Q2 2019 Conference Call. Please be advised that the call is being recorded. At this time, I'd like to turn the call over to Lavina Tluktar, Head of Investor Relations at Moderna. Please proceed.
Thank you, operator. Good morning and welcome to Moderna's 2nd 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 Investors section of our website at www modernatx.com. Today on this call, we have Stephane Bonsal, our Chief Executive Officer Stephen Hogue, our President Tal Zacks, our Chief Medical Officer 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. 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 trials and to the markets 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 scales 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 rerisk a sentinel program, they are important to read through. 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 or most advanced rare disease candidates. Our corporate focus is on 3 priorities: 1st, to execute on the development pipeline 2, to move new development candidates in existing modalities from the lab into the clinic and 3 to invest new development candidates in new modalities. I will review now our most important progress since our last quarterly update in early May.
Starting with PCV, personalized cancer vaccine. We presented positive interim Phase 1 data at the ASCO meeting in June. And since we are happy to report today that since ASCO, we started our Phase 2 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 ketudra monotherapy. We're happy to report today that our Phase 1 for CMV has completed enrolling healthy subjects at doses up to 300 micrograms.
We believe CMB is a large unmet medical need, and we look forward to reviewing and sharing the Phase 1 trial data in the near term. The team continued to execute at a rapid pace in the last 90 days. We advanced 4 new programs into Phase 1 since our May call. 2 programs in immuno oncology started dosing cancer patients, our KRAS vaccine, which is partnered with Merck and IL-twelve intracellular program, which is partnered with AstraZeneca, those are the first patients. 2 programs in infectious vaccines started dosing as well.
Our RSV vaccine mRNA-eleven seventy two partnered with Merck and Ortheka vaccine mRNA-eighteen ninety three, which is funded by the U. S. Agency BARDA. Finally, I'm happy to report that clinical sites are now open and actively recruiting patients in our first rare disease program MMA. We have 3 open sites in the U.
S. And in the U. K, the clinical trial application or CTA was just opened by local authorities. I am very pleased with the company's progress and I'm very thankful for our team's dedication to this execution. We now have 5 immuno oncology programs in the clinic, including PCV in Phase 2 and OX40 soon entering Phase 2.
We have 5 important rare disease program and our team is working hard to dose the first M and A patients and to submit INDs for all rare disease programs. We have 4 vaccines in the clinic for major unmet medical needs: CMV, RSV, the hMPV, PIV combo and Zika. I want to remind you that there are no approved vaccines for any of these harmful pathogens that severely affects 1,000 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 ever 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, Stefan.
As you know, we're advancing our pipeline of medicines in 6 different modalities. In the next few slides, I will highlight the progress we've made this quarter in each of these. So starting with prophylactic vaccines on Slide 13, you will see we have 8 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-sixteen forty seven is now fully enrolled in the Phase 1 trial, and I'll go over this opportunity in greater detail in just a moment.
The RSV Phase 1 study testing mRNA-eleven seventy two dosed its 1st subjects in this quarter and recall that at the last quarterly update, we reported that our partner Merck had just filed the IND. Our Zika program with mRNA-eighteen ninety three also had the IND filed and opened in the Q2, and I'm happy to report that the first subjects the Zika Phase I trial was also dosed. In terms of emerging data, in hMPV and PoV3 or mRNA-sixteen fifty three, we continue to see neutralization titers above baseline at the 2nd interim look 7 months after the last vaccination. For context, in January, we reported the 2 month immunogenicity data. We plan to present the full data from this Phase I study at ID week in the fall.
We're also pleased with the feedback from FDA regarding the development plans for mRNA-sixteen fifty three, where we discussed the potential path forward to evaluate protection against both and PoV-three in a single Phase 3 study. Consistent with these plans, we plan to enroll seropositive toddlers in our next trial. Finally, the Phase 1 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 1 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 1 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 5 components. As a reminder and is shown on Slide 15, mRNA-sixteen forty seven actually contains 6 mRNA sequences, 5 of which encode for this pentamer and one that encodes for the GB protein. We believe the combination of these 2 antigens encoded by mRNA-sixteen forty seven 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 4,157, our personalized cancer vaccine and on the KRAS vaccine mRNA 5,671. 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-four thousand one hundred and fifty seven 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 2 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-four thousand one hundred and fifty seven either as monotherapy in a restricted adjuvant population or in combination with in the metastatic setting. These two arms represent arms A and arms B, respectively, of the Phase 1 study. Have a Part C and Part D that continue to enroll. Our 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-four thousand one hundred and fifty seven with pembrolizumab in patients who are refractory to PD-one inhibitors. Turning now to the interim results we presented at ASCO of this year. We showed that mRNA-four thousand one hundred and fifty seven was safe and well tolerated with no reported DLTs and no Grade 3 or Grade 4 adverse events. We also showed that mRNA-four thousand one hundred and 7 elicited neoantigen specific T cell activation in 10 of the 18 Class I 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 6 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 5 other dosed with the combination of mRNA-four thousand one hundred and fifty seven pembrolizumab had a partial response. 2 of these 5 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 2 trial will help us in Merck to definitively ascertain the incremental benefit of mRNA-four thousand one hundred and fifty seven.
