Moderna Inc (MRNA) — Q1 2023 Earnings Call Transcript

Thank you, Lavina. Good morning or good afternoon, everyone. Today, I will start with a business review. Stephen will then review our clinical programs before Arpa gives an update on our commercial progress and plans. Jamie will present our financial results, and I will come back to close. So in the first quarter, we recorded revenues of $1.9 billion, GAAP net income of $79 million, and GAAP diluted earnings per share of $0.19, cash and cash investments of $16.4 billion at the end of the quarter. We continued in Q1 executing on our capital allocation strategy, prioritizing investments in our business. In the first quarter, we invested $1.1 billion in R&D, continuing investment in late-stage clinical programs and progressing our entire pipeline. SG&A costs were approximately $200 million in the quarter, with continued investment in digital and AI infrastructure and approximately $100 million in capital investments. In 2023, our team has been very active. This includes the acquisition of OriCiro in Japan, collaboration with CytomX, Life Edit, and Generation Bio. All of these investment opportunities further expand the reach of Moderna's mRNA technology. We are growing Moderna's mRNA operating system. Approximately less than $6 million were returned to shareholders with a share purchase of 3.6 million shares in the quarter. Let me turn to Commercial in the first quarter. We continue to expect $5 billion in COVID vaccine deliveries in 2023 from already signed advanced purchase agreements. With $1.8 billion of COVID delivered, we are well on our way to achieve $5 billion in advanced purchase agreements. The commercial team is actively negotiating to sign new contracts with customers in major markets to finalize additional orders that will add to the $5 billion. The U.S. team is negotiating with pharmacy chains, hospital networks, and other customers. As a reminder, the $5 billion of signed advanced purchase agreements does not include any fall 2023 U.S. contracts. So these new U.S. commercial contracts are important to the business as the additional contracts will boost our revenues. The team is also making progress in Japan, in Europe, and other countries in Asia, the Middle East, and also Latin America. We recently signed a new contract in Australia for 2023. Our commercial organization is also preparing for the launch of RSV in 2024, our next respiratory commercial product. They're educating the medical community on the health burden of RSV. Our medical team is participating in major infectious disease medical congresses and sharing the new data that shows a strong profile for our RSV vaccine. To prepare for the RSV launch, our manufacturing team has already begun producing drug substance, the mRNA molecule for the RSV vaccine. The vaccine will be supplied as a prefilled syringe. We believe this will help drive adoption by pharmacists and doctors, compared to some of our RSV products. In oncology, for mRNA-4157, now called individualized neoantigen therapy, or INT, we are scaling up manufacturing to support clinical development and commercial markets. Our commercial team is also working to prioritize tumor types to select for adjuvant Phase 3 studies, in addition to melanoma and lung. Turning to the pipeline. At Vaccine Day, we discussed detailed data from our RSV vaccine presented at research medical meetings. We believe the profile of our RSV vaccine is potentially best-in-class. We shared top-line data on the flu programs, announcing the initiation of a Phase 2 or 3 study, the Phase 3 study that we intend to use for accelerated approval, as well as our strategy for our next-generation flu programs. We also announced the start of Phase 3 for our next-generation COVID vaccine, mRNA-1283, which should be refrigerator-stable. Today, we're also announcing a new program for pandemic readiness for Influenza H5. For latent vaccines, our CMV Phase 3 trial has shown continued progress and is greater than 50% enrolled. I'm also very pleased to announce progress in our early-stage programs for EBV and HIV. Our EBV, as you know, has two programs. The EBV Phase 1 trials to prevent mononucleosis with mRNA-1189 are fully enrolled in adults and also in adolescents. Our EBV trial for the treatment of long-term complications from EBV infection has now started enrolling. For HIV, we will share interim analysis from our Phase 1 study at our vaccine meeting. We also introduced new programs. We are working on vaccines for norovirus and Lyme disease. Lyme is the first bacterial pathogen targeted with our mRNA platform for vaccination. In therapeutics, we participated in the AACR meeting where we presented detailed Phase 2 data from our R&D program partnered with Merck. Later on the call, Stephen will take you through the data presented there. Already, this pipeline is making progress. We're excited to announce a new milestone for our PA program. The Phase 1/2 trial for Propionic academia or PA is now in the dose expansion phase. Additional data from this study will be presented at the American Society for Gene and Cell Therapy later this month in May. The company continues to expand at a rapid pace. We have 47 programs underway, which now reflect the inclusion of new programs in the quarter and the removal of programs that are not continuing to develop. The full disease pipeline can be seen in the appendix of this presentation or obviously on our website. We now have more than 4,000 team members and 17 commercial subsidiaries across America, Europe, and Asia Pacific. In addition to our commercial subsidiaries, we also announced we're opening a Seattle office as a technology hub, where we're hiring data scientists and engineers who will help digitize our business and expand our AI capabilities. I'm also happy to announce Moderna was officially recognized in March as a great place to work by the Great Place to Work Institute. Our $16.4 billion of cash at the end of the quarter is enabling us to scale across our research, development, manufacturing, commercial, and G&A. With that introduction, let me now turn it over to Stephen.

