Great. Welcome, everyone. My name's Jess Fye. I'm a biotech analyst at JPMorgan. And the next company coming up is Moderna. The company's going to give a presentation, and then we're going to go into Q&A. If you have a question, someone could bring you a mic, or you can send them up to me at the iPad. That might be easier. But with that, let me pass it over to the company's CEO, Stéphane Bancel.
Thank you, Jess. Good afternoon. Let me start by reminding you that we'll be making forward-looking statements, and you can find those statements on the SEC or Moderna's website. Today, I'm going to start by talking briefly about the Moderna platform. Then I will recap 2024, and then we'll go into the future, our objectives, our outlook, and important milestones for the year. We started Moderna because we were very intrigued about the possibility to have mRNA as an information molecule to make protein in vivo in the human body. We thought if this was possible, we would be able to make a lot of medicines that cannot be done using recombinant technology. We thought because we use always the same chemicals to make the mRNA that we will have a much higher R&D productivity.
We thought if we could industrialize this platform through process development and manufacturing, we could go much faster than recombinants, and we thought that because we make all the products in the same reactors, we'll have greater capital efficiency, and so from the get-go, we set up our vision to build a platform, the tools, systems, processes to be able to invest in mRNA science, invest in delivery systems, invest in manufacturing to be able to get many, many medicines out for patients and creating value for shareholders on the way.
One of the things that has panned out to be true from those beliefs we had in the early days is that if you look at the last 10-plus years of a company's existence, the difference in probability of technical success of Moderna in red versus the rest of the industry in blue, you can see that in phase I, we are consistently much higher than the industry. Phase II, consistently way higher than the industry. And phase III, a little bit higher. And if you compound those numbers and you look at the probability of an asset to go from phase I to approval, we're actually six times higher than the industry average, which we think is a very important benefit from a value standpoint of this platform. If you recap quickly 2024, we said in terms of sales, we will achieve $3 billion-$3.5 billion in sales.
In terms of actuals, we announced this morning, we should be on the low end of these, $3 billion-$3.1 billion once the team finishes auditing the number. Very importantly, in cash, we said we should finish the year with $9 billion of cash, and I'm very thankful and very pleased to announce that thanks to the hard work of a team in terms of managing expenses, managing CapEx, and also managing working capital, we're able to finish the year at $9.5 billion of cash. The other thing that we delivered during the year was, of course, the approval of RSV, our second product in the company history. We had a very busy year in terms of clinical readouts for phase III. We had four phase III positive clinical readouts, and the first three on that list have actually been filed to the FDA.
I'm also very thankful for the team that have accomplished in only three months three BLA filings. For a company our size and with our track record and history, this is really an amazing accomplishment by our teams. Then if you look across the pipeline, we still have multiple positive data. We had positive data in phase I, II , in Norovirus, in EBV, in VZV. I'm very pleased to report that Norovirus is now enrolling in the phase III study. We could have readouts in 2025 or 2026 based on cases. We've showed some very exciting data in terms of duration of our INT oncology product combined with Keytruda. We've now very exciting three-year data that are actually better than the two-year data.
And we have also showed some early intriguing data in phase I, II for our checkpoint vaccine, a PD-L1 and IDO1 vaccine that has been presented at ESMO earlier in the fall. Also, our rare disease program, PA and MMA, that are both metabolic disease. Now PA is actually, we've announced this morning, currently recruiting patients in its pivotal registration study, which is exciting for patients because today there is no drug available for patients with PA disease. It's a metabolic disease. And MMA should be dosing in its pivotal study soon in 2025. If we look forward, what we shared at R&D Day in 2024 is that our three priorities are pretty clear. The top priority is to drive revenues based on the approved products, COVID and RSV.
But we have been investing heavily over the last few years in a very broad pipeline to diversify from COVID and to drive sales growth again. And so we're really focused on the 10 products that we have the opportunity to launch over the next four years. And also, we're very focused on driving cost efficiency across the entire company. And I will come back on those three topics. So first, in terms of sales, what we saw in 2024 is a stabilization of the COVID market. If you look at the COVID market, and we only have data in retail right now, but the U.S. retail market was actually down 7%, which is much less than in the past.
