Good morning. Welcome to Moderna's Fourth Quarter and Full Year 2019 Conference Call. At this time, all participants are in a listen only mode. Following the formal remarks, we will open the call up for your questions. Please be advised that the call is being recorded. At this time, I'd like to turn the call over to Lavina Talukdar, Head Investor Relations at Moderna. Please proceed.
Thank you, operator. Good morning, everyone. On today's call, we will discuss Moderna's fourth quarter and full year 2019 business update and financial results. You can access the press release issued this morning, as well as the slides that we'll be reviewing by going to the investor section of our website. Speaking on today's call are Stéphane Bancel, our Chief Executive Officer, Tal Zaks, our Chief Medical Officer, Stephen Hoge, our President, and Lorence Kim, our Chief Financial Officer. Before we begin, I would like to remind everyone that this conference call will include forward-looking statements. 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.
We undertake no obligation to update or revise the information provided on this call as a result of new information or future results or developments. I will now turn the call over to Stéphane.
Thank you, Lavina, and good morning, everyone. As you know, we believe mRNA has the potential to be a new class of medicines with the opportunity to address many unmet medical needs. Given the unknowns of working with a new technology, we have been laser focused on managing risk, technology risk, biology risk, execution risk, and financing risk. 2019 was an important inflection year for Moderna. We reported clinically validating data from key programs in two of our modalities, prophylactic vaccines on the left, and systemic secreted and cell surface therapeutics on the right. Data that we believe fundamentally change the risk profile of each of these two modalities that we now call core modalities. As a result, our strategy is to double down in these two core modalities with many important medicines.
We have already announced five new development candidates in these core modalities since January 13 at the JPMorgan conference, three new development candidates in infectious disease prophylactic vaccines, and two in the systemic secreted and cell surface therapeutic modalities. While we double down in core modalities, we are still more than ever interested in understanding the potential of our mRNA technology in our exploratory modalities, cancer vaccines, intratumoral immuno-oncology, localized regenerative therapeutic, and systemic intracellular therapeutic. When we think about it, we have two distinct businesses. This is a significant point in our strategy. Core modalities, we want to scale invest, exploratory modalities, where we are waiting for clinical data to decide on the path forward. Stepping back, I would like to share with you the progression of the company toward a new class of medicines.
In the early days of Moderna's history, our goal was to enter the clinic safely. We spent years investing and developing mRNA science, formulation delivery, and manufacturing. The company pivoted out of that growth phase when we entered the clinic with our H10 influenza vaccine in December 2015. In the clinic, our next goal was to learn how well our technology was working or not. We explored our technologies across six different modalities. We tested 16 different molecules in the clinic in a short four-year period. In 2019, we generated important data in two of these six modalities and identified our first two core modalities, infectious disease prophylactic vaccines and systemic secreted and cell surface therapeutics. We're entering a new phase of the company's development.
Our goal for this next phase of our history is to find multiple BLAs while continuing to explore on our clinical programs in our four exploratory modalities. We are supported to invest aggressively in our science, including inventing new modalities, such as our ongoing collaboration with Vertex. We're fortunate to be able to close the financing earlier this year, so we can maximize our potential to create value and manage risk. Once we find multiple BLAs, our goal will be to scale the company and commercialize a large portfolio of mRNA medicines. Now, Tal will take you through our prophylactic vaccine programs.
Thank you, Stéphane, good morning, everyone. I'll start with a quick reminder on the data generated to date with our vaccines. In over 1,000 healthy volunteers and six positive phase I data sets to date, we've observed a safety profile consistent with the safety of marketed vaccines and the ability to elicit an immune response in the form of neutralizing antibodies. Updates for the ongoing programs are shown on this slide. The CMV phase II dose confirmation study is enrolling well. We completed the second dose cohort and are close to completing the third one. We now expect data readout to come in the third quarter of this year. Our hMPV-PIV3 combination respiratory vaccine has started the HD escalation study, Merck is on track with their RSV program in adults. Zika is also going well, as three of the four dose cohorts have completed enrollment.
Our three new development candidates announced recently are vaccines against pediatric RSV, mRNA-1345, Epstein-Barr virus, or EBV, mRNA-1189, and our vaccine against the novel 2019 coronavirus, mRNA-1273. Stephen will take you through each of these candidates in a minute. CMV is an unmet need as there aren't any approved vaccines, and the burden of disease from CMV infection is significant. Of the 25,000 newborns in the U.S. affected each year, 20% will have permanent neurodevelopmental disabilities. The spectrum of sequelae range from hearing loss, vision loss, microcephaly, and even mortality in 10%-30% of the severely affected infants. We believe our gB and pentamer vaccine has the potential to prevent CMV infection and help thousands of newborns avoid these sequelae. On slide 16, I'll review the most recent data from our CMV program. In January of this year, we shared the seven-month interim data.
