Moderna, Inc. (MRNA) Presents at Cowen 43rd Annual Healthcare Conference (Transcript)

Moderna, Inc. (NASDAQ:MRNA) Cowen 43rd Annual Healthcare Conference Call March 6, 2023 9:10 AM ET

Company Participants

Stephen Hoge - President

Conference Call Participants

Tyler Van Buren - TD Cowen

Tyler Van Buren

Okay. Great. Well, let's go ahead and keep going. Good morning, everyone. It's Tyler Van Buren here, senior biotech analyst at TD Cowen. For this first fireside chat, it's my pleasure to introduce Stephen Hoge, President of Moderna. Thank you very much for being here, Stephen.

Stephen Hoge

Thank you, Tyler. It's exciting.

Tyler Van Buren

So, before we get it started, for the audience, if you guys have questions, feel free to raise your hands as well.

Question-and-Answer Session

Q - Tyler Van Buren

And we'll plan to dig in mostly on the R&D questions, of course, but wanted to kick it off with the commercial one. On COVID, you guys have talked about $5 billion in deliveries for 2023, maybe around $2 billion in the first half, $3 billion in the second half. Can you just discuss your confidence in that number? And then also, talk about potential levers for upside to that number?

Stephen Hoge

Yeah. For sure. So, first, let me just say thank you for having us here and having me here. It's great opportunity.

So, first, that $5 billion, as you just referenced, it's divided almost equally between deferrals from last year's contracts and then advanced purchase agreements for this coming second half. And so, I'll talk about this two somewhat separately.

We expect about $2 billion of deliveries, as you just said, in the first half of this year to happen, those are really the deferrals that happened from last year purchases. And what you'll be left with is about $3 billion of advanced purchase agreements or other contracts, which are mostly with Canada, United Kingdom, Switzerland and Taiwan, and a couple of other small countries. And we feel confident that, that's going to materialize. We do believe there is going to be a booster campaigns in those countries in the coming fall in the Northern Hemisphere.

What's the upside to that, and the reason why I think we described that in our quarterly call as a [bit before] (ph), is the United States, Japan and the European Union, we expect all to purchase vaccines, to run fall booster campaigns, and really that represents even larger portion of the market than we currently have now. There are, obviously, supply of vaccines and the existing contract with some of those countries, but we do see upside from particularly those three large markets.

Tyler Van Buren

Okay. And so, last year, if I recall, I think it was June 30 when they surprised you with a reply with the proper strain. And so, you think they might be a little bit more organized this time around? What's the potential timeframe for strain selection? And again, despite that, you guys were able to get the vaccine ready by September, but maybe you could just review for us how the process will play out this year?

Stephen Hoge

Yes. So, we're guided by the regulators. And I think the U.S. FDA is most clear in defining what their process is, and they actually did that at an advisory committee last month. They expect to make a strain selection decision late May/early June and run through an advisory committee or VRBPAC in this country. They would then define what's the composition of the vaccine they want to see for the fall in the United States. They laid out a very structured scientific way to [learn] (ph) more about that. It will depend a lot upon epidemiology and then the evolution of the virus and how much [immunization] (ph) we continue to see.

But if you were to look today, it's clear that we've kind of moved out of the BA.4, BA.5 and into some XBB.1.5 and a lot of [indiscernible]. As you alluded to, it's probably still a little premature to say what the dominant strain will be. By this time last year, it was BA.1, BA.2, and by the time they made the decision in June, it was BA.4 and BA.5. And so, what we're trying to do as a company is prepare -- be prepared for all outcomes, which is that we're actively following all of the evolving strains and what we're preparing to do is to be able to respond very quickly. We're trying to do as much pre-work as we can when that strain selection happens, so that we can do what we did last year, which is ultimately we're able to support our global boosting campaign with updated vaccines.

Now last year, we had two, as you know, and that added complexity. Our hope is that this year, maybe it's not two. But if it, if it does require different geographies, different countries, choose different path, we need to be ready to meet that challenge as well. We've done it once. And we'll do it again. We hope that second time is a little bit easier.

