The second quarter 2019 conference call. At this time, all participants are in 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 of Investor Relations at Moderna. Please proceed.
Thank you, operator. Good morning and welcome to Moderna's second quarter 2019 conference call to discuss business updates 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 at www.modernatx.com. Today on this call we have Stéphane Bancel, our Chief Executive Officer, Stephen Hoge, our President, Tal Zaks, our Chief Medical Officer, 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. We believe mRNA has the potential to be a new class of medicines. We believe our mRNA medicines have the potential to address large unmet medical needs and to treat diseases that are not addressable by recombinant proteins or small molecules. Due to the platform nature of mRNA, we believe our mRNA medicines provide a higher probability of technical success and faster timelines to clinical files and to the market relative to traditional medicines. We also believe that the manufacturing capital intensity of mRNA is materially lower than recombinant protein, and that our manufacturing cost at commercial scale will be similar to small molecule injectable. Because of this large potential, we continue to focus on managing risk across our portfolio, especially technology risk and biology risk.
We believe that programs within the same modality have similar technology risk, meaning that once we de-risk a sentinel program, they are important with force. As a key example, in the near future, we believe our chikungunya antibody program will be an important clinical readout as it uses the same formulation technology as our MMA program, our most advanced rare disease candidate. Our corporate focus is on 3 priorities. First, to execute on the development pipeline. Two, to move new development candidates in existing modalities from the lab into the clinic. three, to invent new development candidates in new modalities. I will walk you now our most important progress since our last quarterly update in early May. Starting with PCV, Personalized Cancer Vaccine.
We presented positive interim phase I data at the ASCO meeting in June. Since we are happy to report today that since ASCO, we started our phase II head-to-head trial in the adjuvant melanoma setting. We look forward to the readout of this important immuno-oncology program to assess if PCV plus Merck's KEYTRUDA can increase recurrence-free survival versus KEYTRUDA monotherapy. We're happy to report today that our phase I for CMV has completed enrolling healthy subjects at doses up to 300 microgram. We believe CMV is a large unmet medical need. We look forward to reviewing and sharing the phase I trial data in the near term. The team continued to execute at a rapid pace in the last 90 days. We advanced four new programs into phase I since our May call. Two programs in immuno-oncology started dosing cancer patients.
Our KRAS vaccine, which is partnered with Merck, and our IL-12 intratumoral program, which is partnered with AstraZeneca, dosed the first patients. Two programs in infectious vaccine started dosing as well. Our RSV vaccine, mRNA-1172, partnered with Merck, and our Zika vaccine, mRNA-1893, which is funded by the U.S. agency BARDA. I'm happy to report that clinical sites are now open and actively recruiting patients in our first rare disease program, MMA. We have three open sites in the U.S. and in the U.K. the clinical trial application or CTA has just opened by local authorities. I am very pleased with the company's progress, and I'm very thankful for our team dedication to this execution. We now have five immuno-oncology programs in the clinic, including PCV in phase II and OX40 soon entering phase II.
We have five important rare disease program, and our team is working hard to dose the first MMA patient and to submit INDs for all the rare disease programs. We have four vaccines in the clinic for major unmet medical needs, CMV, RSV, the hMPV/PIV3 combo, and Zika. I want to remind you that there are no approved vaccines for any of these harmful pathogens that severely affect thousands each year. We are very pleased to have completed enrollment in our CMV trial, and we look forward to sharing the data with you soon. The company has never been as strong, and we're all focused on continuing to execute and share our progress in the months to come. With this, let me turn to Tal to give you some more color on our development pipeline.
Thank you, Stéphane. As you know, we're advancing our pipeline of medicines in six different modalities. In the next few slides, we'll highlight the progress we've made this quarter in each of these. Starting with prophylactic vaccines on slide 13, you will see we have eight programs in this modality, and we've made significant progress in the last quarter. In total today, we have safety data from over 100 healthy volunteers who have participated in our phase I study, and we remain pleased with the emerging safety and tolerability profile of our vaccines. I'm happy to report that our CMV program with mRNA-1647 is now fully enrolled in the phase I trial, and I'll go over this opportunity in greater detail in just a moment.
The RSV phase I study testing mRNA-1172 dosed its first subjects in this quarter. Recall that at the last quarterly update we reported that our partner, Merck, had just filed the IND. Our Zika program with mRNA-1893 also had the IND filed and open in the second quarter. I'm happy to report that the first subjects in the Zika phase I trial was also dosed. In terms of emerging data in hMPV and PIV3 or mRNA-1653, we continue to see neutralization titers above baseline at the second interim look seven months after the last vaccination. For context, in January, we reported the two-month immunogenicity data. We plan to present the full data from this phase I study at IDWeek in the fall.