But what is very important for us is that what we think is the recurring business of 65-plus people at the highest risk of COVID, as you can see, was only down 2%. So there's good hope that we're getting to the bottom of the COVID market in the U.S. The 64 and under, as you can see, was down 12%. We are entering 2025. We have actually two products to be able to provide to our customers as we go into negotiation for the fall of 2025. And we are getting RSV approved in more and more markets outside the US, giving us the opportunities to increase sales in those geographies. Tomorrow, we communicate. Today, we communicated that guidance for 2025 is $1.5 billion-$2.5 billion compared to the $3 billion-$3.1 billion that we achieved. I think it's important to start by normalizing the year.
We communicated in 2024 that we had around $200 million in the U.S. that was due to returns that we reserved in 2023 because it was the first year that we were a commercial company, and it was very difficult to estimate how much return we're going to get, and then internationally, because of changes in demand for vaccination in our key countries, there's around $400 million from advance purchase agreements that is also not going to be recurring next year, so if you take those out, you actually see that the high end of our guidance is actually a flat year, but as you all know, there are a lot of uncertainties right now, and we wanted to reflect that with a wider guidance. There are uncertainties on vaccination rate. There's uncertainty on competitive environment and market share.
There are uncertainties in terms of the timing of our readiness of our factories in the U.K. and Australia. Depending on when those get approved by local regulators, we will have sales of different levels because, of course, we will still have to order products, but it will be through a tender process, and so this we'll see as the year evolves. For RSV, of course, ACIP recommendations are going to be really important to see what happens to the RSV market. There are some upsides, of course, as well in terms of vaccination rate. There's some upside in terms of market share, and one upside also is in terms of new product sales. As I just said, we filed three products to the FDA, so we could have up to three approvals this year.
But depending on when they happen, which, of course, we don't control, we've decided to not put any new product in that range of the guidance. The priority number two, of course, is to drive sales growth by launching new products. I mentioned the three that we filed in 2024. There's still quite a number of readouts coming that are going to be exciting this year and next year for us to be able to launch those products. Let's now talk a bit about costs. And I think it's important to start by saying that for the company, managing our cash has always been really important. Of course, during COVID, we had to focus on speed for obvious reasons of saving as many lives as we could. And we could never compromise on quality.
Cost was not a high priority as we had to execute at a very high speed. But as we are coming down to an endemic market, the team has been now for more than 18 months very focused on reducing costs. And as you look at cash costs, it's important to see the difference between GAAP cost and cash cost. As you can see here on the 2024 estimate, you have GAAP costs at around $7.2 billion, but cash costs are $6.5 billion because of stock-based compensation, depreciation, and amortization. So it's quite a significant difference. So let me tell you where we have been and where we're going. If you look at the data, we had around $9 billion of cash cost in 2023.
This year, the estimate we will report, of course, the number on our Q4 earnings call is that we should be around $6.5 billion based on how the first three quarters are trending of cash cost estimate for the year. We announced this morning that because of this uncertainty on the top line that we are seeing in 2025, we thought it was responsible and prudent to get ahead of this risk and to reduce our investments into the company just in case we end up at the low end of things, and so we announced we are already taking a lot of actions across the company, across R&D in terms of portfolio, in terms of productivity project, manufacturing, but also SG&A to reduce our cash cost this year.
Because some of those savings will come in the middle of the year, we estimate that there's an additional $500 million of cost savings that will happen in 2026 based on the work that is going to happen in 2025 when you bake in a full year. That is really important for us to be able to have a cost structure of around $5 billion in 2026. If you look at how we're managing the $9.5 billion of cash that we got from COVID proceeds to invest in a business, to launch new products, to diversify the top line, to grow the top line, we basically reduce our net use of cash over the last few years. We intend to continue to reduce that as we launch new products and get to profitability in 2028.
