older-adults.html [4] https://www.yalemedicine.org/news/covid-vaccines-reduce-long-covid-risk-new-study-shows [5] https://www.cdc.gov/rsv/php/surveillance/index.html [6] https://pubmed.ncbi.nlm.nih.gov/36369772/ [7] https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal) [8] Ahmed, S.M., et al., Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis. Lancet Infect Dis, 2014 [9] https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/norovirus [10] https://www.cdc.gov/norovirus/downloads/global-burden-report.pdf SOURCE: Moderna