The safety has been generally well-tolerated. We've not seen any related serious adverse events. Immunogenicity data continues to confirm earlier interim data from the trial and continues to exceed our expectations. Specifically, we continue to see higher neutralizing antibody titers in seronegatives and seropositives in both epithelial and fibroblast assays. If you look at those who have never had CMV, the seronegative group, after the third vaccination, they had neutralizing titers against epithelial cells that were more than 10-fold higher than the level seen in seropositives at baseline. We also saw a nice increase in titers against the fibroblasts. Even in seropositives, people who have been infected, our vaccine is able to boost them 20-40-fold higher above baseline level after the third vaccination. We see early evidence of durability out to 12 months.
These data are what's behind our optimism and belief that we can take this vaccine all the way through to prevent infections in newborns. As mentioned earlier, our phase II dose confirmation study is enrolling well and is currently enrolling the last dose cohort. We now expect data from the first interim analysis in the third quarter of this year. Preparation for the phase III trial that we anticipate will include less than 8,000 participants, including women of childbearing age, are underway. An early estimate of the cost of this trial is in the range of $200 million-$250 million. Now as an opportunity for us, CMV is clearly a blockbuster opportunity. We estimate annual peak sales for a CMV vaccine to be in the range of $2 billion-$5 billion, in line with the estimates of others in the field.
Assuming an average selling price like GARDASIL, a relevant comparator here, we estimate gross margins of about 90% and EBIT margins of approximately 50%. We're excited about the progress towards this opportunity, supported by the fact that just one of the antigens in our vaccine, the gB, when encoded for in a traditional recombinant technology in the past, had already shown a 50% efficacy, which was demonstrated by Sanofi several years ago. We believe that targeting both the pentamer and gB antigens as our CMV vaccine does will be additive to the vaccine's efficacy. As a reminder, our CMV vaccine, mRNA-1647, is wholly owned by us. Let me transition it to Stephen to talk about our new development candidates.
Thank you, Tal. I want to start by introducing three development candidates in our prophylactic vaccines modality that we've recently announced earlier this month. The first is against Epstein-Barr virus, and just want to pause for a moment and give you an overview of the disease. Epstein-Barr virus is a member of the herpes family that includes CMV, and it's spread through bodily fluids, mostly in young children and adolescents. EBV is a major cause of a wide range of diseases, but is the leading cause of infectious mononucleosis in the U.S., accounting for almost 1 million cases annually. Infectious mononucleosis can debilitate patients for weeks to months, and in rare cases can lead to hospitalization and even splenic rupture. Now, EBV infection is also associated with a range of other disorders, including lymphoproliferative disorders, cancers, and autoimmune diseases.
For instance, it is associated with a significant increase in risk of multiple sclerosis. There are currently no approved vaccines for EBV. Our vaccine candidate, mRNA-1189, is designed to provide broad protection against EBV infection and infectious mononucleosis. EBV has a number of surface proteins on its envelope, including GP350, a trimeric complex of GP42, GH and GL, a dimeric complex, and also gB. All of those antigens are important for infecting a range of different cell types, but particularly B cells and epithelial cells. Now, vaccination against only one of those antigens, GP350, which provides only partial B cell protection, reduced the rate of infectious mononucleosis in a prior study by up to 78%, but it did not prevent the rate of infection.
We believe that the combination of multiple antigens, GP350 plus antigens GP42, GH, GL, and gB, will provide an opportunity for broader protection, both of B cells and epithelial cells, very analogous to our approach with the cytomegalovirus vaccine. Now, we estimate that the opportunity is quite substantial. Worldwide direct costs of EBV-linked infectious mononucleosis reach almost $500 million annually, and the indirect costs could exceed $1 billion. Prevention of EBV infection, in addition to the prevention of infectious mononucleosis, could represent a much more significant upside because of the associated increased risk in cancers and multiple sclerosis. These would represent a long-term potential but are not currently a focus of our current clinical development plan.
Pivoting now to our second recently announced program, which is for respiratory syncytial virus in the pediatric population, I want to pause and provide a little bit of an overview of the disease again. RSV is the leading cause of unaddressed severe lower respiratory tract disease and hospitalization in infants and young children worldwide. It's a major cause of hospitalization in this country, accounting for up to 86,000 hospitalizations a year and over 2 million medically attended RSV infections in children under the age of five. Globally, the burden of disease is even more substantial, with over 30 million episodes of acute lower respiratory tract infection annually. We estimate that the direct cost associated with pediatric RSV, disease in the children under the age of five, exceed $2 billion annually. Our target population for this vaccine is the young, under the age of five, children for respiratory syncytial virus.
There is currently no approved RSV vaccine in that population. Our candidate, mRNA-1345, encodes for a stabilized pre-fusion F glycoprotein, analogous to our other efforts in RSV vaccines. mRNA-1345 will use the same proprietary lipid nanoparticle as our hMPV/PIV3 vaccine, mRNA-1653, as well as the CMV vaccine that Tal just described. We believe that neutralizing antibodies elicited by 1345 will lead to a reduction of medically attended RSV disease in the very young. While that's exciting, we actually intend to combine 1345 with mRNA-1653 to create a combination pediatric respiratory vaccine, which will address over 3 million medically attended lower respiratory tract and upper respiratory tract infections annually in the U.S. alone. That combination of mRNA-1345 and 1653 would represent a significant opportunity to address unmet need.