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-five thousand six hundred and seventy one, 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.
Indeed, 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-five thousand six hundred and seventy one is shown on Slide 21. It encodes for the 4 most prevalent mutations of KRAS, which together represent 80% to 90% of KRAS mutations. The genetic sequences that span the mutations are combined into a single mRNA that encodes for all 4 neoantigens. When translated within the cell into a neoantigen protein chain, the cellular protosomal machinery is expected to cleave the chain and present these neoantigens to the immune system to stimulate what we hope will be an active anti cancer T cell response.
The Phase 1 trial for this vaccine, which is being run by our partner Merck has enrolled its first patient and this study will evaluate safety and tolerability of mRNA-five thousand six hundred and seventy one 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 ligands, the triplet and interleukin 12. Starting with mRNA-two thousand four hundred and sixteen, 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 cord at 8 milligram 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-two thousand seven hundred and fifty two or the triplet, which encodes for OX40 ligand and 2 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 1 is ongoing and has both a monotherapy R and a combination arm with durvelumab. I'm pleased to report that the first patient in the combination arm with durvelumab 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, but safety has been a problem when interleukin 12 has been systemically. We believe that the intratumoral mRNA approach should allow for interleukin-twelve 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 AZD-eight zero one.
The Phase IIa 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 and I'll focus on mRNA-nineteen forty four, our antibody against the chikungunya virus. As of today, we've enrolled 6 of the 8 subjects in the 3rd 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-nineteen 44 encodes for an antibody against chikungunya. Now antibodies are a complex protein that require both the heavy and the light chain to come together to form an active protein. So mRNA-nineteen forty four actually includes 2 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 4 single ascending doses of mRNA-nineteen forty four 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 are 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. Now the utility of this program is really twofold. 1, first, as a product that could potentially protect against chikungunya infection by conferring passive immunity. And 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 4 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 mute enzyme deficiency and PCC deficiency, respectively. As you can see, these 2 acidemias are really on the same metabolic pathway. Now the prevalence of both is approximately 325 to 2000 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-three thousand seven hundred and four and mRNA-three thousand nine hundred and twenty seven 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 2 programs for rare pediatric disease vouchers.
The Phase 1 study of our sentinel rare disease program in MMA with mRNA-three thousand seven hundred and four currently has 3 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 will see all the new updates we've announced since December 2018 when we became a public company. And with that, let me turn the call over to Laurence.
Thanks, Tal. In today's press release, we reported our Q2 2019 financial results. Please note these results are unaudited. We ended Q2 2019 with cash, cash equivalents and investments of $1,440,000,000 This compares to $1,690,000,000 at the end of 2018. We are reiterating today our expectation for cash, cash equivalents and investments at December 31, 2019 to be in the range of $1,150,000,000 to $1,200,000,000 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 $256,000,000 for the 1st 6 months of 2019 compared to $160,000,000 in 20 18. These numbers include $22,000,000 $25,000,000 of in licensing payments in the 1st quarters of 2019 2018 respectively as cited in the footnote. After the Q1 of 2019, we have no further in licensing payment obligations to sell script and its affiliate. Cash used for purchase of property and equipment was $18,000,000 in the 1st 6 months of 2019 compared to $66,000,000 in 2018.
And then on revenue, recall that on January 1, 2019, 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 1, 2019. The decrease in total revenue for Q2 in the 1st 6 months of 2019 as compared to 2018 was mainly attributable to this adoption of the new revenue standard. Revenue for Q2 2019 was $13,000,000 as compared to $29,000,000 for Q2 2018. For the 1st 6 months of 2019, revenue was $29,000,000 compared to $58,000,000 in 2018. Total revenue under the previous revenue recognition standard would have been $17,000,000 for Q2 2019 $55,000,000 for the 1st 6 months of 2019.
