Good morning, and welcome to Moderna's 4th 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 would like to
Thank you, operator. Good morning, everyone. On today's call, we will discuss Moderna's 4th 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 Investors section of our website. Speaking on today's call are Stephane Bancel, our Chief Executive Officer Tal Vak, our Chief Medical Officer Stephen Hoag, our President and Lawrence 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 2 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 Stephane.
Thank you, Lavina, and good morning, everyone. As you know, we believe mRNA has a potential to be a new class of medicines with the opportunity to address many unmet medical needs. Given the announce 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 2 of our modalities, prophylactic vaccines on the left and systemic secreted and cell surface therapeutics on the right. Data that we believe fundamentally changed 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 2 co modalities with many important medicines. We have already announced 5 new development candidates in these co modalities since January 13 at the JPMorgan Conference, 3 new development candidates in infectious disease prophylactic vaccines and 2 in the systemic secreted and cell surface therapeutic modalities. While we double down in co modalities, we are still more than ever interested in understanding the potential of mRNA technology in our extraordinary modalities, cancer vaccines, intratumoral immuno oncology, localized regenerative therapeutic and systemic intracellular therapeutic.
So when we think about it, we have 2 distinct businesses. This is a significant point in our strategy. Core modalities, we want to scale and invest, extraordinary modalities, where we are waiting for clinical data to decide on the path forward. So stepping back, I would like to share with you the progression of the company towards 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 6 different modalities. We tested 16 different molecules in the clinic in a short 4 year period.
In 2019, we generated important data in 2 of these 6 modalities and identified our first 2 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 4 exploratory modalities. We're supported to invest aggressively in our science, including investing new modalities, such as our ongoing collaboration with Vertex. We are 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, Thad will take you through the prophylactic vaccine programs.
Thank you, Stephane, and 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 6 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 2nd dose cohort and are close to completing the 3rd one. We now expect data readout to come in the Q3 of this year. Our hMPV PIV3 combination respiratory vaccine has started the HD escalation study and Merck is on track with their RSV program in adults. Zika is also going well as 3 of the 4 dose cohorts have completed enrollment. Our 3 new development candidates announced recently are vaccines against pediatric RSV, mRNA-thirteen forty five, Epstein Barr virus or EBV mRNA-eleven eighty nine and our vaccine against the novel 2019 coronavirus mRNA-twelve seventy three.
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.
And the spectrum of sequela range from hearing loss, vision loss, microcephaly and even mortality in 10% to 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 desequella. On Slide 16, I'll review the most recent data from our CMV program. In January of this year, we shared the 7 month interim data. The safety has been generally well tolerated and 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 3rd 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 to 40 fold higher above baseline level after the 3rd vaccination.
And 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 2 dose confirmation study is enrolling well and is currently enrolling the last dose cohort. We now expect data from the 1st interim analysis in the Q3 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 $200,000,000 to $250,000,000 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 $2,000,000,000 to $5,000,000,000 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 GV antigens as our CMV vaccine dose will be additive to the vaccine's efficacy.
As a reminder, our CMV vaccine mRNA-sixteen forty seven is wholly owned by us. Let me transition it to Steven to talk about our new development candidates.
Thank you, Tal. I want to start by introducing 3 development candidates in our vaccine prophylactic vaccine 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. So Epstein Barr virus is a member of the herpes family that includes CMV and spread through bodily fluids, mostly in the 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 United States, accounting for almost 1,000,000 cases annually. Infectious mononucleosis can debilitate patients for weeks to month and in rare cases can lead to hospitalization and even splenic rupture. EBV infection is also associated with a range of other disorders, including lymphoproliferative disorders, cancers and autoimmune diseases. And for instance, it is associated with a significant increase in risk of multiple sclerosis. There are currently no approved vaccines for EBV.