One of the great opportunities we have is to really bring a lot of products to patients. If you look at the company's pipeline, this is really the late-stage pipeline. I remind you, we have 45 products in the clinic as we speak. But as I said, in our priorities, it's really focusing on those products that we could launch in the next couple of years. We are trying to build a pretty unique respiratory franchise with COVID vaccine, RSV vaccine, flu plus COVID, flu vaccine as well to have a very, very robust franchise. We're also investing in latent virus vaccine against CMV and earlier in the pipeline against other viruses. Also, our Norovirus, which is now in phase III, c ould be the first and only product to market for a while given the other vaccine status in other companies' pipeline.
We think there's a very large unmet medical need for Norovirus. And also, in terms of bundling ability with our channel with our retail channel, we think it would be a very important asset to bring to them in terms of driving their growth of their net income. Of course, we're all extremely excited about cancer, and we cannot wait to have phase III data on our melanoma study combined with Keytruda. As I said before, the phase II data was really exciting. We have enrolled in only 14 months around 1,000 people around the world. It was a great endeavor by the team, and we're looking forward now to get that data from a manufacturing standpoint because those products are individualized. We've also invested in another plant that will not be in the critical path of launch.
As soon as we get the data, hoping it's a confirmation of a phase I, we will be working really hard to prepare, of course, a BLA and to file this for approval. If you look across this portfolio, there's a TAM of more than $30 billion that we can address for some of them, like I mentioned, Norovirus, CMV, and others with no product on the market. Those products will also be a very nice commercial combination with the product that we already have in terms of medical and sales and marketing infrastructure. Also, the rare disease will be an interesting product because we don't need to build new factories for those rare diseases. Again, because of the platform, it will be done in the same factory.
Once the R&D cost is behind us, the cost of sales and marketing, as you know, will be not very high. And so that's going to be also very interesting for patients, but also to create a return for shareholders. So the key milestones that we're looking forward to, of course, is the potential three approvals for the product that we just filed in the fall. And very interesting years with the CMV phase III readouts. We have been told by the DSMB that we need to keep going on the study to go to the final efficacy readout that should happen later this year. We have a phase III for seasonal flu and for Norovirus that could readout this year based on cases. If we don't have enough cases, they will readout next year. I mentioned the INT phase III and the PA and MMA.
They have agreed with FDA endpoints, metabolic decompensation event, sorry, metabolic decompensation event for PA. There's a biomarker endpoint agreed with FDA on MMA. So we think that now with PA recruiting patients in pivotal studies and MMA going to be recruiting very soon, we should be getting data actually pretty quickly. If you look at the key takeaway of today, it is that we achieved $3 billion of sales. We got our second product approved. We're able to restructure the business and file three BLAs during the year. Our three priorities are really what is driving our roadmap. The entire team is very focused on this. There's going to be quite a lot of catalysts and milestones happening this year between the phase III readout and the potential approval. With this, Jess, I'll be happy to take your questions.
Thanks for the presentation. I don't know how to ask this without asking it sort of bluntly, but how conservative is your new 2025 top line guidance? And what changed so much relative to when you last gave us those numbers that it's changing by a billion dollars today?
Sure. So there's a lot of factors. As I mentioned during my remarks, if you look at the $2.5 billion, it's basically the normalization of the $3-$3.1 billion numbers that we see for 2024. And then there's a lot of uncertainty, some that were not clear before the season, before we gave the numbers. Like RSV is a good example. I mean, the RSV market is much lower than we thought. The competitive environment has been much tougher on COVID. And then some countries have changed guidelines of recommendation.
I mean, there are countries where you used to have recommendation 65 plus that now have moved to 75 plus, not in the U.S., but outside the U.S. So there are quite a number of parameters like these that have changed. There's, of course, uncertainty on what will happen to a vaccination rate. And so we also didn't want to include the new products because we have learned from the RSV launch last year that including the new product forecasted sales in the first year is a very dangerous endeavor. So we learned from that mistake, and we did not do it in the guidance for next year. So this is some of the factors that we took into consideration to have a guidance that we can deliver on.
Okay. When you talk about competitiveness in the COVID market, does that mean price or share?
So a bit of both. There's been a lot of pressure on price in 2024 in the U.S. Share has also reduced versus 2023. We think a lot because of price, but also bundling. If you think about Moderna compared to a lot of our competitors, we were in 2024 during contracting season in Q1 or Q2 a one-product company. And so a lot of our competitors in different fields where we are are able with a retail channel to bundle products to provide discounts for bundles that we're not able to provide. So one of the things that we're excited, if you look at 2025, but especially 2026, 2027, is you're going to have potentially a next-gen COVID with a higher efficacy that should be able to help because there's been nobody else with such a product.