Tyler Van Buren

That's great. And do you think it will be most likely bivalent or monovalent?

Stephen Hoge

Personally, I think science supports a bivalent approach. And we've seen that in our own data, in public health official's data. We ran actually a head-to-head clinical trial of bivalent versus monovalent last year in the United Kingdom and showed against some of the earlier Omicron strains with significant improvements in efficacy in preventing COVID-19. Now, again, it's really not our choice alone. We have to be prepared for all [outcomes] (ph), and that's one where we will look to guidance for public health, speak with the FDA, but also CDC, on which choice they make for this coming year. We will be ready whether it's a monovalent or bivalent to move forward. I think from the data I've seen so far, I think, bivalent covered more bases.

Tyler Van Buren

Okay. And there's been some, I guess, uncertainty around booster uptake, right, especially with this last fall, winter season. And I think, [it got to] (ph) a lot of people last year who I thought that they were still protected from Omicron. Obviously, Omicron hasn't happened this year, but maybe can you provide some bookends around what you think booster uptake might look like in the next fall, winter season?

Stephen Hoge

Yeah. I think 2023 -- 2022 was particularly challenging year to do any prediction off of, you just had alluded to it. But a year ago today, we were dealing with Omicron BA.1, and waves and shutdowns happening, and that's in just 12 months. And then, what you went through is, people receiving a fourth dose booster recommended by CDC or someone, I think, globally in the second quarter, and then a bunch of people getting infected with Omicron, probably not BA.1, probably BA.4 or 5 in the summer. That was a big wave in this country, non-seasonal wave. And then, obviously, we've got uptake in the fall of the bivalents. And many people have a hard time reading as do we, as do I, the tea leaves of what that all means, because so many people -- 30% of people received the vaccine, probably more than that actually got infected, all of it happening around the same time. What happens now that we're hopefully more in a seasonal situation where hopefully there isn't a summer wave of an XBB or Omicron variant, and therefore, people are more available for vaccination when [they got flu] (ph).

I think the best predictor may not be COVID. Candidly, I think that the best predictor probably is the influenza seasonal market. In this country, even this winter, COVID led to three times the hospitalization, three times the death of influenza. And the approach that -- and so that's just this last few months, right? That's in the face of all the vaccines and all the prior vaccines that happened. And the CDC data shows clearly you can reduce those with boosters. And so, if you look at the influenza market, actually closer to 50% of the Americans received booster every year, over the age of six months, particularly above the age of 50, those over -- at higher risk, you see numbers that are 60%, 70%. And so, our assumption is that, that market, the older adult portion of, in particular, which looks more like 100 million doses every year of influenza vaccine, probably is the best predictor of what a seasonal COVID looks like for this year, because we don't expect people -- we hope there's no summer wave, and we expect people do want to be protected against respiratory viruses that cause hospitalization death. And as I said, as it stands right now, COVID is bigger threat than flu.

Tyler Van Buren

Yeah. All right. Let's move to flu. mRNA-1010, you got immunogenicity results recently, superior on A, inferior on B. You'll have vaccine efficacy data potentially by the end of the quarter. What do you need to show with that vaccine efficacy data to obviously match the superiority that you're seeing with immunogenicity and potentially file?

Stephen Hoge

Yeah. So, it's important that the immunogenicity study was a safety immunogenicity study. We're happy with the safety results. And I think you covered it well. We've talked about net superiority on influenza A for three out of four endpoints and non-inferiority on fourth, and then didn't make non-inferiority on the B's. That wasn't a huge surprise. It was -- we were always aiming higher on the A's than we were on the B's. And the reason is because the epidemiology of influenza, the disease burden in adults, which is what this vaccine is being developed for, in its first instance, is 95% to 99% influenza A.

In fact, as we announced in that same press release, our influenza A efficacy, our influenza efficacy study, which is running in the Northern Hemisphere this year in the United States and Europe, has collected over 200 cases. And we said over 99% of them -- over 99%, you do the math, that means one case, right? Because if there were two cases, it [won't] (ph) be 99% exactly. There's one case of B and 199 of A's. And that's just further evidence -- that's actually the -- that's what the cost driver is. When you say people are going to be hospitalized or they're coming down with flu in this country, that's what driving it. And that's why we thought when we've moved forward a year ago with that candidate, we really want to focus on let's hit the home run A's and let's just cover what's needed to, from a regulatory perspective, on the B's.