Thank you, Stephane. Good morning or good afternoon, everyone. Today, I'll review the clinical progress in R&D at Moderna in the first quarter and highlight select data from the past few months that have been presented. The core of our respiratory portfolio is made up of vaccines against COVID-19, flu, and RSV, which are either commercial or in Phase 3. We're advancing second-generation vaccines, including our second-generation refrigerator-stable COVID-19 vaccine candidate, mRNA-1283, which is rapidly enrolling in its Phase 3 study, and two next-generation influenza vaccines that are in Phase 2. We believe combination vaccines will be the future of our respiratory franchise. We're pleased that we now have five different combination vaccine candidates in early clinical trials, including two specifically designed for pediatric populations. With 11 programs in clinical trials, including four in Phase 3 and covering five different respiratory viruses, we believe this represents the broadest and most advanced portfolio of respiratory virus vaccine candidates. Now turning specifically to COVID. The FDA recently provided updates on several fronts. Our Omicron-targeting bivalent COVID-19 vaccine targeting the original MBA 45 strains is now our only authorized formulation in the United States with a simplified and streamlined regimen for both children and adults. Individuals, 65 years of age and those with certain kinds of immunocompromise are now eligible to receive additional doses as needed or recommended by their physicians. As we look to the fall, the strain selection for an updated composition for fall 2023 boosters is now expected to come at the June 15 VRBPAC meeting. Moving to RSV, we're pleased by the profile of our vaccine in older adults with high and consistent efficacy against RSV lower respiratory tract disease across populations in our large Phase 3 study. At two recent medical meetings, we've shared data showing our vaccine's efficacy was consistently high across all age groups, including in the oldest adults and in participants with preexisting comorbidities that put them at higher risk. mRNA-1345 has also shown a favorable tolerability profile with adverse events mostly grade 1 or grade 2, mild to moderate. As we shared during Vaccines Day, we have not seen any cases of Guillain-Barré syndrome or other severe demyelinating events in the trial. Moving to flu. Our Phase 3 efficacy study in the Northern Hemisphere, P302 is ongoing. Last month, we announced that the study did not accrue sufficient cases to declare early success at the interim analysis and that the DSMB recommended that we continue the study. That trial is still accruing cases through the end of this flu season, with an update expected this summer. The preliminary immunogenicity data from that P302 study showed that HAI neutralizing titers were consistent with superiority for both A strains and non-inferior immunogenicity for the B strains when compared to the licensed flu vaccine. I am pleased to announce that we've initiated our Phase 3 P303 flu study with an updated formulation of mRNA-1010. P303 is testing an update designed to increase the HAI neutralizing titers against the B antigens. This is an immunogenicity study and is expected to enroll approximately 2,400 adults this spring. We believe this study will support our initial flu filing and the potential for a 2024 launch if approved by regulators. Now turning to our latent vaccines, our CMV vaccine Phase 3 study in women of childbearing age is ongoing and has enrolled more than 50% of participants. We also have an ongoing Phase 1/2 adolescent dose-ranging study with this vaccine that will expand potential eligible populations. As Stephane mentioned earlier, we continue to make significant progress against all of our latent vaccines in earlier-stage clinical trials, including candidates against EBV, HIV, and VZV. As Stephane mentioned, our EBV vaccine includes two candidates, mRNA-1189 and mRNA-1195, and are in clinical trials for prevention of infectious mononucleosis and for the prevention of longer-term sequelae of EBV infection, respectively. At Vaccines Day, we were pleased to share interim results of our HIV vaccine, mRNA-1644, which continues to advance. Our pipeline in therapeutics targets unmet needs across immuno-oncology, rare diseases, cardiovascular disease, and autoimmune diseases. All the trials in these therapeutic areas are ongoing. Today, I'll highlight a few of the recent updates. On Slide 16 are the data shared at AACR from our Phase 2 study in adjuvant melanoma with a combination of our individualized neoantigen therapy plus KEYTRUDA versus KEYTRUDA alone. The Kaplan-Meier curve for relapse-free survival shows here an overall, there was a 44% reduction in the rate of relapse or death with a combination of INT and KEYTRUDA compared to KEYTRUDA alone. We are encouraged by the continued separation of the two curves with a follow-up at 18 months. Note that there are very few participants beyond the 140-week cutoff at the right of this slide, less than 10 participants in total. Thus, as the data continues to mature with additional follow-up time, we remain cautiously optimistic that this picture will get even better. Now on Slide 17, I want to briefly highlight some of the additional data that was shared at AACR. The subgroup analysis confirmed the strength of the treatment effect across two important markers that are known to predict responses to KEYTRUDA. Again, on this slide, we're looking at the relapse-free survival. On the left side, the results are stratified by high tumor mutational burden in red and low tumor mutational burden in blue. In each case, the solid lines are for the INT combination, and the dashed line is for KEYTRUDA monotherapy control. If you start by looking and comparing the control arms for KEYTRUDA, you will note that the TMB high participants, the red dashed line, have a higher relapse-free survival than the TMB low participants in the blue dashed line. This is expected because of what we know about KEYTRUDA, and shows that the controls are performing as we expect. Now moving to the INT combination arms, the solid lines and comparing them against the dotted lines of the same color, you can clearly see that the INT combination led to higher relapse-free survival for both TMB high and TMB low patients. This highlights the robustness of the response for INT. It's also quite exciting to note that the improved response rate seen in the blue TMB low population, which historically does not respond as well to KEYTRUDA. On the right, you'll see the result as stratified by PD-L1 status. As with the TMB analysis, PD-L1 is known to predict response rates to immunotherapy. As you can see by the dashed lines for KEYTRUDA monotherapy control groups, the relapse-free survival curves look better for PD-L1 positive tumors, these are the red dashed lines, and worse for patients unfortunate enough to have PD-L1 negative tumors, the blue dashed lines. This isn't surprising as KEYTRUDA monotherapy acts by blocking the PD-1, PD-L1 access. Again, as with TMB on the left, the solid lines on the RFS curves for the combination show the combination of INT, red denotes PD-L1 positive, and blue denotes PD-L1 negative. In both cases, there is an increase in the rate of relapse-free survival with the combination treatment. It is encouraging to note again that the response rates are significantly improved for the PD-L1 negative patients. Indeed, the hazard ratio in this subgroup analysis is 0.162. Now pulling back, these data highlight that the observed improvement in relapse-free survival seen in the initial analysis of our Phase 2 study looks broad-based across subgroups with an indication of a potentially important benefit, even in patients who have a higher risk of progression, whether due to PD-L1 status or tumor mutational burden compared to KEYTRUDA monotherapy alone. These positive data are just the beginning for this ongoing study. We'll be sharing additional data from the Phase 2 study at ASCO, including distant metastasis-free survival, which was a secondary endpoint in the primary analysis just conducted, and the same data cuts that I just shared. This protocol calls for subsequent analysis at 51 events, which is when we will also be updating the Kaplan-Meier curves for recurrence-free survival with longer follow-up time across the full population, and we eagerly await those updates. INT has received breakthrough therapy designation in the United States and PRIME designation in Europe, which will facilitate frequent dialogue with regulators as we work to quickly advance this treatment for patients. As Stephane mentioned earlier, we plan to initiate our Phase 3 study in adjuvant melanoma in 2023 and rapidly expand to additional tumor types, including non-small cell lung cancer. We're working closely with our partner, Merck, to explore additional opportunities within KEYTRUDA approved indications and beyond that label. Finally, a quick update on our propionic acidemia program. Our Phase 1/2 study is ongoing and currently enrolling patients in the 0.9 milligrams per kilogram cohort. We have identified a dose for expansion and have moved into that expansion arm in the study. I'm pleased to announce just yesterday that a clinical update through the earlier time point earlier this year, including an update on safety and the rate of major metabolic compensations from the higher dose cohorts and including longer-term follow-up from the lower dose cohorts will now be presented at the American Society of Gene and Cell Therapy Meeting on May 18. The abstract for that presentation is now available and can be found in the link on this slide. We look forward to sharing a lot more about the progress of this medicine and our other rare disease programs in the months ahead. With that, I'll turn the call over to Arpa.