So our vaccine candidate, mRNA-eleven eighty nine, 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 GP. 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 infection in the prior study by up to 7 reduced the rate of infectious mononucleosis in the 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 have to make that
the opportunity is quite substantial. Worldwide direct costs of EBV linked infectious mononucleosis reach almost $500,000,000 annually and the indirect costs could exceed $1,000,000,000 But prevention of infection, EBV infection, in addition to the prevention of infection monoclonalosis, 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 2,000,000 medically attended RSV infections in children under the age of 5. Globally, the burden of disease is even more substantial with over 30,000,000 episodes of acute lower respiratory tract infection annually. And we estimate that the direct costs associated with pediatric RSV disease in the children under the age of 5 exceed $2,000,000,000 annually. So our target population for this vaccine is the young under the age of 5 children for respiratory distress and tissue virus.
There is currently no approved RSV vaccine in that population. Our candidate, mRNA-thirteen forty five, encodes for a stabilized prefusion F glycoprotein analogous to our other efforts in RSV vaccines. MRNA-thirteen forty five will use the same proprietary lipid nanoparticle as our hMPV PIV3 vaccine, mRNA-sixteen fifty three, as well as the CMV vaccine that Tal just described. And we believe that neutralizing antibodies 5
with
5 with mRNA-sixteen fifty three to create a combination pediatric vaccine respiratory vaccine, which will address over 3,000,000 medically attended lower respiratory tract and upper respiratory tract infections annually in the U. S. Alone. That combination of mRNA-thirteen forty five and 1653 would represent a significant opportunity to address unmet need. The current plan is to develop 1345 and 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.
Now the 3rd vaccine that we announced earlier this month is our mRNA vaccine against the SARS CoV-two virus recently named the novel coronavirus that's associated with COVID-nineteen disease. MRNA-twelve seventy three 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 Institutes of Allergy and Infectious Diseases, 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 7, and earlier this week, that batch was shipped to the NIH for the Phase 1 study. NIAID will conduct that Phase 1 study under their own IND in the near term. Now pivoting to our 2nd core modality.
Earlier this year, we did announce 2 additional programs in the autoimmune therapeutic area in our systemic secreted and cell surface therapeutics. And as we described them at JPMorgan, I won't go into great detail, but to briefly recap them here. IL-two, our IL-two program, mRNA-six thousand two hundred and thirty one, encodes for a long acting tolerizing IL-two. 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-six thousand two hundred and thirty one can lead to a substantial increase in Treg cells without increasing activated cells. That provides an opportunity to reestablish immune balance across that might be relevant for a wide range of autoimmune diseases.
There are a number of different recombinant IL-two based therapeutics that have shown potential, and we will be advancing this program into the clinic in the near term. 2nd program we announced earlier this year was PD L1 mRNA-six thousand nine hundred and eighty one. 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-six thousand nine hundred and eighty one will be IV infusion using the same LNP as our mRNA encoded antibody, mRNA-nineteen forty four, that had previously been described. And in preclinical disease models across a wide range of autoimmune conditions, we've demonstrated ability to modify the disease. As you can see in 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, Steven. 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-four thousand one hundred and fifty seven is in a randomized Phase 2 trial for the treatment of adjuvant melanoma. The combination of PCV with KEYTRUDA against KEYTRUDA alone and it's recruiting well. KRAS vaccine mRNA-five thousand six hundred and seventy one is an ongoing Phase 1 study and this one is led by Merck and it has a monotherapy as well as a combination with KEYTRUDA R.
Our intratumor immuno oncology therapeutics, we have 3 programs in this modality. All of them are in combination with PD-one 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 therapeutic modality, AstraZeneca is conducting a Phase IIa 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 2 INDs open now in both MMA and PA methylmalonic acidemia and propionic acidemia. I'm pleased to announce that the 1st patient in MMA has enrolled in this trial. They are in the observation period right now. This trial is now open at 7 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 Laurence to describe the rest of our pipeline where we go from here.
Thank you, Tal. So on Slide 29, you see a graphic that represents our whole development pipeline as it stands today. 1st and foremost, we're focused on the advancement and execution around this development pipeline. You heard 3 significant things from us today around the CMV vaccine, where the Phase 3 preparation is very much underway. You read the Phase 2 enrollment for that CMV vaccine as ahead of schedule.
