Moderna Inc (MRNA) — Q4 2022 Earnings Call Transcript

Thank you, Kevin. Good morning, everyone and thank you for joining us on today’s call to discuss Moderna’s fourth quarter and full year 2022 financial results and business update. You can access the press release issued this morning as well as the slides that we will be reviewing by going to the Investors section of our website. On today’s call are Stephane Bancel, our Chief Executive Officer; Stephen Hoge, our President; Arpa Garay, our Chief Commercial Officer; and Jamey Mock, our Chief Financial Officer. Before we begin, please note that this conference call will include forward-looking statements made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Please see Slide 2 of the accompanying presentation and our SEC filings for important risk factors that could cause our actual performance or results to differ materially from those expressed or implied in these forward-looking statements. With that, I will now turn the call over to Stephane.

Thank you, Lavina. Good morning or good afternoon everyone. Welcome to our Q4 2022 conference call. Today, I will start with a quick business review of 2022. Stephen will then review our clinical programs before Arpa gives an update on our commercial progress and plans. Jamey will then present our financial results and I will come back to share some posts on where we are heading. We are pleased to report today revenues of $19.3 billion for fiscal year 2022, GAAP net income of $8.4 billion, and GAAP diluted earnings per share of $20.12, cash and investment balances of $18.2 billion at the end of the year. We continued our disciplined capital allocation policy, reinvesting first in our company. In 2022, we invested $3.3 billion in R&D, our highest level of R&D investments ever. We invested $1.1 billion in SG&A and $400 million in capital investments. We made investments in Metagenomi for access to new gene editing enzymes and Carisma in oncology. We announced an investment in CytomX and the acquisition of OriCiro in Japan to continue to streamline our manufacturing processes. And just yesterday, we announced the collaboration with LifeEdit. $3.3 billion was returned to shareholders through a buyback of 23 million shares. I am proud of the strong results by our team in 2022 as we made history with a number of outstanding accomplishments for patients. In respiratory vaccines, we developed new products with remarkable speed, getting the mRNA-1273.214 against Omicron BA.1, the strain recommended by WHO and mRNA-1273.222 against Omicron BA.5, the strain asked by the U.S. FDA. We developed 1273.222 in less than 2 months. We are able to protect millions of people from potentially severe disease resulting from new COVID strains. Our RSV vaccine went from Phase 1 start to Phase 3 data in 24 months and met its primary efficacy endpoint in the Phase 3 trial. In oncology, our personalized cancer vaccine was the first demonstration of positive results from an mRNA cancer treatment in the randomized clinical trial. In rare diseases, our propionic acidemia program showed early positive clinical results in a repeat dose chronic disease setting in reducing metabolic decompensation events in patients. And we announced what we hope will become the first effective inhaled mRNA therapy in humans as our partner, Vertex, entered a Phase 1 trial using our technology in the therapy for cystic fibrosis patients who lack the CFTR protein. Finally, we had our first ESG Day and published our first ESG report, providing additional transparency in how we conduct our business. I want to take a moment this morning to touch on the transition of the Moderna Executive Committee. As we announced in late 2022, Marcello Damiani decided to retire as Chief Digital Officer after more than 7 years with the company. Marcello joined Moderna before our first clinical trial and we are today a digital-first company, as a testament to his ability to scale digital resources. I am grateful to Marcello for his contributions during the early years of Moderna. I am excited to have worked already with Brad Miller since early January. Brad brings a wealth of enterprise solution and platform organization experience in several of the top technology companies. This will be instrumental as Moderna scales into a fully-integrated biotechnology company. I want to also share with you that Juan Andres, currently President of Strategic Partnership and Enterprise Expansion, has informed me of his decision to retire and will be retiring at the end of May. Juan has played a tremendous role since joining Moderna in 2017 from Novartis, where he led all manufacturing for them. Juan served as Moderna’s Chief Technology, Operations and Quality Officer where he led our manufacturing from an early-stage clinical development company to a commercial company. I believe Juan did a historic job with his team in 2020 and 2021 to scale Moderna for global commercial launch during the pandemic. It is unbelievable that he led the team from having made across our entire portfolio, less than 100,000 doses in 2019 to more than 800 million doses in 2021, all during the pandemic. We and hundreds of millions of people across the globe who received the Moderna COVID-19 vaccine owe Juan our gratitude. I believe very few manufacturing leaders would have led such an achievement. Most recently, Juan has focused on building out our organization to support Moderna’s growing pipeline, leading our efforts in producing personalized cancer vaccine. Jerh, who used to work for Juan at Novartis, has joined us since early fall and has been leading manufacturing since then. I am thankful for Juan who has ensured a very smooth transition, helping Jerh every step of the way. Upon his retirement at the end of May, Juan’s responsibility will transition to Stephen Hoge, President of Moderna, to integrate PCV across all functions, with Jerh leading the manufacturing of PCV for multiple Phase 3s, and of course, for getting commercial-ready. On behalf of the entire Moderna team, I want to thank Juan for his continued leadership and wish him and his wife, Marina, the best of a well-deserved retirement. I am deeply thankful to have counted him for so many years as a partner at Moderna, and more importantly, for more than 20 years as a friend and a mentor. We will miss him. The company continues to expand at a rapid pace. We now have 3 commercial COVID-19 vaccine products. We have 4 development programs in Phase 3. We have expanded our commercial portfolio very soon. Overall, we have 48 programs underway with a team of 3,900 members and now present on the ground in 16 commercial subsidiaries across Americas, Europe, and Asia-Pacific. Our $18 billion of cash balance at the end of the year is enabling us to scale across research, clinical development, manufacturing, commercial and G&A. With that, let me ask on to Stephen.