Thank you, Stephen, and good day to everyone. I will first start with a review of sales in the quarter. On Slide 22, we summarized the composition of our sales in the first quarter. As you'll see on the chart, our sales to Europe were $0.6 billion and sales to the rest of the world were $1.3 billion. Approximately $1.8 billion in sales from previously announced advanced purchase agreements were delivered in the first quarter of 2023, representing the vast majority of the $2 billion expected in the first half of 2023. As a reminder, U.S. sales for COVID vaccines are expected to begin in the second half of 2023, with updated strain forecasts. Now as we turn to Slide 23, looking at the 2023 COVID deliveries, today, we are reiterating a minimum of approximately $5 billion in COVID vaccine deliveries from current advanced purchase agreements. We continue to expect additional orders from key markets. Of the $5 billion in 2023 deliveries from previously announced advanced purchase agreements, $2 billion, as I mentioned earlier, are expected to be delivered in the first half of 2023. We have already delivered $1.8 billion of that $2 billion in the first quarter, with substantial fulfillment to Japan and the European Union. We expect to deliver the remaining approximately $3 billion in previously announced advanced purchase agreements in the second half of this year. Additionally, we expect new sales in the U.S., Japan, the European Union, Asia, and Latin America. I'm happy to announce that the commercial team has signed a contract with the Australian Government for 2023. Our discussions with commercial buyers in the U.S. are positive, and I will elaborate on that shortly. In our discussions with commercial customers in the U.S., it is clear that our customers are aware that COVID is still a substantial health burden. Throughout 2022, COVID continued to be a leading cause of hospitalizations. Data available through September 2022 listed COVID as the third leading cause of death in the U.S., only after heart disease and cancer, as shown in the first chart on the left. The chart on the right-hand side shows the most recent data available for U.S. hospitalizations for COVID, flu, and RSV. As you'll see, with current season hospitalizations of over 600,000 for COVID, the hospitalization rate for COVID is almost triple that of flu as well as more than triple that of RSV. There continues to be a clear need to protect against severe COVID infections, and our customers recognize that need. For the full of 2023, we expect the U.S. market volume to be approximately 100 million doses. As we highlighted earlier in the year, the successful transition of our U.S. COVID business from a government-driven to a commercial-driven model is critical. We have made great progress on this front, executing on our action plan to rapidly develop this commercial market. Importantly, the commercial team is in active discussions with customers throughout the U.S. We are contracting with national and regional pharmacies, integrated delivery networks, government health providers, including the VA, the CDC, and the Department of Defense, for purchasing organizations and other providers. In addition, our established national distribution infrastructure and our Moderna Direct e-commerce site is fully operational. Our global supply chain is in place to handle all U.S. customer needs, including prefilled syringes and single-dose vials at the time of launch. I'm excited to share some of the launch preparation activities for the updated COVID-19 vaccine for fall vaccination campaigns. We believe these activities will drive consumers to get vaccinated. First, we are taking an omnichannel approach via tailored digital messaging to healthcare providers. This multifaceted approach will allow us to drive broad awareness and continue to emphasize the ongoing need for COVID production. Later this year, we will be disseminating customized content to drive physician demand across immunizing physicians, institutional decision-makers, as well as influencers. We are also partnering with our customer base across the different commercial segments to assist with their fall immunization programs. We believe there's an opportunity to continue to provide education, both to staff as well as to patients. We believe there is also an opportunity to harmonize and simplify the vaccination process for patients who are going in to skip their flu vaccine. Consumer promotion will be focused primarily in the fall of this year, driving patients to seek Moderna's COVID vaccine through significant DTC efforts. As I mentioned earlier, we are looking to simplify the experience for our consumers who are already going in to receive their seasonal influenza vaccine this fall. We are energized for this fall season. Moving on to Slide 27, I will update you on our second near-term commercial opportunity, which is RSV. We are excited for the expected 2024 launch of our RSV vaccine, and the commercial team is undertaking a number of activities to ensure that we develop what we hope will be a large share of that market as quickly as possible. We are already raising awareness of the health and economic burden of RSV by generating and presenting detailed data from our Phase 3 study at major medical meetings. Our medical team has shared additional data showing that vaccine efficacy is consistently high across all tested age groups as well as in participants with preexisting comorbidities. The figures on the right-hand side of the slide detail efficacy data in these important subgroups; as we share these data at medical congresses, we are encouraged by the feedback from key opinion leaders on our data and the application of our mRNA platform to prevent RSV. We're engaging with payers and ITAC to ensure access upon launch. The commercial team is active in local markets preparing for a commercial launch in 2024. Specifically, we are building our digital capabilities so that we will be able to efficiently educate customers as soon as the vaccine is approved. As we invest in prelaunch activities, we have already begun manufacturing components of the vaccine and prefilled syringes. We are excited about the profile of the products we will be launching into these large respiratory markets. As we discussed at Vaccines Day, the estimated total addressable markets for our three key respiratory vaccines are substantial, with COVID, RSV, and flu offering potential addressable markets of $15 billion, $6 billion to $8 billion, and $6 billion to $9 billion, respectively. We believe we can take a sizable share of this roughly $30 billion respiratory market. The commercial team is well underway in preparing for RSV and flu launches in 2024. We believe our opportunity in the respiratory market will continue to expand beyond 2024 with our next-generation vaccines and, importantly, with future combination vaccines, positioning us to drive share over time. Now on to Slide 29, I want to share with you how the commercial team is helping identify eligible patient populations in the adjuvant and neoadjuvant settings for various tumor types. Along with our partner, Merck, we have already announced that we will start Phase 3 trials in adjuvant melanoma and adjuvant non-small cell lung cancer. There is an annual population of over 130,000 new patients in the U.S. and Europe in these two indications. Patient populations for additional potential adjuvant and neoadjuvant tumor types are listed on the right-hand side. Our commercial teams are working closely with our clinical teams to identify the largest unmet needs for addressable tumor types for individualized neoantigen therapy. We are excited to be launching into a space where we have one medicine for one patient in areas of great need in cancer. Given the individualized approach, we are reimagining our commercial model, along with our partner, along with the patient care journey, end-to-end. With that, I will turn it over to Jamie.

