Q2 2025 Moderna Inc Earnings Call
Lavina Talukdar: Good day and thank you for standing by. Welcome to Moderna's second quarter 2025 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised today's conference is being recorded. I would like to hand the conference over to your speaker today, Lavina Talukdar, Head of IR. Please go ahead.
Good day, and thank you for standing by. Welcome to Moderna's second quarter 2025 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press *1,1 on your telephone. You'll then hear an automated message advising that your hand is raised. To withdraw your question, please press *1,1 again. Please be advised that today's conference is being recorded. I would like to end the conversation.
Stephane Bancel: Thank you, Kevin. Good morning and good afternoon, everyone. Thank you for joining today's call to discuss Moderna's second quarter 2025 financial results and business updates. 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; and James 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 two of the accompanying presentation and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements. With that, I will now turn it over to Stephane.
Will you speak today, Lavina, to Lupar, head of IR? Please go ahead.
Thank you, Kevin. Good morning and good afternoon, everyone. Thank you for joining today's call to discuss Moderna's second quarter 2025 financial results and business updates.
You can access the press release issued this morning as well as the slides that will be reviewing by going to the investor section of our website.
On today's call our Stefan Bonsall, our chief executive officer, Stephen Hogg, our president and Jamie 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.
In these forward-looking statements.
James Mock: Thank you, Lavina. Good morning or good afternoon, everyone. Thank you for joining us today. I will start with a quick review of Q2. James Mock will present our financial results and outlook. Stephen Hoge will review our clinical programs. Then I will come back and share key priorities and catalysts before we take your questions. Let me start with a review of our financials. In the second quarter, our revenues of $0.1 billion and the loss of $0.8 billion were in line with our expectations. They reflect the highly seasonal nature of our respiratory vaccine business. We ended the quarter with $7.5 billion in cash and investments.
With that, I'll now turn it over to Stefan. Thank you, Lavina. Good morning or good afternoon, everyone. Thank you for joining us today.
I will start with a quick review of Q2. Jimmy will present our financial results and outlook.
Steven will review our clinical programs and then I will come back and share key priorities and catalysts before we take your questions,
Let me start with a review of financials in the second quarter of Revenue of 0.1 billion and the loss of 08 billion were in line with expectations.
And they reflect the highly seasonal nature of our respiratory vaccine business.
We entered the quarter with 7.5 billion in cash and Investments.
James Mock: We remain highly focused on financial discipline. I am very pleased to announce that continued cost reduction efforts across the company in the second quarter of 2025 led to a 35% reduction of cost of sales, R&D, and SG&A combined compared to the second quarter of 2024. As you know, we are very focused on cash costs. I am happy to report that on a cash cost basis, we reduced operating expenses by $581 million in Q2 2025 versus Q2 2024, which is a 40% reduction year over year. During the quarter, we made solid progress across our three strategic priorities. Priority one, curbing use of our commercial products. We made strong progress in securing three approvals from the U.S. FDA.
We remain highly focused on financial discipline.
I am very pleased to announce that continued cost reduction efforts across the company in Q2 2025 led to a 35% reduction in the cost of sales on the NSG Anda combined compared to Q2 2024.
As you know, we are very focused on cash cost and I'm happy to report that on a cash cost basis. We reduce operating expenses by 581 million in q222 2024, which is a 40% reduction year over year.
During the quarter, we made solid progress across our free strategic priorities.
Priority 1 growing use of our commercial products.
James Mock: On May 31, we were very pleased to announce the FDA approval of mNEXT Spike, our next-generation COVID vaccine that has shown even higher efficacy than our parenting Spikevax vaccine. In mid-June, we received FDA approval of our mResVera vaccine for high-risk individuals aged 18 to 59. As a reminder, we are also approved for adults 60 and older in the U.S. and in 38 other countries. In July, the FDA granted full approval of our Spikevax COVID vaccine for high-risk children aged 6 months through 11 years. This vaccine has previously been used under EUA. This approval supports our broader goal of driving use of our commercial products and driving the company back into sales growth.
We met strong progress in securing free approvals from the U.S. FDA.
On May 31st. We were very pleased to announce the FDA approval of M, Next bike, or next Generation. Coid vaccine, that has shown even higher efficacy than our powering Spike back vaccine.
in mid June, we received FDA approval of MREs via vaccine for high-risk individual aged 18 to 59
As a reminder, we also approved for adult 60 and older in the US and in 38 over countries.
This approval support of broader goal of driving use of our commercial products and driving the company backed into sales growth.
James Mock: On our second priority, advancing our pipeline to drive sales growth, we are very happy to announce positive and strong phase three efficacy data for flu, which we believe will advance both our flu program and our flu plus COVID combination program. Stephen Hoge will discuss these results shortly. Our third priority, executing with financial discipline. The second quarter 2025 marked the fourth consecutive quarter we have reduced combined R&D and SG&A expenses by double digits year over year. Additionally, in the second quarter, we expanded our cost reduction plan well beyond what we announced in the first quarter. We estimate that these measures will take an additional $400 million out of 2025 cost structure we previously laid out.
On our second priority.
I've been single pipeline to drive sales growth.
We are very happy to announce positive and strong phase 3, efficacy data for flu, which we believe will advance both our food program and our food plus Co combination program.
Steven will discuss these results shortly.
And our third priority is executing with financial discipline.
The second quarter of 2025 marked the fourth consecutive quarter in which we have reduced combined R&D and SG&A expenses by double digits year-over-year.
In the second quarter, we expanded our cost reduction plan well beyond what we announced in the first quarter.
James Mock: This cost reduction includes a very difficult decision that we announced yesterday to reduce headcount by around 10% to better align Moderna's cost structure and capabilities with current business conditions, while also sustaining investments in our mRNA pipeline. This decision was obviously not made lightly. It impacts people who have dedicated themselves to our mission, teammates and friends who have built Moderna. I want to express, on behalf of the entire executive committee, our deepest thanks to all of those affected for what they have contributed to the company. These colleagues will always be part of the Moderna story. Finally, before I hand to James Mock, you may have seen that in the last couple of hours, the U.K. Court of Appeal issued its decision. The court has decided to uphold the High Court's finding that Moderna's EP949 patent is valid and infringed by Pfizer and BioNTech.
We estimate that. These measures will take an additional 400 million dollar out of 2025 cost structure with previously laid out.
This cost reduction includes the very difficult decision that we announced yesterday to reduce headcount by around 10% to better align our cost structure and capabilities with current business conditions, while also sustaining investments in our mRNA pipeline.
these decision was obviously not made Legacy.
It impacts people who have dedicated themselves to our mission, teammates and friends who are billed Moana.
I want to express on behalf of the entire executive committee or deepest. Thanks to all of those affected for what they have contributed to the company.
His colleagues will always be part of the moderna story.
Finally, before I to J me, you may have seen that in the last couple of hours, the UK court of appeal, issued its decision.
The court has decided to uphold the High Court's finding that the modernized EP 949 patent is valid.
James Mock: Moderna will continue to pursue and enforce its patent rights globally to protect its innovative mRNA technology. James?
And infringed by FAA Environment Tech.
what I will continue to pursue and enforce its pattern rights globally to
Stephen Hoge: Thanks, Stephane, and hello, everyone. Today, I will cover our second quarter financial results, our updated 2025 full-year outlook, and share our strategy to achieve our 2027 operating cost targets. Let us begin with our second quarter financial results on slide seven. Net product sales were $114 million, primarily driven by COVID vaccine sales. The U.S. accounted for approximately 80% of sales this quarter, with the remainder from international markets. While product sales declined 38% compared to the second quarter of 2024, sales were slightly above our expectations due to a stronger than expected U.S. spring booster season. We also recorded $28 million in other revenue, bringing total revenue to the quarter to $142 million. The year-over-year decline in other revenue was primarily driven by a $30 million upfront licensing payment that was recognized in the second quarter of last year.
protect its innovative amount of Technology, Jamie
Thanks Satan, and hello everyone. Today I'll cover our second quarter Financial results. Our updated 2025 full year outlook and share our strategy to achieve our 2027 operating cost targets.
Let's begin with our second quarter Financial results and slide 7.
That product sales were 114 million primarily driven by Co vaccine sales.
80% of sales this quarter, with the remainder from international markets.
While product sales declined by 38% compared to the second quarter of 2024.
Sales were slightly above our expectations due to a stronger-than-expected U.S. Spring booster season.
We also recorded $28 million in other revenue, bringing total revenue for the quarter to $142 million.
The year-over-year decline in other revenue was primarily driven by a $30 million upfront licensing payment that was recognized in the second quarter of last year.
Stephen Hoge: Cost of sales for the quarter was $119 million, which was relatively flat compared to $115 million last year. It represented 105% of net product sales this quarter, up from 62% in the prior year, driven primarily by lower volume. R&D expenses were $700 million in the second quarter, down 43% from last year. The decline was primarily driven by the wind-down of our respiratory trials and lower clinical manufacturing costs. We also had year-over-year reductions in preclinical and external service costs, reflecting ongoing portfolio prioritization and productivity efforts. Last year's results also included an expense for a priority review voucher. SG&A expenses were $230 million for the quarter, down 14% year over year. The decrease reflects broad-based cost reductions across external services, personnel, and commercial activities as we continue to streamline operations and manage expenses with discipline.
Cost of sales for the quarter was $119 million, which was relatively flat compared to $115 million last year.
It represented 105% of net product sales this quarter, up from 62% in the prior year, driven primarily by lower volume.
R&D expenses were 700 million in the second quarter down, 43% from last year.
The decline was primarily driven by the wind down of our respiratory trials and lower clinical manufacturing costs.
We also had year-over-year reductions in pre-clinical and external service costs reflecting ongoing portfolio prioritization and productivity efforts.
Last year's results also included an expense for a priority review. Voucher
Sgna expenses were 230 million for the quarter down 14% year-over-year.
Decrease reflects broad-based cost, reductions across external Services personnel, and Commercial activities, as we continue to streamline operations and manage expenses with discipline.
Stephen Hoge: Our income tax provision for the quarter was immaterial, consistent with the prior year. We continue to maintain a global valuation allowance against the majority of our deferred tax assets, which limits our ability to recognize tax benefits for the quarter. Net loss for the quarter was $825 million, a $454 million improvement compared to a $1.3 billion loss in the second quarter of 2024. Loss per share was $2.13, an improvement from a loss of $3.33 in 2024. We ended Q2 with cash and investments of $7.5 billion, down from $8.4 billion at the end of Q1. The decrease was primarily driven by the operating loss for the quarter. Moving to slide eight, I will share our updated 2025 financial framework. For total revenue, we are updating our 2025 projected revenue range to $1.5 to $2.2 billion, reflecting a $300 million reduction at the high end.
Our income tax provision for the quarter was immaterial consistent with the prior year.
We continue to maintain a global valuation allowance against the majority of our deferred tax assets.
Which limits our ability to recognize tax benefits for the quarter.
Net loss for the quarter was $825 million.
A $454 million improvement compared to a $1.3 billion loss in the second quarter of 2024.
Lost per share was $2.13, an improvement from a loss of $3.33 in 2024.
We ended Q2 with cash and Investments of 7.5 billion down from 8.4 billion at the end of q1.
The decrease was primarily driven by the operating loss for the quarter.
Moving to slide 8, I will share our updated 2025 financial framework.