So now what is it -- what do -- your question is what -- how do we need to see it go forward with filing at this point? Well, the efficacy results are really the gold standard, right? In immunogenicity and immune bridging and surrogates, are all for accelerated approvals. But if you run an efficacy study, that's what the regulatory vote standard is. And it is against all of influenza that we're trying to achieve that outcome. And year in, year out, that influenza is H1 and H3, it's influenza A with very, very small amounts of B in this population.

So, I think if we see non-inferior efficacy or superior efficacy in that study, our expectation would be that that's met the gold standard, the regulatory guidance, not for accelerated, but for full approval, and we'd engage regulator around that. There is a -- the regulators may say -- it's up for them to decide, but they may say, "Great. Thank you for that. You're right. But we would love to see you increase your titers on B even though it's not driving efficacy." And if they did, we would, obviously, respond to that. We think, as we announced last month, we already have ways to increase the titers of B, even though we don't think that those will necessarily contribute to efficacy in the population. And so that would be a conversation we have with regulators.

But I think any non-inferior efficacy or superior efficacy in our ongoing study would be the basis for full approval, at least that would be the approach we'd take into those conversations.

Tyler Van Buren

Okay. That's very helpful. Are you able to state what the non-inferiority margin is for the immunogenicity study so we can at least get some sense of what the minimum threshold is for superiority on A?

Stephen Hoge

So, generally, that's a discussion with regulators and different regulators have different perspectives on it.

Tyler Van Buren

Got it.

Stephen Hoge

Non-inferiority, I would say, generally, rather than give you any individual regulatory position on it, because they -- again, there will be differences, as you want to exclude a lower bound of 10% or minus 10%. But again, it's fact and case specific. And it's important to note that many of the enhanced flu vaccines, actually, in different ways, all of them -- maybe not all of them, most of them have failed to meet immunogenicity endpoints on B at some point, either in their primary study or in follow-on studies when they went from trivalents to quadrivalents. It's actually not uncommon thing that vaccines receive full approval despite challenges with influenza B. And the reason is the same as I said up front, which is, for the most part, people recognize that's not what's driving disease. It's more of -- the influenza B are included because they drive disease in young population. You want to have a single vaccine across if you can. But that's why, generally, there've been multiple instances as well precedent of approval for that.

So, I think the point -- estimate point even that you raised about [indiscernible] vaccine questions, it's really going to be a totality of data conversation with agencies, but the precedents are pretty clear that there are lots of approvals that have happened even for enhanced vaccines where they have not met all of the endpoints from immunogenicity. And even in some of the enhanced vaccines, there are approved enhanced vaccines that had -- where approved accelerated, had an obligation to demonstrate efficacy and failed to demonstrate efficacy subsequently. Vaccines on the market from the vaccines that had did not head around five seasons worth of those vaccines to get there and they were sold throughout.

So, my point is, influenza is uniquely complicated space from a regulatory framework and a public health perspective. And regulators will want to see the totality of that data. We'll want to see it all in the side of the path forward, and it's really hard to give an absolute [whack away] (ph).

Tyler Van Buren

Yeah. Okay. That's very helpful. I guess, with respect to your next-gen candidate with better potential matching against B, what can you say about the improvements you made? And when might that be able to reach the clinic and potentially get on the market?

Stephen Hoge

So, second part of that question quickly, we're actually starting that study very shortly. I think that could move very quickly. Because it's really just an immunogenicity endpoint, right? I mean, think of something that's more in line with what we've been seeing with the COVID updates, right, not once you've established safety and hopefully soon efficacy of the platform. And I think it's possible. I'm not guaranteeing anything, but possible that actually that is the product that gets launched, because you bundle all of that together, right? And bear in mind that these vaccines change their composition every year as a part of being flu vaccines and seasonal. And so, it's very normal to do that. And in fact, the changes that we made are -- just as a reference, are even much more modest than the changes we make when we update COVID vaccines or the flu vaccines we'll be doing normally. And so, we think it's well within reason that, that actually it could be a product that ultimately gets launched, again, subject to discussion with the regulators and ultimately with the data sets. And I don't have the data. I don't know. And then, no fault for them to decide.