Thank you, Stephane. Good morning or good afternoon, everyone. Today, I will review our progress against our key clinical programs. I will start with our respiratory vaccines. We have approved our Phase 3 development programs against the big three respiratory viruses, COVID-19, RSV, and influenza. I will share some additional data on these in a moment, including some presented this morning on our older adult RSV Phase 3 trial. We are also advancing a portfolio of next-generation programs against these viruses, including mRNA-1283, which is a next-generation COVID-19 booster that is referred to as stable. We also have multiple next-generation flu programs. We seek to increase the breadth of coverage against influenza by adding additional antigens that are not present in currently available flu vaccines. Lastly, our respiratory portfolio includes a large number of combination vaccines to provide protection against multiple respiratory pathogens, which has advantages for many stakeholders, including healthcare providers, payers, and consumers. These include combinations of COVID, flu, and RSV as well as two pediatric vaccines that include additional viruses that are important in children, including hMPV and PIV3. As we prepare for endemic COVID in 2023 and beyond, we wanted to briefly recap the recent VRBPAC committee discussions and recommendations. At the January VRBPAC meeting, the committee voted to harmonize the primary series and booster dose vaccines, which is an important step to simplify future guidance. The FDA also indicated that it expects to convene VRBPAC to determine vaccine strain composition for the ‘23/24 season in the second quarter of this year. We believe that our mRNA platform has demonstrated its ability to deliver variant match vaccines on accelerated time horizons, and we believe we are therefore well-positioned to deliver whatever composition update the FDA and other public health agencies recommend. Moving to RSV, as you know, we shared the top-line results from our Phase 3 RSV study in older adults earlier this year. Today, we shared additional data that was presented this morning at RSVVW. The top-line results we have seen are incredibly encouraging, and we are grateful to the FDA for breakthrough therapy designation for mRNA-1345, which further emphasizes the significant health impact of RSV in older adults and the high unmet need. In the top-line data presented in January, the mRNA-1345 demonstrated 83.7% vaccine efficacy and the primary endpoint of lower respiratory tract disease with two or more symptoms. 1345 was found to be generally well tolerated, and there were no safety concerns identified by the Data and Safety Monitoring Board. In the data presented today at RSVVW, we confirmed that 1345 was well tolerated and has an acceptable safety profile. Solicited adverse reactions were mostly Grade 1 or Grade 2, and to date, most solicited adverse reactions were mild to moderate, with the most common adverse reactions being injection site pain, headaches, myalgia, and arthralgia. Vaccine efficacy was consistently high across all age groups and in participants with pre-existing comorbidities that are at highest risk. Please refer to the scientific and medical meetings section of the Moderna Investor Relations website to see the full RSVVW presentation. We are very encouraged by these data and look forward to filing a Biologics License Application with the FDA in the first half of 2023 as things proceed. With the option of using a priority review voucher, we might see regulatory action on this filing in late 2023 or early 2024. Now moving to flu. Last week, we shared with you data from our Phase 3 immunogenicity and safety study in the Southern Hemisphere, study P301. In this study, our first-generation vaccine, mRNA-1010, demonstrated superiority on seroconversion rates for influenza A H3 and H1 and superiority on geometric mean titers for H3 and non-inferiority on geometric mean titers for H1. mRNA-1010 did not meet non-inferiority on seroconversion or titers for the two influenza B strains. Our separate Phase 3 efficacy study in the Northern Hemisphere, study P302, has now accrued over 200 confirmed cases of influenza-like illness, almost all of which are influenza A, which is expected—this was expected as the overwhelming majority of influenza burden in older adults is caused by influenza A, including over 95% of hospitalization in the most recent season. Based on the case accrual in P302, we now expect the independent DSMB will review the first interim analysis of efficacy in that study in the first quarter of this year. Now, let’s take a look at our latent vaccines on Slide 14. Our CMV vaccine is in an ongoing Phase 3 study, and we have begun dosing participants in the Phase I/II adolescent dose-ranging study. Our EBV vaccine to prevent infectious mononucleosis is in Phase 1, while our EBV vaccine to prevent long-term sequelae of EBV is in pre-clinical development. We have two HIV Phase 1 trials ongoing, and our HSV vaccine is in preclinical. Our VZV program has begun dosing participants in a Phase 1/2 study, which I will discuss further on the next slide. The VZV study is a Phase 1/2 randomized safety and immunogenicity study evaluating mRNA-1468 against Shingrix. This is a relatively large study, enrolling 500 seronegative older adults in multiple doses and dosing intervals and a 12-month study follow-up. Over 35% of participants will be 70 years and older, which is in line with the largest disease burden of shingles. Now, let’s take a look at our therapeutics portfolio on Slide 16 and I will highlight a few of the programs. We have recently reported strong top-line data for our personalized cancer vaccine, which I will talk to in a moment. In immunooncology, we are working to address disease burden beyond PCV with our checkpoint and triplet programs, both of which are in Phase 1 trials in various tumor types. In rare diseases, our Phase 1/2 PA program continues to enroll patients and we are looking forward to selecting a dose in the expansion arm. I will provide a brief update on that in just a moment. Earlier this year, our partner, Vertex, announced initiation of a Phase 1 trial in cystic fibrosis patients, which is our first inhaled pulmonary mRNA therapeutic program. In cardiovascular, we announced Relaxin has initiated dosing in the Phase 1 study. Both of these study initiations represent important milestones for Moderna as we expand our modalities in therapeutic areas. In December, we shared exciting top-line data from our Phase 2 personalized cancer vaccine program, testing the combination of PCV and KEYTRUDA against KEYTRUDA alone in the setting of adjuvant melanoma. KEYTRUDA is the standard of care in that setting. In this study, we showed the addition of our personalized cancer vaccine treatment mRNA-4157 to KEYTRUDA reduced the risk of recurrence or death by 44% compared to KEYTRUDA alone. This was the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial, and we are pleased to announce that 4157 has received breakthrough therapy designation from the FDA. Along with our partner, Merck, we are excited about these results and expect to launch multiple late-stage confirmatory studies for PCV in 2023, starting with melanoma and then moving to non-small cell lung cancer. We are planning to explore additional indications for 4157, where we believe there is a strong biological rationale for immune-stimulating approaches. These include early-stage and metastatic settings and will include indications where KEYTRUDA is not yet approved. Finally, we expect to release full data from our Phase 2 study at an oncology meeting this spring and in an upcoming publication. Now moving to PA, since our update at our R&D Day, the PA Paramount study has made good progress. Our fourth cohort is now fully enrolled, and we are currently enrolling patients in our fifth cohort, which doses at 0.9 milligrams per kilogram every 2 weeks. We are encouraged that to-date we have not observed any dose-limiting toxicities. All patients and families have opted to continue treatment electively in our open-label extension study across all prior dose cohorts. The next step in this trial will be to review available data and determine a dose for expansion. I will now hand the call over to Arpa Garay, who will provide an update on our commercial activities.