For total revenue, we are updating our 2025 projected revenue range to $1.5 to $2.2 billion.
Stephen Hoge: This change is primarily due to a timing shift of UK COVID shipments from the second half of 2025 into the first quarter of 2026. The timing shift for the UK shipments is due to the government's use of their fiscal year minimum product purchase for the spring campaign in 2026. Our deliveries will now deliver in Q1 2026. This represents the vast majority of the $300 million impact. Importantly, the timing shift does not impact the total value of our long-term multi-year contract with the UK government. Our updated revenue range continues to reflect the uncertainties in vaccination rates, the competitive market environment, the size of the RFP market, and timing of licensure of our factories and product approvals in Australia and Canada. On a geographic basis, we are updating U.S. product sales. We are expecting U.S.
Reflecting a $300 million reduction at the high end.
This change is primarily due to a timing shift of UK Co shipments from the second half of 2025, into the first quarter of 2026.
The timing shift for the UK shipments is due to the government's use of their fiscal year, minimum purchase product purchase.
For the spring campaign in 2026, our deliveries will now occur in Q1 2026.
This represents the vast majority of the 300 million dollar impact. Importantly, the timing shift does not impact the total value of our long-term, multi-year contract with the UK government.
Our updated revenue range continues to reflect the uncertainties in vaccination rates, the competitive market environment, the size of the RC market, and the timing of licensure of our factories and product approvals in Australia and Canada.
Stephen Hoge: product sales of $1.0 to $1.5 billion, international product sales of $0.4 to $0.6 billion, and other revenues of approximately $100 million, where the majority is international. For U.S. product sales of $1.0 to $1.5 billion, the high end of the range assumes flat year-over-year performance after adjusting for last year's $200 million prior period return reserve reversal. The low end of the range factors the potential combined impacts from lower vaccination rates and competitive market pressures. For international product sales of $0.4 to $0.6 billion, the low end of the range is mainly from secured contracts, while the high end factors in incremental revenue from active tenders. The range now also reflects the shift in shipments for the UK from the second half of 2025 to the first quarter of 2026.
On a geographic basis, we are updating the U.S. product sales. We are expecting U.S. product sales of $1.0 to $1.5 billion, international product sales of $0.4 to $0.6 billion, and other revenues of approximately $100 million, where the majority is international.
For U.S. product sales of $1.0 to $1.5 billion, the high end of the range assumes flat year-over-year performance after adjusting for last year's $200 million prior period return reserve reversal.
The low end of the range factors in the potential combined impacts from lower vaccination rates and competitive market pressures.
For international product, sales of 0.4, to 0.6 billion, the low end of the range is mainly from secured contracts.
while the high-end factors in incremental revenue from active tenders,
The range now also reflects the shift in shipments for the UK from the second half of 2025 to the first quarter of 2026.
Stephen Hoge: For other revenues of $100 million, we have already recognized $50 million in the first half of the year and expect a similar amount in the second half. The majority of the revenue is associated with our new manufacturing sites, but also includes some grant collaboration, licensing, and royalty revenue. The split of our Q3 and Q4 revenue mix will be dependent on timing of regulatory approvals across the world and the number of days available to ship in the third quarter. We expect a revenue split of 40% to 50% in Q3, with the balance in Q4. Our cost of sales estimate of $1.2 billion remains unchanged and reflects year-over-year improvements in manufacturing efficiency, offset by increased costs associated with the go-live of our new international manufacturing sites. Newly introduced tariffs are not expected to have a material impact on our cost of sales.
For other revenues of $100 million, we've already recognized $50 million in the first half of the year and expect a similar amount in the second half.
Revenue is associated with our new manufacturing sites but also includes some grant collaboration licensing and royalty revenue.
The split of our 3Q and 4q revenue mix will be dependent on timing of regulatory approvals across the world.
And the number of days available to ship in the third quarter.
We expect a revenue split of 40 to 50% in Q3 with the balance in Q4.
Our cost of sales estimate of 1.2 billion remains unchanged and reflects year-over-year Improvement in manufacturing efficiency.
Offset by increased costs associated with the go-live of our new international manufacturing sites.
Stephen Hoge: We continue to monitor changes to global tariffs. We are lowering our R&D expense forecast from $4.1 billion to a range of $3.6 billion to $3.8 billion due to Phase 3 trial wind-downs, continued portfolio prioritization, and productivity. Our revised R&D guidance projects an increase in the second half versus the first half, driven by the seasonality of vaccine spend, as well as studies in support of regulatory approvals. SG&A expenses are still expected to be $1.1 billion. Similar to last year, we expect higher SG&A expenses in the second half of the year, primarily due to commercial-related activity, but also due to severance charges associated with the workforce reduction we announced yesterday. We expect taxes to be negligible in 2025. Our capital expenditures projection has been lowered from $400 million down to $300 million due to our continued prioritization and efficiency gains.
Newly introduced tariffs are not expected to have a material impact on our cost of sales.
We continue to monitor changes to Global tariffs.
We are lowering our R&D expense forecasts from $4.1 billion to a range of $3.6 to $3.8 billion due to Phase 3 trial wind-downs, continued portfolio prioritization, and productivity.
Our revised R&D guidance projects an increase in the second half versus the first half, driven by the seasonality of vaccine spend, as well as studies and support of regulatory approvals.
SG&A expenses are still expected to be $1.1 billion, similar to last year. However, we expect higher SG&A expenses in the second half of the year.
Primarily due to commercial-related activity, but also due to severance charges associated with the workforce reduction we announced yesterday.
We expect taxes to be negligible in 2025.
Our capital expenditure is projection, has been lowered from 400 million down to million dollars due to our continued prioritization and efficiency gains.
Stephen Hoge: We still expect to end 2025 with approximately $6 billion in cash and investments. Moving to slide nine, as discussed on last quarter's call, we are planning a total reduction in annual GAAP operating expenses of over $6 billion from $11 billion in 2023 to $5 billion or less in 2027. On a cash cost basis, which excludes stock-based compensation, depreciation, and amortization, we are decreasing annual operating expenses from $8.9 billion in 2023 to our midpoint target of $4.2 billion in 2027, which is a reduction of over 50%. Our revised 2025 GAAP operating expense range is now $5.9 billion to $6.1 billion, a $400 million reduction at the midpoint from our previous guidance of $6.4 billion. This updated guidance puts us on track to achieve the first $5 billion of our overall $6 billion reduction in annual GAAP expenses in two years.
We still expect, in 2025, to have approximately $6 billion in cash and investments.
Moving to slide 9, as discussed on last quarter's call, we are planning a total reduction in annual GAAP operating expenses of over $6 billion.
from 11 billion in 2023 to 5 billion dollars or less in 2027,
On a cash cost basis which excludes stock-based, compensation depreciation and amortization.
We are decreasing annual operating expenses from 8.9 billion dollars in 2023.
To our midpoint target of $4.2 billion in 2027.
Which is a reduction of over 50%.
A revised 2025 gap. Operating expense range is now $5.9 to $6.1 billion.
A hundred million dollar reduction at the midpoint from our previous guidance of 6.4 billion.
This updated guidance puts us on track to achieve the first $5 billion of our overall $6 billion reduction in annual Gap expenses in 2 years.
Stephen Hoge: Our updated 2025 guidance includes $0.9 billion in non-cash expenses from stock-based compensation, depreciation, and amortization. Excluding those non-cash items, we now project a 2025 cash cost of approximately $5.1 billion at the midpoint of the range, a $400 million reduction from our previous cash cost estimate of $5.5 billion. The strong progress in cost reductions to date has been a company-wide effort. While we continue to drive additional cost reductions in all areas, the largest source of future reductions will come from R&D, which represents over 60% of our cost base. On the next slide, I want to share our strategy to achieve our 2027 operating expense targets in more detail. On slide 10, you can see our GAAP and cash cost targets for 2025 versus 2027.
Our updated 2025 guidance. Includes 0.9 billion non-cash expenses from stock based compensation depreciation and amortization.
Excluding those non-cash items, we now project a 2025 cash cost of approximately $5.1 billion.
At the midpoint of the range.
A hundred million dollar reduction from our previous cash cost estimate of $5.5 billion.
The strong progress in cost reductions to date has been a companywide effort.
While we continue to drive additional cost reductions in all areas, the largest source of future, reductions will come from R&D, which represents over 60% of our cost base.
On the next slide, I want to share our strategy to achieve our 2027 operating expense targets in more detail.
On slide 10, you can see our gap in cash, cost targets for 2025 versus 2027.
Stephen Hoge: At the midpoint of our ranges, we are targeting a $1.1 billion GAAP cost reduction from $6 billion in 2025 to $4.9 billion in 2027, and a $900 million cash cost reduction from $5.1 billion in 2025 to $4.2 billion in 2027. There are four primary drivers to achieve this goal, which are all relatively evenly split in impact. First, a reduction in R&D expenses from the completion of our large phase three trials. We are already seeing the impact of the completion of most of our respiratory trials in 2025, and we will start to see future cost savings by 2027 from the completion of our phase three trials for CMV and norovirus. This includes both direct trial costs, as well as reductions in clinical manufacturing and other related overhead. These cost reductions will be partially offset by select investments in the pipeline, such as our oncology portfolio.
At the midpoint of our ranges, we are targeting a 1.1 billion. Gap cost reduction from 6 billion dollars in 255 to 4.9 billion in 27.
And a 900 million cash cost reduction from 5.1 billion in 25 to 4.2 billion dollars in 27.
There are four primary drivers to achieve this goal, which are all relatively evenly split and impact.
First, a reduction in R&D expenses from the completion of our large phase 3 trials.
We are already seeing the impact of the completion of most of our respiratory trials in 2025.
And we'll start to see future cost savings by 2027.
From the completion of our Phase 3 trials for CMD and the neural virus.
This includes both direct trial costs as well as reductions in clinical manufacturing and other related overhead.
Ology portfolio.
Stephen Hoge: Second, we will continue to drive manufacturing efficiencies, which will impact both cost of sales and R&D. We have already made strong progress over the past few years to optimize our manufacturing footprint from endemic level demand of our COVID vaccine. We expect to drive additional savings through process improvements, as well as reductions in future inventory write-downs. For example, in 2024, we had a half a billion dollars of inventory write-downs, which we are actively driving to reduce in 2025 and beyond. Third, we continue to drive procurement savings. Some of the savings from the renegotiated contracts already taken place will not be fully realized until 2026. Additionally, we have a strong pipeline of new savings initiatives.
Second, we will continue to drive manufacturing efficiencies, which will impact both cost of sales and R&D.
we've already made strong progress over the past few years, to optimize our manufacturing footprint from endemic level demand of our Co vaccine
We expect to drive additional savings through process improvements, as well as reductions in future inventory," wrote Downs.
For example, in 2024, we had a half a billion dollars of inventory. Write Downs, which we are actively driving to reduce in 2025 and Beyond.
Third, we continue to drive procurement savings.
Some of the savings from the renegotiated contracts that have already taken place will not be fully realized until 2026.