We're also pleased with the feedback from FDA regarding the development plans for mRNA-1653, where we discussed the potential path forward to evaluate protection against both hMPV and PIV3 in a single phase III study. Consistent with these plans, we plan to enroll seropositive toddlers in our next trial. Finally, the phase I data for influenza vaccines against H7 and H10 were published in the journal Vaccine. Let me now spend a few minutes on CMV. As noted before, the phase I trial for CMV is fully enrolled. CMV is a common pathogen that is a leading cause of birth defects. The burden of disease is significant, where approximately 25,000 newborns are infected each year in the U.S. alone. Currently, there aren't any vaccines against the CMV virus on the market.
That's because CMV has proven to be a challenging vaccine to manufacture using traditional technologies, given the structure of one of the antigens, the pentamer, which we think is required to elicit a protective immune response. We believe these challenges can be overcome with our mRNA-based vaccine, as our technology lends itself to producing the pentameric viral antigen by encoding for the simultaneous translation of its five components. As a reminder, and it's shown on slide 15, mRNA-1647 actually contains six mRNA sequences, five of which encode for this pentamer and one that encodes for the gB protein. We believe the combination of these two antigens encoded by mRNA-1647 will produce potent and durable antibody titers against CMV that have the potential to protect against infection. We look forward to the phase I results soon. Let me now turn to cancer vaccines.
You will see the programs in this modality on slide 17, and I'll focus on mRNA-4157, our personalized cancer vaccine, and on the KRAS vaccine, mRNA-5671. Recall that we and our partner, Merck, announced the phase II trial earlier this year. The phase II design is a randomized trial testing the combination of mRNA-4157 in combination with pembrolizumab against a pembrolizumab monotherapy control arm in high-risk melanoma patients in the adjuvant setting. I'm happy to report today that the phase II is up and running and that the first patients have consented to the trial. Interim safety, tolerability, and immunogenicity data from our phase I were the basis for the decision to move to phase II. We presented these interim data with mRNA-4157, either as monotherapy in a resected adjuvant population or in combination with pembrolizumab in the metastatic setting.
These two arms represent arms A and arms B, respectively, of the phase I study. We have a part C and part D that continue to enroll. Part C histologies include microsatellite stable or MSS, colorectal cancer, and head and neck squamous cell carcinoma. We and our partner, Merck, have also added an additional cohort in part B, where we will be testing the combination of mRNA-4157 with pembrolizumab in patients who are refractory to PD-1 inhibitors. Turning now to the interim results we presented at ASCO of this year. We showed that mRNA-4157 was safe and well-tolerated, with no reported DLTs and no grade 3 or grade 4 adverse events. We also showed that mRNA-4157 elicited neoantigen-specific T-cell activation in 10 of the 18 class 1 neoantigens in the one patient treated at the top dose where apheresis was performed.
While these data were obtained with the first version of our vaccine that included up to 20 neoantigens, we're now selecting for up to 34 neoantigens using our proprietary algorithm. For the data presented at ASCO, the patients were dosed with the PCV that had the 20 neoantigens, and all patients who have enrolled since April in both the phase I and phase II studies have been receiving the 34 neoantigen version. At ASCO, while the clinical data are early and preliminary, we did report six responses in part B of the study in the metastatic setting. One of these was a complete responder to pembrolizumab monotherapy, prior to receiving the personalized cancer vaccine, and five other dosed with the combination of mRNA-4157 and pembrolizumab had a partial response. Two of these five PRs were patients who were previously treated with checkpoint inhibitors.
While these early signals are trending in the right direction, we believe that our phase II trial will help us and Merck to definitively ascertain the incremental benefit of mRNA-4157. Moving now to the KRAS vaccine. I'm also pleased to announce that the first patient in our phase I trial testing KRAS vaccine mRNA-5671 was dosed. As a reminder, KRAS is a key regulator of cell proliferation and survival. Mutation in the KRAS gene caused dysregulated cell proliferation, and it's one of the best-studied oncogenes. It is the most commonly mutated oncogene, and it drives over 20% of human cancers, predominantly in the pancreatic, lung, and colorectal cancers. The team at the NCI led by Steve Rosenberg had shown at the end of 2016 that the recognition of a mutated KRAS epitope by T cells can lead to cancer regression.
A quick overview of mRNA-5671 is shown on slide 21. It encodes for the four most prevalent mutations of KRAS, which together represent 80%-90% of KRAS mutations. The genetic sequences that span the mutations are combined into a single mRNA that encodes for all four neoantigens. When translated within the cell into a neoantigen protein chain, the cellular proteasomal machinery is expected to cleave the chain and present these neoantigens to the immune system to stimulate what we hope will be an active anticancer T cell response. The phase I trial for this vaccine, which is being run by our partner, Merck, has enrolled its first patient, and the study will evaluate safety and tolerability of mRNA-5671, both as monotherapy and in combination with KEYTRUDA in patients with metastatic non-small cell lung, colorectal, and pancreatic cancers that harbor the KRAS mutations.