And importantly, in Phase 1 MMA has enrolled its 1st subject. So we're really focused on executing across the entire breadth of the pipeline.
And then the other key thing
you heard today is that the preclinical programs continue to grow and you will have heard that we announced in the 1st 2 months of the year 5 new development candidates. This is indicative of the productivity that we expect out of the research platform. But the fleet to 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 2 data with a 3 month interim analysis in the Q3 of this year and a Phase 3 start in 2021.
And with the rest of the vaccines, you'll see a number of additional Phase 1 readouts that we would expect to occur as well as advancement of these newly nominated development candidates toward the clinic. If you look at the next category of systemic secret therapeutics or antibody against jikungunya will continue to progress through further development of a dose cohort and will continue to advance preclinical work towards IND filings. And 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 Q4 and full year 2019 financial results. Please note these results are unaudited as of this call.
We'll be filing a lot of your financials shortly with the e-ten ks. We ended 2019 with cash, cash equivalents and investments of 1.26 $1,000,000,000 This compares to $1,690,000,000 at the end of 2018. Net cash used in operating activities was $459,000,000 for 20 19 compared to $331,000,000 in 20 18. And cash used for purchases of property and equipment was $32,000,000 for 2019, a significant drop versus $106,000,000 in 2018. We placed our Norwood Moderna Technology Center manufacturing facility in service in mid-twenty 18.
Revenue for Q4 2019 was $14,000,000 compared to 35,000,000 dollars for Q4 2018. And for the full year, revenue was $60,000,000 compared to $135,000,000 in 2018. 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 1, 2019. And so the decreases in revenue are largely attributable to the adoption of this new revenue standard, together with the completion of the initial 4 year research period under the 2016 work agreement. Total revenue under the previous revenue recognition standard would have been $15,000,000 for Q4 2019 $95,000,000 for the full year 2019.
R and D expenses for Q4 2019 were $119,000,000 compared to $150,000,000 for Q4 2018 and for the full year 2019 R and D dollars were $496,000,000 compared to $454,000,000 in 20.18. 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 and A expenses for Q4 were $26,000,000 compared to $38,000,000 in Q4 2018. And for the full year, G and A expenses were $110,000,000 compared to $94,000,000 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. And 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 and E. I'd point you primarily to the bar chart, which shows the quarter by quarter progression of this metric.
And 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 3 licensing milestone payments we owed to CellScrip, which was $22,000,000 I don't expect this downward trend to continue to decline quarterly in 2020, but 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. And so as a result, we'll reiterate our guidance for 2020, which is that net cash used in operating activities and purchase of PP and E will total between $490,000,000 $510,000,000 That approximate $500,000,000 of cash investment into our business is put into context in the next slide versus the cash that's available to us for investment. Here you see our year end cash balance of 1.2 $6,000,000,000 And on top of that is a net proceeds of approximately $550,000,000 from our equity offering, which includes the exercise of the underwriters option to purchase additional shares that we anticipate to close later today. And then as we've mentioned before, we have approximately $185,000,000 in potential future grants available to us as well.
And so these amounts sum up to $2,000,000,000 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 Stephane to close.
Thank you, Laurence, Tal and Stephen. On Slide 35, you can see an update on Mona's profile. Our company has never been stronger. Our pipeline, preparing for CMV Phase 3, formadacine in or preparing for Phase 2, driven Phase 1 trials ongoing and 10 positive clinical readouts. Our programs in development, 7 vaccines where there are no approved vaccines on the market.
Most of these vaccine candidates have multibillion dollar annual pixel opportunities. As I shared in our 2019 shareholder letter, we believe our invasive vaccines are going to be very large business Moderna, with long term annuity like opportunity and a high EBIT margin. 5 immuno oncology drugs in the clinic, 5 rare disease programs with our 1st Phase 1 started for MMA, 2 autoimmune diseases program. The foundations of Moderna have never been stronger. Our clinical experience is now more than 1700 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 1 dosing in only 42 days. And 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 files ready to ship to the clinic.