Stephen Hoge: Fourth, we announced the workforce restructuring yesterday that impacts approximately 10% of our employees and will lower our employee base to under 5,000 by the end of the year, versus 5,800 at the beginning of the year. Headcount reductions are always difficult decisions as they impact valued colleagues who have contributed meaningfully to our mission. However, these actions are necessary to reshape our capabilities and align to our long-term operating cost structure. In summary, in just two years, the team has made tremendous progress towards our four-year, roughly $5 billion cash cost reduction plan. By the end of 2025, we have taken nearly $4 billion of cost out of the business and have an achievable plan to remove another $1 billion over the next two years. We remain committed to breaking even on a cash cost basis in 2028 and will adjust spending as necessary.
Additionally, we have a strong pipeline of new savings initiatives forth.
We announced the workforce for structuring yesterday that impacts approximately 10% of our employees and will lower our employee base to under 5,000, by the end of the year versus 5,800 at the beginning of the year.
Headcount, reductions are always difficult decisions as they impact value colleagues with contributed meaningfully to our mission.
However, these actions are necessary to reshape our capabilities and aligned to our long-term operating cost structure.
In summary in Just 2 years. The team has made tremendous progress towards our 4-year roughly 5 billion, cash cost reduction plan.
By the end of 2025, we have taken nearly $4 billion of cost out of the business and have a plan to remove another $1 billion over the next 2 years.
Stephen Hoge: With that, I will now turn the call over to Stephen Hoge.
We remain committed to breaking even on a cash cost basis in 2022 and will adjust spending as necessary.
With that, I will now turn the call over to Stephen.
Lavina Talukdar: Thank you, James Mock, and good morning or good afternoon, everyone. Today, I'll review progress across our pipeline. Slide 12 is a review of our prioritized pipeline. As Stephane Bancel stated earlier, we have announced significant updates for many of these programs, including the recent approval for mNEXT Spike, an expanded label for mResVera, and approval of our pediatric Spikevax COVID vaccine, which was previously available in the United States under an emergency use authorization. In the quarter, we also reported strong vaccine efficacy results from our phase 3 seasonal flu trial, and we continue to make progress in the rest of the prioritized portfolio, where we are targeting a total of eight additional potential filings through 2028. Moving to slide 13, which outlines the latest developments of our late-stage respiratory portfolio, I'll start with our COVID vaccines, Spikevax, and mNEXT Spike.
Thank you, Jamie, and good morning or good afternoon, everyone.
Today, I'll review progress across our pipeline.
Slide 12 is a review of our prioritized pipeline as Stefan stated earlier. We have announced significant updates for many of these programs, including the recent approval for M. Next Spike and expanded label for Mia and approval of our pediatric. Spikevax Co vaccine
which was previously available in the United States under an emergency use authorization.
In the quarter. We also reported strong vaccine, efficacy results from our phase 3 seasonal. Flu trial.
And we continue to make progress in the rest of the prioritized portfolio, where we are targeting a total of 8 additional potential filings through 2028.
Moving to slide 13, which outlines the latest developments of our late stage respiratory portfolio.
Lavina Talukdar: As mentioned earlier, we are very pleased with the FDA's approval of mNEXT Spike, our next-generation COVID vaccine, which has shown strong relative vaccine efficacy compared to Spikevax in its phase 3 trial, including in the 65 and older age subgroup and in those with risk factors for severe COVID-19. mNEXT Spike was approved in the U.S. for individuals 65 and older and for people 12 to 64 with at least one risk factor. An extensive analysis of the phase 3 clinical data for mNEXT Spike was published last month in The Lancet, and the link to the publication can be found on this slide. We submitted the annual updates for our COVID-19 vaccines for the currently recommended LP.8.1 strain in the quarter and expect mNEXT Spike and Spikevax will be available this fall in the United States.
I'll start with our Co vaccines Spike facts, and the next Spike.
As mentioned earlier, we are very pleased with the fda's approval of them next Spike. Our next Generation Co vaccine, which is shown strong relative vaccine efficacy compared to spike vaccine in its phase 3 trial, including in the 65 and older age subgroup. And in those with risk factors for severe Co 19,
And next Spike was approved in the US for individuals, 65 and older. And for people 12 to 64 with at least 1 risk factor.
An extensive analysis of the phase 3 clinical data form. Next Spike was published last month in the Lancet and the link to the publication can be found on this slide.
Lavina Talukdar: Speaking of Spikevax, the vaccine was recently approved by the FDA for high-risk children ages 6 months to 11 years. Spikevax had previously been available to this age group in the U.S. only under an emergency use authorization. Earlier this week, Spikevax also received EMA approval for the current season update LP.8.1 strain update for the coming season. For RSV, our mResVera vaccine was approved by the FDA on June 12 for individuals ages 18 to 59 with at least one risk factor. The CDC subsequently adopted the ACIP recommendation for the 50 to 59-year-old age cohort in this group, which means that recommendations for our vaccine are now consistent with competitors. For our seasonal flu vaccine, we announced positive results from our phase 3 efficacy study. We are very pleased with the results, which I'll talk through on the next slide.
We submitted the annual updates for our COVID-19 vaccines for the currently recommended lineage P.1 strain in the quarter and expect them. Next Spike and Spikevax will be available this fall in the United States.
speaking of spikevax, the vaccine was recently approved by the FDA for high-risk children ages 6 months to 11 years,
Spikes Ex had previously been available to this age group in the U.S. only under an Emergency Use Authorization.
Probably there, this week. Spike facts. Also received EMA approval for the current season of date lp8, 1.1, uh, strain update for the coming season,
For our speed, our M rezbi of vaccine was approved by the FDA on June 12th for individuals, a ages 18 to 59 with at least 1 risk factor.
The CDC, subsequently adopted, the acip recommendation for the 50 to 59 year old age cohort in this group, which means that recommendations for our vaccine are now consistent with competitors.
Lavina Talukdar: We expect these flu results will also support our discussions with regulators about our flu plus COVID combination vaccine, and we have begun consultations with regulators on the submission requirements for both vaccines. On slide 14, I will discuss the very encouraging P304 flu vaccine efficacy data released during the quarter. In this 40,000-person study conducted across 11 countries, our seasonal flu vaccine, mRNA 1010, demonstrated relative vaccine efficacy that was 26.6% higher than the licensed standard dose comparator in adults age 50 and above. Safety and tolerability of mRNA 1010 were consistent with previously reported phase three results, and the majority of solicited adverse reactions were mild. Importantly, strong relative vaccine efficacy was observed for all three influenza strains contained in the vaccine, including H1N1, H3N2, and the B.victoria strain. Likewise, the relative vaccine efficacy was consistently strong across age groups, risk factors, and previous vaccination status.
For both vaccines.
On slide 14, I will discuss the very encouraging P304 flu vaccine efficacy data released during the quarter.
In this 40,000 person study conducted across 11 countries, our seasonal, flu vaccine, and more in a 1010. Demonstrated relative relative vaccine efficacy that was 26.6% higher than the licensed standard dose comparator in adults age, 50 and above
Safety. And tolerability of mRNA 101010 work consistent with previously reported phase 3 results, and the majority of solicited, adverse reactions were mild.
Importantly, strong relative vaccine efficacy was observed for all three influenza strains in the vaccine, including H1N1, H3N2, and the B Victoria strain.
Lavina Talukdar: In the important 65 and older demographic, relative vaccine efficacy was a strong 27.4%. We look forward to presenting these data at an upcoming medical conference, and we are preparing to file for FDA approval for this vaccine. Now turning to our non-respiratory vaccine and rare disease portfolios. In our phase three CMV efficacy study for mRNA 1647, we have now accrued sufficient primary endpoint cases for the final analysis. The analysis has not yet been conducted, and the company remains fully blinded at this time. We've submitted an amendment to the analysis plan to add important powered secondary endpoints that we hope will increase the scientific value of the results. Once the updated analysis plan is formalized, we will proceed with the analysis of primary and secondary endpoints, which we expect to complete in the fall. Our phase three norovirus study is now accruing cases in its first season.
Likewise the relative vaccine, efficacy, was consistently strong across age, groups, risk factors and previous vaccination status.
In the important. 65 and older demographic relative vaccine efficacy was a strong 27.4%.
We look forward to presenting these data at an upcoming medical conference, and we are preparing to file for FDA approval for this vaccine.
Now, turning to our non-respiratory vaccine and rare disease portfolios in our phase, 3 CMV efficacy study for mRNA 1647, we have now a crude sufficient primary endpoint cases for the final analysis, the analysis has not yet been conducted and the company remains fully blinded at this time.
We've submitted an amendment to the analysis plan to add important powered secondary endpoints that we hope will increase the scientific value of the results.
Once the updated analysis plan is formed, we will proceed with the analysis of primary and secondary endpoints which we expect to complete in the fall.
Lavina Talukdar: As with other studies, the interim analysis of efficacy is dependent on case accrual, and depending upon the rate of case accrual, the study has been designed so that it may proceed to a second season of enrollment if necessary. In rare diseases, our Propionic Acidemia, or PA, program is currently in a registrational study, and we believe we are on track for a potential 2027 approval. For Methylmalonic Acidemia, or MMA, we plan to initiate the registrational trial this year. We continue to advance our oncology portfolio with significant progress across our individualized neoantigen therapy, known as mRNA 4157, mRNA 4359, previously called Checkpoint, and our early-stage oncology pipeline. In collaboration with Merck, we have several late-stage studies underway for mRNA 4157. As a reminder, the phase 3 trial in adjuvant melanoma is fully enrolled and accruing cases towards its interim analysis.
Our phase 3 normal. Virus study is now our current cases in its first season. As with other studies, the intro analysis of efficacy is dependent on case acral. And depending upon the rate of case acral, the study has been designed so that it may proceed to a second season of enrollment if necessary.
In rare diseases, our propionic acidemia or PA program is currently in a registration study and we believe we are on track for a potential 2027 approval.
For methylmalonic acidemia or MMA, we plan to initiate the registrational trial this year.
We continue to advance our oncology portfolio with significant progress across our individualized neoantigen therapy known as Intisar, mRNA-4359, previously called Checkpoint, and our early-stage oncology pipeline.
In collaboration with Merck, we have several late-stage studies underway for Anticipate.
Lavina Talukdar: Our phase 2 adjuvant renal cell carcinoma trial is fully enrolled as well. As we have disclosed previously, we have two phase 3 studies in non-small cell lung cancer, one phase 2 study in high-risk muscle invasive bladder cancer, and one phase 2 study in high-risk non-muscle invasive bladder cancer. We have also expanded our mRNA 4157 program into a phase 2 study in first-line metastatic melanoma. This could be the first of many studies using mRNA 4157 and Keytruda together in metastatic indications. Following on from mRNA 4157, mRNA 4359 is now in a phase 2 study in first-line metastatic melanoma and first-line metastatic non-small cell lung cancer, and we are currently enrolling patients in the lung cancer portion of that study.
As a reminder, the Phase 3 trial in adjuvant melanoma is fully enrolled and a crew in cases toward its interim analysis.
Our Phase 2 agent renal cell carcinoma trial is fully enrolled as well.
And as we have disclosed previously, we have two Phase 3 studies in non-small cell lung cancer, one Phase 2 study in high-risk muscle invasive bladder cancer, and one Phase 2 study in high-risk non-muscle invasive bladder cancer.
We have also expanded our Intisar program into a Phase 2 study in the first-line metastatic melanoma.
This could be the first of many studies using Anticipar and Key treated together in metastatic indications.