Of note in this trial, we are selecting for specific HLA subtypes that, based on the signs, are most likely to respond. For the intratumoral immuno-oncology programs, we're progressing with all three of our development candidates, OX40 ligand, the triplet, and interleukin-12. Starting with mRNA-2416, which encodes for OX40 ligand, which you will recall is a potent co-stimulator that promotes T cell proliferation, the phase I is completing the dose confirmation cohort at eight milligrams, and in parallel, we're progressing to start the phase II cohort in patients with advanced ovarian cancer. Slide 26 shows a schematic of the phase I trial and the phase II cohort. Turning to mRNA-2752 or the triplet, which encodes for OX40 ligand and two pro-inflammatory cytokines, interleukin-23 and interleukin-36 gamma.
The rationale here is to stimulate T cells through the presence of OX40 ligand while attracting the T cells to the tumor site with the local expression of these cytokines. By injecting the tumors directly, we expect the cytokines to act locally within the tumor microenvironment. The phase I is ongoing and has both a monotherapy arm and a combination arm with durvalumab. I'm pleased to report that the first patient in the combination arm with durvalumab has been dosed. We've also made progress with MEDI1191 in our interleukin-12 intratumor injection program, partnered with AstraZeneca, as the first patient in this trial was dosed. Recall that interleukin-12 is a potent immune modulator associated with a type 1 interferon response and production of interferon gamma. Its activity against cancer has been described in the literature, safety has been a problem when interleukin-12 has been administered systemically.
We believe that the intratumoral mRNA approach should allow for interleukin-12 to act locally in the tumor microenvironment while avoiding the toxicity seen with systemic administration. Let me touch for a moment on the localized regenerative therapeutics and AZD8601. The phase II-A in coronary arterial bypass graft population is ongoing. Our partner, AstraZeneca, continues to open additional sites in Europe, with a clinical trial application now also open in Germany. Let me move ahead to our systemic secreted therapeutics. I will focus on mRNA-1944, our antibody against the chikungunya virus. As of today, we've enrolled six of the eight subjects in the third dose cohort. Before I get to the trial design and the strategy around this program, I wanted to take a few minutes to highlight the program, which is DARPA-funded. mRNA-1944 encodes for an antibody against chikungunya.
Antibodies are a complex protein that require both a heavy and a light chain to come together to form an active protein. mRNA-1944 actually includes two mRNAs, one that encodes for the heavy chain and one that encodes for the light chain. Once formed, we expect the antibody to be secreted into the bloodstream, where we will be watching to see if it confers passive immunity against the chikungunya virus as expected. On slide 36, you will see the trial design. The key objectives of the trial are to evaluate the safety and tolerability of four single ascending doses of mRNA-1944, and to evaluate the pharmacokinetics of the drug and the pharmacodynamics of the anti-chikungunya virus antibody levels, which together will describe the dose response curve.
We're collecting assay data to see if the antibody levels neutralize the virus, which we believe will ultimately speak as to whether or not this antibody we encode for is indeed functional. The utility of this program is really twofold. First, as a product that could potentially protect against chikungunya infection by conferring passive immunity. Second, as this program uses the same lipid nanoparticle formulation that is shared with our other programs in the rare disease indications that we're pursuing, it could inform the risk profile of those other programs as well. Lastly, on systemic intracellular therapeutics, where we have four development candidates, I'll highlight our rare disease programs, methylmalonic acidemia or MMA, and the closely associated disease propionic acidemia or PA. Both MMA and PA are inborn errors of protein metabolism that are caused by MUT enzyme deficiency and PCC deficiency, respectively.
As you can see, these two acidemias are really on the same metabolic pathway. The prevalence of both is approximately 325 to 2,000 patients in the U.S. Patients are identified during newborn screening, and current regimens are palliative. They consist of strict diet restrictions and oral and IV medications. Really, the best treatment that we currently have available for suitable patients today is a liver transplant. Both mRNA-3704 and mRNA-3927 encode for intracellular proteins that act within the liver cell and act on the mitochondria. Both programs also have FDA orphan drug designation, EMA orphan drug status, and FDA rare pediatric disease designation, which upon approval, will qualify the two programs for rare pediatric disease vouchers. The phase I study of our sentinel rare disease program in MMA with mRNA-3704 currently has three sites open, and we are actively recruiting patients.
In parallel, the natural history study continues to enroll well with a total of 71 patients across both MMA and PA enrolled.
Let me close with slide 42, which shows you the breadth of our pipeline in one place. You'll see all the new updates we've announced since December 2018, when we became a public company. With that, let me turn the call over to Lorence.