In terms of the changes we made, they're, obviously, as I alluded to, pretty minor. We haven't disclosed what they are yet for competitive reasons, which we haven't done that yet. We will at the appropriate time scientifically give some transparency to what we did. But it's a pretty straightforward exercise, increasing titers from our perspective.

Tyler Van Buren

Okay. Great. And I want to finish flu with a couple of general questions. So, obviously, the potential advantage of your platform is that you have the rapidity of manufacturing in a group strain selection. But if you look at the data, the strain mismatch occurs basically every three to four to five years. Maybe correct me if I'm wrong. So, how can you potentially demonstrate that post approval? Will that come from your studies or real-world data?

Stephen Hoge

I think the answer will be a bit of both. We certainly expect to see real-world data. So just to give you quickly the background on what you said, one in six years, maybe one in five, one in seven, it sort of bounce around, there will be a strain mismatch. It'll be a bunch of different reasons. But the short version of it is people have to pick the vaccine composition in February and March, because they make it in eggs. And then, either the eggs evolve the virus in a way that doesn't look like the virus, which happens, [indiscernible] that patient, or they pick wrong six months later, six months earlier. We don't have that problem. We were actually currently -- we just talked about COVID, it's anticipating peaking in June, and we're going to set ourselves up with flu to do the same.

In a mismatch year -- [we'll have to partner] with public health to do that, but they've never had the option. But in a mismatch year, efficacy can be terrible. We've all seen the news stories on that now. You're going to the -- you go to your pharmacy, your doctor's office, and you get a vaccine, it's really not expected to protect you. And so, the opportunity for benefit there is it's one in five years. Even if you were non-inferior in four out of five years or even in our current studies, you just get the same, but you were the only one that worked in the fifth year. On average, you're 20% better, right?

And from a healthcare system perspective, nobody's really happy with those expensive years. And, obviously, nobody wants to go to their pharmacy or doctor's office to be told they got the wrong vaccine. And so, from our perspective, heavy focus on this first-generation product is get it approved and show public health that we can update it later in the season and have better matching and avoid those mismatch years, and essentially even if we're no better on efficacy, create more value to the healthcare system.

Now, the question of where we going to have to show that, I think for now, it's we're going to probably do a bit of both. So, we are always going to have real-world effect in the studies that look at how the vaccine performs. The CDC will do those as well. And those are really important. And so, every year, vaccines get rolled out, a better matched vaccine would show better effectiveness in the data as monitored by public health officials, CDC in particular. And then that would provide, obviously, publication evidence. But we will probably also take the opportunity in a mismatch year to consider looking at efficacy. Because, again, it will be the difference between getting a functioning vaccine and nothing, and the opportunity to run a efficacy study, it's not a huge effort when you know your competitor, they've improved the vaccine. [indiscernible] vaccines are mismatched.

And so, it'll -- we'll make that decision at that time and then kind of also what else we got going on. But I think we will look at to demonstrate that potential, and then ultimately get credit for that.

Tyler Van Buren

Okay. That's helpful. So, some vaccine veterans I've spoken with have talked about the importance of room temperature, stability, and prefilled syringes. So, how close are you guys to potentially achieving that?

Stephen Hoge

Yeah. I think you mean refrigerated non-frozen stability or...

Tyler Van Buren

Yeah.