Lavina Talukdar: We are pleased that the data from the phase 1B study of mRNA 4359 plus Keytruda in checkpoint inhibitor refractory PD-L1 positive patients was accepted as a mini oral presentation at ESMO. We look forward to presenting these findings at the meeting in October. In early-stage oncology, we are also dosing patients in our phase 1 tumor-targeted antigen therapy, mRNA 4106, and the INDs for our cell therapy enhancing antigen therapy, mRNA 4203, and our T-cell engager, mRNA 2808, are also now both open. We are pleased by our growing oncology pipeline and the continued strong momentum of the large mRNA 4157 clinical trial program in partnership with Merck. With that, I will hand over to Stephane.
Following on from, in mRNA 4359 is now in a phase 2. Study in first-line, metastatic melanoma and first-line, metastatic, non small cell, lung cancer, and we are currently enrolling in patients in the lung cancer. Portion of that study.
We are pleased that the data from the Phase 1B study of MRA-4359 plus Keytruda in checkpoint inhibitor-refractory, PD-L1 positive patients was accepted as a mini oral presentation at ESMO. We look forward to presenting these findings at the meeting in October.
In early-stage oncology, we are also dosing patients in our Phase 1, tumor-targeted, antigen therapy mRNA-41106.
And the end for our cell therapy, enhancing engine therapy, and more in a 4223, and our T-cell engager. And we're in a 2888 as well. Now, both open.
We are pleased by our growing oncology Pipeline and the continued strong momentum of the large and tisman clinical trial programs in partnership with Mark.
James Mock: Thank you, Stephen and Jamie. As you know, we have three priorities. Priority one drives sales of approved products. Priority two focuses on a late-stage pipeline where we can drive product growth for approvals, and priority three delivering on our cost efficiency across the company. Our first priority is to drive the use of mNEXT Spike, Spikevax, and mResVera vaccines. We entered the third quarter of 2025 with pre-approved products in the U.S., and we are seeing a growing number of approvals in countries worldwide. For priority two, we are focused on delivering up to 10 products approval, which we believe will drive sales growth for the company. Together, these 10 anticipated products target an addressable market that is over $30 billion. In Q2, we secured U.S. approvals for mNEXT Spike and mResVera for high-risk people, and we are exciting data in flu, enabling flu and flu-COVID combo.
With that, I'll hand over to Stefan. Thank you, Stephen and Jamie.
As you know, we are free priorities 41 Drive sales of approved, products, priority 2, focus on the last stage pipeline, but we can drive for the growth for provis.
Across the company.
Our first priority is to drive the use of mRNA vaccines, Spikevax, and mRNA-based therapeutics.
We enter the third quarter of 2025 with free approved products in the US.
And we are seeing a growing number of approvals in countries worldwide.
For Pro 2, we are focused on delivering up to 10 product approvals, which we believe will drive sales growth for the company.
Together, these 10 anticipated products target an addressable market that is over $30 billion.
In Q2, we secured U.S. approvals for the MX bike and Razia for Highway People.
James Mock: On the cost side of the house, we have demonstrated our commitment to cost discipline through the reduction achieved last year in 2024 and also in 2025 to date. We remain confident in our ability to further streamline our operation structure for the remaining of 2025 to 2027. Jamie just took you through our plans to cut an additional $400 million of our 2025 cost structure, and we are not done. We have many new projects in the works to reduce costs further. These cost reduction activities we have in place give us even greater confidence in our plan to reduce our cash costs to $4.2 billion in 2027. These actions are very important to help us achieve our cash per cubit target in 2028. As we make these cost improvements, we are seeing continued use of AI across Moderna.
I wish to discuss exciting data related to flu and enabling flu through the CoV combo.
On the cost side of the house. We've demonstrated our commitment to cause this period for reduction achieved and last year in 2024, and also in 2025 today.
We remain confident in our ability to further streamline. Our operation structure for the remaining of 25 to 2027.
Can we just took you through our plans to cut an additional 400 million dollar over 2025 cost structure?
And we are not done.
We have many new projects in the works to further reduce costs.
This cost reduction activities, we have in place.
If there's even greater confidence in our plan, to reduce our cash cost to $4.2 billion in 2027,
These actions are very important to help us achieve our cash break-even targets in 2028.
James Mock: We rolled out GPT Enterprise in 2024 and established widespread GPT literacy across the entire organization. Today, 100% of our knowledge workers are active daily users of ChatGPT. As you can see on slide 22, GPT use has grown very fast at the company, and in 2025, we enhance our AI tools to allow for deep research capabilities, allowing for the creation of comprehensive reports without compromised quality of output. An example of a deep research application is the creation of target product profiles. This AI-based activity greatly reduces the amount of time it takes our product planners to create marketing strategies. We're excited about how AI has already improved our business, and given the doubling of AI capabilities every six to seven months, we're working hard to continue to reinvent our company across each business process, department, and team.
As we make this cost improvements, we are seeing continued use of AI across moderna. We rolled out GPT Enterprise in 2024 and established. Widespread GPT literacy across the entire organization.
Today, 100% of knowledge workers are active, daily users of charges.
As you can see on site 22, GPT users have grown very fast at the company.
And it's 25. We enhance our AI tools to allow for deep research capabilities, allowing for the creation of comprehensive reports without compromising the quality of output.
An example of a deep research application is the creation of target product profiles.
This AI based activity, greatly reduces the amount of time it takes on product planners to create marketing strategies.
We're excited about how AI has already improved our business.
And given the doubling of AI capabilities every 6 to 7 months, we are working hard to continue to reinvent our company across each business process, department, and team.
James Mock: We're excited about the coming months and quarters as we have a lot of important catalysts. First, of course, the potential approvals of seasonal flu and the flu plus COVID combo programs based on the data Stephen Hoge shared with you. We're also eager to get the CMV phase 3 efficacy data later this year. Norovirus phase 3 readout is, of course, subject to case accruals. In oncology, we look forward to the readout of our ongoing intismarin phase 2 five-year durability data in adjuvant melanoma. Of course, we look forward to a phase 3 adjuvant melanoma trial readout for intismarin. As Stephen Hoge said, in oncology, we're looking forward to sharing the Checkpoint phase 1B data at ESMO in Berlin in October. As a later date, we look forward to sharing the phase 2 data of this program.
We're excited about the coming months and quarters, as we have a lot of important catalysts.
First.
Of course, the potential approvals of seasonal fruit and the Fruit Plus Co combo programs based on the data Stephen shared with you.
We're so eager to get the CMV phase 3 efficacy data later this year.
No, overall space. Free result is of course subject to case across
In oncology we look forward to the result of our ongoing in this era, Phase 2, 5 year durability data in advance melanoma.
And of course, we look forward to a phase 3 add event trial without for in
Said in arcology, we are looking forward to sharing the checkpoints Phase 1. Bit data, there's more in Berlin in October.
James Mock: PA is already in registration study, and MMA will be very soon. I'm pleased with the progress we have made on all three of our priorities over the course of the first six months of the year. We now have three products approved by the U.S. FDA. We are highly encouraged by the progress in the pipeline and very pleased by flu. On financial discipline, we have accelerated our plan for cost efficiency and expect to deliver an additional $400 million of cost savings this year. I want to thank the team for all the great work that was done this quarter. We are very focused on executing those priorities going forward. This work allows us to be focused on our mission to deliver the greatest possible impact to people for mRNA medicine. With this operator, we'll be happy to take questions.
And as a later date, we look forward to sharing the phase 2 Data of this program.
P is already in restration, studying and MMA will be very soon.
I'm pleased with the progress. We have made on all 3 of our priorities over the course of the first 6 months of the year.
We now have free products approved by the US FDA.
We are highly incorrect about the progress in the pipeline and very pleased by Fuel.
And on financial discipline, we have accelerated our plan for cost efficiency and expect to deliver an additional $400 million of cost savings this year.
I want to thank the team for all the great work that was done this quarter.
We are very focused on executing those priorities, going forward.
This work allows us to focus on our mission to deliver the greatest possible impact to people for a Mana medicine. This operator will be happy to take questions.
Lavina Talukdar: Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press star one one on your telephone. If your question has been answered or you wish to remove yourself from the queue, please press star one one again. We will pause for a moment while we compile our Q&A roster. Our first question comes from Salveen Richter with Goldman Sachs. Your line is open.
Thank you, ladies and gentlemen, if you have a question or a comment at this time, please press star, 1, 1 1 on your telephone. If your question has been answered or you wish to move yourself from the queue, please press star 1 on again. We'll pause for a moment while we compile, our Q&A roster.
Our first question comes from Salvian Richer with Government's Actual Line. The line is open.
Q1: Good morning. Thanks for taking my question. I was wondering if you could put the changes to CMV in context for us and just help us understand the rationale behind the addition of these secondary endpoints. Secondly, as we look to the individualized neoantigen therapy, and I know we are going to see some data at ESMO, could you help us understand the cadence of data reads over maybe the next 12 months or so as we look to some of the other programs to mature? Thank you.
Lie. As we look to the individualized neurons and therapy and I I know we're going to see some data at esmo. Could you help us understand the Cadence of data reads, um, over maybe the next 12 months or so, as we look to some of the other programs to mature, thank you.
Stephen Hoge: Thank you, Salveen. First, on CMV secondary endpoints, we are pleased to now have sufficient primary endpoint cases, which, as you know, were based on primary prevention of infection on an immune adjudicity endpoint, so antibodies against antigens, not in the vaccine. There is a lot of other data that will help inform the potential value of a CMV vaccine, including looking at things like the presence of virus in bottling fluids and/or other markers or measures of infection that could be quite relevant for the use of the CMV vaccine across a wider range of populations, including even in the congenital CMV space.
Stephen Hoge: Given that this is now the final analysis, and as we have accrued a large number of cases and a lot of data, including against some of those secondary potential endpoints, we wanted to make sure that we reflected those in the final analysis plan as we hope that we will see a positive primary endpoint and also get the benefit of some of those secondary powered endpoints in the totality of data that we come out of the study. I will just remind you again that the best approach for doing this is while we are completely blinded. The company does not know the results on the primary or any of the secondary.
Thank you, sine. Um, so first on CMV secondary endpoints. Um, obviously, we're, we're pleased to know have, uh, sufficient primary endpoint cases, uh, which as, you know, we're based on primary prevention infection on, um, in immunogenicity employees. So antibodies against antigens not in the vaccine, but there's a lot of other data that will help inform the potential value of a CMV vaccine. Um, including looking at things like the presence of virus in bottling fluids um and or other markers or measures of infection. Um, that could be quite relevant for the use of the CMV vaccine across a wider range of populations. Including even in the congenital CMV space.
Um, given that this is now the final analysis. Um, and as we've accrued a large number of cases and a lot of data, including against some of those secondary potential end points, we wanted to make sure that we reflected those in the final analysis plan, as we hope, uh, that we will see a positive primary endpoint and also get the benefit of some of the secondary powered endpoints in the totality of data that we come out of the study. Um, I'll just remind you again that the best approach for doing this is while we are completely
Stephen Hoge: We are just making sure to protect the integrity of the study, that we update the statistical analysis plan and receive approvals for it prior to initiating that analysis with an unblinded team, at which point we would then become unblinded to the results after the DSMB. This is just making sure we are protecting the integrity of the study, and we think it is a prudent decision to take a little bit of time here to update all those documents prior to conducting the analysis. We really look forward to that result in the fall. As it relates to the cadence of results on intismarin, we are fully enrolled in the Phase 3, as we noted, for the confirmatory study in melanoma. We are accruing events.