We talked about potentially the flu plus COVID combo, but also the Norovirus. So if you look again at the next couple of years, we should be able to be quite an attractive partner to the retail channels, helping them drive growth. If you think about it, this is how they drive revenue growth. If the VCI is not moving from the market, it's not helping them. It's not helping us. So we think this is going to put Moderna in a quite different competitive position over the next couple of years.
Okay. It also looks like you've been able to identify more expense to pull out of the cost structure sooner than expected. And if I recall in the past, I think you had characterized at least 2025 and maybe even the next year to an extent having less flexibility in the cost structure. So how are you able to do it? A nd were any products paused or shelved to achieve that?
It's a great question. So it goes back to what we have been saying all along, which is we want to invest the proceeds of COVID during the pandemic to build shareholder value, to bring new products to patients for the mid and long term. We don't think keeping the cash in T-bills is going to be the way to create shareholder value. And we know the platform works. I mean, if you think about it, for many, many years in the company history in the early days, we didn't know. We believe the platform should work, but we didn't know. Now we have two products approved. We have four positive phase III. So we know the platform works.
So, we think the best thing we can do for shareholders is to invest their capital to drive new products and to drive value in such a way. But at the same time, we also say that we're going to be very careful and disciplined about our cash burn and our investments. And so, because as we realized through the fall, those changes and the uncertainty that we have that I just described, because there's a possibility that we will be below the $2.5 billion, we needed to get ahead of it, not behind it.
And so what we discussed with the team through the fall, looking at the top line that I just described and the budget, and we discussed with our board when we presented the budget to the board is to say we have to get ahead of this just in case we are in midpoint of the guidance or in the low range of the guidance. We cannot pedal back after and we need to get ahead of this. And so we looked across the entire P&L, both in terms of R&D portfolio, i.e., prioritization. We're also looking at it in terms of productivity. Same thing in manufacturing. There's still a lot of things we can do in terms of manufacturing productivity. And same thing in G&A. We're looking at everything.
Also on the CapEx, there are some projects that we wanted to do that we say, look, we're going to wait a bit before doing those projects. The plant in Canada, U.K., and Australia, as we spoke about, are almost finished. So we're just having the tail end of that. The Norwood plant is finished, as we said. The plant for the cancer, the INT product, the personalized, individualized product is also mostly done. So the CapEx also is coming down. And the team is doing also a lot of work with suppliers in terms of pricing, renegotiation, in terms of working capital. So the team is really working on all the levels that we have because every dollar matters. And we want to have those dollars to invest in the business and, of course, to be as efficient as we can.
Got it. So I think the 2028 break-even guidance, I think you had kind of penciled in a $6 billion top line for that year. But now if we're talking about OpEx materially lower than that in the short term, should we think about the 2028 kind of required revenue being lower, or do you still kind of see the products stacking up to $6 billion of revenue in 2028, even with the pullback on the fall?
Yeah. So it goes back to the fact that we want to be responsible and disciplined and careful. As I said, we've run this company for most of its history, being extremely focused on cash and runway. You have the same chairman, you have the same CEO, you have the same president of the company, you have the same leadership that has gone through building this company.
We made one mistake, which is, I mean, we made a lot of mistakes, but we made one big mistake, which is we were too rational about the vaccination rate in the U.S. and the way it was going to transition from pandemic to endemic. If you think about it, last year in the U.S., in the 65 and above, you had three times more people hospitalized of COVID than flu. Three times. Not 2%, three times. But yet the vaccination rate of COVID is significantly lower than flu. It doesn't make any logical or scientific sense. Well, we were most probably too logical, too scientific, and we were wrong. But we learned from that, which is reflected in the guidance, and we are also reflecting that into our cost structure.
If I had known this information two years ago that we should not be rational, that people at high risk, like 65 and above, will get more vaccination because of a risk of high hospitalization, we would have reduced the investments earlier. But that's one of the mistakes we made. We were too rational. I think we're not the only one, but we were too rational. And so we learned from it and we moved forward. We need to learn from our mistakes.