We are great partners with AZ, Merck, Vertex, but also DARPA, PADA, SEPI and the Gates Foundation. As we said on November quarterly call, we are working on expanding that network of partners as we speak. With refinancing our great capital and our cash balance, we're in a fortunate position to invest up to $2,000,000,000 towards building the leading mRNA company. We are thankful to our investors for their trust and partnership as we build this unique company. For 2023, our priorities are very clear.
Priority number 1, execute on our development pipeline with a special focus on CMV Phase 3 starts. Priority number 2 is creating new development candidates in the 2 core modalities. We already have 5 in the last 2 months only. And priority number 3 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. Marcelo D'Amiani and his team will share a progress since opening Norwood in July 2018 on the digital front, including use cases of artificial intelligence and machine learning.
We hope to host many of you for our 1st 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, helping with value creation, capital allocation and probability of success of our mRNA vaccines. In June, we look forward to hosting our 3rd 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 4th R and D Day, where as usual in New York, we will 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. 1, find multiple BLAs and launch multiple medicines, which we own commercially. And 2, continue to explore modalities in the clinic and invest in science. We have 2 core modalities and are now laser focused on filing multiple BLAs and then scaling modular to maximize the impact on patients. We're 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 medicines from the lab to approval will be materially higher than traditional medicines. Speed, our track record speaks louder than words.
Coronavirus from sequencer shipping clinical grade product in 42 days. Evidence of greater capital efficiency relative to traditional recombinant technology is becoming apparent. We can do new DCs like EVV and Pedafucarasvi without additional capital invested. I have never been more optimistic about Moda's future and potential since joining Gazanpare 2 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 $2,000,000,000 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're excited by the opportunity to bring forward a new class of medicines for patients. I'd like to thank the great team of Moderna employees working hard every day and sometime every weekend to make decision a reality. I would like to thank the many people who participate in our clinical studies, including patients, healthy volunteers and physicians. I will select 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 questions.
Thank you. Our first question is from Matthew Harrison from Morgan Stanley.
I guess 2 for me. So 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? And then secondly, maybe just on CMV well, actually on MMA, Can you just talk about how enrollment is going for additional patients? What sort of led you to be able to get that first patient in? And if you see promise in terms of being able to rapidly enroll additional patients? Thanks.
Thanks, Maggie. 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 think the trial now will be run by the NIH and 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. But we'll update everybody once we have a clear picture of that. Obviously, this is a rapidly changing environment. On MMA enrollment, so right now we've got one patient enrolled.
We do not yet have the second and third, but 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. So and then we can go down in age. So 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 needed potential for benefit is.
So 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. And just following up on Matt's question first. What 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 bio threat or pandemic vaccine such as coronavirus?
And then 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 Paul. Let me take that. I think what does it take to get licensure is an evolving field. I mean, 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 protection because there'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. And I think the next phase is going to be to get into a GARDAS alike 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. So 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 on for Salveen. Just a few here from me. So 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?
So just thinking about the monetary opportunity there to Moderna. And then on the chikungunya antibody program, how much follow-up time exists since like the initial patient was first dose and then since he was received a second dose? And are you guys seeing any signs of like innate immune response? And then I have a follow-up.
Good. So Stefan, 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 the only focus is to get the 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 chicken guinea monoclonal antibody. These data are emerging. We're giving you an execution update on to in terms of where we are once I have a full sense of the data set there. I'll of course update everybody.
Great. And then just lastly, so outside of the Phase 2 CMV update in 3Q, what programs are you expecting to have data this year?
We as you know, we don't guide to specific timing on various milestones. I'd refer back to the slide, which had the RISH Catalyst calendar and clinical data calendar that we refer 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 1 vaccine studies for RSV and Zika have been running since last year.
And other instances, you'll trichungungin antibody program is a relatively small study in healthy volunteers. But 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. So 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 1 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?
And then I've got one more.
Thanks, Alex. It's Tal. Look, on the personalized cancer vaccine, it's a Phase I. So data continues to come in. Once we have a full Cogent data set there, we will be disclosing it.