So, the company does not know, the results on the primary or any of the secondary. Um, we are just making sure to protect the Integrity of the study that we update the statistical analysis plan and receive approvals for it. Prior to initiating that analysis with an unblinded team, at which point, we would then become blind of the results after the dsmb. And so this is just making sure we're protecting the Integrity of the study. Uh, and we think it's a prudent decision to take a little bit of time here to to update all those documents prior to conducting the analysis really look forward to that result in the fall.
Stephen Hoge: We continue to hope that we will be able to have a successful interim analysis for efficacy on that study on the timelines we previously mentioned. We have a number of other studies that are randomized. Actually, all of the Phase 3 and Phase 2 studies are randomized controlled studies, and several of those could read out similarly in the near term, including the studies in bladder cancer, and particularly those that are largely enrolled, as well as renal cell carcinoma. Those are event-driven. As is always the case for event-driven studies, it is hard for us to predict exactly when we will have sufficient data to conduct those interim analyses.
Um, as it relates to the Cadence of results on in um, you know, we're fully enrolled in the phase 3 as you as we noted uh for the confirmatory study in melanoma. Um, we are a crewing events, uh we continue to hope that um uh that we will be able to have a a successful in room analysis for efficacy on that study uh, on the timelines. We previously mentioned um we have a number of other update. Um, another of other um studies that are randomized, actually all of the phase 3 and Phase 2 studies are randomized. Controlled studies. Um, and several of those could read out similarly, in the, in the near term, um, including um, you know, the studies in bladder cancer. Um, and particularly, uh, those that are largely enrolled as well as renal cell carcinoma. So, uh, those are event driven. And so, as is always the case for events and studies, it's hard for us to predict exactly when we'll have sufficient data.
Stephen Hoge: I do believe that in the coming year or two, there will be a consistent cadence of results from these randomized studies that will come out, hopefully first with a successful phase 3 adjuvant melanoma study, but really soon thereafter with some of these phase 2s and then moving into the lung cancer space.
Data to conduct those interim analyses. But I do believe that in the coming year or 2, there will be a consistent Cadence of results from these randomized. Studies that will uh come out. Hopefully first with us successful phase 3 edge of a melanoma study but really soon thereafter with some of these phase 2s. And then moving into a lung cancer space
Lavina Talukdar: Thank you. One moment for our next question. Our next question comes from Elaine de Mereaux with UBS. Your line is open.
Nike 1 moment for our next question.
Our next question comes from Elena with UBS. Your line is open.
Q2: Hey, guys. Thanks for taking the question. Can you discuss how we should think about pricing for the COVID vaccine in the U.S. this year and what your expectations are for net price, or I guess how pricing this year would compare versus last year, and any takeaways from your contracting discussion so far? Thanks.
For taking the question.
Thanks for the co vaccine in the US this year and what your expectations are for net price, or I guess how pricing this year would compare versus last year and any takeaways from your Contracting discussion so far, thanks.
Stephen Hoge: Sure. Thanks, Ellie. So, you know, what I'd say is in the U.S., we've given a range of $1 to $1.5 billion. As I mentioned in my prepared remarks, we put in variability for competitive pressures, which gets into contracting and pricing, to your point, to the heart of your question, as well as vaccination rates. First on vaccination rates, if you look at the first half, as I mentioned, when we look at the spring booster, it was down roughly 10% or 11%. That makes us feel good. It's a smaller sample size, but as we go into the second half, it's the only barometer we have heading into the second half. As it pertains to pricing and contracting, contracting is basically complete now. We will look to the second half, and pricing is also complete in there. We're also looking at mNEXT Spike in there as well.
Sure. Thanks Ellie. Uh, uh yeah. So you know what I'd say is in the US, we've given a range of 1 to 1.5 billion dollars and as I mentioned, in my prepared remarks, we put in uh variability for competitive pressures, which gets into Contracting and pricing to your point uh to order your question as well as vaccination rates.
Yeah, first time vaccination rate to be, look at the first half as I mentioned when we look at the spring booster it was down roughly 10 or 11% so that makes us feel good. It's a smaller sample size but as we go into the second half it's the only barometer we have heading into the second half.
Stephen Hoge: I would say just right now, all those factors are within the range, and we have confidence within that range. I don't really want to be specific on pricing or our share at this point, but it's factored into our range, and we feel confident in it.
As it pertains to pricing and Contracting. Contracting is basically complete now. Uh, so we will look to the second half and pricing is also complete in there. We're also looking at uh, MX spike in there as well. I would say just right now, all those factors are within the range and we have confidence within that range.
So I don't really want to, you know, be specific on pricing or our share at this point, but it's factored into our range and we feel confident in it.
Q2: Understood. Thanks.
Understood. Thanks.
Lavina Talukdar: One moment for our next question. Our next question comes from Michael Yee with Jeffries. Your line is open.
1 moment for our next question.
Our next question comes from Michael you with Jeffrey, your line is open.
Q3: Hey, guys. Thank you. Appreciate the opportunity for two questions. One is on CMV. I just wanted to follow up for Stephen Hoge and maybe just talk to expectations about what you guys think is a positive readout both on VE, but also what is a good readout on a secondary endpoint that would help payers or patients or clinicians think about the value of CMV given this novel type of vaccine for patients. Then second, obviously, there have been various changes within FDA and CBER and within the ASIP. I just wanted to understand if you think that the dialogue remains very positive and how you expect things going forward. Thank you.
Hey guys. Thank you. Uh,
Appreciate the opportunity for 2 questions. 1 is on CMV. I just wanted to follow up for Stephen and maybe just talk to expectations about what you guys think is a positive readout both on VE. But also, what is a good readout on the secondary endpoint that would help payers or patients or clinicians? Think about the value of CMV, uh, given this novel type of vaccine, uh, for patients and then second, um, obviously there has been various changes within FDA and severe and within the asip, I just wanted to understand if you think, uh, that the dialogue remains very positive and how you expect things going forward.
Stephen Hoge: Great. Thank you, Michael, for both. First, on the CMV results, we powered the study, and as we've said, believe the product will have an impact if the vaccine efficacy against the primary endpoint is better than 49.1%. That was the lower bound acceptability threshold for the primary analysis against prevention of infection. You might say, "Well, 49% or 50%, is that a substantial benefit?" If you think of all of the burden of disease associated with CMV over a lifetime, a 50% reduction in that would be a pretty profound benefit, we believe, on public health and for individuals. There is complexity in terms of the individual indications because prevention of infection is one thing, but there's going to be a need to demonstrate value. Some of that will be demonstrated post-approval with some of the real-world evidence generation studies that always happen around vaccines.
Great. Thank you, Michael for both. Um, so first on the um, CMV, uh, results. Uh, we powered the study and as we've said, um, believe the product will have an impact. Uh, if the vaccine efficacy against the primary endpoint is, you know, better than 49.1%. That was the
Stephen Hoge: We wanted to maximize the value we could get out of secondary endpoints in this study because we have such a rich study of information. Those include looking at things that you might think of as the persistence of virus in the blood or in the urine, the shedding, and whether or not you were able to control that latent infection. I'll remind you that in our EBV vaccine phase one study, which we'd shared previously a year ago, we were able to show quite strong impacts on the rates of virus, the presence of virus, of pollen over time in patients that were EBV positive who'd received our EBV vaccine, a different program, which shows the level of control that we were excited to see in that program.
Lower bound acceptability, um, threshold for the, uh, for the primary analysis against prevention infection. Um, that's because, you know, you might say, well, 49% or 50%, um, is that a substantial benefit? If you think about all of the burden of disease, associated with CMV over a lifetime, a 50% reduction in that would be a pretty profound, uh, benefit. We Believe on public health and for individuals. Um, there is complexity, uh, in terms of the individual indications because prevention of infection is 1 thing, but there's going to be a need to demonstrate value. Um, some of that will be demonstrated post-approval and with some of the, you know, real world evidence generation studies that always happen around vaccines. But we wanted to maximize the value. We could get out of secondary endpoints in this study because we have such a rich study of information, um, and those include looking at things that you might think of, as the Persistence of virus in the blood, or in the urine, um, the the, uh shedding. Um,
and and whether or not um, you were able to control that latent infection
Stephen Hoge: If we saw something similar here in CMV, we think that would speak to the potential benefit about the risk of congenital transmission from, let's say, a pregnant mother who's becoming infected to her unborn child, as well as other potential benefits related to the chronic issues, health issues that can come from CMV. Obviously, for those, we don't have a pre-specified hypothesis in the primary endpoint, but we would love to see efficacy as good or better than what we're seeing in the primary of 49%. So 49% feels good for us. That's where we designed the study, and we are looking forward to it. Obviously, we hope to do better than that, but we will ultimately look to the totality of the data to understand the value of the product and given the burden of CMV in health systems and for individuals.
Mind you that in their EBV vaccine Phase 1 study, which we shared previously, a year ago we were able to show quite strong impacts on the rates of the virus. The presence of the virus over time in patients who were EBV positive and had received our EBV vaccine demonstrated different programs, which shows a level of control that we were excited to see in that program. If we saw something similar here in CMV, we think that would speak to the potential.
Benefit about the risk. The risk of congenital transmission. Uh from let's say a pregnant mother who's becoming infected to her uh to her inborn child as well as other potential benefits related to The Chronic issues, health issues that can come from CMV. Obviously for those, uh, we we don't have a prespecified hypothesis in the primary endpoint but we would love to see efficacy as good or better, uh, than what we're seeing in the primary of 49.
Stephen Hoge: We're quite hopeful that we'll be able to demonstrate that value quite quickly, including out of this Phase 3 study with the new secondary endpoints. As it relates to the CBER changes and some of the ACIP changes, I'll just say that we continue to work closely with our review teams across all of our products. We are very grateful for the three approvals that happened in the last quarter. I will note that they happened on time, and that was through the, obviously, the incredibly diligent work of the folks at FDA to conduct those reviews in a rigorous way. We continue to feel that those productive dialogues are going on now, even on our existing files for the seasonal update.
Stephen Hoge: We will always make sure that we provide prompt and fully transparent answers to the agency and work closely with them so that they can conduct that work, and we're incredibly grateful for that. As well as the CDC and ACIP, where we get questions that they need information on so that they can guide public health, we'll make sure that we provide that information. We look forward to working with both CDC, ACIP, FDA, and CBER to continue to advance our pipeline and our mission.
Percent. So, 49% feels good for us. That's where we designed the study, um, and we are looking forward to it. Obviously, we hope to do better than that. Um, but um, we will ultimately look to the totality of the data to understand the value of the product, and given the burden of CMV in, in, in health systems and for individuals, we're, we're quite hopeful, um, that we'll be able to demonstrate that value quite quickly, including out of the space tree study with the new secondary endpoints, as it relates to the sber, um, changes in some of the acip changes, you know? I'll just say that we continue to work closely with our review teams across all of our products. Uh, we are very grateful, um, for the 3, approximately that happened in the last quarter, I will note that they happened on time, um, and that was through the obviously the incredibly diligent work of, uh, of the folks that FDA, uh, to conduct those reviews in a rigorous way. Um, and we continue to feel that those productive dialogues are going on now. Even upon even on our existing files for the seasonal update. Um,
We will always make sure that we provide prompt and fully transparent answers to the agency and work more closely with them so that they can conduct that work. We’re incredibly grateful for that.