The current plan is to develop mRNA-1345 and mRNA-1653 independently in the near term through their initial clinical studies, but we would combine them prior to registrational studies and ultimately advance a joint product. The third vaccine that we announced earlier this month is our mRNA vaccine against the SARS-CoV-2 virus, recently named the novel coronavirus that's associated with COVID-19 disease. mRNA-1273 is an mRNA vaccine that encodes for a pre-fusion stabilized form of the spike protein of that novel coronavirus that had been selected by Moderna in collaboration with the National Institute of Allergy and Infectious Diseases, and the Vaccine Research Center, which are both part of the NIH. The first clinical batch for our phase I, including finishing and filling of vials, was completed on February 7th, and earlier this week that batch was shipped to the NIH for the phase I study.
NIAID will conduct that phase I study under their own IND in the near term. Pivoting to our second core modality. Earlier this year, we did announce two additional programs in the autoimmune therapeutic area in our systemic secreted and cell surface therapeutics. As we described them at JP Morgan, I won't go into great detail, but to briefly recap them here. Our IL-2 program, mRNA-6231, encodes for a long-acting tolerizing IL-2. As you can see in the lower right-hand corner on this page, we've demonstrated in non-human primates that a single subcutaneous injection of mRNA-6231 can lead to a substantial increase in Treg cells without increasing activated cells. That provides an opportunity to reestablish immune balance that might be relevant for a wide range of autoimmune diseases.
There are a number of different recombinant IL-2 based therapeutics that have shown potential, and we will be advancing this program into the clinic in the near term. Second program we announced earlier this year was PD-L1, mRNA-6981. It's an mRNA-encoded PD-L1 to send a tolerizing signal to immune cells. In this case, we are expressing PD-L1 on the myeloid antigen-presenting cell, and the purpose of that is to drive a tolerogenic phenotype, a reestablishment of immune homeostasis in effector cells, including T cells and B cells. mRNA-6981 will be an IV infusion using the same LNP as our mRNA-encoded antibody, mRNA-1944, that had previously been described. In preclinical disease models across a wide range of autoimmune conditions, we've demonstrated ability to modify the disease, as you can see on the lower right-hand corner, one example, which is collagen-induced arthritis.
The first indication in which we're going to be bringing the PD-L1 program forward is in autoimmune hepatitis, a disease we see of compelling unmet need. With that, I'll turn it back over to Tal to talk about our other work in the exploratory modalities.
Thank you, Stephen. Let me just briefly review these modalities that we consider exploratory, but obviously make up a significant part of what we do in clinical research and give you a sense where we are in the prosecution of these programs. Starting with the cancer vaccines, our personalized cancer vaccine, mRNA-4157, is in a randomized phase II trial for the treatment of adjuvant melanoma. The combination of PCV with KEYTRUDA against KEYTRUDA alone, and it's recruiting well. KRAS vaccine mRNA-5671 is an ongoing phase I study, and this one is led by Merck, and it has a monotherapy as well as a combination with KEYTRUDA arm. Our intratumor immuno-oncology therapeutics, we have 3 programs in this modality. All of them are in combination with PD-1 inhibitors.
Dosing of patients is ongoing, and I look forward to the future to being able to demonstrate whether the ability to influence the immune system in this manner will be helpful to these patients. On the regenerative therapeutics modality, AstraZeneca is conducting a phase II-A in patients with our mRNA that encodes for vascular endothelial growth factor, and that's in patients that are undergoing CABG, coronary artery bypass grafting. That study continues to enroll. In the systemic intracellular therapeutics, we have two INDs open now in both MMA and PA, methylmalonic acidemia and propionic acidemia. I'm pleased to announce that the first patient in MMA has enrolled in this trial. They're in the observation period right now. This trial is now open at seven institutions in the United States, and we're continuing to look for additional patients to enroll while we follow this first patient closely.
With that, let me turn it over to Lorence to describe the rest of our pipeline and where we go from here.
Thank you, Tal. On slide 29, you see a graphic that represents our whole development pipeline as it stands today. First and foremost, we're focused on the advancement and execution around this development pipeline.
You heard three significant things from us today around the CMV vaccine, where the phase III preparation is very much underway. You heard that the phase II enrollment for that CMV vaccine is ahead of schedule, and importantly, in phase I, MMA has enrolled its first subject. We're really focused on executing across the entire breadth of the pipeline. The other key thing you heard today is that the preclinical programs continue to grow. You will have heard that we announced in the first two months of the year five new development candidates. This is indicative of the productivity that we expect out of the research platform. What this leads to on the next slide is a robust list of clinical data and next steps across the pipeline. If you scan the page, you'll see a lot of readouts coming in the near term.