Stephen Hoge

Yeah, refrigerated stability. There is some room temperature, but vaccines are not generally sort of room temperature unless they're [indiscernible], and flu is in prefilled syringes. So, first on the dosage form, on both points, heavy focus area. And we're trying to prepare ourselves to be look like that, refrigerated, prefilled syringe across our platform. In the short term, when we're dealing with launching products, we are looking to make single dosage forms, so prefilled syringes. We do have prefilled syringe and single-dose vials, some countries prefer one versus the other. It's a bit of dealer's choice there. But those single-dosage forms are things that we expect to do in our COVID vaccines, our RSV vaccine, which launches last -- next year, as well as eventually influenza, again, subject to us completing the clinical trials that are ongoing ultimately, in all cases, subject to regulators approving them. But we think technologically, that's possible. And so, the single-dose form is the first step.

Refrigerated, we are also working on. That's more of a second-generation improvement for all of those. It will be easier for flu and RSV than it was for COVID. COVID is an incredibly large mRNA, as we all know, making a spike protein, it's a very, very large protein, and that really dictates a lot of our shelf life. And so, it's much easier for us in some of the newer vaccines. And as I think we announced recently, with our 1283, our -- I think, it's second-generation COVID vaccine, generation is getting a little confusing these days, that is targeting actually a refrigerated storage form. And so, even COVID, we hope to move to that space in the coming year or two.

Tyler Van Buren

Okay. Great. So, let's move to RSV. Do you have any high-level takeaways from the recent advisory committee with Pfizer and Glaxo?

Stephen Hoge

We feel really positive about it. The -- clearly their support, when you -- we've started to share our data. Our lead investigator presented some of the initial data at RSVVW, and we'll, obviously, publish that as well. But we're really pleased with our efficacy and [indiscernible] profile and encouraged that the advisory committee felt really -- felt positively, I guess, voted positively for both of those products.

I think we believe that it's going to be a lifelong journey. This will be for decades. This is a virus that's been with us for our entire lives and feel like flu. We're going to continue to need to boost people forever. And in that sense, we're playing -- we're focused on making sure that we bring forward what we hope will be the best product overall from efficacy and safety tolerability optionality, the ability to combine storage conditions, all those sorts of things.

But what I would say from the advisory committee conversations is, it's really encouraging that path has now been trailblaze, and, we hope to very quickly move through that ourselves with our own filings, which are hoping to complete in the first half of this year, and then subject to the FDA reviewing this, we'll have our own chance at [indiscernible].

Tyler Van Buren

Okay. And for the combination respiratory vaccines, obviously, you guys need to focus on getting the individual components approved first. But when could a combination respiratory vaccine become a reality? What should that progression look like through a combination franchise?

Stephen Hoge

Yeah. So, the good news of a combination is the pathway there is some way simpler and clearer, right? If you get the mono -- our strategy is pretty clearly, we're going to go get the individual pathogen vaccines approved. And those are the ones where you have to run efficacy studies, like large safety and efficacy studies. Yeah, costs a lot of money, involves tens of thousands -- we recruited 75,000 people last year. But then, as you move out of those approvals, what you then go start doing is the combination studies.

Combination studies are non-inferior immunogenicity and safety studies. You just put them together and you pick your final two, and you create that combination, and it's much quicker. It's again, think of it as the difference between the bivalent updates or the sequence updates that we did last year versus first approvals. And that will go really quickly. Because you don't need to go generally -- we don't expect that we need to go run efficacy studies with vaccines. We've got the efficacy. We're just showing combination, non-interference, good safety, and you go. There is a contingency, though, which is that you have to get the combination of individuals approved. And so, we're -- obviously there with COVID, we are optimistic on RSV, we got a little bit of work to do on flu, we're going to get there hopefully quickly. And then, once those are approved, we can do those combos.

We are starting the research and development now. So, we're running clinical studies on a range of different combos, because we can answer some of those questions at risk. But if there are small changes to what we're doing on individuals, we want to reflect those in the final Phase 3 study that are on board. So, it is contingent on getting those -- our focus is on getting those first-generation monos approved, working our way through the big three very quickly here, and then we will go very fast. Like, think of what we did with the COVID updates on the combos, and then roll those out shortly thereafter. And so, we're prepared most of that work, and -- I don't have an update on today, but we're ready to go as soon as we get the monos.

Tyler Van Buren

Okay. So, let's move to oncology with PCV.