Thanks, Tal. In today's press release, we reported our second quarter 2019 financial results. Please note these results are unaudited. We ended Q2 2019 with cash equivalents and investments of $1.44 billion. This compares to $1.69 billion at the end of 2018. We are reiterating today our expectation for cash equivalents, and investments at December 31st, 2019, to be in the range of $1.15 billion-$1.20 billion, consistent with the guidance given on our call in March. We remain focused on allocation of our shareholder capital towards value-driving investments in our portfolio and platform. Net cash used in operating activities was $256 million for the first six months of 2019, compared to $160 million in 2018. These numbers include $22 million and $25 million of in-licensing payments in the first quarters of 2019 and 2018, respectively, as cited in the footnote.
After the first quarter of 2019, we have no further in-licensing payment obligations to CellScript and its affiliates. Cash used for purchases of property and equipment was $18 million in the first six months of 2019, compared to $66 million in 2018. On revenue, recall that on January 1st, 2019, we adopted the mandated revenue recognition standard, ASC 606, using the modified retrospective transition method applied to those contracts which were not completed as of January 1st, 2019. The decrease in total revenue for Q2 on the first six months of 2019 as compared to 2018 was mainly attributable to this adoption of the new revenue standard. Revenue for Q2 2019 was $13 million as compared to $29 million for Q2 2018. For the first six months of 2019, revenue was $29 million compared to $58 million in 2018.
Total revenue under the previous revenue recognition standard would have been $17 million for Q2 2019 and $55 million for the first six months of 2019. R&D expenses for Q2 2019 were approximately $128 million, compared to $104 million for Q2 2018. For the first six months of 2019, R&D expenses were $259 million compared to $195 million in 2018. The increases in Q2 in the first six months of 2019 as compared to 2018, were primarily due to an increase in personnel-related costs, including stock-based compensation, an increase in clinical trial and manufacturing costs, an increase in lab supplies and materials, and an increase in consulting and outside services. G&A expenses for Q2 2019 were approximately $29 million, compared to $21 million in Q2 of 2018. For the first six months of 2019, G&A expenses were $56 million compared to $38 million in 2018.
The increases in Q2 in the first six months of 2019 as compared to 2018, were mainly due to the additional costs of operating as a publicly traded company, including an increase in personnel-related costs and stock-based compensation, consulting and outside services, and insurance costs. With that, I'll hand the call back over to Stéphane.
Thank you, Lorence. To close our remarks, I would like to reiterate that our team is focused on executing on our three priorities: advancing the development pipeline, inventing new development candidates in the existing six modalities, and inventing new modalities. The team at Moderna executed across the board during the quarter. To summarize quickly the highlights of the quarter. We initiated the PCV phase II trial, with first patients consenting to participate in the trial. Our CMV vaccine study is fully enrolled. We started four new clinical trials, two in immuno-oncology and two in infectious disease. Vertex Cystic Fibrosis Research Collaboration. As you might recall, in July 2016, Moderna and Vertex announced an exclusive research collaboration and licensing agreement aimed at the discovery and development of mRNA therapeutics for the treatment of CF.
Based on preclinical work to date, Vertex has extended this collaboration through the first quarter of 2020 with options to extend further based on future progress. Pulmonary mRNA delivery represents a potential new route of administration for Moderna. I am pleased with the progress we've made to date and look forward to the rest of 2019 and 2020 as we approach critical data readouts. I will particularly look for the CMV phase I data and the chikungunya antibody phase I data in the near term. As a reminder, the chikungunya antibody is the first monoclonal antibody encoded by mRNA technology to be dosed in a human. Because RSV and Zika are dosing healthy subjects, these trials should complete soon, and if positive, we intend to transition to phase II.
We now have five immuno-oncology programs in the clinic, two of which are already dosing in combination with approved checkpoint inhibitors, Merck's KEYTRUDA for PCV and AstraZeneca IMFINZI for our triplet. Our teams, working with clinical trial sites, are focused on the milestone of dosing our first patients with MMA. We believe mRNA has the potential to be a new class of medicine. We see a large product opportunity ahead of us, and we are energized by the potential to bring these important medicines to patients. Four vaccines for large unmet medical needs where there is no vaccines approved today. That is a unique opportunity to help millions, and as such, create large commercial products. Five immuno-oncology programs, which all have the potential to improve the response of PD-1 or PD-L1 checkpoint inhibitors.
Five rare disease programs for conditions like MMA and PA, where children born with a missing or defective protein urgently need a treatment that addresses the underlying cause of their disease. A cardiology program, VEGF, which will transform the care of patients who have suffered an MI. This is only the first wave of innovative products. Stephen Hoge and his team are working hard to move new innovative development candidates from the labs into the clinic. The productivity of our mRNA platform is significant. We dose our first clinical trial in December 2015. In just 3 and a half years, we started 16 programs in the clinic, and we've had a high success rate. The team did get 19 R&D or CTAs opened by local authorities.