Okay. You also updated us on the interim for the CMV phase III trial. And I think in the past you had suggested that the final data could come mere months after the interim. Is that still the right way to think about when we could next year on that study?
That's correct. So if you look at the number of cases required for the first analysis, which just happened to the final analysis, the second and final analysis, it's not a lot of cases in difference. And so if you look at the, as you know, those studies, when they enroll, there's an acceleration in enrollment. So it's not surprising that you should be able to accelerate the number of cases without. And so we confirm that based on where we are now and the cases we are seeing, we should be able pretty rapidly, not weeks. We are talking months, obviously, be able to get the data. When we get the information from the DSMB, like we've always done, we will share it publicly.
Okay. What about INT? So you've completed enrollment now for the phase III for melanoma. When can we hear that data?
Yes. We completed the enrollment around September. The phase III started in July 2023. The teams across the board with our colleagues at Merck, they did a really great job to get this done. As you know, we have to manufacture every product for every individual. And if you look at the phase II data, you started to see separation from the Keytruda only arm at around 12 plus months. If you just play the calendar forward, 2026, it's tough to be precise on when because, again, it's case-driven. But 2026 should be when we get the melanoma phase III data with that. As I said, the plant will not be in critical path. The plant could have been on critical path for the potential accelerated approval, but because we're going for full approval now, of course, the plant should not be critical path.
And so we're going to be waiting like all of you for the data. And hopefully, if we get data confirming the phase II, we will be filing the data with our Merck colleagues as fast as possible and getting the product to patients because we think the benefit could be really substantial. As you know, the data at the three-year mark two out of three people have no distant metastases, which, of course, is the leading cause of death, is metastases. And so we think this product with no incremental toxicity compared to Keytruda, which people are going to get anyway.
So if you think about a risk-reward standpoint, you have a product where two out of three people could be three years out with no distant metastases with the same tox profile of Keytruda alone. And so we think that this is a product that is going to benefit a lot of patients. And so we are really eager to get this product to patients as fast as we can.
Okay. And what about the other INT trials? For example, the phase three for lung or kind of is there anything that we could learn before we flip the card on the phase three melanoma trial, anything in 2025?
So because all those studies have an enrollment curve and they're all timing to readout, it's really hard to predict are we going to get or not additional data from those studies before we see the melanoma phase III. Like we've done in the past, when we have data, we'll share it at medical conferences. We have done that consistently. But at this stage, it's really hard to predict precisely when we're going to get those data.
Okay. But when you get melanoma, we won't be waiting on manufacturing. It's all clear.
Yes. Manufacturing is not going to be critical path for the launch of a melanoma INT.
Okay. One of the products where I think we will get pivotal data this year is Norovirus, right?
We could. So as I said, and we said before, because it's a case-based study, if we get the number of cases, we could read out this year. If we don't, we're going to have to go second season. Same thing for the flu efficacy study. Those are all case-driven studies. So it depends on the attack rate and the number of cases happening. So that's an event-based study. We will, of course, update the community based on what we learn. But it's possible. But it's really hard sitting here in early January to know.
How do you envision the market opportunity for a product like that?
So we're quite excited about Norovirus, and we're excited because we spoke to hospital leaders. We spoke to our retail customers. There's no product on the market. If you think about the target population and you start adding all the layers of target population, it's actually quite a lot. You have, of course, the elderly who are hurt by Noro, including long-term care facility, of course. If you think about healthcare workers, there's a lot of healthcare workers every year who get sick because of a Norovirus infection that they get from one of their patients, whether it's a nurse or a doctor. And when you think about the number of medical workers in this country and around the world, it's a lot.
And then you have also educators. I'm sure anybody who has young kids or remembers having a young kid might have gotten sick a couple of times with kids in daycare or in lower grades in kindergarten and so on. So that's another population, the educators, who is highly motivated because bringing from work a disease where you get your own family sick in addition to yourself is not fun. There's, of course, also some other opportunities like cruise ship and overseas that we've also had discussions there. So when you start to add all those numbers, it's actually a pretty large addressable population. For anybody who has had Norovirus, this is really not a fun experience to have Norovirus. So we think that this is a virus that's pretty well known. We think the go-to-market strategy will be through the retail channel.