Unidentified Analyst

Tyler, I have few questions. Actually, what do you think about -- what is the likely dose for that combo dosing that you're going to need? How much in each and in total? Where do you think that's going to shake out?

Stephen Hoge

It'll depend a lot on -- just depend a lot on immunogenicity that comes from those early studies. And so, as it stands right now, our primary dose that we've taken forward in COVID, as you all know, is 25 micrograms, it's bivalent. That's with our 1273 platform. But we're actually doing a much lower dose in the second-generation product. And so, I can't even tell you, within COVID whether it is going to be 50 micrograms or that much lower dose within flu and -- within RSV, it's 50 micrograms. And within flu, we've been evaluating 50 micrograms in the existing studies. If those are approved, then you'd add those to it. We expect that, that's likely additive, A plus B plus C equals the dose. But I think we have to wait for the data to confirm that.

Unidentified Analyst

So, you're talking about sort of at a minimum 150?

Stephen Hoge

If it were those three approved dose levels, that's a reasonable estimate. But I would remind you that I think, actually, our COVID vaccines already going through an update. So, I think we'll see what that looks like as we go forward. We may or may not do that. And we haven't made that decision. So, it's at this point, speculative sort of pick a dose. We'll wait to see the data.

Tyler Van Buren

All right. So, PCV, obviously, at 0.56 hazard ratio is really impressive. Expectations are certainly going to be high going to the update presentation, whether that's at ACR, ASCO or both. What else should we be paying attention to that maybe is not [obvious] (ph) from the top-line data release?

Stephen Hoge

Yeah. So, we're thrilled by that data. I think we will look to at ACR and hopefully ASCO both providing updates, clinical updates. We will look to publish very shortly here and we already submitted publications on the data. There is a lot of very exciting stuff to see. And we want to make sure we get it out in a peer review context in the right forum.

I think the things that I would -- we will all want to be looking at, the shape of those curves, the Kaplan-Meier curves, and the evolution of that hazard ratio over time. I'll give you a top-line number, 44% reduction, 0.56 is a hazard ratio. But the question is, is that 0.56 all the way through? Or as generally as happened in immunotherapy, and this is true for checkpoint inhibitors like KEYTRUDA, does that improve? As you look at the piecewise, does the relative benefit become more superior over time? That's a stronger signal that you really got the immune system controlling that disease.

The other thing I will be looking for we are studying right now is the translational biomarker data. Can we predict those responses, right? We're giving the total top-line 0.56 as a hazard ratio, that's all comers. That's randomized by nothing other than that they enrolled in the study. Buy, obviously, you'd expect that there are going to be criteria that might allow you to show -- select those patients who are even in a more stronger respond, and that would lead to a higher benefit of improved hazard ratio. Some of that is ongoing. We've got to do that, and that's what we'll be sharing in successive presentations when we pull that together.

But those are the kinds of signals that would suggest not only is the picture, robust and strong, but there may be populations that, that are already really strong or importantly if the hazard ratio is improving over time from a piecewise perspective. But actually, the statistics are going to continue and get stronger. That all of which might suggest, as we hope will be the case that at some point, this randomized 150-person Phase 2b study that we ran might be able to become basis of an accelerated approval. And we have to follow. It's too early to say, but we are hopeful that the data will mature that work. It's randomized against standard controls statistically significant benefit, that's a quite a reasonable place to start that study.

Tyler Van Buren

Very interesting. So, what's your level of confidence with respect to that data translating into the metastatic setting, as well as other indication like lung?

Stephen Hoge

I'm very confident -- very confident is danger word. I'm much more confident on translating into other adjuvant settings, then I would be into metastatic settings. And that's really based on the mechanism of action of drug, right? Our -- what we do is specifically increase the number of tumor specific T cells that are able to see new agents in that tumor and go clear it. But even with a really bulky tumor, the history of that is, the immune system at his body won't suffice, out number, it's outgone. Even checkpoint inhibitors, PD-1s, don't do great, if it's too late.