And the question to why we don't consider this core, I think for us core is one that we have gotten the requisite from oncology to believe it will translate into a clinical benefit. And I think that's true both for the vaccines clearly and it's also true for the secreted and the surface protein expression because the chikungun immunoclonal antibody actually reached what would otherwise be therapeutic levels of a protein. So that's why it's core. I think in oncology, until you actually show that your 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. And then 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, Sema and others.
So any color you can give on this partnership would be great. Thanks.
Yes. We don't generally comment on research. We continue to work with Vertex. We're pleased to be working in the DTR space, but we don't have any updates at this time.
All right. Our next question is from Cory Kasimov from JPMorgan. Go ahead please.
Good morning guys. Thank you for taking my questions. 2 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-twelve seventy three for coronavirus? And then secondly for the CMV program, I mean, if you could just kind of broadly talk about what a win would look like in that interim update for the Phase 2 we'll get in 3Q?
Is this more or less kind of looking to replicate the Phase I results in a larger group of patients or other nuances we should be thinking about? Thanks.
So Cory, good morning, Stephan. So I'll take the first one on manufacturing capacity. I think the pension is just too early to know precisely. First, we don't overdose, Then we'll finish, there is Norwood, CMO capacity, especially new sites, so just way too early to comment on that. But we're working out to get as much as we can.
Hi, Corey, it's Tal. Let me answer your question on CMV Phase 2. So I think in a nutshell, the goal here is, as you say, to replicate what we saw in the Phase 1. But I'd like to be able to do that, of course, in data set so that our confidence in picking the right dose for Phase 3 is there. And that has to do both with replicating the nice immunogenicity that we've seen, but being able to kind of plan a clear flag on what we expect in terms of the safety and tolerability profile that would enable us to get into a Phase 3 trial.
Okay. Thank you.
Our next one is from Hartaj Finch of Oppenheimer and Company. Go ahead please.
Great. Thank you. I have just a question on CMV. With the Phase II results coming up in the Q3 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 kind of a confidence interval as to when you think the Phase 3 could read out and by which time you could be in the market 2024, 2025, 2026? And then just a follow on to that, which is that you've currently stated the opportunity as $25,000,000,000 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, Hart. This is Paul. Let me start by answering the first question. So 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 2 years.
Now that still needs, of course, vetting with regulatory authorities. So I want to make sure I caveat that appropriately. Once that we have 2 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. So you can do the math from there.
Yes. And Stefan, I'll take the second one on CMV, what we take to get to $5,000,000,000 type of number. I think a few things. The first one is, as we explained at the R and D Day in September, it will take getting an indication approval in women in childbearing age, which as you know is our first one. Then to get into an adolescent approval like the HPV Cardocel and thirdly, to get to 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 the population level address for individuals and their own immune system and their own health. Another dimension, of course, is competitive landscape. I will be the only one in the market for next 10 years are going to be with 1 competitor, 2 competitor or 5 competitors. You can come back on that if you're interested moving further. And then it's population growth.
There's a lot of emerging markets that are not only growing inside in our population growth, but also in terms of dollar invested in EBITDA. If you think about 5 year, 10 year, 15 year timeframe, that's the impact the model that we have for getting to around $5,000,000,000 annual pixels.
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 Few questions for you all related on CMB. 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? Is there differences between U. S.
And Europe? How current they are as it guides you sort of for powering assumptions in your Phase 3? And then a second question that we asked me that is as you're in a phenomenal 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, and we have the study we're looking through and thank you again for taking the questions.
Hi, Sameet. Saul. Let me take your first question. It's a great question and it's one that obviously keeps me up at night. I think the literature is out there in terms of incidence rates and infections, but it's also clear from that literature that there's a high level of variability and 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. So 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 hit the incidence rate that people have described. And I'm pretty confident in the ballpark of where we are powering the study to be able to reach it.