We know we have a special opportunity, and we are committed to delivering on the promise of our science and bringing forward a new class of medicines to patients. I would like to end our remarks by thanking the many people who participate in our clinical studies, including patients, healthy volunteers, and physicians. I would also like to thank the great team of Moderna employees working hard every day to make our vision a reality. With that, we are now happy to take any question.
Ladies and gentlemen, if you'd like to ask a question, please press star then one. If your question has been answered and you'd like to remove yourself from the queue, please press the pound key. Once again, to ask a question, that's star then one. Our first question comes from Salveen Richter of Goldman Sachs. Your line is open.
Great. Thanks for taking our questions. This is Andrea on for Salveen. My first one is, how are you thinking about positioning for your KRAS vaccine in the context of growing competition in the space? Then I have a follow-up.
Hi, this is Tal. Thanks for the question. Look, first of all, I'm really happy that we finally have therapies that are emerging as effective against KRAS mutations. I think that progress for the field is tremendous. I think it's still early days. Let me make two points. First, the exact nature of the activity and against which mutations, and in our case, which mutations and which HLAs still needs to be defined. I don't see them even on, if you look at the patient distribution necessarily, as competing. Second, I think more importantly on the fundamentals, I think what our vaccine is trying to do and what the emerging inhibitors are trying to do are very different things in terms of patient benefit.
I think the history of small molecule targeted therapies has been terrific in the sense that it's translated into real benefit for these patients, but we struggled to turn them into curative intent treatments. I think on the other hand, the immuno-oncology approaches were successful, have translated into a much more durable effect. My expectation is, down the road, if both of these approaches are successful, you would expect them to have complementary benefits for the patients. I'm really excited in the coming years to see how that story plays out.
Maybe, Stéphane, just to add one thing, as Tal described in his remarks, the mRNA that we designed is actually coding for four mutations, G12D, G12V, G13D, and G12C.
Great. Just on your MMA program, how many patients right now are enrolling in your clinical study that have been rolled over from the natural history study?
In the clinical study, we have not yet enrolled. We're actively recruiting. In the natural history study, there have been 71 patients enrolled to date.
Sorry. Do you anticipate, I guess, rolling any patients over from that natural history study or no?
It is a possibility. We're looking at it.
Got it. Thank you so much.
Our next question comes from Matthew Harrison of Morgan Stanley. Your line is open.
Hey, good morning. Thanks for taking the question. Two from me. The first one is, can you just comment broadly how we should think about safety so far in the chikungunya study, given that you're through almost a third cohort? I don't know if you can comment on what the stopping rules are from a safety standpoint. Second question is on OX40 ligand. Can you talk about what you need to do in this phase II study to be able to take that to the FDA? I guess what I'm asking is how can we think about potential regulatory path forward with that molecule? Thanks.
Sure. Look, let me start with the chikungunya. The study's ongoing, so I can't really comment on the data until we see the totality of the picture there, and then we'll describe it for you. It's a healthy volunteer study, so stopping rules are what you would expect in these typical studies. In terms of OX40 ligand, the regulatory path, if you look at where we're expanding into the phase II cohort, we're going after ovarian cancer. I think in that setting, checkpoint inhibitors are not yet approved. It's because they really have marginal activity as monotherapy. If we can demonstrate that the combination has a clear benefit to patients, I think the path to approval will be relatively straightforward. That's how we're looking at it. Did that answer your question, Matthew?
It did. Thanks, Tal.
Our next question comes from Ted Tenthoff of Piper Jaffray. Your line is open.
Great. Thank you very much, and thank you for the update. Lots of good progress. My question is, and I apologize if this was asked, but with respect to the triple, my concern here is certainly not activity, especially with durvalumab, but are you doing any special immune safety analysis or any special additional safety analysis just because of the potential potency of the triple therapy? Thanks.
Thanks, Ted. That's a really good question. I wish I had a wiser answer for you. The reality is that we're looking at the safety, I think, in the traditional way that people do in clinical trials, maybe colored by a better understanding over the years of what the safety profile of the checkpoint inhibitors alone is. We're looking for whatever autoimmune phenomena, et cetera, and all the other adverse events that one would expect from checkpoint inhibitor monotherapy, and assessing very carefully to see whether we exceed it. If there's any other safety signal that is attributable to the triplet, then I think we've got two ways of finding it. First, recall we're dosing as monotherapy, so that'll give us a clear view on the safety profile just of the triplet. Second, in the combination arm, we're looking carefully at all the clinical characteristics.
Unfortunately, I think as a field, it's very hard to predict the adverse reactions that one sees, and they're not very frequent. All you can do at this point is maintain a careful visual for what's expected and make sure you're not missing anything unexpected. I don't know if that answers the question. I'm not sure I've got a better one.