And I think the principle behind the cancer vaccine from our perspective is this is something that's has a safety and tolerability profile that kind of looks like your COVID booster, you can't dose it, but it actually prevents your cancer from coming back. And that tolerability and safety profile is differentiated in cancer. And the idea that it's almost having you risk would probably say, not how do I use it late, how do I use it early? I only get into a place that feels like I'm un-intercepting and doing more prophylaxis.

So, where we feel about -- how we feel about how it's going do with adjuvant in the Stage 3 space, I feel like in non-small cell lung cancer and other adjuvant indications where the KEYTRUDA or the general PD-1 labels are strong mutual benefit, and there's still headroom, right? There's still -- a large number of people are not responding, like they were in melanoma. We expect to get there very, very quickly. And I -- there's really no reason from a biology perspective, from a mechanism of action perspective that you wouldn't expect the benefit to be similar, because we're just adding specific T cell populations in the same way.

I think metastatic is a bigger challenge. That tumor is built up defenses that are deeper and stronger. The reason why checkpoints aren't working there is this issue. I think the more likely situation for what you will see benefit is, as I would just saying like a minute earlier, Stage 3a, Stage 2 disease, those are different types of studies that have never been run before. People haven't wanted to give checkpoints in those context always, but I would ultimately be biologically more convinced that that's going to be the result.

So, adjuvant, Stage 3, we're going full speed. We will keep our eye out on metastatic. We do have some early data from our Phase 1s and 2 -- Phase 1, I should say. And there are some Stage 4 patients in the current study, but I'm more optimistic about the adjuvant.

Tyler Van Buren

Okay. That's helpful. We're getting a bit on time, but I have to ask you one question about the therapeutic pipeline.

Stephen Hoge

Thank you.

Tyler Van Buren

What's your favorite program? And why? What's your favorite child?

Stephen Hoge

Oh, in therapeutics. I -- it's a -- this is a really tough one. I am -- I'm very excited about the PA data for propionic acidemia, it's our first rare metabolic disease. We've announced an update in September. We expect further updates this year -- September last year. We expect further updates this year. The key question for us is, can we get that into a pivotal study or an expansion arm, a [indiscernible] study, a single arm study that would lead to approval. That would be the first time that we demonstrate that we do chronic dosing.

We're well over a year and many of those patients are 18 months, two years, and we're -- everybody on that study has chosen to stay in the open label extension even -- across all the doses. That's -- that kind of uniform engagement from patients and their families is, I think, a really strong signal and their physicians. I think that program has a chance to -- if we can find that dose and expand it quickly, can go very, very quickly. And I think that will be an exciting moment for us.

Tyler Van Buren

Okay. So, I'll end the chat as I normally do. So, in closing, what aspect of the Moderna story do you believe is most underappreciated by investors?

Stephen Hoge

I don't think people have -- I still don't think it's obvious how much we do. We have 48 development programs. We just ran very quickly through some stuff. We didn't cover everything we do. We've got cancer in a big way working. We've got rare diseases working. We're in pulmonary diseases with cystic fibrosis with Vertex. And we run -- ran -- I can't even count the number of Phase 3 studies last year. We're talking about RSV and flu, and we're going to do some work on flu, we got combos coming. We enrolled 75,000 patients last year.

What's perhaps not obvious is that we're still a pretty small company. And technologically, what we're doing pound for pound doesn't look like anybody else. And I think that there's some time the desire to look at Moderna as a portfolio of individual products and say, "Wow, it's good, but does it add up and how it's going." I think if you ever take a step back and say, "Okay. But how was this company that was 800 people three years ago, doing $35 billion of revenue and creating 1.5 billion doses and contributing to pandemic.

And at the same time, getting multiple other products approve across things as range, you know, as very -- as RSV and cancer and PA." And that ultimately comes down to our platform mindset, the network effect we get across that, how quickly we're able to learn and leverage our infrastructure. And if we are eventually right across even just the four or five things that you and I talked about today, I think some people are going to have to realize that there's -- that kind of leverage is exceptional in terms of efficiency of time, of capital, and obviously, of healthcare impact.

Tyler Van Buren

That's great. Well, Stephen, thank you very much for your time.

Stephen Hoge

Thank you.