Um, as well as the CDC and acip where we get questions, um, that they need information on so that they can guide Public Health. We'll make sure that we provide that information and we look forward to working with, uh, both CDC, acip and FDA and see where, uh, to continue to advance our Pipeline, and our mission.
Q3: Thank you.
Lavina Talukdar: One moment for our next question. Our next question comes from Tyler Van Buren with TD Cowan. Your line is open.
Thank you. 1 moment for our next question.
Your line is open.
Q4: Good morning. This is Greg on for Tyler. Do you have any early indications of what demand for COVID vaccines might look like this upcoming fall and winter season based on interactions with customers, or will we need to wait to see early uptake at the end of this month or early next month? Thank you.
Hey good morning. This is Greg on for Tyler. Uh do you have any early indications of what demand for Co vaccines might look like this upcoming fall and winter season based on interactions with customers or will? We need to wait to see early uptake at the end of this month or early next month. Thank you.
Stephen Hoge: Look, I think first, let's separate the outside the U.S. versus inside the U.S. part of that question. I think that that's probably more focused on the U.S. But outside the U.S., many of our government customers are purchasing through advanced purchase agreements, so those indications are pretty firm, and you can see that even in how we're guiding forward. Some of those are under advanced purchase agreements. Others are under tenders that have been completed and published in those countries, and that feels quite stable. In the U.S. with customers, what I'd say is we saw a quite solid spring booster campaign. If you look from March 1 forward, the actual volumes in the spring booster campaign in the U.S. were only slightly down from last year.
Yeah, um, look, I think, uh, first, let's separate the outside the US versus inside. The US part of that question. I think that that's probably more focused on the US. But outside the US, um, many of our, uh, our government customers are purchasing through advanced purchase agreements and so those indications are pretty firm and
Stephen Hoge: If you actually look at the 65-plus population, which is the core population we think going forward, given the new labels and framework for recommendation, it was actually down only 1% or 2% from March 1 to the end of the quarter of June 30, which I think speaks to the realization that those at high risk of severe COVID-19 continue to be compliant with public health recommendations and want to protect themselves even in the spring campaign. That has been the same experience, therefore, of our customers in the retail channel and elsewhere where they have seen that evidence in the last four months. As we look to the fall, we obviously have some uncertainty, both about what the ultimate ACIP recommendation will be, as well as some of the other market uncertainties that exist.
Even how we're guiding forward. Um and so some of those are under Advanced purchase agreements. Others are under tenders that have been completed and published in those countries and that feels, you know, quite stable in the US, uh, with customers. What I'd say is, uh, we saw a, you know, quite um, solid, uh, spring booster campaign. If you, if you look from March 1st for, um, the actual volumes in the spring booster campaign in the US, uh, were, um, uh, only slightly down, um, from last year. And if you actually look at the 65 plus population, which is the core population, we think going forward given uh the new labels and uh framework uh for recommendation. Um, it was actually down down only 1 or 2%, from March 1st to the end of the, the quarter of June 30th um which I think speaks to the realization that those at High.
High-risk, um, of Sevier Co. 19 continue to be compliant with public health recommendations and want to protect themselves, even in the spring campaign.
Stephen Hoge: We all want to be prepared to deliver a season that could be in line with prior seasons if the trends continue from the spring till now. So we're going to remain cautiously optimistic. Certainly, our customers are preparing to make sure they have vaccines available if their customers and patients show up, and the early signs are encouraging, but we need to be careful going into the fall. We think we really won't know until the end of the third quarter, until the end of September, as is always the case for our seasonal business, which is we'll really get a clear picture in the first six weeks of the season as we launch.
Um, that has been the same experience therefore of our customers, um, in the retail Channel and elsewhere where they have seen that evidence, um, in, uh, the last 4 months. And as we look for the fall, um, we obviously have some uncertainty both about what the ultimate acip recommendation will be, um, as well as some of the other Market uncertainties that exist, uh, but we all want to be prepared, um, to deliver a season that could be on in line with, um, with prior Seasons if, um, the trends continue from the spring till now, so we're going to remain cautiously optimistic certainly. Our customers are preparing to make sure they have vaccines available if their customers and patients show up, um, and the early signs are encouraging but we need to be careful going into the fall. We think we really won't know until the end of the third quarter, um, until the end of September as we always the case for our seasonal business, which is we'll really get a clear picture in the first 6 weeks of the Season as we as we launched.
Lavina Talukdar: Thank you. One moment for our next question. Our next question comes from Jeff Meacham with Citigroup. Your line is open.
Thank you. One moment for our next question.
Our next question comes from Jeff Meacham with Citigroup, your line is open.
Q4: Hi. Good morning, guys. This is Charlie on for Jeff. Two real quick questions. You mentioned additional cost-cutting areas that you could target. You noted that R&D is a primary driver of costs right now. How might you balance the need to bring later-stage infectious products to market and also the need to shift away from seasonality factors that current products have? On CMV, do these secondary endpoints, the decision to add them, do they come on the back of interactions or discussions from FDA? Some color in that would be really helpful. Thank you.
Hi, good morning guys. This is Jolly on for Jeff, uh, 2 real quick questions, you know you mentioned um additional cost cutting area that you could Target. You know you you noted that R&D is a primary driver of costs right now. Um, you know, how might you balance me to bring later stage infectious products market? And also, you know, the need to shift away from seasonality factors that current products have. And then, uh, second on CMV the, the secondary endpoints, that is the decision to add them, you know, did they come on the back of or interactions with discussions from FDA? Uh, you know, some color and that would be really helpful. Thank you.
Stephen Hoge: Sure. Yeah. Thanks, Charlie. I think the first question was on how we are balancing our late-stage pipeline. We still think we are investing quite a bit in our late-stage pipeline. So $3.6 billion to $3.8 billion is still significant, particularly we are very conscious of where we are from a revenue standpoint. We have made this decision and really stood by it for the last two years. We laid this out in 2023 that we were going to invest in our late-stage pipeline. We continue to do that. We are actively adjusting as we go, and we will continue to adjust as we go. That is why we are taking our cash costs from $9 billion down to $4 billion. At the end of the day, you also mentioned seasonality. We think we are building a diversified portfolio that is not just seasonal.
Sure. Yeah, thanks, Charlie. So, um, I think the first question was on how we are balancing our late-stage pipeline. I mean, we still think we are investing quite a bit in our late-stage pipeline. Um,
So 3.6 to 3.8 billion is still significant. Particularly we are very conscious of where we are from a revenue standpoint and we've made this decision and really stood by it for the last 2 years.
Stephen Hoge: We do want to complete the respiratory portfolio that will be stronger when we have all the products together and give us more ability to compete. When you look at CMV, our oncology pipeline, and our rare disease pipeline, those are not as seasonal. We believe that we are balancing both the need to complete the respiratory portfolio, invest in our late-stage pipeline, and invest in diversification in the company. We have been doing that for the last two years, and we will continue to do it, but we have had to adjust it down. We did have greater ambitions, but we will continue to adjust and have adjusted, and I think that is what we are seeing.
We laid this out in 2023 that we were going to invest in our late stage pipeline. We continue to do that, we are actively adjusting as we go and we will continue to adjust as we go. And that's why we're taking our cash costs from 9 billion dollars down to 4 billion dollars. But at the end of the day you also mentioned seasonality. We think we are building a diversified portfolio. That is not just seasonal. We do want to complete the respiratory portfolio that will
Be stronger when we have all the products together and give us more ability to complete compete. But then when you look at CMV our oncology Pipeline and our rare disease pipeline, those aren't as seasonal. Uh, and so we we believe that we are balancing both the need to complete the respiratory portfolio invest in our late stage Pipeline and invest in diversification in the company.
And we've been doing that for the last 2 years and we'll continue to do it. Uh,
James Mock: To add to James Mock's point, we have also said that we will not invest in Phase 3 studies for new latent vaccines. As you know, we have EBV, HSV, and other vaccines, but we also said that we might be looking for partners, either project financing or pharma partners. The rare diseases are, of course, small in terms of dollars. We also said we are going to focus on PMM for now. We will advance more programs later, but now we need to be financially disciplined. In oncology, as you know, for intismarin, Merck is paying 50% of the cost, which is why, as James Mock explained, we have discussed this mechanical effect that is based on the strategy we decided to pursue to make sure that we drive back the company to profitability in 2018.
EBV HSV and other vaccines. But we'll also say that we might be looking for partners. I have a project financing or Pharma partners and, you know, the rare disease of course, small in term of of dollars. We will associate. We're going to focus on pnma for now would Advance more programs later. But now we need to be financially disciplined. And, you know, as, you know, for insur and Merc is paying 50% of the cost, which is why, as Jimmy explained, we have this mechanical effect that is based on the strategy, we decided to pursue to make sure that we drive back the company to possibility in 28.
Q3: Andy question.
Stephen Hoge: On the CMV question, just a little, again, sort of overall framing on this, we remain blinded to the primary results and the secondary results that are in the study. The interim analysis that we announced much earlier in this year was only on that primary endpoint. That is the design of those studies. But as we did not meet the criteria for early success in that interim analysis, we then proceed to the final, and the final has much more information in it. Obviously, we leave the primary endpoint unchanged, and we will test against that. But if that is successful, there is an opportunity to pass down the alpha to powered secondary endpoints, as well as there is a final opportunity for us to say, are we getting all the information we want from the blinded analysis prior to that unblinding event?
Stephen Hoge: Internally at Moderna, we identified that we have actually been very successful in collecting data in the course of the study across a range of different potential endpoints, and we wanted to elevate some of those into that secondary endpoint analysis. In order to do that while blinded, we have to then update the statistical analysis plan. We did consult with regulators as we are doing that, and we want to make sure that that is done in the utmost to a gold standard, high integrity way prior to conducting the analysis so that we can get the full benefit of that additional information that is in the study. Again, we remain blinded. This is just a diligence matter of making sure we get this updated in the right way, and then we will look forward to proceeding forward with that analysis.
Any questions and on the CMV question? Um, uh, so, uh, we, um, so just a little, again, sort of overall framing. On this, uh, we remain blinded, uh, to the primary results and the secondary results that are in the study, uh, the the interim analysis that we announced much earlier. In this year was only on that primary end point. That's the design of those studies. But as we did not meet the criteria for early success in that in our analysis, we then proceed to the final and the final has much more information in it. Um, obviously we leave the primary endpoint on changed and we'll test against that, but if that is successful, there is an opportunity to pass down the alpha to powered secondary endpoints as well as there's a final opportunity for us to say are we getting all the information we want from the blinded analysis prior to that, I'm binding event. Um and
In our internally in maderna. Um, we, uh, we identified that there is, we've actually been very successful in collecting data in the course of the study across a range of different potential endpoints, um, and we wanted to elevate, um, some of those at into that secondary endpoint analysis. Um, in order to do that, while blinded we have to then update the uh statistical analysis plan. We did consult with uh Regulators as as we are doing that. Um, and we want to make sure that that is done, you know, in the utmost to to a gold standard Integrity Way prior to conducting the analysis so that we can get the full benefit of that additional information that is in the study.