R and D expenses for Q2 2019 were approximately $128,000,000 compared to $104,000,000 for Q2 2018. And for the 1st 6 months of 2019, R and D expenses were $259,000,000 compared to $195,000,000 in 2018. The increases in Q2 in the 1st 6 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 and A expenses for Q2 2019 were approximately $29,000,000 compared to $21,000,000 in Q2 of 2018. And for the 1st 6 months of 2019, G and A expenses were $56,000,000 compared to $38,000,000 in 2018.
The increases in Q2 in the 1st 6 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. And with that, I'll hand the call back over to Stephane.
Thank you, Laurence. To close our remarks, I would like to reiterate that our team is focused on executing our 3 priorities, advancing the development pipeline, inventing new development candidates in the existing 6 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 PTE Phase 2 trial with 1st patient consenting to participate in the trial. Our CME vaccine study is fully enrolled.
We started 4 new clinical trials 2 in immuno oncology and 2 in infectious disease. Fabtech cystic fibrosis research collaboration. As you might recall, in July 2016, Moderna and Vertex announced an exclusive research collaboration and licensing agreement and at the discovery and development of mRNA therapeutics for the treatment of CF. Based on preclinical work to date, Vertex has extended this collaboration for the Q1 of 2020 with options to extend further based on future progress. Preliminary mRNA delivery represents a potential new route administration for Moderna.
I am pleased with the progress we've made to date and look forward to the rest of 2019 2020 as we approach critical data readouts. I will particularly look for the CMV Phase 1 data and the chikungunya antibody Phase 1 data in the near term. As a reminder, the chikungunya antibody is the 1st monoclonal antibody encoded by mRNA technology to be dosed in a human. Because RSV and Zika are building healthy subjects, this trial should complete soon and if positive, we intend to transition to Phase 2. We now have 5 immuno oncology programs in the clinic, 2 of which are already building in combination with approved checkpoint inhibitors, Merck Kedudra for PCV and AstraZeneca in Twin Z for our triplets.
Our teams working with clinical trial sites are focused on the milestone of dosing our first patient 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. 4 vaccines for large unmet medical needs, where there is no vaccine approved today. That is a unique opportunity to help millions and as such create large commercial products.
5 immuno oncology programs, which all have the potential to improve the response of PD-one or PD L1 checkpoint inhibitors. Fibrolysis programs for conditions like MMA or MPA, where children born with a missing or defective protein urgently needs a treatment that addresses the underlying cause of their disease. The cardiology program, Begel, which will transform the care of patients who have suffered an MI. And this is only the 1st wave of innovative products. Stephen Hogg 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 2016. In just three 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 and 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 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 questions.
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? And 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.
So let me make 2 points. First, the exact nature of the activity and against which mutations and in our case, which mutations and which HLA still needs to be defined. So I don't see that even on if you look at the patient distribution necessarily as competing. 2nd, and 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, immuno oncology approaches were successful, have translated into a much more durable effect. And so my expectation is down the road, if both of these approaches are successful, you would expect them to have complementary benefits for the patients. And I'm really excited in the coming years to see how that story plays out.
And maybe Stefan just to add one thing. As Tal described in his remarks, the mRNA that we designed is actually coding for mutation, GD12D, G12D, G13D and G12C.
Great. And then 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?
So 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. 2 for me. So the first one is, can you just comment broadly how we should think about safety so far in the chicken green studies given that you're through almost the 3rd cohort? I don't know if you can comment on what the stopping those are from a safety standpoint.
And then second question is on OX40 ligand. Can you talk about what you need to do in this space to study to be able to take that to the FDA? I mean, I guess what I'm asking is, how can we think about potential regulatory path forward in that molecule? Thanks.
Sure. Look, let me start with the chikungunya. The study is 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. And so if we can and 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. So that's how we're looking at it.
Did that answer your question, Matthew?
It did. Thanks, Tom.
Our next question comes from Ted Tenthoff of Piper Jaffray. Your line is open.
Great. Thank you, Doug Rex, and thank you for the update. Lots of good progress. So 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 dermalone. 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 and 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 may be colored by a better understanding over the years of what the safety profile of the checkpoint inhibitors alone is. And so we're looking for whatever autoimmune phenomena, etcetera, and all the other adverse events that one would expect from checkpoint inhibitor monotherapy and assessing very carefully to see whether we exceeded. If there's any other safety signal that is attributable to the triplet, then I think we've got 2 ways of finding it.
First, recall, we're dosing as monotherapy, so that will give us a clear view on the safety profile just of the triplet. And second, in the combination arm, we're looking carefully at all the clinical characteristics. And unfortunately, I think as a field, it's very hard to predict the adverse reactions that one sees and they're not very frequent. So 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.
And then 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? Or is this really the aim not just treating lung, but really systemic disease? Thank you.