We've guided for the CMV readout, the phase II data with a three-month interim analysis in the third quarter of this year and a phase III start in 2021. With the rest of the vaccines, you'll see a number of additional phase I readouts that we would expect to occur, as well as advancement of these newly nominated development candidates toward the clinic. If you look to the next category of systemic secreted therapeutics or antibody against chikungunya, we'll continue to progress through further development of a dose cohort and will continue to advance preclinical work towards IND filings. You just heard from Tal that the rest of our programs will be progressively moving forward here towards clinical data. On slide 31 in today's press release, we reported our fourth quarter and full year 2019 financial results. Please note these results are unaudited as of this call.
We'll be filing audited financials shortly with the 10-K. We ended 2019 with cash equivalents and investments of $1.26 billion. This compares to $1.69 billion at the end of 2018. Net cash used in operating activities was $459 million for 2019, compared to $331 million in 2018. Cash used for purchases of property and equipment was $32 million for 2019, a significant drop versus $106 million in 2018. We placed our Norwood Moderna Technology Center manufacturing facility in service in mid-2018. Revenue for Q4 2019 was $14 million, compared to $35 million for Q4 2018. For the full year, revenue was $60 million, compared to $135 million in 2018. We recall that in January 2019, we adopted the mandated revenue recognition standard, ASC 606, using a modified retrospective transition method applied to those contracts which weren't completed as of January 1st, 2019.
The decreases in revenue are largely attributable to the adoption of this new revenue standard, together with the completion of the initial four-year research period under the 2016 work agreement. Total revenue under the previous revenue recognition standard would have been $15 million for Q4 2019, and $95 million for full year 2019. R&D expenses for Q4 2019 were $119 million compared to $150 million for Q4 2018, and for the full year 2019, R&D dollars were $496 million compared to $454 million in 2018. The decrease in Q4 was mainly due to a decrease in our in-licensing payments to CELLSCRIPT and its affiliates and a reduction of our lab supplies and materials.
The increase for the full year 2019 was mainly driven by an increase in personnel-related costs, including stock-based comp, driven by an increase in the number of employees, as well as higher clinical trial and manufacturing costs. G&A expenses for Q4 were $26 million, compared to $38 million in Q4 2018. For the full year, G&A expenses were $110 million, compared to $94 million in 2018. The decrease in Q4 was primarily driven by a decrease in stock-based comp, mainly attributable to certain performance-based equity awards, with vesting or commencement contingent on the IPO in 2018. The increase for the full year 2019 was mainly due to the additional costs of operating as a publicly traded company, including the increases in insurance, consulting, and outside services and facility costs.
On the next slide, we show the progression of selected cash flow line items, namely our net cash used in operating activities and our purchases of property and equipment. The table shows you our GAAP results by period with a total operating cash flow plus PP&E. I'd point you primarily to the bar chart, which shows the quarter-by-quarter progression of this metric. You'll see that our cash use shows a steady reduction through 2019. I would note that Q1 contained the impact of the last of the three licensing milestone payments we owed CELLSCRIPT, which was $22 million. I don't expect this downward trend to continue to decline quarterly in 2020. For the full year, you can see how we ended up overall flat versus 2019 when we thought about expectations, even with the advancement of our pipeline through the clinic.
As a result, we'll reiterate our guidance for 2020, which is that net cash used in operating activities and purchases of PP&E will total between $490 million and $510 million. That approximate $500 million of cash investment into our business is put into context on the next slide versus the cash that's available to us for investment. Here you see our year-end cash balance of $1.26 billion, and on top of that is the net proceeds of approximately $550 million from our equity offering, which includes the exercise of the underwriter's option to purchase additional shares that we anticipate to close later today. Then, as we've mentioned before, we have approximately $185 million in potential future grants available to us as well.
These amounts sum up to $2 billion in available cash, which we expect to invest in our business, and that represents a significant cash runway of multiple years. I'll now hand it back to Stéphane to close.
Thank you, Lorence, Tal, and Stephen. On slide 35, you can see an update on Moderna's profile. Our company has never been stronger. Our pipeline, preparing for CMV phase III, four medicines in or preparing for phase II, the event phase I trial is ongoing, and 10 positive clinical readouts. More programs in development. Seven vaccines where there are no approved vaccines on the market. Most of these vaccine candidates have multi-billion dollar annual peak sales opportunities. As I shared in our 2019 shareholder letter, we believe our innovative vaccines are going to be very large business Moderna, with long-term annuity life opportunity and a high EBIT margin. Five immuno-oncology drugs in the clinic. Five rare disease programs with our first phase I started for MMA, two autoimmune diseases program. The foundations of Moderna have never been stronger. Our clinical experience is now more than 1,700 healthy volunteers and patients.
The team is strong, with more than 800 employees who care deeply about our mission and are proud of and energized by our progress. I would like to thank our entire team. I would like to extend a special thank you to those who made the coronavirus vaccine from sequence to shipping to NIH for phase I dosing in only 42 days. We are proud to be included with those many companies working on a possible response to this continuing global health emergency. Norwood, these are fully digital, fully integrated facility that enables the execution of our pipeline, all the way from raw materials to finished vials ready to ship to the clinic. We have great partners with AZ, Merck, Vertex, but also DARPA, BARDA, CEPI, and the Gates Foundation. As we said on November quarterly call, we are working on expanding that network of partners as we speak.