Thank you, Stephen and good day to everyone. I will start with a review of sales on Slide 20. In the fourth quarter, total product sales were $4.9 billion. In the U.S., our sales were $1 billion, sales in Europe approximated $2.2 billion, and sales in the rest of the world were $1.6 billion. We ended the full year strong, with total product sales for 2022 of $18.4 billion. Sales in the U.S. for the full year were $4.4 million, sales in Europe were $6.7 million, and in the rest of the world were $7.3 billion. We are reiterating approximately $5 billion in COVID sales for delivery in 2023 from our currently signed advanced purchase agreements and deferrals. We do expect additional sales from key markets such as the U.S., EU, and Japan. Slide 21 summarizes the current composition of sales for 2023. We have advanced purchase agreements from Canada, Kuwait, Switzerland, Taiwan, and the United Kingdom. We expect these sales to be recognized upon delivery of vaccines in the second half of 2023. Additionally, we expect further sales from deferrals from 2022 contracts. These deferrals are from the countries listed on the slide and are expected to be mainly recognized from deliveries in the first half of 2023. Together, these advanced purchase agreements and deferrals total approximately $5 billion in sales for 2023. We do expect additional sales from key markets, including the United States, EU, and Japan, as well as Australia and other countries in Asia and Latin America. In the U.S., contracting discussions with commercial customers are ongoing, and we will provide visibility into expected U.S. sales at a future date after we complete these discussions. In our discussions with commercial customers in the U.S., it is clear to us that our customers recognize that COVID is still a substantial health burden. Throughout 2022, COVID continued to be a leading cause of hospitalizations and deaths. If you look to the chart on the left-hand side, what you will see here is data available through September of 2022: COVID was the third leading cause of death in the United States, only after heart disease and cancer. If you look to this right-hand side, from October 1, 2022, to January 31, 2023, hospitalizations from COVID in the U.S. are nearly 450,000, more than double from flu and nearly 3x higher than RSV in that same 4-month period. There continues to be a clear need to protect against severe COVID infections, and our customers recognize that. Given this need, we estimate the U.S. fall 2023 COVID market volume to be approximately 100 million doses. We base this assumption after looking at 2022 vaccination rates and including potential recommendations for a two-dose booster series for high-risk individuals. Taken together, the doses administered represent roughly 30% of the U.S. population. A few factors that can impact this volume include viral evolution, regulatory recommendations, as well as vaccine understanding and uptake by consumers. Moderna’s commercial organization is prepared for the transition to a commercial market in the U.S. Let me now take you through how we have been preparing to go to market. First and foremost, we are committed to access, which I will explain in greater detail in just a moment. To ensure coverage of our vaccine, we are engaged in discussions with private customers as well as public entities such as the VA, CDC, and the Department of Defense. We are increasing awareness and educating consumers as well as healthcare providers about the benefits of booster vaccinations in alignment with public health agencies such as CDC and ACIP. We are reaching healthcare providers and consumers through innovative digital outreach programs. We have built the infrastructure needed to fulfill customer orders and shipments, and our commercial and medical organizations have been scaling to execute on this plan, and we are ready for the transition to a commercial market in the United States. Very importantly, as we enter the commercial phase of the endemic COVID market, we want to emphasize our commitment to vaccine access for everyone in the United States, regardless of their ability to pay. For all insured individuals in the United States, consistent with preventative health services requirements, current reimbursement rules will be sustained. As an ACIP-recommended vaccine, Moderna’s COVID vaccine will continue to be available for zero out-of-pocket costs for individuals with insurance. We are proud to say that for uninsured or underinsured people in the United States, Moderna will be launching a patient assistance program that will provide COVID-19 vaccines at no cost. Let me now summarize our COVID vaccine outlook. In 2023, we expect COVID sales of approximately $5 billion. Additionally, we are expecting sales from U.S. commercial market orders, EU, Japan, and other countries. We will provide visibility into these sales after we complete ongoing discussions with governments and customers. We understand COVID continues to be a burden on healthcare systems, and this continues to be an important point as we discuss the value of booster vaccinations with our customers. In the U.S., we expect commercial market volumes to be approximately 100 million doses in 2023, and Moderna’s commercial organization is prepared for the transition to a commercial endemic market. Last but not least, we are committed to patient access in the United States. I now want to turn to another launch in the respiratory vaccine space that the commercial team is preparing for, our RSV vaccine in 2024. As you heard from both Stephane and Stephen earlier, we are very pleased by our Phase 3 RSV vaccine results. Stephen’s organization will be filing for the approval soon, and we expect it may be approved in late 2023 or early 2024. With the potential approval fast approaching, I am very excited for the RSV vaccine launch and I want to provide additional color into the launch plans. The RSV launch will leverage the existing commercial infrastructure that is already in place for COVID, and we will continue to invest to support it, ensuring strong execution. Both COVID and RSV markets overlap considerably as we look at our target customers, as well as potential target patients and audiences, and we will leverage this overlap between the two markets. We will ensure awareness of RSV disease and the associated economic burden of RSV in older adults across key stakeholders such as healthcare providers and payers. Upon approval of our RSV vaccine, we will educate consumers on key attributes of our vaccine. These planned activities will be initiated in 2023 and in full force upon approval. We have the added benefit of an in-place commercial infrastructure built for COVID. Many of these resources can be leveraged for flu as well into the future. I look forward to keeping you updated on our progress throughout this year. And with that, I will turn it over to Jamey.