So, Ted, it's Steven Hogue.
Hey, Steven.
So first of all, we're it's a research collaboration with Vertex, 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 probably provide specifics about that. Generally, our approach with Vertex in CF has been to address the unmet needs in CF, particularly for those patients who are prone for those need for CFTR and focusing intensively on the pulmonary disease. But obviously, without commenting specifically in the CF example, pulmonary delivery is a route of administration that could be valid for other systemic diseases or other applications as well.
Thanks a lot. Looking forward to the yes, sorry, go ahead.
That's it.
Great. Awesome. Looking forward to CME 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. I have 2 as well. So I guess first, if you can 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? I mean beyond the CMB and chikungunya updates, what else has a chance of occurring in that time period?
And will we see new clinical data at your R and D day in September?
And then
I have one follow-up.
Harry, good morning, Stefan. So I will not comment on the R and D. I hope you come to R and D. 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 percent of the economy of these products. We believe there's very large medical needs out there. And so the CMB data are going to be very important, we believe, for the company. RSV and Zika because they're in Phase 1 in healthy subjects and they are dosing as we speak should read pretty quickly.
And as I shared, the plan is to remove those Phase 2 assuming we have good data into the clinic. I remind you that the we have already in the past shown in a good transition from primates into humans into our vaccines that have positive data. And so we look forward to this data in human. PCV, of course, will take a little bit of time because we started the Phase II that's the important study. It's recruit for that Phase II, you know, allopathy patients across the world.
And then it's of course, we can't survive our enrollment. KRAS is going to be interesting. We all believe it's a big medical need for big tumor types. So we are directing to patients in Phase 1. So we'll be sharing observation at different clinical meetings of what we see in the clinic.
In the intratumoral, because it's oncology and regarding the triplet in combination with PD-one, OX40 will be in Phase 2 soon and also will be in combination with a checkpoint and they will be taking IL-twelve forward.
Same thing, we
will update the different clinical meetings, clinical observation. HF is recruiting. And then, I mean, as we discussed, the cheek antibody is very important for us. And then getting the first studies in the clinic. Virides are going to go straight into patients.
As we commented before, we are starting the MMA as a dose that has been shown in animal models having some benefit. And so I think the next few months and the next few quarters are going to be quite rich data wise. We have now I mean, if you've got 13 drugs for us in the clinic, that's a lot of potential data we have.
Okay, great. And then the follow-up is regarding your personalized cancer vaccine 4,157 program. Any near term plans for exploring indications beyond resected melanoma patients that are at high risk of relapse or PD-one refractory? And what do you see as the potential of this program and indications that may have considerably less neoepitodes?
Thanks for that, Corey. 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. And so that's why we focused in the histology that we have in the Phase 1 and that's why we went to an adjuvant setting even within melanoma for a definitive study of the Phase 2.
I think once we have a clear proof of concept, clearly, we will begin to explore some of those additional indications, but there's not any current plans
to do that. And I think, Corey, Stephane to tell us remarks. If you think about it going back to Laurent's comments, we are very disciplined about capital allocation. So 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 interested today. But unfortunately, we cannot 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 the plate that will not be reasonable. And so we want to be very disciplined. And just one example, that there's a lot of things, trust me that the clinical team as you know Sally is an oncologist by trying we love to be trying the clinic to help those patients, but 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 derisking.
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 of 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.
So thank you, Jennifer, for your question. I think it'd be great if you can join us at the R and D Day because we will spend quite some time on CMV commercial opportunity. As we've discussed in the past, there are many populations from the women in the age of bearing a child, adolescents women that you might want to protect. There's also discussion about partners of those pregnant women. There's also discussion because human novel is our world CMV.
Do you go down in age to try to eradicate CMV? So there's a lot of different segments that we will discuss quite at length on the R and D day. But this is why I think we believe CMV, if you take a 10, 20 year timeframe and if you look at all the 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. And 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 on capital allocation and investments. But we are very much in mind of how do we maximize over time this opportunity to get the largest label that we can for CMV, they can be given to the largest population we can around the world, not only in the U. S.
Thank you so much. And the other question is for the hMPV PIV3 vaccine, could you possibly give us some comments or color on any new understanding of the tighter 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. But it is a respiratory virus, so one draws similar parallels from the experience with flu. And you get a sense from the totality of our understanding of
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 1 is supportive of our ability to immunize. Recall though that the target population here is in seronegative infants, right? So ultimately, we're going to have 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. So 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 questions.
Our next question comes from Hartaj Singh of Oppenheimer and Company. Your line is open.