Again, with the retail channel being very interested to bring more and more vaccination possible for the customers of those pharmacies, we think that's going to be also a lot of drive there to drive their own business. So we're quite optimistic about Norovirus. Now what we need to see is, of course, the phase three data.
Okay. And what gives you confidence that you'll be successful there?
So again, with biology, you always have to be humble. We know that mRNA technology works. We've had some interesting data in terms of seroconversion, neutralizing antibody, T cell, and so on in the phase I too. So based on the fact that we've had COVID and RSV approved, 2024, we had four phase III positive with vaccine platform. We think there's a high confidence that this should work. But again, given it's biology, given there's a lot of diversity in the type of different strain of Norovirus that circulate, we have to be cautious until we see the data.
Okay. Maybe coming back around to RSV, why will or maybe will not 2024 represent a benchmark for what that market looks like going forward?
So I think there's a lot of variable, a lot of unknown that public health leaders are trying to navigate as they learn about having new vaccines available for this virus. The virus has been with us, of course, for a long time, but vaccines have been available for only one and a half seasons so far.
So what I think you see is what I've been told by some of my colleagues that have been doing vaccine development all their lives, is that when you launch a new vaccine, COVID apart because it was a pandemic, usually it takes several cycles of ACIP recommendation to get real-world evidence to fine-tune the recommendations, both on the efficacy, but also, of course, on safety. And so we anticipate that as the healthcare leader, public health leaders get more and more data, they will fine-tune their recommendations. We're in active discussions with them, as you can imagine. And so the piece that is clear is there's still way too many Americans hospitalized every year because of RSV. Some of them lose their lives to RSV.
And so we collectively with public health leaders want to work to figure out what's the right frequency of boosting, what's the right use of a product, in which population, comorbidity factors, all those things. Actually, there's still a lot to be learned. But I'm confident that over time, the public health leaders, as they get the data, they want to protect people, will be able to find the right recommendation to protect as many people as we can. But it's going to be a durable franchise because RSV is not going away. And the populations in most countries are getting older pretty fast.
Okay. Maybe speaking of public health leaders, in what way can kind of the new administration and kind of the incoming leadership in some of the public health organizations impact or change how vaccines are developed, approved, or recommended, if at all? And does Moderna expect any changes there?
So I think it's a bit too early to know exactly what's going to happen and what's going to change and not change. The piece that we are confident in, I think every elected leader and every public health leader in those agencies, CDC, FDA, CMS, and so on, want to protect the American people, want to make America healthy again. And so vaccine is a very important tool. If you think about vaccines in the elderly, if a recommendation was to be changed, the impact will be seen in the same season, which actually you might see an increase in cost. Just let's look at cost in the same season because, as we know, a 70-year-old person that is hospitalized is going to cost much more that same year by being hospitalized with very high cost.
And so there's a lot of doctors, scientists in all those agencies that know the facts and will be able to provide to the new elected leaders those facts so that they understand the benefit and the risk-benefit in terms of vaccinations that has been known and demonstrated for a long time. And so we're going to collaborate with the new administration, like we've always done with every administration in every country where we operate. And we believe that focusing on the data and the risk-reward ratio will be the right way to do it.
So maybe kind of building off of that question, what, if anything, do you think is kind of most misunderstood in the Moderna story right now?
Oof, how long do you have? I think, look, if I were to describe to you, let's take the midpoint of this year's range and tell you there's this new biotech company named X that has $2 billion of sales, two products approved, $9 billion in the bank, just filed three new BLAs, and has potentially six phase 3s with outcomes coming soon. I think most people will say, "Wow, this is pretty cool. This really rarely happens," right? And that's where we are today. The thing that happened to Moderna that was never in our plans was the pandemic. The pandemic happened. We were an 800-person company. I'm so proud of what the team has achieved to run so hard and work so hard to deliver what we delivered. One of the two vaccines that really got us back to normal lives.