Thanks, Arpa and hello everyone. This morning, I will cover our 2022 financial performance and provide a framework for our 2023 financial outlook. Moving to our fourth quarter results, starting on Slide 29, total product sales decreased by 30% year-over-year to $4.9 billion. The decrease in 2022 was mainly driven by lower sales volume compared to overall higher demand in the prior year. Cost of sales was 39% of product sales compared to 14% of product sales in 2021. The key driver of the increase in cost of sales as a percent of product sales was a catch-up royalty payment to the National Institute of Health, or NIH, of $400 million, representing 8% of product sales in the fourth quarter. In December 2022, we entered into a non-exclusive patent license agreement with the National Institute of Allergy and Infectious Diseases and institute or center of the NIH to license certain patent rights concerning stabilizing prefusion coronavirus spike proteins and the resulting stabilized proteins for using COVID-19 vaccine products or 2P technology. Pursuant to the agreement, we have agreed to pay low single-digit royalties on future net sales of our COVID-19 vaccines. Our cost of sales also includes a charge of $297 million for inventory write-downs related to excess and obsolete COVID-19 products and expense for unutilized manufacturing capacity, and CMO wind-down costs and related charges of $376 million, and a loss on firm purchase commitments and related cancellation fees of $281 million. These charges other than royalties are driven by costs associated with surplus production capacity, overall lower demand, and a shift to our most recent Omicron BA.4/5 targeting COVID-19 bivalent booster. Research and development expenses were $1.2 billion, which increased by 87% versus prior year. The increase in R&D spend continues to be driven by our clinical trial expenses, particularly with our Phase 3 studies for RSV, seasonal flu, and CMV. The increase in R&D was also driven by the acquisition of a Priority Review Voucher and an increase in personnel-related costs due to increased headcount. Selling, general, and administrative expenses were $375 million, also reflecting an increase of 87% year-over-year. The growth in spending was primarily driven by continued investments in personnel and outside services in support of our marketed products and company build-out. The effective tax rate was 11% compared to 10% last year. After-tax net income decreased by 70% to $1.5 billion. Diluted earnings per share in Q4 decreased by 68% to $3.61. Now turning to our full year 2022 financial results on Slide 30. Total product sales for the full year 2022 were $18.4 billion, an increase of 4% year-over-year. The growth was mainly attributable to customer mix and a higher average selling price in 2022 in certain markets. Cost of sales was 29% of product sales compared to 15% of product sales last year. The increase was driven by higher write-downs for excess and obsolete inventory related to our COVID-19 vaccines, unutilized manufacturing capacity, and losses related to future purchase commitments for raw materials. The key drivers for these charges are similar to the drivers in Q4. Costs associated with surplus production capacity, overall lower demand for the year, in particular from low-income countries, and rapid product advance shift from our original vaccine to Omicron targeting COVID-19 bivalent boosters. The previously mentioned catch-up royalty payment to NIH of $400 million is also a driver of the increase year-over-year. The effective tax rate was 13% compared to 8% last year. As a reminder, we had a net operating loss carry-forward of $2.3 billion at the end of 2020, which resulted in a non-recurring benefit to the reported tax rate in 2021. After-tax net income of $8.4 billion decreased 31% versus prior year. The decrease in net income was primarily due to higher cost of sales, higher other operating expenses, and a higher effective tax rate. Diluted EPS decreased 29% to $20.12. Now turning to cash and cash deposits on Slide 31. We ended 2022 with cash and investments of $18.2 billion, compared to $17 billion at the end of the third quarter. The increase was driven by our commercial activity. Cash deposits for future product supply reduced from $3.8 billion at the end of the third quarter to $2.6 billion by the end of the year. Now turning to Slide 32. I wanted to give an update on the progress we have made on our capital allocation priorities. Our top investment priority has been and will continue to be reinvesting in our base business across multiple areas. Research and development spending increased 65% year-over-year from $2 billion in 2021 to $3.3 billion in 2022, and we are projecting an additional increase to approximately $4.5 billion in 2023. The clinical data from our PCV, RSV, and flu trials were encouraging and further validate the potential of our mRNA technology. We are also investing in our digital capabilities, the commercial build-out of the organization, as well as expanding our manufacturing footprint. We plan to significantly accelerate our capital expenditures in 2023 as we expand both our international and U.S. manufacturing footprint. Our second investment priority is to seek attractive external investments and collaboration opportunities that will enable and complement our platform. We’ve recently announced several new transactions, and I’m happy to report that we have successfully closed our acquisition of OriCiro Genomics in the first quarter of 2023. OriCiro is a great example of the companies we are evaluating to enable our mRNA platform. It will create substantial value from both the speed and cost viewpoint and impact our pre-clinical, clinical, and commercial pipeline for years to come. Our collaboration with LifeEdit, which we announced yesterday, is another example of an attractive external investment opportunity. We believe the combination of Moderna’s mRNA platform with LifeEdit proprietary gene editing technologies, including base editing capabilities, has the opportunity to advance potentially life-transformative or curative therapies for some of the most challenging genetic diseases. We are in multiple active discussions regarding additional external collaboration opportunities, and we will be disciplined in our approach. After evaluating internal and external investment opportunities, we then assess additional uses of cash. In 2022, we repurchased 23 million shares for $3.3 billion at an average price of $143 per share, and we have $2.8 billion of share repurchase authorization remaining. Now, let’s turn to our 2023 financial framework on Slide 33. As Arpa mentioned earlier, we currently have COVID vaccine sales of $5 billion contracted for delivery in 2023. We are actively working on preparing for the private market and government contracts in the U.S. and additional contracts for Europe, Japan, and other key markets. To help you with your modeling purposes, we expect first half ‘23 sales to be approximately $2 billion. Our total cost of sales includes the cost of goods manufactured, third-party royalties, as well as logistics and warehousing costs. We expect full year 2023 reported cost of sales to be 35% to 40% of sales. This includes royalties of approximately 5% of sales, which are payable to UPenn and CellScript for modified chemistry licenses, and to NIAID and NIH for the 2P license that I mentioned earlier. The increase in cost of sales as a percent of product sales compared to 2022 is primarily driven by presentation mix change as we move from a pandemic to endemic setting, with single-dose applications significantly increasing in volume. Longer term, as the endemic market normalizes and we add additional respiratory and other products, we expect our cost of sales as a percent of sales to significantly decrease from the rates we’re experiencing in 2023. For R&D and SG&A, we expect full year expenses to be approximately $6 billion, with approximately $4.5 billion in R&D. The increase is driven by our maturing development portfolio and the global scale-up of our company. We expect a negligible provision for income tax in 2023. Finally, we expect capital expenditures of approximately $1 billion. The increase is primarily due to investments in expanding our manufacturing footprint. This concludes my remarks concerning our financial performance, and I will turn the call back over to Stephane.