Stephen Hoge: We have done that in consultation, obviously, with regulators, but we initiated that ourselves. Last point, I can just underscore, we will still expect this in 2025. At this point, we have the data in hand. It is literally just making sure we dot our I's and cross our T's before conducting that analysis this fall.
So again, we remain blinded. This is just a diligence matter of making sure we get this updated in the right way. And then we'll look forward to proceeding forward with that analysis. Um, and we have done that in consultation, obviously, with regulators, but we initiated that ourselves. Um, last point I just...
We will still expect this in 2025. At this point, we have the data in hand. It is literally just making sure we dot our i's and cross our t's before conducting that analysis this fall.
Lavina Talukdar: Thank you. One moment for our next question. Our next question comes from Courtney Breen with Bernstein. Your line is open.
Thank you. 1 moment for our next question.
Our next question comes from Courtney Breed with Bernstein. Your line is open.
Q2: Hi, Moderna. Thanks so much for taking my question today. A couple of pieces that I wanted to just touch on. First, with the INT, it looks like you have added the first-line melanoma in there. As you think about patients being treated over the course of their disease, you are already hitting them in the early stages, the adjuvant space, and now popping up with a new first-line trial for the metastatic space. Could you imagine a world where patients might get an INT twice in the course of their disease state if they were to progress, or will this be a more narrow patient population in the first line, those that perhaps have not had it in an earlier stage? The second question that I did want to ask was just in terms of the employee headcount cost-cutting that you have just announced.
Hi Madonna. Thanks.
A couple of pieces that I wanted to just touch on First, with the, the int. Um, it looks like you've added the first line melanoma in there. Um, as you think about kind of patients being treated over the course of their disease, you've already kind of hitting them in the, in the early stages, the adequate space and now popping up with a new first line trial for the metastatic space. Could you imagine a world where patients might get, uh, kind of an INT twice in the course of their of their disease state? If they were to progress,
Q2: Can you just add some more context? And apologies if I have missed this, on where you are focused with removing some of that headcount. Are there any places that you are adding to enhance efficiencies? Just talking about what the ins and outs might look like to get to that new employee headcount. Thank you.
Um, or will this be a more narrow patient population in the first line, those, that perhaps haven't had it in in an earlier stage. Um, the second question that I did want to ask was just in terms of the, the, the kind of employee headcount cost cutting that you have just announced. Um, can you just add some more context and and apologies, if I've missed this on kind of where you are focused with kind of removing some of that headcount, are there any places that you're adding to kind of enhance efficiency? Um, and so, just talking about kind of what the the ins and outs might look like to get to that new employee headcount, thank you.
Stephen Hoge: Great. Thank you. I will take the INT question first. We, as you mentioned, are looking at first-line metastatic melanoma. We look forward to a day when melanoma patients broadly are getting INTs early in the adjuvant setting. But right now, the reality is, as we are not yet approved and being used in that space, there is still a substantial need in front-line metastatic. Your question was, could we expect a world maybe in that distant future where we are being used in both places? I think the answer is yes. I will remind you, it is an individualized treatment. It is an individualized treatment we make on a biopsy of your tumor at the time in which it happened.
Stephen Hoge: So it is conceivable that you could get a durable benefit in the adjuvant setting and maybe very much more distantly have a metastatic event, and the neoantigens in your tumor might have changed. So the actual INT you would get in that front-line setting would actually be updated for the evolution of your own personal cancer, and that would be a world where you can obviously see the potential for treating early and treating late. That is speculative in the sense that it is far out there, and we will have to prove those things. Certainly, we could see a world where people are receiving different versions of their individualized neoantigens therapy throughout the treatment of their cancer.
James Mock: I think the second question on employee scrutiny, if you look at it, there are a few buckets. Clearly, in the manufacturing, driven by productivity, whether it is technology productivity or processes or other things we are doing. In R&D, as we talked about a lot, and again, this is part of the strategy, we are not investing in new Phase 3 study in respiratory. As those phase out, of course, there are some capacities that we need to resize, as you can imagine, and we are not starting new ones. We are not starting no latent Phase 3. G&A has a lot of productivity across the board. We will, of course, continue to hire. I think if you check a week ago, there are still like 150 positions on Moderna's website right now. We are hiring as we need to grow the business to prepare the launches.
It's conceivable that you could get a durable benefit in the edge of a setting and maybe very much more distantly have a metastatic event and the Neo antigens in your tumor might have changed. So the actual int you would get in that Frontline, setting would actually be updated for the evolution of your own personal cancer. And that would be a world where you can obviously see the potential for treating early and treating weight. Um, that's speculative in the sense that it's far out there and we'll have to, uh, prove those things. Um, but certainly, we could see a world, um, where people are receiving different versions of their individualized neurons and therapy, uh, throughout the treatment of their cancer.
And I think the second question on employees called me. If you look at it, basically there are a few buckets, fairly known, manufacturing driven by productivity.
James Mock: Of course, this is very important.
Whether it's technology productivity or processes or other things where they're doing, you know, and as we talked about a lot and I can just part of a strategy there, we are not investing in new phase 3 study in respiratory. So as those phase out, of course, they are some capacity that we need to kind of resize as you can imagine. And we, we're not starting new ones. We're not starting no late and place for it. And then G is a lot of productivity across the board. So we will of course continue to hire. I think if you check and check having a week ago there still a 1050 position on modernized website right now. We are having as we need to grow the business to prepare the launches. So of course this is really important.
Lavina Talukdar: Thank you. One moment for our next question. Our next question comes from Corey Kasmoff with Evercore ISI. Your line is open.
Thank you. 1 moment for our next question.
Our next question comes from Corey cmov with evercore isi. Your line is open.
Q3: Hi. This is Adi on for Corey. I wanted to ask a little more on the decision to start the first-line metastatic melanoma trials for intismarin. What does this suggest about what you are learning about the product, where it might be best suited to work, and your evolving confidence in the program?
Hi. This is Addie on for Corey. Um, I wanted to ask a little more on the decision to start the first line, metastatic melanoma, trials, or interim. What does it suggest about? What you are learning about the product where it might be best suited to work and your evolving confidence in the program?
Stephen Hoge: Thank you for the question. Look, we continue to follow the randomized Phase 2B results from our adjuvant melanoma study, and I think as we have seen in the repeated updates, and we hope to provide future updates on that, as was mentioned previously, we continue to have enthusiasm from that study, and that really lays the foundation for why we are optimistic about the overall program. If you look across where we have made with our partner Merck the most sizable investments, we have obviously been looking most substantially in the adjuvant settings. That makes sense to us where the burden of the tumor is the lowest and where your immune system has the greatest chance of achieving a really significant response.
Stephen Hoge: I do not want to lose sight of the fact that we still believe adjuvant settings are important. I will also note that we have gone for some monotherapy, smaller studies that we are starting to look at, which have us looking even earlier than adjuvant in some ways. We are quite enthusiastic about the program potential from adjuvant and earlier. That said, we also want to assess diligently whether or not there is an opportunity for us to do late stage, particularly in the metastatic indication, and that is where metastatic melanoma made the most sense. It was also enabled by some progress we have really made on the manufacturing side.
Yeah, thank you for the question. Um, look, we uh, we continue to follow the randomized phase 2B results from our agent anima study. And I think as we have seen in the repeated updates and we hope to provide a future updates on that as I mentioned previously, um, we continue to have enthusiasm from that study, uh, and that that really lays the foundation for why we are optimistic about, um, the overall program, um, our, you know, our, if you look across where we have made with our partner Merc the most sizeable Investments, uh, we have obviously been looking most substantially in, um, the add event settings, um, and that makes sense to us where the burden of the tumor is the lowest and where your immune system has the greatest chance of achieving a really significant response. And so, you know, I don't want to lose sight of the fact that we still believe agent settings are important. I'll also note that we've gone
Stephen Hoge: I will just make the last comment on the metastatic indication is that those are patients that if they are unfortunately at that stage, they tend to progress quite quickly, and we need to be sure that we can deliver highly efficiently, highly reliably a product for them inside of six weeks, or hopefully even better from a quick turnaround perspective, so that they can start being treated by the drug post-enrollment in the study. It is quite pragmatic to say let us build up the capability in the adjuvant and early space, but then now go in a targeted way and look in later stage. What we have really seen in the intismarin clinical portfolio over now many studies and over 1,000 patients treated is this opportunity for us to look in the late stage with a rapid turnaround and highly efficient manufacturing system.
For some monotherapy smaller studies that we're starting to look at, which have us looking even earlier than than adant in, in some ways. And so, we're, we're quite enthusiastic about, um, about the program Potential from agent. And earlier that said, we also want to assess diligently whether or not there's an opportunity for us to do, um, uh, late stage in, uh, you know, particularly in the metastatic indication and that's where metastatic melanoma made the most sense. Um, it was also enabled by some progress. We've really made on the manufacturing side, um, now we'll just make the last comment on met. The metastatic indication is that those are patients that if they're unfortunately, at that stage, they tend to progress quite quickly. And we need to be sure that we can deliver highly efficiently. Highly reliably, a product for them, uh, inside of 6 weeks, or hopefully, even better from a quick turnaround perspective. So if they can start being treated by the drug post enrollment in the study, um, and so it's quite, you know, it's quite pragmatic to
Stephen Hoge: I do not want to lose sight of the fact that we still really believe in the adjuvant space. That is the major place that we are betting, but we do believe that earlier than adjuvant and perhaps in the front-line are worth looking at as well, and we are going to be doing that in the studies that we just announced.
Say, let's build up the capability in the advert in early space but then now go in a targeted way and look in later stage and what we really seen in the anticipation clinical portfolio over. Now many, you know many studies and and over a thousand patients treated is this opportunity for us to look in the late stage with a rapid turnaround, highly efficient manufacturing system but I don't want to lose sight of the fact that we still really believe in the ad space. That is the major place that we're betting, but we do believe that
Earlier than Adant and perhaps in the front line are worth looking at as well. And we're going to be doing that in the studies that we just announced.
James Mock: Got it. To follow up, can you discuss any regulatory interactions you have had on the path ahead for Checkpoint ANT? I see on slide 12 that it is now expected to be filed for approval by 2028. Thank you.
About it and then just to follow up. Uh, can you discuss any regulatory interactions? You have had and the path ahead for checkpoint AMT. I see on slide 12, that is now expected to be filed for approval by 2028. Thank you.
Stephen Hoge: Thank you for that question. So 4359, we have been engaging with regulators. Those are early stage. I will not get into the specifics of them. I will remind you, we are just now moving into phase two, and so these are really phase one stage conversations, which would make it premature to go too much into specifics. That said, we are investing behind the program, and as we announced at the last quarter, we are investing as though this could become one of our submissions over the next three years. As you identified sort of by 2028, that really is a statement about our prioritization of the program and our conviction given the very early stage data and not necessarily a statement about anything we have done either out of phase two and subsequent discussions with regulators about approval timelines.
Stephen Hoge: So it is our prioritization of the program that brings that forward, but we believe it is possible.
Question. So, uh, 4359, um, you know, we have been engaging with Regulators. Those are early stage, I won't get into the, um, into the specifics of them. I'll remind you, we're just now moving into phase 2. And so, these are really Phase 1 stage conversations, which would make it premature to go too much into specifics. That said, uh, we are investing behind the program. And as we announced at the last quarter, we were investing as though, this could become 1 of our uh, submissions over the next 3 years as, as if, you know, as you identified sort of by, by 2028, that really is a statement about our prioritization of the program and our conviction, given the very early stage data, um, and not necessarily a statement about, um, anything we've done. Either out of phase 2 and subsequent discussions with Regulators about approval timelines. So it's our prioritization of the program that that brings that forward, but we believe it is possible.