That's all right. That makes a lot of sense. I appreciate that. Just a really quick high-level question. With respect to the CF collaboration, are there any novel delivery modalities that are being incorporated for that disease? Is this really the need not just treating lung, but really systemic disease? Thank you.
Ted, it's Stephen Hoge.
Thanks, Stephen.
First of all, it's a research collaboration with Vertex, and we're excited to continue it based on the preclinical progress to date. As a part of our general research activities, we do look broadly at a range of different delivery modalities. We have obviously made progress in one direction here, but we haven't yet defined a development candidate, at which point we'd probably provide specifics about that. Generally, our approach with Vertex and CF has been to address the unmet needs in CF, particularly for those patients who are eligible for CFTR, and focusing intensively on the pulmonary disease. Obviously, without commenting specifically on the CF example, pulmonary delivery is a route of administration that could be valid for other systemic diseases or other applications as well.
Okay. Thanks a lot. I'm looking forward to. Yeah, sorry, go ahead.
No, that's it. Yeah.
Great. Awesome.
Great.
I'm looking forward to the CMV data and see you guys in September. Thanks.
Thank you.
Our next question comes from Cory Kasimov of JPMorgan. Your line is open.
Hey, good morning, guys. Thanks for taking my questions out too as well. I guess first, can you just walk us through the cadence of what you see as the key validating clinical updates we should expect in the next 12 months or so? Beyond the CMV and chikungunya updates, what else has a chance of occurring in that time period? Will we see new clinical data at your R&D Day in September? I have one follow-up.
Cory, good morning. Stéphane. I will not comment on the R&D day. I hope you come to the R&D day. We will make sure that we give a good update on everything we know then. On the next 12 months, as you can see on slide 46 on the presentation. As I discussed in my comments, CMV is very important. As you know, we believe it's a very large opportunity. We own 100% of the economic of this product. We believe there's very large medical needs out there. The CMV data are going to be very important, we believe, for the company. HIV and Zika, because they're in phase I in healthy subjects, and they are dosing as we speak, should read pretty quickly. As I shared, the plan is to remove those to phase II, assuming we have good data into the clinic.
I remind you that we have already in the past shown a good translation from primate into humans into our vaccines that had positive data. We look forward to this data in humans. PCV, of course, will take a little bit of time because we started the phase II. That's an important study. We need to recruit for that phase II. We know 150 patients across the world. It's, of course, looking at survival in four months. KRAS is going to be interesting. We all believe there's a big medical need in three big tumor types. We are directly into patients in phase I. We'll be sharing observation at different clinical meetings of what we see in the clinic. In the interesting role, because it's oncology and we are dosing, the triplet is in combination with PD-1.
OX40 will be in phase II soon, and also will be in combination with a checkpoint. AZ is taking IL-12 forward. Same thing, we will update the different medical meetings on clinical observation. VEGF is recruiting. As we discussed, the chikungunya antibody is very important for us. Getting the first rare disease in the clinic. The rare diseases are going to go straight into patients. As we commented before, we are starting the MMA at a dose that has been shown in animal models having some benefit.
I think the next few months and the next few quarters are going to be quite rich data-wise. We have now many few 13 drugs progressing in the clinic. That's a lot of potential data we have.
Okay, great. The follow-up is regarding your Personalized Cancer Vaccine mRNA-4157 program. Any near-term plans for exploring indications beyond resected melanoma patients that are at high risk of relapse or PD-1 refractory? What do you see is the potential of this program and indications that may have considerably less neoepitopes?
Thanks for that, Cory. It's Tal. It's a question that we've asked ourselves since the beginning of this program. I think strategically and philosophically, what we want to do with this program is first to go where the likelihood of success is the highest, before we look for areas that are more challenging. That's why we focused in the histologies that we have in the phase I, and that's why we went into an adjuvant setting even within melanoma for a definitive study of the phase II. I think once we have a clear proof of concept, clearly we will begin to explore some of those additional indications. There's not any current plans to do that.
Yeah. Maybe, Cory, Stéphane to add to Tal's remarks. If you think about it, going back to Lorence's comments, we are very disciplined with capital allocation. Of course, there could be a lot of different things one could think of trying with Personalized Cancer Vaccine, as you think about all the patients that are untreated today. Unfortunately, before we have an important de-risking, we cannot expand too much because we have so many opportunities of products across the portfolio. We could be increasing the burn to a place that will not be reasonable. We want to be very disciplined. That's just one example. There's a lot of things, trust me, that the clinical team, as you know, Tal, is an oncologist by training, who love to be trying in the clinic to help those patients.
We just have to be very disciplined with capital allocation and how much we spend and where we spend it and when we spend it based on de-risking.