Thank you, Jamey, Arpa, and Stephen. Let me now share some thoughts about where we’re heading. I’m really excited to see our mRNA platform and the investments we have made in science over the last 11 years leading to such a promising pipeline. We anticipate a number of important developments. Let me start with our first franchise, respiratory vaccines. In COVID boosters, we are working for the switch to the U.S. commercial market, and we anticipate being able to quickly meet the full 2023 market needs for updated vaccines after VRBPAC and the FDA make this transaction in the spring of 2023. We plan to submit the RSV vaccine for regulatory approval in the first half of 2023, and as you heard from Arpa, we will be ready to launch the RSV vaccine in late ‘23 or early ‘24. In flu vaccine, for the Northern Hemisphere, mRNA-1010 Phase 3 trial, the Data and Safety Monitoring Board is expected to complete its interim efficacy analysis in the first quarter of 2023 of the second franchise latent virus vaccine. It’s progressing very well with a broad spectrum of programs. In our large CMV Phase 3 study, we look to complete the enrollment. For EBV, HIV, and VZV programs, our next milestone will be Phase 1 data. Let me review the milestones for mRNA therapeutics programs. For personalized cancer treatment, we expect to start our Phase 3 study in partnership with Merck in adjuvant melanoma, and we expect to rapidly expand to additional tumor types, including non-small cell lung cancer. Full Phase 2 data will be presented at an upcoming oncology meeting and published in a top-quality medical journal. In PA, we plan to select those and begin the expansion arm of our Phase 1/2 study. MMA, we will have Phase 1/2 data. The next milestone for heart failure drug by Relaxin will be Phase 1 data in patients. In inhaled therapeutics, our partner Vertex expects to complete its single ascending dose study and initiate a multiple ascending dose study. To continue to build the best version of Moderna, we have established seven priorities for 2023. Priority number one, execute the operational and sales plan for COVID booster for fall of ‘23. Priority number two, build an unrivaled seasonal respiratory vaccine franchise. Priority number three, execute a bold campaign of cancer vaccine studies. Priority number four, advance rare metabolic disease programs. Priority number five, drive rapid advancement and growth of our latent vaccine portfolio. Priority number six, deliver the next-generation pipeline and platform. As we said before, this is just the beginning. Priority number seven, build a culture of perpetual learning and strengthen our processes and digital systems as we want to scale the company to another level. On Slide 39, some key dates for 2023 Moderna Investor Days. April 11 will be our Annual Vaccines Day. September 13 will be Annual R&D Day, where we will present development pipeline key updates. December 7 will be our second ESG Day. Now that we have delivered on the promise of mRNA science with our first product launch, our mission has evolved. Our mission is to deliver the greatest possible impact to people for mRNA medicine. We are passionate about our ability to have a profound impact on humanity. We believe we have a technology to eliminate or greatly reduce human suffering caused by respiratory viruses, latent viruses, many cancers, regenerative diseases, and a growing list of other diseases. We believe we can have an impact on disease treatment, with our therapeutic first and then with our gene editing programs. This is just the beginning. With that, the team and I are free to now take your questions.

Good morning, thank you for taking my questions. Could you speak to the regulatory strategy for flu, given the miss on the B strains for immunogenicity? And if you are confident in the interim efficacy analysis, given the abominating prevalence of influenza?