Thanks, Arpa, and hello, everyone. This morning, I will cover our Q1 financial performance, review the framework for our 2023 financial outlook, and provide a quick recap from our recent Vaccines Day presentation. Moving to our first quarter results, starting on Slide 31. Total product sales decreased 69% year-over-year to $1.8 billion. The decrease in 2023 is consistent with our expectations and mainly driven by lower sales volume compared to the prior year. Cost of sales for the first quarter of 2023 was $792 million, in addition to our unit-driven manufacturing costs. This includes royalties of $86 million and the following charges: $148 million for inventory write-downs related to excess and obsolete COVID-19 products, unutilized manufacturing capacity of $135 million, and losses on firm purchase commitments and related cancellation fees of $95 million. These charges, other than royalties, were driven by costs associated with surplus production capacity and an overall lower demand forecast primarily from lower-income countries. Cost of sales as a percent of product sales was 43% compared to 17% in Q1 2022. The increase was driven by the aforementioned charges over lower product sales compared to the prior year and higher manufacturing costs as we switch to smaller dose vials as well as lower product sales to absorb fixed manufacturing costs. Research and development expenses were $1.1 billion, which increased by 104% versus the prior year. The increase in R&D spend continues to be driven by clinical trial-related expenses, particularly with our Phase 3 studies for RSV, seasonal flu, and CMV. The increase in R&D was also attributable to increases in personnel-related costs due to increased headcount and our recently announced collaboration agreements with Life Edit and Generation Bio. SG&A expenses were $305 million, reflecting an increase of 14% 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 related commercialization activities as well as our company expansion. Income tax provision was a net benefit of $384 million for the first quarter, driven by our full-year outlook, which includes international provisions, R&D credits, and nonrecurring items. Net income was $79 million compared to a net income of $3.7 billion last year. Diluted earnings per share were $0.19 compared to a diluted earnings per share of $8.58 in Q1 2022. We ended Q1 with cash and investments of $16.4 billion compared to $18.2 billion at the end of the fourth quarter of 2022. The decrease was driven by a reduction of cash deposits as we delivered products against prepayments and our share buyback activity. Cash deposits for future product supply declined from $2.6 billion at the end of 2022 to $1.8 billion by the end of Q1 2023, in line with our expectations. Now turning to Slide 33, I want 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 the base business across multiple areas. As mentioned earlier, R&D spending in the first quarter increased 104% year-over-year, and we continue to project R&D investments of approximately $4.5 billion for the full year of 2023. As discussed at our Vaccines Day presentation, the majority of this investment is for our respiratory vaccine franchise, which we expect to generate significant returns in the relatively near term. 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. As previously announced, we successfully closed our acquisition of OriCiro in the first quarter, and the integration of the operations is well underway. Additionally, we entered into two collaboration agreements during the quarter with Life Edit and Generation Bio. We are in multiple active discussions regarding additional external collaboration opportunities, and we'll continue to be disciplined in our approach. After evaluating internal and external investment opportunities, we then assess additional uses of cash. In the first quarter of 2023, we repurchased 3.6 million shares for $526 million. We had $2.3 billion of share repurchase authorization remaining as of March 31, 2023. Now let's turn to our updated 2023 financial framework on Slide 34. We continue to have advanced purchase agreements for COVID vaccine sales of approximately $5 billion for delivery in 2023, and we are in active negotiations for commercial market and government contracts in the U.S. and additional contracts for Japan, the EU, and other key markets. We continue to expect first-half sales to be approximately $2 billion. Due to the seasonal nature of our respiratory business, we expect sales in Q2 of $0.2 billion to $0.3 billion. We continue to expect fiscal year 2023 reported cost of sales to be 35% to 40% of sales, which includes 5% royalties. For Q2, we expect cost of sales between $0.5 billion and $0.6 billion. Due to the seasonal nature of our business, we expect our cost of sales in the first half of the year to be above the range of 35% to 40% and then reduce our average through the second half of the year. For R&D and SG&A, we continue to expect full-year expenses to be approximately $6 billion, with approximately $4.5 billion in research and development. We now anticipate a full-year tax benefit of $0.3 billion to $0.5 billion, driven by R&D credits, international provisions, and nonrecurring items. Finally, we continue to expect capital expenditures of approximately $1 billion. Before I turn the call back to Stephane, for those who weren't able to attend or haven't seen the webcast from our Vaccines Day presentation, I wanted to quickly recap the financial takeaways. Given the current significant investment in our respiratory franchise, we wanted to lay out the potential return we envision by the year 2027 for this franchise. Picking up where Arpa ended her earlier remarks, we believe the market size for COVID, RSV, and flu will be over $30 billion by 2027, and we expect to capture $8 billion to $15 billion of this marketplace. While our cost of goods sold percentage will remain elevated in the short term as we transition from a pandemic to an endemic environment, we believe this should normalize to a 20% to 25% range by 2027. We also laid out a $6 billion to $8 billion cumulative R&D investment required over the next three years, which will then normalize to a routine maintenance amount of 10% of respiratory vaccines revenue by 2027. Finally, we like the characteristics of the respiratory vaccine franchise, given the highly flexible cost base, low capital intensity, durable future revenue, and high potential return, which could lead to $4 billion to $9 billion of free cash flow annually with further room for growth. This concludes my remarks, and I will now turn the call back over to Stephane.