With the financing, our grant capital, and our cash balance, we're in the fortunate position to invest up to $2 billion towards building the leading mRNA company. We are thankful to our investors for their trust and partnership as we build this unique company. For 2020, our priorities are very clear. Priority number one, execute on our development pipeline with a special focus on CMV phase III start. Priority number two is creating new development candidates in the two core modalities. We already have five in the last two months only. Priority number three is to develop new development candidates in new modalities. Stay tuned here. As a reminder, these are the events we are hosting for analysts and investors in 2020. Our first manufacturing and digital day is next week on Wednesday at our Norwood facility in Massachusetts. A webcast will be available on our website.
Juan Andres and his team will share many new insights, including how the team delivered coronavirus vaccine in 42 days from sequence to shipping. Marcello Damiani and his team will share the progress since opening Norwood in July 2018 on a digital front, including use cases of artificial intelligence and machine learning. We hope to host many of you for our first Vaccine Day in New York City on April 14, for a deep dive into our mRNA vaccine modality. We'll discuss, among other things, clinical data, business model, how we think about value creation, capital allocation, and probability of success of our mRNA vaccines. In June, we look forward to hosting our third Science Day to be able to share with you the many progress the team has made on mRNA science and delivery since Science Day 2019.
In September, we'd also like to welcome you for our fourth R&D Day, where as usual, in New York, we'll review in detail clinical data. As I shared in my introduction, Moderna is entering a new phase of its development as a company. Our goals are clear. One, file multiple BLAs and launch multiple medicines which we own commercially. Two, continue to explore modalities in the clinic and invest in science. We have two core modalities and are now laser-focused on filing multiple BLAs and then scaling model to maximize our impact on patients. We are continuing to realize our vision. We have over 12 innovative medicines currently in the clinic. We are only getting started. mRNA is an information molecule. Because of that, we believe that the probability of technical success for our medicines from the lab to approval will be materially higher than traditional medicines. Speed.
Our track record speaks louder than words. Coronavirus from sequence to shipping clinical-grade product in 42 days. Evidence of greater capital efficiency relative to traditional recombinant technology is becoming apparent. We can do new diseases like EBV and pediatric RSV without additional capital invested. I have never been more optimistic about Moderna's future and potential since joining as employee number two in 2011. I believe mRNA is going to be a new class of medicines, and I believe Moderna is the leading company in that field. With $2 billion to invest, a great team of science, our IP, and our manufacturing site at Norwood, we will work to accelerate our leadership in the months and quarters to come. We are excited by the opportunity to bring forward a new class of medicines for patients.
I would like to thank the great team of Moderna employees working hard every day, and sometime every weekend, to make this vision a reality. I would like to thank the many people who participate in our clinical studies, including patients, healthy volunteers, and physicians. I would also like to recognize all our commercial partners, non-commercial partners, who work with us and share our vision to deliver transformative medicines for patients. With that, we are now happy to take any question.
Thank you. As a reminder, if you'd like to ask a question, you can press star one on your telephone keypad. Our first question is from Matthew Harrison from Morgan Stanley. Go ahead. Your question please.
Hey, good morning. Thanks for taking the question. I guess two from me. One on coronavirus, and I think this is just so people understand. Could you just broadly comment, it sounded like NIH needs to file an IND, and then they would obviously start the clinical study. What is your involvement at this point, and are you taking any steps related to ramping manufacturing or any other steps related to this? Secondly, maybe just on MMA, can you just talk about how enrollment is going for additional patients? What led you to be able to get that first patient in? If you see promise in terms of being able to rapidly enroll additional patients. Thanks.
Thanks, Matthew. This is Tal. Let me take both of these questions. As it relates to coronavirus, our part here was to manufacture and ship it. I defer to them to provide updates when they will. You asked about scale up. I think we're looking at everything that it would take and how to actually get it done. We'll update everybody once we have a clear picture of that. Obviously, this is a rapidly changing environment. On MMA enrollment, Right now we've got one patient enrolled. We do not yet have the second and third, We're actively working with sites to find them. The age barrier, I think, continues to be a difficult one. We only have to find the first three, Then we can go down in age.
I am confident that we will eventually, but I continue to have a dialogue with the agency on trying to reduce that need so that enrollment can be unhooked from that, and we can get into the age population where we believe the greatest unmet need and potential for benefit is. I'll update everybody as soon as we have progress in that field.
Thank you.
Thank you. Our next question is from Ted Tenthoff of Piper Sandler. Your line is open.
Great. Thank you very much. Just following up on Matt's question first, maybe you can just remind us again so that everybody understands it, because we've been getting a lot of questions on this. What is the process for licensure of a biothreat or pandemic vaccine such as coronavirus? With respect to CMV, again, great progress just across the board here. Ultimately, what do you see as sort of the vaccination paradigm or timing of vaccinations for women of childbearing age? Thanks so much.