I’ll take that. Thanks, Salveen for the question. Look, I think the honest answer is we’re still having incomplete information to provide guidance on the regulatory strategy. At this point, we are looking to the efficacy results from the P302 study that I described, which will guide us on that filing strategy. It’s important to note that efficacy, ultimate demonstration of non-inferior efficacy against an approved vaccine was always going to be required for full approval, and the only thing that you could do with immunogenicity would be an accelerated approval path with an obligation to subsequently demonstrate efficacy. We are encouraged that the data that we’ve seen from our immunogenicity and safety study, which is running in the Southern Hemisphere, P301, shows superiority on three out of four endpoints for the influenza A strains, which drive the overwhelming majority of disease, and the population of interest here are older adults, who account for over 99% of the cases in our efficacy study. The first interim efficacy analysis that we’re conducting now in P302 will evolve over 200 cases, and 99% of them are influenza A, and it will be our first chance to see the performance of the vaccine in terms of prevention of influenza-like illness from flu A. That is the first interim analysis. It’s quite possible, as you would expect in any efficacy study, that—need to go to a second subsequent interim analysis and accrue even more cases to demonstrate either non-inferiority or superiority in that study. What we will do is we will wait for the results from the DSMB and gauge from that. Based on those results, obviously, if we do see efficacy, that is the gold standard for proceeding with regulatory filing and full approval. If we do not yet meet that threshold, then we will be looking forward to subsequent interim analyses in that study.

Great. Thank you.

Thank you. Just quickly follow Salveen’s question. Do you need to show superiority in order to receive approval regarding the efficacy study? And then quickly on the revenue. Did I hear correctly that the existing contract of $5 billion mainly will be in the second half ‘23? If that’s the case, is it fair to say that total COVID revenue in 2023 should be around $7 billion? And then regarding the $2 billion in the first half ‘23, how much will be from the U.S. market, i.e., out of an estimated 100 million doses in the U.S., what could be your market share?

I’ll take the first question. Thanks, Gena for that. So first on superiority. You do not need to demonstrate superiority to get a flu vaccine approved. That’s well precedent. Non-inferior efficacy is the threshold. Our goal, though, over time is absolutely to develop a superior influenza vaccine. If we don’t see it with the first-generation product, which is mRNA-1010, I would note that we have four other programs – flu programs in development, at different stages of clinical trials, that are looking to do even better than perhaps flu mRNA-1010. And our goal over time would be to demonstrate that we have a superior influenza vaccine. But it is not actually required for approval. Non-inferiority should suffice. I’ll turn it over to Arpa for the other questions.

Sure. Yes, I can take the second question. In terms of the total sales, we are anticipating about $2 billion of the $5 billion in the first half of the year, and none of that $2 billion is coming from the U.S. market. The remaining advance purchase agreements that we have of $3 billion will be coming in the second half of this year. Now, that $5 billion is just the total that we have from advanced purchase agreements as well as deferrals from 2022. We do anticipate additional sales from the U.S., Japan, EU, and other markets, and we believe the majority of these sales will be in the second half of 2023.

And then your market share regarding the U.S. market?

We continue to believe in the strong, differentiated profile of our products. We do not have any updates on market share projections as we are currently in discussions with customers right now for fall 2023 contracting.

Thank you.

Great. Good morning, thanks for taking the question. I was hoping to ask about the regulatory strategy for PCV, and specifically, how you’re thinking about the potential for filing off the Phase 2 dataset, as well as how you’re thinking about the timelines for enrollment in the Phase 3 program and how that may impact the timeline for potentially filing off the Phase 2 dataset? Thanks.

Great. Thank you, Matt for the question. We’re obviously really pleased yesterday to announce that we received FDA breakthrough designation therapy for the PCV program. That allows us to rapidly accelerate our conversations with the FDA and other regulators on the path forward for filing 4157. As you noted, the Phase 2b study that we’ve run is a randomized study compared against the standard of care with KEYTRUDA alone, and has already shown a significant benefit of a 44% reduction of recurrence rate or death. That study is ongoing, and we’re continuing to follow over time and conduct additional interim analyses. It is possible that those – in fact, we would hope that those data mature and continue to get stronger and stronger. It’s entirely possible that in our discussions under breakthrough with FDA and others that we will come up with a path forward for beginning the filing process based on that Phase 2 and potentially proceeding with accelerated approval. In this country and globally, if there is a path forward, we haven’t yet engaged with the FDA on because the breakthrough happened yesterday. But if there is a path forward, that would require us to rapidly enroll a confirmatory Phase 3 study. We are working quickly now to try and stand up that confirmatory Phase 3 melanoma study and enroll as fast as possible. We’re not ready yet to guide on how quickly that will be, but we are fully aware of the fact that if there is a path forward for accelerated approval, the enrollment of that Phase 3 may be gaining, and therefore, we want to have it enrolled as quickly as possible. So at this point, we’ve just received the breakthrough designation, we’re engaging with regulators, and we’re going to try and develop that path forward. But it is theoretically possible that there is an accelerated approval path, and that we would need to enroll that Phase 3 study based on recent regulatory guidance, more generally to the industry. We’re working hard to make sure that we can do that as fast as possible here, while continuing to conduct the additional interim analyses and see the maturity of this data continue to proceed, and hopefully, the strength of the benefit provided by the combination to be further validated.

Great. Thank you very much. And thanks for all the detail on the call today. My question, I had to go back to flu for a minute and just with respect to the follow-on candidates, including I think the one that’s pentavalent hemagglutinin and then fixed hemagglutinin and then also into the neuraminidase, the candidates at that neuraminidase, what should be our expectation both in terms of timing for data here? And how do you ultimately see your seasonal flu product offering evolving? Thanks.