And finally, I would note that in the trial of this type, you have the ability to actually on an ongoing basis monitor the incidents 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. So ultimately, the trial size will come down to the number of cases, and that's one that you can monitor in almost real time. So,
good morning, Yasmeen, it's Stefan. On the manufacturing process and why mRNA is such a powerful molecule. I think a few things. I mean, the first thing is, it's a liquid based process to make mRNA, which is cell free. So that drives to a very small reactors compared to other technologies, especially if you compare to recombinant is the most staggering changes and to for given output just the size of our reactors, which of course has a big impact on your CapEx, including all your purification technologies, because you just have less details to go through the color and then so on.
So everything is much, much cheaper across the board. As we talk in the past, because M1 is an information molecule, it is the same process for Zika or for CMV or for coronavirus. So drives incredible flexibility and incredible time to the clinic because 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 like traditional technologies to invest a new process just for corona, we should be working at it as we speak and 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.
And the other piece is time, which is the cycle of time to make M and A is days, not weeks. And so when you think about how we can use an asset, I mean, once you make Google Adeloft, you can basically change the disposable equipment and use the same room or the same team to make another product. And so if you can go in a few days, make mRNA versus a few weeks to make our components before you're going to go into finish, that's a massive use of your capital infrastructure in terms of just CapEx turnover.
Thank you, Tim. And we look forward to seeing you in Boston next week.
Right.
And next one is from Alan Carr of Needham. Please go ahead.
Hi, thanks for taking my questions. I have 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? And then also around RSV, 1345 versus 1172, how are they different? And how does this fall outside of the agreement that you already have with Merck around RSV?
And the last thing is, can you go over the your overall manufacturing capacity at the Norwood facility right now across all programs, the total capacity? And 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. So let me take the first one on exploratory and core. So yes, if you go back to the strategy, we started with 6 modalities in the clinic to say we cannot manage the unknown, unknown. And so because of the exciting opportunity to create a new class of medicine, we are very focused on managing the unknown technology risk.
And so we tried to look 6 technology in parallel, So we could learn from the clinic where to invest more because the money is a information molecule making it a platform and where ever you wanted to fix, if you learn something about the science, fix that science if you can or decide that you are stopping investing in that opportunity, you want to deploy your capital wisely, where you know the technology is working. So that was kind of a premise as we started. And so what is happening with this pivot in the company history is that now we have a clinical data we've gathered for prophylactic vaccine and systemic therapeutics. We believe those are core, I. E.
In our opinion, we believe the technology risk is on 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 say doing only 1 program per exploratory modality seems too risky for us because you have biology risk and there's always biology risk. But we always say the few 2, 3 programs kind of make sense for us. As what you see, so do we intend to invest more shareholder capital on more intratumoral, for example, as an example of one of the 4 exploratory.
Right now, the answer is clearly no. We want to see what we get from OX40, IL12 and the triplets. But 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. And of course, in those programs where we get positive signal, we'll take those as fast as we can to be there because those medicines will be needed for patients. Stephen, you want to talk about RSV?
Just quickly on RSV. So Alan, as you referenced, we have a partnership with Merck in respiratory syncytial virus, just a monotherapy vaccine. There are 2 candidates in Phase I study. V172 is the one that is currently being conducted. And those are targeting the elderly target product profile.
And so there is a nearly equal burden of disease in the elderly, 170,000 hospitalizations a year in this country. We're excited to be working with Merck in that elderly population. We have a right in our agreements, as we disclosed, to conduct development of an RSV vaccines towards a respiratory combination, and that has been our intent. And so we are that is separate from Merck's prerogatives in RFC.
Thanks, Stephen. And on the last question on manufacturing capacity. So maybe let me talk with Steve 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 rates, we do not want to invest in a big manufacturing capacity commercial plants until we have of course BLA approved, fully risk management. But we've always said our long term vision is to have now would 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 efficiencies, very different worlds. So that's kind of a pre coronavirus world, previous plans. And the post coronavirus in the last few weeks, I go back to my Proyce sensor 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 and when we have a better picture, we will share it.
Great. Thanks for taking my questions.
Thank you. This ends our Q and A session. I would now like to hand the call back to Stephane Bancel.
Well, thank you for your question, 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.