Thank you, Jamie, Arpa, and Stephen. Let me share some thoughts before we close into Q&A. Moderna's promising commercial outlook has several development projects come to fruition. In COVID, we are finalizing discussions with customers. I believe that we'll see significant additional contracts in the U.S., in Japan, and around the world for 2023. COVID is not going away, and governments are getting ready for vaccination campaigns in the fall. I'm pleased that we have begun prelaunch market development and risk manufacturing for RSV, which we expect to launch in 2024. In oncology, the team is making great progress. We expect to deliver key milestones on our development pipeline in the remaining eight months of 2023. We expect regulatory authorities to give us direction on COVID strain with the June VRBPAC meeting, and we expect to launch an updated COVID-19 vaccine for the fall of 2023. We plan to file for approval for the RSV vaccine, and our Phase 2/3 study should be fully enrolled by this summer, and we expect data in Q4. For INT cancer therapy, we expect to make additional Phase 2 updates, launch our Phase 3 study in adjuvant melanoma, and expand into additional cancer types. We'll continue to make progress in our revenues portfolio. We will present data for PA on May 18. This is a very exciting time for us at Moderna, and I would like to thank our teams for all their hard work and their commitment to our mission. Our platform is firing on all cylinders. In infectious disease vaccines, look at the data and the portfolio of respiratory, latent, and now entering a bacterial vaccine. I am very excited by where INT is and is going. Furthermore, rare diseases with PA followed by programs like MMA and GSD1a will give some key updates this year. On September 13, we have our annual R&D day, where we will present new development pipeline data, and on December 7, we'll be hosting our second annual ESG day. We believe that the incredible progress we have made across all of our modalities positions our company for long-term financial success. The mission of our company motivates our entire team to come to work every day to deliver the greatest possible impact to people through mRNA medicine. We believe we have a technology that can eliminate or greatly reduce human suffering caused by respiratory viruses, latent viruses, bacteria, cancer, regulating disease, and a growing list of diseases. We work to bring many of our more promising technologies to market in the next several years and remain committed to fulfilling our mission. With this, we'll take questions. Operator?