And through that, we went from zero sales to $18 billion in 2021, $18 billion in 2022, and went down to $6 billion, and then $3 billion-ish last year. And we might be again using the midpoint at $2 billion next year. But the proceeds of COVID have first taught us a lot. We've got two products approved. We scaled up manufacturing to literally make billions of doses. We had made 100,000 doses in 2019.
So we are focusing on the three priorities I gave you, which is drive sales for existing product, focus on the products that are just in front of us over the next couple of years to diversify away from COVID, to drive sales growth again. We have the capital to do it. As you see with our actions announced today, we're going to continue to be very disciplined on the cash. We are not shy of partnering.
Last year, we did a partnership with Blackstone when we were very thankful for this partnership where they are funding the phase 3 efficacy study of Flu. So not using shareholder capital to do that. We're diversifying the risk of the portfolio. We partnered with Merck on cancer because they're a really, really good company in selling oncology products like Keytruda. We have a partner we didn't talk even about with Vertex in lung disease for inhaled mRNA for the kids that don't respond. So I think the piece people have been worried about the top line, and we're triaging stress points as we can. Like everybody, we are for the first time in our careers learning how to move from pandemic to endemic. Have we done everything perfect? No.
We just talked about earlier about we being too rational about thinking more people will get vaccinated in the high-risk population. And so we're recalibrating the business, but the science is working. We have two products approved, three final products. We're going to get more products coming. So I'm really excited about the next few years. I'm really, really excited about the next few years. It's going to be quite an interesting impact we can have on patients and the value we can create for shareholders as a consequence.
Okay. So you have kind of outlined a number of milestones for the company, a lot of clinical events coming out over the next couple of years. If you were to focus the investors in this room on kind of what's the most important thing that's going to kind of bring Moderna to kind of its next upswing?
Yeah. So, the way I think about the portfolio is through the respiratory franchise. Those phase three costs are mostly behind us. We're going to drive sales growth because when you're going to have the COVID, RSV, and then COVID-flu, and flu, and then Norovirus again through the retail channel, you're going to drive sales growth. You're going to have incredible manufacturing efficiency in terms of margin because we don't need to build another factory. It's the beauty of a platform. You make a lot of COVID, and the week after, you can make in the same room with the same people a lot of Flu, and then the week after, a lot of Norovirus, and you do it the way you want in terms of mix. So think about the incremental gross margin of a new product. It's going to be pretty high.
The R&D is behind you because you pay for the study, and it's all sold by the same team through the same channel, so that's what's going to get us back to sales growth first, but then the big value inflection point, of course, is INT. If you look at INT and again, the data we had, the three-year survival data is stronger than the two-year survival data. We don't see that often in oncology, I think. Two out of three people benefited from the data in the phase 2 study. That is not 5%, 10%. This is two out of three people. This is a massive clinical impact, and so if you think about INT and how the biology works, could we see a world where INT works in quite a number of tumors?
We do believe this is why we're investing aggressively across a lot of different trials, as you described. Merck knows a lot about oncology and knows a lot about Keytruda. And so I don't think they will be investing like this if they did not believe in the mechanism of action of our INT product, being able to individualize to your own T cell, the signature of your own cancer-based biosequencing of your tumor compared to your healthy cells. We have a lot to learn about INT. Could INT work in monotherapy earlier in disease? It's possible. We've had some interesting anecdotal signals in some of our basket studies in early days without Keytruda. Could that change care? Could you see a world where we've increased diagnostic, earlier detection?
You propose to somebody that is in early discovery of a cancer, really early stage, stage one, an INT monotherapy with a side effect of a vaccine that will transform cancer. Is it going to work? We have to run the studies. If again, you think not in quarters, but in the next years, a bit like a lot of oncology products have done that have been successful, is you start with one indication and you keep increasing. Not everything works. Oncology is still a very complex disease that we don't understand everything. If I look at the coming years, how our science works and what we've learned and we continue to learn about the mechanism of action of this cancer product, do I think it could become the largest product of Moderna? For sure. I do believe so.
It won't happen next year, but that's the next big catalyst after getting back into sales growth with the short-term product, some of them having already been filed to the FDA.
Great. Thank you.
Thank you.