Okay. Makes a lot of sense. Thanks for taking the questions.
Thank you.
Our next question comes from Alan Carr of Needham. Your line is open.
Hi, this is Jennifer speaking for Alan. I have a couple questions. First question is, I was wondering if the team can give us some color on the commercial strategy and possibly specific patient groups that you may be planning to target for the CMV assets. Thank you.
Thank you, Jennifer, for your question. I think it'd be great if you can join us at the R&D Day because we will spend quite some time on CMV commercial opportunity. As we discussed in the past, there are many populations from women in the age of bearing a child, adolescent women that you might want to protect. There's also discussion about partners of those pregnant women. There's also discussion because human are a reservoir of CMV. Do you go down in age to try to eradicate CMV? There's a lot of different segments that we will discuss quite at length on the R&D Day.
This is why I think we believe CMV, if you take a 10, 20-year time frame, and if you look at all the other vaccines like the HPV vaccine and the Prevnar vaccine and those very important vaccines, the life cycle management of those products can be very important. We have our eyes very much on how do we go about this. Again, we cannot do all the indication at the same time. It's going back to the discipline of capital allocation and investments. We have very much in mind of how do we maximize over time this opportunity to get the largest label that we can for CMV, so it can be given to the largest population we can around the world, not only in the U.S.
Oh, thank you so much. The other question is for the hMPV/PIV3 vaccine. Could you possibly give us some comments or color on any new understanding of the titer level needed to progress this asset? Thank you.
This is Tal. I think that our understanding of the titers there is going to be based mostly on the preclinical modeling and what we've seen to date that is protective. Unfortunately, there is no vaccine on the market, so we don't really have a correlate of protection like we have from influenza. It is a respiratory virus, so one draws similar parallels from the experience with flu. You get a sense from the totality of our understanding of the science on the respiratory viruses, what are the titers like. I think what we've seen in the phase I is supportive of our ability to immunize. Recall, though, that the target population here is in seronegative infants, right?
Ultimately, we're going to have to define our ability to reach significant titers and boost to the maximal of the immune response capability to respond in that population down the road. I think it may not be a very black and white answer because I think it will take inference from multiple lines of reasoning from science and from clinical studies and from other vaccines, I think, to come to that. Does that help you?
Yes. Thank you so much for taking my question.
Thanks, Jennifer.
Our next question comes from Hartaj Singh of Oppenheimer & Co. Your line is open.
Great. Thank you for the questions. I just have two. One is, I know that you've mentioned that the chikungunya antibody is very important. Can you just talk maybe a little bit about that? If you see the proof of concept in manufacturing the antibody, we're using mRNA, then see efficacy on the vaccine side. Antibodies are over $100 billion in sales per year. What other areas could you go into? Would you see yourself being in vaccines? Are there other types of antibodies, other types of diseases that would be amenable to your approach in that regards? Or is that just looking too far into the future? I got a quick follow-up.
Good morning, Stéphane. As you know, we have disclosed for our 21 development candidates, and we don't comment on future plans in research. Obviously, as I shared in my remarks, we think it's a very important milestone. It's the first time that using mRNA technology, an antibody is being produced in a human. That's an important technology that, as you commented, has a lot of different applications. What we try to do always as the portfolio of the assets that we develop with our shareholders' capital is to be thoughtful about managing biology risk, technology risk, and to create important innovative products for patients. That's always a big driver for us.
If you look back to one of my closing slides, if you look at our portfolio today, for most of the products that are in the pipeline, there is no product on the market with big enough medical need, and there is no solution on the market. We are always thoughtful about all those things. It would, of course, become a very important tool in our Moderna toolbox. As you know, partnering is also an important part of our strategy. If you go back over time, we've done 4 partnerships with Merck, 3 with AZ. We're very, of course, happy with the decision by Vertex to expand the collaboration. That's also technology that can be made available to a partner. This is an important piece of Moderna's toolbox.
Great, Stéphane. That helps a lot. Just had a question on your manufacturing strategy. I visited the Norwood facility. Really kind of cool stuff going on there. It is clinical-grade sort of material and research material. Can you just talk a little bit about how you're thinking about your commercial grade material? You're getting to the point now where you might have one or two, whether rare or diseases where you might be able to get to the clinic fairly rapidly, and the regulators want to see a sort of a clinical to commercial strategy. If you could just talk a little bit about that, which of your modalities actually requires more intensity from a commercial manufacturing perspective than others? Thank you.
That's a great question. On the commercial front, as we've shared in the past, Norwood is able to do commercial. It is not ready today. We have to do much work around validation and the quality systems and so on. The infrastructure of the plant itself has been built so that the site can be brought to commercial readiness and being able to do pivotal studies, registration studies out of Norwood. What we also shared, and it's again going back to our focus on managing risk, we will not have to build a commercial facility before we have our first commercial product approved. That's a very important part of Moderna strategy to de-risk the company. We can launch product out of Norwood. We can do phase III out of Norwood. We will get the site ready on time so that we can do that.