Thanks, Ted. It's Tal. Let me take that. I think what does it take to get licensure is an evolving field. The pathways to licensure are well understood, and they encompass everything from finding surrogates of protection to demonstrating efficacy. What is it going to take here? I don't think anybody knows. I think all options are currently open, but it's a rapidly evolving field, and you can imagine that there actually is not yet a surrogate of protection because it's a very new virus, and people are still working to develop those assays and models. I would give NIH a lot of credit for being at the forefront of that effort, and we're closely collaborating with them on these efforts. As it relates to the vaccination paradigm for CMV, I think the starting point here is clearly going to be in women of childbearing age.
That's where you would anticipate the greatest benefit, I think the next phase is going to be to get into a GARDASIL-like population of adolescents, because obviously you want to start protection as early as possible, given that's what the disease we're trying to prevent here is ultimately going to be infants born to women. We're going to try and get down to that age group as we develop this vaccine.
Okay. Great. Thank you very much.
Thank you. Our next question is from Salveen Richter of Goldman Sachs. Go ahead, please.
Thanks for taking the question. It's Ross for Salveen. Just a few here from me. Just quickly on coronavirus, what's the potential monetary opportunity here? Do you guys have any details around agreements with the NIH about funding to you guys? Just thinking about the monetary opportunity there to Moderna. On the Chikungunya antibody program, how much follow-up time exists since the initial patient was first dosed and then since he received his second dose? Are you guys seeing any signs of innate immune response? I have a follow-up.
Good. Stéphane, I'm going to start with the first one. On corona, our only focus as a team is public health. People are sick all over the planet. People are dying. That is our only focus, is to get a vaccine as fast as we can, safely, partnering with the right people to get it done.
Let me answer. If I understood correctly your question on the chikungunya monoclonal antibody. These data are emerging. We're giving you an execution update in terms of where we are. Once I have a full sense of the data set there, I'll of course update everybody.
Great. Just lastly, outside of the phase II CMV update in 3Q, what programs are you expecting to have data this year?
As you know, we don't guide to specific timing on various milestones. I'd refer back to the slide which had the rich catalyst calendar and clinical data calendar that we referred to. That list of events that included data readouts as well as advancement of programs, is a list that comprises all the next steps. Some of those have advanced fairly far along. For instance, I would note that the phase I vaccine studies for RSV and Zika have been running since last year. In other instances, you'll recall that, as you pointed out, the chikungunya antibody program is a relatively small study in healthy volunteers. Again, we're focused on advancing all these programs as rapidly as we can towards data.
Great. Thanks.
Next question is from Geoff Meacham of Bank of America. Go ahead, please.
Hey, guys. This is Alec on for Geoff. Thanks for taking our questions. Two questions from me. My first is on your PCV program, and I guess the KRAS vaccine as well. Have you guys seen any updated data from these studies, including the ongoing phase I for the PCV since ASCO? Just trying to get a sense of why this modality hasn't made the cut for your core franchises, given it's one of the more advanced in terms of clinical development. I've got one more.
Thanks, Alec. It's Tal. On the personalized cancer vaccine, it's a phase I, data continues to come in. Once we have a full cogent data set there, we will be disclosing it. As a question of why we don't consider this a core, I think for us, core is one that we have gotten the requisite pharmacology to believe it will translate into a clinical benefit. I think that's true both for the vaccines clearly, it's also true for the secreted and the surface protein expression, because the chikungunya monoclonal antibody actually reached what would otherwise be therapeutic levels of a protein. That's why it's core.
I think in oncology, until you actually show that the pharmacology that you're describing, in this case, immunology and T cell immunology, until you actually demonstrate that that translates into a clinical benefit for patients, it's hard for me to call it core.
Got it. That's very helpful. Thanks. Secondly, do you have any updates on the CF partnership with Vertex? We've seen Vertex partner with some other gene therapy approaches from CRISPR Therapeutics, Semma, and others. Any color you can give on this partnership would be great. Thanks.
Yeah. We don't generally comment on research. We continue to work with Vertex. We're pleased to be working with them in the CFTR space, but we don't have any updates at this time.
All right. Our next question is from Cory Kasimov from JP Morgan. Go ahead, please.
Morning, guys. Thank you for taking my questions. Two of them for you. First is another one on coronavirus. Thinking a little bit further out, just curious what kind of manufacturing capacity you anticipate having to, say, looking out to 2021 even, should you need to manufacture mRNA-1273 for coronavirus? Secondly, for the CMV program, if you could just broadly talk about what a win would look like in that interim update for the phase II we'll get in 3Q. Is this more or less to kind of looking to replicate the phase I results in a larger group of patients, or are there other nuances we should be thinking about? Thanks.
Cory, morning. It's Stéphane. I'll take the first one on manufacturing capacity. I think the punchline is just too early to know precisely, because we don't have the dose. To finish, there is Norwood CMO capacity, potentially a new site. Just way too early to comment on that. We are working out to get as much as we can.