I have two quick questions. The first one is regarding the U.S. commercial opportunity in the second half this year. You are in discussion with both the commercial and government peers. Is 110 to 130 still a good benchmark? How is the pricing play out between these two groups? When will you start to see clarity on actual contracts and orders? And then my second quick question is regarding your expectation for the ASCO update for your PCV program?

Great. So I will start with the first two questions on commercial and then hand it over to Stephen to discuss ASCO. In terms of pricing across the U.S. market, we anticipate our list price when we have our updated vaccine to be in the range of 110 to 130. As you're aware, in the commercial market, we will be providing differentiated discounts across different payer types, from government agencies to commercial players as well. In terms of the timing of the orders, we are actively in negotiations with U.S. customers. We are encouraged on two fronts. First and foremost, our customers appreciate and understand the significant health burden that continued success with COVID and they want to partner with us to ensure that as many of their patients can get vaccinated to protect themselves from potential hospitalizations and severe diseases. The other thing we continue to be very encouraged by in our conversations with different customers is that they recognize the full real-world evidence behind our vaccine's effectiveness and profile. Thus, we anticipate that over the next four to six weeks, we will begin to see some more clarity around contracting, which will continue through the end of Q2 and early into Q3.

Gena had a question on ASCO? Okay. Sorry. Gena, regarding the date at ASCO, there are two presentations, two sets of data that will be shared. The first will focus on the distant metastasis-free survival. As you know, DMFS is another surrogate of overall survival. The protocol for the Phase 2 study included in the first analysis looking both at RFS and DMFS was a secondary endpoint, and we'll be presenting that data for the first time at ASCO. The second data that will be shared in poster form will involve some data on biomarkers and additional insights on the performance of INT across populations. This additional data will provide insight into the mechanism of action of the product, as well as further stratification of risk, leading us to believe we have more confidence in the signal we're seeing indicating potential benefit for INT in the Phase 2 study.

With regard to the PA data that we're going to see at ASGCT, could you just frame that for us? I think in the past, you've talked about 25% being clinically meaningful as you look at relative risk reduction in major decomposition events here and what the translatability is from that to MMA and GSD1 and OTC and your overall rare disease franchise? And then a second question for COGS, how are you thinking about beyond 2023? And in the context of your assumed market share of the respiratory franchise revenue as you look out to 2027, which you noted, how do you think about profitability in the context of this OpEx spend, including kind of your R&D and SG&A outlook?

Thank you for the question. I'll take the rare disease portion of that on PA first. As we shared last September, after a data cutoff from the PA study last September after a couple of dose levels. We saw slightly more than a 50% reduction in the rate of metabolic decompensation. These are severe events that will ultimately be the endpoint that we're measuring for this drug in terms of benefit. We will share further updates at ASGCT, which will include at least six months at the third dose level and some emerging data at the next dose level. I don't want to get ahead of sharing what that data is, but we will be looking for the strength of that benefit as we go up in dose, and we hope to improve from that 50% reduction in metabolic decompensation. We'll also see much more follow-up time in terms of total time on the drug across the entire study, helping to build that case moving forward. Now regarding the relationship to other programs, propionic acidemia, PA, is a sister disease to methylmalonic acidemia, MMA. As we grow more confident about the data we're seeing in PA, we think it generally translates well into MMA and other conditions, including OTC.