Thanks for the question, Ed. So let me start with the most advanced program, obviously, is our 1010 program, which we’ve talked about. We have done an update to that vaccine that we think will increase the B immunogenicity for those populations for whom that matters, and we expect to advance that in clinical study quite quickly. That, in combination with the efficacy data that we were just talking about with P302, is probably the most important information for guiding our next step on the second-generation products. Our multiple—sorry, penta and hexavalent vaccines as well as the 1020, 1030 programs, which include neuraminidase, are all in various Phase 1 studies. We have shown repeatedly over the last couple of years that we can proceed very quickly in the subsequent Phase 3 pivotal studies once we select one of those candidates to move forward. The important gating information is understanding how our first-generation product is performing in terms of efficacy. We are waiting for that information before proceeding forward. We expect at least one, if not multiple, of these second-generation products would move into subsequent pivotal studies, Phase 3 studies. In those cases, because we would be looking to demonstrate some superior efficacy against a broader range of influenza strains or better protection against influenza-like illness because we have included additional antigens, we would expect those studies to include both immunogenicity and safety and efficacy endpoints as we move forward. We will make a selection on which we might move forward based on the ongoing interim analysis of efficacy from our 1010 program.

Great. Thank you very much.

Hi. Thanks. Good morning. A couple of follow-ups on the flu vaccines and also a PCV question for Stephen. I guess could you clarify – do you have a hypothesis around why these strains were not non-inferior, and what the ramifications are for that, either for this flu vaccine, or also for the infection study, and what that would mean for combinations? So first of all, just to clarify what’s going on there with the B strain, the ramifications for flu vaccine? And then my second question is on PCV. Obviously, we are excited about the adjuvant data. There is also a competitor reading out in metastatic melanoma this summer, so I wanted to understand how we should compare and contrast that and if you could walk us through how to think about metastatic and what competitors might show? Thank you.

Thank you, Michael for both questions. So, first on the flu, we are still looking into the data, and we are going to develop a more complete picture of what we think happened in the influenza B immunogenicity study. A couple of important points to note: these are active comparator studies. When you look at non-inferiority on seroconversion or titers, it’s important to note that we are going at the standard-dose influenza vaccine active comparator. Between the Phase 2 study and the Phase 3 Southern Hemisphere study, there were changes in the composition of those active comparators, and the comparator use, and so that can drive some difference. The second thing is that they were different populations, and so we went from a Northern Hemisphere to a Southern Hemisphere, and that can drive some differences in background history of influenza illnesses. But the most relevant aspect is we expected the influenza B neutralizing titers to be lower. We thought that was acceptable because at the end of the day, our goal was to achieve non-inferiority, not to demonstrate superiority. Whereas for the influenza A strains, we wanted to maximize those neutralizing titers and the potential for benefit because influenza A drives the illness in older adults, which is where our first-generation product focuses. We aimed for non-inferiority on the influenza B. As you said, we did not meet that in terms of non-inferiority, and we will continue to pull apart the reasons why. An update will allow us to improve immunogenicity against the Bs to the extent that will be important going forward, not just for younger populations but perhaps from a regulatory perspective. As regards to PCV, we are encouraged by the adjuvant melanoma data. We have some early metastatic data from our prior Phase 1 studies. In the Phase 2 study, there was some stage 4 disease. We did not conduct it only in the first-line metastatic setting, and we’re looking forward to understanding the performance of a competitive product in that space because it may identify an opportunity for us to move into earlier stages of treatment. For now, our approach has been to focus on areas where checkpoint, including KEYTRUDA, is the standard of care and has demonstrated a strong signal, leading us to expand from adjuvant melanoma into non-small cell lung cancer and, ultimately, will go into other adjuvant indications where there is immediate biologic benefit. As others enter into the space, if they show benefits in other lines of therapy, we will proceed quickly in those directions.

Hey guys. Good morning. Thanks for taking the question. For RSV, a few years from now, do you expect it to be a 2-player, 3-player, or perhaps a 4-player market when including J&J? And how do you believe that the tolerability profile compared to others based on the full data presented this morning?

Sure. I can take the first portion of that question. At this point, there are obviously three companies that have rolled out their Phase 3 pivotal efficacy studies and are proceeding towards filing. I don’t have a specific view on J&J’s adenovector virus program, and otherwise, it’s still unclear about their regulatory path forward. On the question of reactogenicity and tolerability profile, as we presented today or our collaborator presented today at RSVVW, we see a favorable tolerability profile. Grade 3 adverse reactions, whether local or systemic, were all below 2% for any of the individual symptoms and actually compared relatively favorably with a placebo group. The most common adverse reactions were injection site pain, headaches, myalgia, and arthralgia. We’re pleased with our high efficacy of 83%, which I believe is among the best. As we presented today, that efficacy holds up nicely for older populations, those over 70, as well as those with higher comorbidities. It’s important, however, to do cross-trial comparisons, and ultimately, it will fall for public health officials to make those decisions. We are really encouraged by both the efficacy and tolerability profile of 1345 and look forward to filing and ultimately to the commercialization of that product. Arpa, would you like to add anything regarding the market going forward?

Sure. I would say we do anticipate it being at least a 3-player market with Moderna, Pfizer, and GSK. There is a possibility of a 4-player market if J&J has a regulatory path forward with their adenovector virus vaccine. Nothing more to add there.