Hi, Cory, it's Tal. Let me answer your question on CMV phase II. I think in a nutshell, the goal here is, as you say, to replicate what we saw in the phase I. I'd like to be able to do that, of course, in a larger data set so that our confidence in picking the right dose for phase III is there, and that has to do both with replicating the nice immunogenicity that we've seen, but being able to plant a clear flag on what we expect in terms of the safety and tolerability profile that would enable us to go into a phase III trial.
Okay. Thank you.
Our next one is from Hartaj Singh of Oppenheimer & Company. Go ahead, please.
Great. Thank you. I have just a question on CMV. With the phase II results coming up in the third quarter and then the phase III getting going, could you talk a little bit about how you could speed it to market? I know that a lot will be dependent on the phase II results, but can you give us some sort of a confidence interval as to when you think the phase III could read out and by which time it could be on the market, 2024, 2025, 2026? Just to follow on to that, which is that you put the CMV opportunity as being [audio distortio] $5 billion, which seems to make a lot of sense because as you get to broader and broader immunity.
Can you just broadly walk us through what kind of patient populations would you want to sort of have the vaccine broaden into to get to that higher point of that range? Thank you very much.
Hi, Hartaj. This is Tal. Let me start by answering the first question. Look, the timeline for CMV, roughly speaking, once we get in, we anticipate fairly aggressively to be able to complete enrollment within 18 months. I anticipate the duration of the trial to be two years. That still needs, of course, vetting with regulatory authorities. I want to make sure I caveat that appropriately. Once we have two years on everybody on study, then it's a matter of analyzing, looking at the results, and filing, and that's where I think the timelines are pretty well understood for what's achievable in our industry. You can do the math from there.
Yes. Stéphane, I'll take the second one on CMV. What will it take to get to a $5 billion type of number? I think a few things. The first one is, as we explained at the R&D Day in September, it will take getting an indication approval in women in childbearing age, which as you know, is our first one. To get into an adolescent approval, like the HPV GARDASIL. Third is to get into pediatric. As we shared, humans are the reservoir for CMV. We believe there's a very important public health opportunity here to vaccinate newborns in the pediatric setting.
That has been done, as you know, successfully with rubella, to eradicate the virus, and to make sure that humans don't get infected by this virus, which has a lot of long-term negative impact on health, both at a population level as well as for individuals and their own immune system and their own health. Another dimension, of course, is competitive landscape. Are we going to be the only one on the market for next 10 years, or are we going to be with one competitor or two competitor or five competitors? We can come back on that if you are interested in going further. It's population growth. There's a lot of emerging markets that are not only growing in size in terms of population growth, but also in term of dollar invested per inhabitants, if you think about five-year, 10-year, 15-year time frame.
That will impact the model that we have for getting to around $5 billion annual peak sales.
Great. Thank you.
Our next question is from Yasmeen Rahimi of Roth Capital Partners. Go ahead, please.
Hi, team. Thank you for taking my questions and thank you for the tremendous progress that you're making quarter- over- quarter. A few questions for you, all related on CMV. The first one is, can you give us a little bit more color on how we think about how current the numbers are in regards to infection rates? If there are differences between U.S. and Europe, how current they are as it guides you sort of for powering assumptions in your phase III? A second question that would possibly add is as you are in a predominant part of being able to scale up, and we're going to learn more in manufacturing on March 4. Can you enlighten us what are aspects that are unique when you're scaling up an mRNA therapeutic versus other RNA modalities?
Just so we have a little bit of color in the amounts that you're working through and thank you again for taking the questions.
Hi, Yasmeen. It's Tal. Let me take your first question. It's a great question, and one that obviously keeps me up at night. I think the literature is out there in terms of incidence rates and infections. It's also clear from that literature that there's a high level of variability. It's not just on a continental level, U.S. versus Europe. There's actually local geography, socioeconomic status, a lot of things that play into that. How are we thinking about it in terms of designing the trial, which is obviously I think where your question is going to. I think the goal here is to design both a large trial and a broad enough trial in terms of sites and population so that on average, we are able to hit the incidence rate that people have described.
I'm pretty confident in the ballpark of where we are powering the study to be able to reach it. Finally, I would note that in a trial of this type, you have the ability to actually, on an ongoing basis, monitor the incidence in real time so that the only risk you're really taking if you're missing it is you follow subjects for longer and you catch up the cases. Ultimately, the trial size will come down to the number of cases, and that's one that you can monitor in almost real time.
Morning, Yasmeen. It's Stéphane. On the manufacturing process and why mRNA is such a powerful molecule. I think a few things. The first thing is it's a liquid-based process to make mRNA, which is cell-free. That drives to a very small reactors compared to other technologies, especially if you compare to recombinant is the most staggering changes. Two, for a given output, just the size of a reactors, which of course, has a big impact on your CapEx, including all your purification technologies, because you just have less liters to go through the columns and so on. Everything is much, much cheaper across the board. As we talked in the past, because mRNA is an information molecule, it is the same process for Zika or for CMV or for coronavirus.