Salveen, maybe I'll take the COGS question. To reiterate, this year is between 35% to 40% of sales. As you mentioned, we'll go to 20% to 25% by 2027. I’m not sure it's a perfectly straight line, but let me give you the factors that will improve that over time. First is volume. Increasing volume over time as we add new products should provide better leverage overall. Predictability should help this, as this is a highly uncertain season this year transitioning to an endemic phase. I believe the average selling price will continue to rise as well. What might offset that a little is the increased single-dose vial or prefilled syringe presentation over time, and we've budgeted for some of that in 2023. Overall, we feel confident regarding inventory levels decreasing and cost as a percent of sales being reduced. As it pertains to the 2027 P&L and what that means for overall company profitability, we haven't issued guidance on that. I will reiterate that the respiratory vaccine business should generate between $4 billion to $9 billion of revenue, and we will see. We're excited about our pipeline and will do the best for all stakeholders. If it makes sense to reinvest profits back into the business, we will do that.

This is Tara on for Tyler. I know you mentioned a little bit about timing. But specifically, what we're wondering is, once the COVID strain is selected for the fall and winter season next month, how long approximately do you think it will take to finalize the commercial contracts in the U.S. and abroad? And then separately outside of the U.S., does the recent announcement regarding the ongoing negotiation with Pfizer in Europe actually create an opportunity for you guys to perhaps drive a larger contract in Europe than previously anticipated?

Thank you for the question. Regarding the timing of contracting in the U.S., while we are waiting for the final variant strain to be selected in the middle of June, we have already initiated contracting conversations based on an FDA-selected variant. We anticipate seeing some of these contracts being signed over the next several weeks leading into the third quarter. From an EU perspective, we're encouraged by the news that the EU is in renegotiations with Pfizer. This signals that the EU likely does not want to rely on one sole supplier. Also, the EU recognizes the value in the effectiveness and safety of our COVID-19 vaccine. We will continue to work with them on opportunities to protect the roughly 140 million individuals in the EU who are at high risk of COVID infection. We will share updates as we receive them.

Two areas I wanted to ask on PCV, or shall I say, INT cancer therapy. Stephen, you've talked and mentioned there in the slides around time as well as breakthrough designation. I think you mentioned that you do have a discussion with the FDA around your recent data. Can you just talk to the scenarios around a potential accelerated approval, the argument that you have to bring this to patients sooner, or do we really have to wait years to run the Phase 3? Talk a little bit about how you feel about that this year. And then the second question, I think, is also important with regard to RSV. Obviously, we'd love to see a diversification of revenues. This could be coming next year. How do you see your revenue opportunity in 2024? Is that a payer battle or a couple of competitors out there, where is your advantage, and how do you see yourself with market share and revenues next year?

Thank you, Mike, for the question. I'll take the INT one. It is still early in this discussion about what it will take to bring this notion forward to patients. Even in the Phase 2 study, while the data is really exciting, it's probably premature to say that it's sufficient for proceeding directly to accelerated approval. Conditions over the next year or couple of years may arise that could make it appropriate for us and regulators to consider accelerated approval. In the short term, the data is still maturing. We haven't released the distant metastasis-free survival data yet, which we will do at ASCO. This will help build a more comprehensive picture as DMFS evaluates the aggressive nature of relapses. We have additional biomarker data that will also come at the ASCO presentation, but we think we need to see a lot more maturation of this data before making any decisions about accelerated approval. We also must consider our Phase 3 study enrollment when contemplating any with regulators. Thus, our main focus is starting that Phase 3 study and quickly enrolling. Regarding RSV, we are excited about our revenue opportunities. The profile of our vaccine appears favorable when we analyze the Phase 3 data for safety and efficacy, which positions us strongly in a competitive landscape. As we look towards 2024, the RSV vaccine will be seasonal, and negotiations will happen with a range of payers. We will actively embed ourselves within the U.S. commercial market.

Regarding RSV, we continue to be very excited about our opportunity to position ourselves effectively in the market. The profile of our vaccine, when compared to our colleagues in the market, positions us well to capture significant market share. We believe we can establish dominance in this sector. As this market evolves and expands, we plan on raising awareness of the health and economic burden of RSV, which will guide our entry into the market.

Great. I was just wondering on INT, if you can comment at all about the design of the Phase 3 in lung there. And then just what's driving that confidence to move forward at this point? Can you just remind us of any data you have at this point on that front?

Yes. There are a couple of factors at play here. We did look in the Phase 1 study at non-small cell lung cancer patients. Those were not adjuvant patients, but we have data on their clinical histories, which supports our confidence in the therapy. Our strength comes from the mechanism of action we are observing in the current data, which translates well across risk factors in the Phase 2 study we’ve conducted, giving us confidence in pursuing adjuvant indications more broadly for non-small cell lung cancer.

A couple of follow-ups on some of the questions that have been asked already. First, on the U.S. COVID contracts for the fall, should we expect updates as those are finalized in real-time or more like a combined sort of status report, for example, with 2Q results early on in the third quarter? Second, with the shift to an endemic phase for COVID, do you see any opportunity for improved pricing for COVID vaccines outside the U.S., for example, in Europe? And lastly, on RSV, how soon do you believe RSV needs to be approved for you to participate in contracting for 2024?