We also always have a contract manufacturer strategy. We never want to be single source for the company. That would be way too risky. We have, as we speak, contract manufacturers that have also commercial capabilities from their site and the quality system ready. If you think about the different product on the portfolio, which is your second question, the big impact is mostly on the back end, which is on filling the vials. If you think about it, mRNA for vaccines, the dose are very, very tiny. You don't need a lot of mRNA drug substance to supply actually millions of vials. If you go back to the data we have published, our vaccines show efficacy, 2,500 micrograms per human. In half a kilo or a kilo, you can do a lot of doses, as you can do the math.
For rare disease, because the N of patients is low, you also don't go into gigantic quantities. Of course, in oncology, it's a different ball game. Again, that would be a very happy problem to manage when we get there. On the back end, Norwood does not have the ability to do millions of vials of fillings, but that's something that is readily available to contract manufacturing. That is why we feel very confident that with the current infrastructure that we have, we have the ability to do pivotal, to do commercial. If we have to manage the back end with more vial capacity, we will get and contract that out with an existing partner or a new partner. We have time for that.
If we needed more capacity, one thing to remember about Norwood is that we can increase the capacity of Norwood tremendously versus the current capacity. We are only working with 2 day shifts. We could put, of course, a night shift. We don't have shifts on weekends. Right there, you have a lot of capacity available. We can move the warehouse out of the site. The warehouse doesn't have to be on the site. You have right away more GMP facilities that you can access your utilities. The QC lab can also be moved out of the plant. It can be moved on the parking lot, you just build a new building. Here again, you go with more GMP capacity. The pre-clinical, all the robotics of pre-clinical, same thing, it's currently in a GMP suite, but doesn't have to be, because it's pre-clinical material.
There again, you can move it to the parking lot or in a new building. If you think about the manufacturing strategy of Moderna, Norwood was a big investment. We think it's a strategic investment. We cannot deliver on the mission of a company or the pipeline without Norwood. We really built Norwood so that this becomes a central node for us that is there for a very long term, so that we do not have to invest CapEx in the years to come at a high level. We will not build a commercial plant until we're product approved. That would be way too risky.
Great. Thank you, Stéphane. That's great.
Our next question comes from Alec Stranahan of Bank of America Merrill Lynch. Your line is open.
Hey, guys. Thanks for taking my questions. Congrats on the progress. I just had a couple. Maybe first on the hMPV/PIV3 combination vaccine. Do you have a sense of the sort of data we'll likely see in October? Will we see data outside of antibody titer comparison? Is the phase I-B toddler study necessary as per your conversations with the FDA before you begin a phase III? I have one more.
Thanks, Alex. It's Tal. Yeah, in October, we'll present the totality of the data as we have it, so you'll see the antibody titers, you'll see the total of the safety. You'll see what you typically see when we describe the totality of the study. I believe that's been accepted to IDWeek. In terms of the seropositive toddlers, yes, I think that is consistent with the development path that one would expect and that the agency concurs in terms of the next step in the development path here. Ultimately, remember that the target population here is infants, so there's a pretty structured and rigorous way by which you work your way down into that population.
Okay, great.
Now, given the sensitivity to the pediatric population, we wanted to make sure that we've got clarity from the agency in terms of designing that study, and that's why we put in the press release, and we discussed that interaction.
Definitely understand that's a sensitive patient population. Shifting gears to your KRAS vaccine 5671. We've seen data from Amgen and others that are pretty encouraging on G12C, although it seems maybe there's a subgroup that requires additional combination therapies. I was just curious, on the KRAS vaccine, what your thoughts are for it as monotherapy, and also in terms of combination with checkpoint inhibitors. Thanks.
I'll give you two versions of the answer, one on the science and one as a drug developer. On the science, unquestionably, one would want to combine these as early as possible, because we think there's an orthogonal benefit, as I described previously. One would expect these get combined with checkpoint inhibitors in addition. As a drug developer, you want to get confidence first that each individual has merit on its own before you go into the combination. I think for us, it's critical to demonstrate that the cancer vaccine as such, in combination with a PD-1 inhibitor, can actually mediate responses. I think once we get to that stage, we will obviously have a keen interest in pursuing the right combinations with the inhibitors, depending on where they are at that point in time. Alex, did that answer your question?
Yes. That's great. Thank you.
There are no further questions. I'd like to turn the call back over to Stéphane Bancel for any closing remarks.
Thank you for joining us today and for your questions. We look forward to seeing you during our upcoming third annual INDs Day in New York City. This meeting will be held during the morning of September 12th. Have a wonderful day. Thank you.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.