Drives incredible flexibility and incredible time to the clinic because you do not have to invent the process for every vaccine or every molecule, as the team has shown in the last few weeks with coronavirus. If we have had traditional technologies to invent a new process just for corona, we'll still be working at it as we speak. We most probably not even have started to make the product. In our case, we are able to just do a tiny bit of optimization for the very large molecule that this mRNA is and then go right into production thanks to this aspect of a platform that we have. The other thing is time. The cycle time to make mRNA is days, not weeks. When you think about that, we can use an asset.
Once you make one lot, you can basically change the disposable equipment and use the same room or the same team to make another product. If you can go in a few days to make mRNA versus a few weeks to make a recombinant before you're going to go into field finish, that's a massive use of your capital infrastructure in terms of just CapEx turnover.
Thank you, team, and we look forward to seeing you in Boston next week.
Great.
Thank you. If you would like to ask a question, you could press star one on your telephone keypad. Again, it's star one on your telephone keypad to ask a question. The next one is from Alan Carr of Needham. Please go ahead.
Hi. Thanks for taking my questions, a couple of them. One of them is, can you clarify between your exploratory and your core modalities? Does this mean that you don't plan to add any more new programs to your exploratory until they become core? Also, around RSV, mRNA-1345 versus mRNA-1172, how are they different, and how does this fall outside of the agreement that you already have with Merck around RSV? The last thing is, can you go over your overall manufacturing capacity at the Norwood facility right now across all programs, the total capacity? Without regard to coronavirus, what are your long-term plans in terms of your needs for capacity, in terms of adding manufacturing capacity in the long term? Thanks. As you go commercial.
Good. Thanks for those three questions. Let me take the first one on exploratory and core. Yes, if you go back to the strategy, we started with six modalities in the clinic to say we cannot manage the unknown. Because of the exciting opportunity to create a new class of medicine, we are very focused on managing the unknown technology risk. We tried all those six technology in parallel, so that we could learn from the clinic where to invest more, because mRNA is an information molecule making it a platform. Wherever you wanted to fix, if you learn something about the science, fix that science, if you can, or decide that you stop investing in that opportunity. You want to deploy your capital wisely where you know the technology is working. That was kind of a premise as we started.
What is happening with this pivot in the company history is that now we have a clinical data we gathered for prophylactic vaccine and systemic therapeutics. We believe those are core. In our opinion, we believe the technology risk is off the table, meaning we want to deploy our capital to make innovative medicine and take those to the clinic, because it's exactly the same technology, same manufacturing process than the ones who already have the positive clinical data. On the exploratory front, yes, we want to be very cautious, and that has been the case for years. We said doing only one program per exploratory modality seems too risky for us because we have biology risk, and there's always biology risk. We always said a few two, three programs kind of make sense for us. That's what you see.
Do we intend to invest more shareholder capital on more intratumoral, for example, as an example of one of our four exploratory right now? The answer is clearly no. We want to see what we get from OX40, IL-12, and the triplet. Like we've done with those two modalities that have migrated from exploratory to core in the last few months, if we get signal, the team has a lot of ideas of what other things we could do. Of course, in those programs where we get positive signal, we take those as fast as we can to BLA, because those medicine will be needed for patients. Stephen, you want to talk about RSV?
Just quickly on RSV. Alan, as you referenced, we have a partnership with Merck in respiratory syncytial virus, just a monotherapy vaccine. There are two candidates in phase I study. V172 is the one that is currently being conducted. Those are targeting the elderly target product profile. There is a nearly equal burden of disease in the elderly, 170,000 hospitalizations a year in the U.S. We're excited to be working with Merck in that elderly population. We have a right in our agreements, as we disclosed, to conduct the development of an RSV vaccines towards a respiratory combination, that has been our intent. That is separate from Merck's prerogatives in RSV.
Good. Thanks, Stephen. On the last question on manufacturing capacity. Maybe let me try to tease about a pre-coronavirus world, which we talked about in previous calls or in previous discussion, which is our manufacturing long-term plan is to use Norwood to make development material like we are doing today, and to launch our commercial products like CMV, Zika, and the others out of Norwood. Because of how Norwood was designed, we've always said to manage financing risk, we do not want to invest in a big manufacturing capacity commercial plant until we have our first BLA approved. Clearly risk management. We've always said our long-term vision is to have Norwood focus on development so that we have a commercial site and hopefully down the road, as we scale the company several around the planet that are just focused on commercial products.
We believe based on our experience in previous pharmaceutical companies that having dedicated focus per site is really important for success. Development requires nimbleness. Commercial requires scale and efficiency. It's very different worlds. That's kind of a pre-coronavirus world previous plans. The post-coronavirus plan in the last few weeks, I go back to bio producer a few minutes ago, which is we are looking at a lot of options both internally, externally, CMO partners, to figure out what's the right path forward. When we have a better picture, we will share it.
Great. Thanks for taking my questions.
Thank you. That ends our Q&A session. I would now like to hand the call back to Stéphane Bancel.
Well, thank you for your question, and especially thank you for your trust into our ability to make mRNA an important new class of medicines. We hope to see many of you next week in Norwood for what I believe will be an exciting manufacturing and digital day. Thank you.
Thank you. This concludes today's conference call. Thank you all for attending. You may now disconnect.