In terms of providing updates for U.S. commercial contracts, we are not currently committing to real-time updates. However, we will provide updates during our quarterly calls regarding our status on U.S. commercial contracts. As for ex-U.S. pricing, we do not comment on our pricing structure. For most countries outside of the U.S., we're still in a centralized government procurement model. Thus, we haven't set endemic or more traditional commercial pricing yet. Finally, regarding RSV contracting, we target a 2024 launch, and we believe we will have the contracts in place in time for that launch.

Maybe if you could just elaborate a little bit on your confidence in the updated formulation targeting the B strains in influenza. And if you can comment on the dose level, if this is studying a higher absolute dose. And just maybe in terms of this compound, but also just broader, the flu platform as you add additional antigens, just your thoughts on reactogenicity here and then broadly, with the additional balance of these compounds? And then second, just in RSV. Just a bit of housekeeping. I guess, do you still plan to file this quarter?

Yes. Regarding the flu question, we have strong immunogenicity data from the P302 study that shows we have met non-inferiority or superiority for the B strains. Our confidence is high that we can clear this bar, supported by that data, even before making improvements in the B strain update for our current Phase 3 study. We also have preclinical data supporting our time in the update. As for the dose, we are not changing the dose for the 1010P303 study. It will still be 50 micrograms. Looking more broadly at our respiratory pipeline, we are investigating various dosages; we have seen increased tolerability profiles in several candidates. So the approach will depend on specific vaccines and their requirements. Currently, we don't believe there's a critical limit. Regarding RSV, yes, we're working closely with regulators on our global filing, which includes all markets for which we hope to commercialize that product and launch next year. Of course, we'll keep you updated as we move through that regulatory process.

Maybe on IMT, I think you've been highlighting the opportunity in the adjuvant and neoadjuvant settings. However, I wonder if you could comment on what's the plan in the metastatic settings, is there a place for INT in metastatic settings? And maybe related to it, are you planning to update the metastatic head and neck cancer dataset that we have seen at 2021? Any color there would be much appreciated.

We do think that INT can occupy roles in both earlier and later stages. There is a huge opportunity we perceive, and we believe that a lot is to focus on adjuvant indications. While we have some intriguing signs in the metastatic head and neck study you referenced, we are following the evolution of our data and waiting for indications to make more robust decisions on those fronts. We are committed to pursuing pivotal studies in adjuvant settings while being attentive to any potential positive outcomes in the metastatic domain. Regarding the earliest timeline for the COVID plus flu combo potential, we are targeting a launch in 2025, pending successful approval of the flu vaccine first.

This is Alec on for Geoff Meacham. Given the breadth of your clinical pipeline and potential opportunities for new vaccines, how does Moderna prioritize assets or indications to go after? Once the data has, let's say, proof of concept for its line disease, what is your clinical strategy in terms of targeting additional bacterial indications? And then just finally, how are you thinking about capital deployment for the INT program?

It is indeed a challenge we have. We are seeing a very high success rate in starting pivotal studies across our pipeline. We prioritize opportunities where our technology is well validated and where there is a large unmet medical need. Those conditions also tend to have large financial demands. In terms of our engagement in the bacterial landscape, we want to address unmet needs, like Lyme disease. We aim to demonstrate proof of concept quickly before pushing additional bacterial targets forward. Lastly, regarding the INT program, we pursue aggressive growth around that, given the burden of disease, with a great social, financial, and technical return. We aim to balance responsible investments with fast progress across indications we believe in.

Your line is open. You can ask your question.

This is Erica on for Hartaj today. In the slides, you have provided the estimated 2027 respiratory product sales range with the high end being almost double what is below. I'm curious if you can talk about the extent to which the standalone versus combination share of respiratory vaccines affects this revenue range and whether you see market cannibalization by the combo vaccines? Secondly, a question on the pediatric RSV program: the burden of disease for children caused by RSV is immensely high; can you talk about your progress in the context of competition in the pediatric RSV program and your potential timelines for development?

Sure, thank you. I will start with the first question regarding the respiratory opportunity. We are hearing significant enthusiasm from both consumers as well as our customer base regarding combination vaccines. We believe that it will enhance compliance and adherence to address the broad respiratory burden of disease by putting these two, potentially three vaccines, into one. As we think about the commercial opportunity, we do believe combinations will represent the majority of the opportunity as we look towards 2027. We also do anticipate some cannibalization of the monotherapy vaccines, as you're indicating. Regarding the pediatric RSV question, we've been working in this sector since we ventured into RSV. We have ongoing clinical trials including monotherapy and combination vaccines targeted at pediatric populations. We deeply recognize the high unmet need and are committed to this area. Regarding timelines for development, we will share updates on our clinical research and data as it becomes available. We are keen to adapt our methodologies based on the insights we gain.

Thank you, everybody, for joining us today and for your questions. The next month is going to be exciting, with PA data on May 18 and new INT data at ASCO in early June. Have a great day. Bye.