Great. Thank you for the questions. I just have 2. One is, I know that you've mentioned that the ChikV or ChikV antibody is very important. Can you just talk maybe a little bit about that if you see the proof of concept, manufacturing the antibody, we're using mRNA and then see efficacy on the vaccine side.
Antibodies are over $100,000,000,000 in sales per year. I mean, 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?
And then I got a quick follow-up.
So good morning, Stefan. So as you know, we have disclosed 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 a MarnED technology, an antibody is being produced in a human. And so 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 we have in the pipeline, there is no product on the market with big enough medical need and there is no solution in the market. And so we are always comfortable about all those things. But it will be of course become a very important tool in our Molina toolbox.
As you know partnering is also an important part of our strategy. If you go back over time, we've done 4 partnership with Merck through with AD. We're very, of course, happy with the decision by Vertex to expand the collaboration. And so that's also the technology that can be made available to a partner. So this is an important piece of the modular toolbox.
Great, Hassan. That helps a lot. And then just had a question on your manufacturing strategy. I mean, I visited the Norwood facility, really, really kind of cool stuff going on there. It is clinical grades of material and research material.
Can you just talk a little bit about how you're thinking about your commercial material? I mean, you're getting to the point now where you might have 1 or 2, whether rare or diseases where you might be able to get to the clinic fairly rapidly and the regulators want to see us over clinical to commercial service strategy. Can you just talk a little bit about that? And then which of your modalities actually requires more intensity from a commercial manufacturing perspective than others? Thank you.
It's a great question. So on the commercial front, as we've shared in the past, Now would be able to do commercial. It is not ready today. We'll have to do much work around validation and the quality systems and so on. But 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 the commercial facility before we have our 1st commercial product approved. That's a very important part of Moderna's strategy to derisk the company. So we can launch product out of Norwood. We can do Phase 3 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. So we have, as we speak, contract manufacturers that have also commercial capabilities from their sites and their quality system already. And 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 virus. Because if you think about it, mRNA for vaccines, the dose are very, very tiny.
So you don't need a lot of mRNA drug substance to supply actually millions of virus because if you go back to the data we have published for vaccines show efficacy in 2,500 micrograms type per human. So in ultra kilo or kilo, we can do a lot of doses that can do the math. And so and for the R and D because the N of patients is low, you also don't go into gigantic quantities. Of course, in our product, it's a different ballgame. But 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 buys or fillings, but that's something that is readily available for contract manufacturing. So that is why we feel very confident that we have the with the current infrastructure that we have, we have the ability to do pivotal to the commercial. If we have to manage the back end with mobile capacity, we will get and contract that out with an existing partner or a new partner. We have time for that. And 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 shift. We could put of course a 9 shift. We don't have shift on weekends. So 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. And 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. It just be the new building.
And here again, you go with more GMP capacity. The preclinical, all the robotics for preclinical, thing is currently in the GMP suite, but doesn't have to be because it's preclinical material. So there again you can move it to the parking lot on your new building. So if you think about the manufacturing strategy of Moderna, now it was a big investment. We think it's a strategic investment.
We cannot deliver on the mission of the company or the pipeline without Norwood. But we really beat Norwood so that this becomes the central node for us that is therefore very long term, so that we do not have to invest CapEx in the years to come at a high level. We will not be in the commercial plant until we have product approved that will be way too risky.
Great. Thank you, Tom. That's great.
Our next question comes from Alex Shanahan of Bank of America Merrill Lynch. Your line is open.
Hey, guys. Thanks for taking my questions and congrats on the progress. I just had a couple. So maybe first on the hMPV, PIV3 combination vaccine. Do you have a sense of the sort of data we'll likely see in October?
And will we see data outside of antibody tighter comparison? And is the Phase 1b TALER study necessary as per your conversations with the FDA before you begin a Phase 3? And then I
have one more.
Thanks, Alex. It's Noel. Yes, so in October, we'll present the totality of the data 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. And I believe that's been accepted to ID Week. 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. So 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.
Right, right. That's a sensitive patient population. And then shifting gears to your KRAS vaccine, 5,671. 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. So 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.
Yes. So I'll give you 2 versions of the answer, 1 on the science and 1 on the drug developer. On the science, unquestionably, one would want to combine these as early as possible, because we think there's orthogonal benefit as I described previously and one would expect these get combined with checkpoint inhibitors in addition. As a drug developer, you want to get confidence first that you're 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 the PD-one 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 Stephane Bentel for any closing remarks.
Thank you for joining us today and for your questions. We look forward to hosting you during our upcoming 3rd Annual R and D Day in New York City. This meeting will be held during the morning of September 12. 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.