Great. Good morning. Thanks for taking the question. Following up on flu or mRNA-1010, just to be very clear, if you hit on non-inferiority in the efficacy Northern Hemisphere study, do you think that mRNA-1010 would be approvable in spite of missing on non-inferiority on the B strains? And related to that, would you envision the approval only being for older adults? And on RSV, can you comment on the expectation for dosing frequency for your RSV vaccine? And how do you think about value and potential pricing of that vaccine, maybe benchmarking off of other vaccines for that age group? Thank you.

Yes. Thanks for those questions. So, let me take the flu stuff first. Again, the full approval standard is a head-to-head efficacy study. If we demonstrate non-inferior efficacy against an approved vaccine in the population of interest, which in this case in P302 is 50-plus adults, we do believe that could form the basis of an approval. At the end of the day, immunogenicity results are only surrogates for efficacy, and ultimately, efficacy is the gold standard. That’s what’s required for traditional approval. So it will depend upon data and discussions with regulators around that data package, but it is certainly plausible and likely that if we meet efficacy in the efficacy study, that that would be sufficient to move forward for full approval. It doesn’t mean there may not be questions about demonstrating non-inferior immunogenicity with influenza B strains or other things in subsequent studies, but we do believe there is a possibility there. We are currently studying mRNA-1010 only in older adults. So the P301 was in 18-plus, and P302 is in 50-plus. We will eventually evaluate our influenza vaccine in younger populations over time, which will involve age de-escalation, dose finding, and bridge down from an immunogenicity perspective, very much like what we did with COVID. Our initial filings for approval, if they proceed based on data, would be in adults and older adults principally, as we will follow next with pediatric populations. As I said earlier, this may involve using updated B antigens to increase immunogenicity in that population. On RSV, we have not yet clarified the dosing frequency. RSV is a seasonal virus, and what we have is breakthrough disease as we get older. We do not yet know how frequently individuals will need an RSV vaccine, whether it will be seasonal or less frequent. Typically, the initial recommendations will come from ACIP as well as from regulators around that frequency. None of the three products that have read out in Phase 3 have a clear answer on the durability of that efficacy yet. Arpa, do you want to take the next part of the question regarding value and pricing?

Sure. So from a pricing philosophy perspective, Moderna is committed to pricing that reflects the value of our vaccines. In terms of what they deliver to patients, to societies, and the healthcare systems, we will ensure full access for patients regardless of their ability to pay. Our pricing will reflect full recommendations from ACIP as we get the filing and ACIP recommendations. I cannot share any additional details on what sort of range that pricing might fall into, but it will be consistent with our overall pricing philosophy.

Hey guys. Thanks so much for taking the question. Just another on flu, any more details on the titer level specifically that you saw, or when we will get more details on the titer levels? And how should we think about the importance of having titers above that 40 benchmark versus demonstrating non-inferiority? What is the comparator vaccine titers in your Phase 3 did very well and were well above 40? How should we think about the implications then, say, you are at 30 or near 40, what that would mean from a regulatory standpoint as well as a commercial standpoint in interpreting the immunogenicity idea? Thanks.

All very good questions, and the short answer is we are looking into that data right now. We will provide an update, I’m not exactly sure when we’ll have that, but we do have the Vaccines Day Investor Meeting coming up in April during the spring, and will publish that data as it comes in. You’ve highlighted key challenges in active comparator studies for influenza, particularly, that you can see high titers, but if your active comparator performs very well against one of the strains, that can impact your ability to demonstrate non-inferiority statistically. The challenge is even more complicated for older adults, where influenza B strains might not drive the indication in this setting, and overall, two strains may be of much lower concern. There have been active debates about the B/Yamagata strain, whether it even should be included in quadrivalent vaccines in some recent WHO discussions. We will look at this data and develop our strategy to engage with regulators accordingly about how we proceed. The most important thing, though, is continuing with the efficacy studies to establish whether we have non-inferior, or even superior efficacy for mRNA-1010, which is the goal.

Hi. Good morning. Thanks for taking my questions. Two from us, the first one on the 4157-KEYTRUDA combo program. Just curious, if you could give us a little bit more color on how we should think about the cadence of the additional trial starts. Is it something that will be a more stepwise and measured approach? Or should we expect sort of full force kind of multiple trial starts approach? And then secondly, on rare disease, outside of your MMA, GSD, and PA program, what is the next rare disease program that we can expect to enter the clinic? Thank you.

Thank you for those questions. So on 4157, I just want to reiterate our prior guidance, I don’t want to expand it too much. We aim to move into those pivotal studies, which are Phase 3 confirmatory studies for melanoma and non-small cell lung cancer, both in adjuvant settings this year. You can look at Merck's history and their ability to execute those studies, enroll quite quickly, and we hope, working together with them, to be able to do at least as well. We will look to enroll those at least as quickly as other confirmatory Phase 3 studies. I don’t want to give more specific guidance on that enrollment timeline, except to say we want to go as fast as possible. I will also clarify, too, from an accelerated approval perspective, if that pathway were to become available based on the current Phase 2 data—again, that is subject to future conversations with regulators. If there is a path forward, we would indeed want to have started those confirmatory studies, but won't need to have them fully enrolled. Therefore, we have double impetus, and we’re moving very quickly to enroll them. On rare disease, moving out of preclinical and into clinical, I would say we have a clinical program for MMA, which you referenced. That MMA program is another area we expect to see additional data following the encouraging performance of the propionic acidemia PA program. For programs in preclinical, we also have programs against OTC and PKU, and those are both programs we hope to move into clinical testing in short order.

Thank you very much everybody for joining us and for the many thoughtful questions. We look forward to hosting you for Vaccine Day on April 11. It will be live in Boston for those of you who can join us and also of course virtual. Have a great day. Thank you.