Lavina Talukdar: Thank you. One moment for our next question. Our next question comes from Luca Esse with RBC. Your line is open.
Thank you. One moment for our next question.
Q3: Great. Thanks so much for taking my question. Maybe one, Stephane Bancel, bigger picture, can you maybe just talk about business development here? We have obviously seen a lot of assets being in-licensed from China, including obviously one of your competitors that actually in-licensed the assets and even flipped it to pharma for some mean-to-profits. Given your long-term ambition to become a key player in oncology, are you actively spending time in China? If so, are you just looking at strengthening your mRNA capabilities, or are you open to other modalities? Then maybe second, Stephen Hoge, can you just talk about the COVID plus flu? How should we think about the sequence of the filing here with the FDA? Is it fair for us to think that you first need to get approved for flu monotherapy and then you can file the combo, or can you possibly do both concurrently?
Our next question comes from Luca SE with RBC, your line is open,
Well great thanks so much for taking my question. Maybe 1 Stephan bigger picture. Can you maybe just talk about business development here? Um, we've obviously seen a lot of assets being utilized from China, including obviously 1 of your competitor that actually in licensed the assets and even flipped it to Pharma for some meat to profits, uh given your long long term.
Ambition to become a key player in oncology. Are you actively spending time in China? And if so are you just looking at strengthening your mRNA capabilities or your? Are you open to other modalities?
Q3: Any color there, much appreciated so we can think about timelines. Thanks so much.
James Mock: On the first question, as we have said before, we have such a productive platform on mRNA that we have an abundance of assets. Actually, what we are doing, as you heard on the cost structure, is we are deciding not to take forward to Phase 3 assets that we believe deeply into, pick EBV, for example, because we want to be financially disciplined. We have said we believe this vaccine is really important for patients. As you know, we have two programs in EBV. There is a prophylactic program to prevent mononucleosis and potentially long-term sequelae of MS, and there is a potential therapeutic program for people that are already sick.
And then maybe second Stephen, can you just talk about the coid plus flu? How should we think about the sequence of the filing here with the FDA? Is it fair for us to think that you first need to get approved for flu monotherapy? And then you can file the combo or can you possibly do both concurrently I guess any color there much appreciated so we can take you about timelines. Thanks so much. So, on the first question, as we've said before, we have such a productive platform on the money that we have an abundance of assets and actually what we are doing. As you heard on a cost structure, is we are deciding not to take forward to phase 3 asset that we believe deeply into PBB, for example, uh, because we want to be financially deeply. But we've said, we believe these vaccines is really important for patients. As you know, we have so far. How many BV? There's a proactive program to prevent monopolies and potentially a long-term secular of Ms and there's a potential therapeutic program for people that are already sick.
James Mock: We believe those programs have to move forward, which is why, as we have said on previous calls, we are actively talking to potential pharmaceutical partners and potential project financing partners for several of those assets that we cannot prosecute forward alone because they are great assets, but we need to be financially disciplined at the same time. We have always thought that partnering is a great way to access assets that are non-mRNA technology. A good example, of course, is our important strategic partnership with Merck with Keytruda. We could have decided to develop our own PD-1, and we really do not think this was the right thing to do. Partnering with Merck in the modeling and approved product and the right capabilities was.
James Mock: We are always going to look at the biology. That is what has always driven us to try to find the best way to help patients and to create the best asset. If it needs a partnership, we will do so.
Uh, and we believe those programs have to move forward, which is why. As we've said on previous calls, we are actively talking to potential pharmaceutical partner and potential product financing partners for several dollars. I said that we cannot prosecute forward alone, uh, because they are great assets, but we need to be financially disciplined at the same time. Uh, we've always thought that partnering is a great uh, way to access assets that are non amounted, technology. I mean a good example, of course is all important strategic partnership with Merck with qudra. You know, we could have decided to develop our own pd1 and we don't think this was the right thing to do but partnering with m in an approved product and the right capability is was so we always going to look at the biology. That's what has always driven us to try to find the best way to help patients and to create the best asset. And if you need the partnership, we will, we will do. So
Stephen Hoge: Thanks for the question on the COVID flu combo. Look, I will first say concurrent is certainly possible. You were asking whether it is theoretically possible. I think we think it is. As a practical matter, there will probably be some sequencing. As a practical matter, in the case of the U.S. FDA, it is likely that the flu vaccine will be sequenced first for all of the reasons that are obvious. That a chance to review that efficacy data from that flu vaccine feels very important for ungating the flu-COVID combination. The one caveat I would put on that is there are markets where we continue to proceed with our flu-COVID vaccine application, including in Europe, where we believe we are going to be able to amend that file to include the flu efficacy data.
Um, and thanks for the question on the co flu combo. Um, so look, I'll I'll I'll first say, uh, concurrent is certainly possible when you're asking whether it's theoretically possible. Um, I think we think it is, um, but as a practical matter, there will probably be some sequencing. And as a practical matter in the case of the US FDA, it's likely that the flu vaccine will be sequenced first for all of the reasons that are obvious, it's that the chance to review that epicc data from that flu vaccine feels very important for uh for on getting the flu coid combination. Um, now the 1 cavitt.
Stephen Hoge: The answer is ultimately, depending on the different regulators in different markets, it is possible that we could proceed in parallel, but for pragmatic reasons, we may proceed in sequence in some. That does not mean that we are delaying for one to be approved before we submit, but we are allowing substantially flu to proceed before proceeding with the flu-COVID. Again, market to market, different answers.
Where we continue to proceed with our flu, coid vaccine application uh including in Europe uh where um we have uh we believe we're going to be able to amend that file to include the flu efficacy data. And so the answer is ultimately dependent on the different Regulators in different markets. Um, it is possible that we could proceed in parallel, but for pragmatic reasons, we may proceed in sequence and stuff. Um, that doesn't mean that we're delaying for 1 to be approved before we submit. But we are allowing substantially fluid to proceed before. Uh uh, before proceeding with the flu Co again Market to Market its different answers.
Q3: Thank you so much.
Lavina Talukdar: One moment for our next question. Our next question comes from Gina Wang with Barclay. Your line is open.
Thank you so much.
Question.
Our next question comes from Jina Hwang with barklay, your line is open.
Stephane Bancel: Thank you for taking my questions. I have two, maybe just follow flu/COVID comments or discussion here. So, any latest thoughts regarding flu combo submission requirement? This is specifically regarding the FDA. The second, regarding the CMV, how do you decide the statistical hierarchy for the secondary endpoint? Also, given the study basically already completed, is it fair to say in two months we will see the data?
Thank you for taking my questions. Uh, I have a 2. Uh, maybe just follow flu co uh, comments here or discussion here. So, uh, any latest thoughts, regarding flu combo, submission requirement. Um, this is a specifically regarding the FDA and the second regarding the CMV. Um, how do you decide the statistical hierarchy, for the secondary endpoint and also given the study, uh, basically already completed, is it fair to say in 2 months? We will see the data.
James Mock: Very specific questions. Thank you, Gina, for all of them. On the flu/COVID, we are actually beginning those consultations with the FDA. We will wait for us to have guidance from them on what their requirements are. From the previous review, it was clear that we needed to submit the flu efficacy results and confirm the correlative protection from that study that we now have. We will go back and confirm that that is necessary, as well as understand any other information the FDA would want to see in the application. When we have had that consultation, we will be able to provide more clarity. I do not have that now. As far as CMV, in terms of the hierarchy, we have not yet disclosed what the powered secondary endpoint will be or some of the other things that we are looking at.
Um, very, very specific questions. Thank you Gina, for all of them. Um, so on the, uh, flu Co um, uh, we are, we are actually beginning. Those consultations with the FDA. Uh, and so, um, I, you know, we'll wait for a week for, for us to have guidance from them on what their requirements are. But from the previous, uh, review, it was clear that we needed to submit the fluency results, um, and confirm that, you know, Coral water protection from that study that we now have. Uh, and so we will go back and confirm. Um, that that is necessary, as well as understand any other uh, information, the FDA would want to see in the application 1. We've had that consultation, we'll be able to provide more clarity. I don't have that now, um, the as far as, um, CMV, uh, in terms of the hierarchy, um, we, uh, we have not,
James Mock: We will once we are obviously unblinding the study. What we are looking to do is a hierarchical testing, as you can imagine, so that we are passing the alpha down to that secondary. We are also making sure that we characterize all of the additional secondary endpoints that we think will be useful in terms of characterizing the performance of the vaccine on a number of different immunologic and virologic measures. Last question, when will we see the data? We have completed the study. We are going to be diligent and careful and dotting our I's and crossing the T's. We have not completed the analysis. Will we have most of the data? I would say that we are completely blinded to those results.
Yet disclosed what the powered secondary endpoint will be or some of the other things that we are looking at. Um, and we will, once we have once we on blinding the study. Uh but but these just, you know what we're looking to do is a hierarchical testing as as you can imagine. So that we're passing the alpha down to that secondary and then we're also making sure that we characterized all the additional secondary endpoints that we think will be useful. Uh in terms of characterizing, the performance of the vaccine uh on a number of different immunologic envirologic measures measures
James Mock: It will take some time to first make sure that we have all the appropriate approvals on the updates to the statistical analysis plan everywhere we want. Then we will initiate the analysis. There will be some period of time for an unblinded statistical team to conduct all the correct analysis and review that with the DSAB. Then we will be informed. We do expect that to happen this fall. I will not say whether or not we expect it to happen within the next two months because, honestly, I do not exactly know today how much time it takes to go through those approvals and complete those analyses. We are quite confident that it will happen promptly.
Um at last question. Um uh when will we see the data? Um uh we have completed the study. Uh we are going to be diligent and careful and dotting our eyes and crossing the t's we have not completed the analysis. And so will we have most of the data we you know I would say that we are completely blinded uh to those results. And so we'll take some time to First. Make sure that we have all the appropriate approvals on the update to the statistical analysis plan uh everywhere once and then we will initiate the analysis and there will be some period of time for a an unblinded statistical team to conduct all the correct analysis and review that with dsmb and then we'll be informed. We do expect that to happen. This fall.
I will not say whether or not we expect it to happen within the next 2 months because honestly, um, I don't exactly know today how much time it takes to go through those approvals and complete those analysis but we're quite confident that it will happen properly.
Stephane Bancel: Thank you.
Lavina Talukdar: Ladies and gentlemen, this concludes the Q&A portion of today's conference. I would like to turn the call back over to Stephane for any closing remarks.
Thank you.
Stephen Hoge: Thank you, everybody, for joining us today. We really appreciate it. We look forward to speaking to you in the next days or weeks. Have a nice day and a good weekend. Thanks.
Lavina Talukdar: Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day.
Hello, ladies and gentlemen, this include the Q&A portion of today's conference. I'd like to turn the call back over to Stefan for any closing remarks. Well, thank you everybody for joining us today. We really appreciate it. We look forward to speaking to you in the next days or weeks have a nice day and a good weekend. Thanks, ladies and Gentlemen, let's conclude today's presentation. You may now disconnect and have a wonderful day,