Q3 2019 Earnings Call

At this time, all participants are in listen only mode.

Operator: Following the formal remarks, we will open up the call for your questions. Please be advised that this 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.

I'm going to formal remarks, we will open up the cool for your question.

Please be advised that this call is being recorded.

At this time I like to turn the call over to the vena to look door head Investor Relations. Im wondering are please proceed.

Thank you operator, good morning, and welcome to the during this third quarter 2019 conference call to discuss business updates at the National Michelle you can access the press release issued this morning as well at the flights it won't be reviewing if I go into the investors section of our website today on this call we had stuff on bugs out our chief executive.

Lavina Talukdar: Good morning, and welcome to Moderna's third 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. Today on this call, we have Stphane Bancel, our Chief Executive Officer, Tal Zaks, our Chief Medical Officer, Stephen Hoge, our President, and Lawrence Kim, our Chief Financial Officer. Before we begin, I would like to remind everyone that this conference call will include forward-looking statements. Please see slide 2 of the accompanying presentation and our SDC 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 developments or updates. I will now turn the call over to Stephane.

Officer Cows Act, our Chief Medical Officer, Steven Ho, our President and Mark can 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 your company presentation and our S. T 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 statement, we undertake no.

Oh obligation to update or revise the information provided.

On this call after there's lots of new information or future developments are uptick I will now turn the call over to Stefan.

Lavina Talukdar: Thank you, Lavina, and good morning, everyone. We are committed to building mRNA as a new class of medicines, with Moderna's position to remain the leader in the field. As you know, we believe our mRNA medicines have the potential to help patients by addressing large and medical needs and treating diseases that are not addressable by recombinant proteins or small molecules. Through the platform nature of mRNA, we believe our mRNA medicines provide a higher probability of technical success and faster timelines for clinical trials. We also believe that the manufacturing capacity intensity of mRNA is materially lower than recombinant protein and that our cost of manufacturing at commercial scale will be similar to small molecule injectables. We continue to focus on managing risk across the portfolio, especially technology and biology risk. In the quarter, we were proud to share positive Phase 1 data for two important milestones, our CMV vaccine and our antibody against the Chikungunya virus, delivered IV. We showed that we successfully immunized seronegative subjects with CMV and boosted seropositives.

Thank you and every now and good morning, everyone.

We are committed to be didn't come out and there as a new customer medicines, we model that position to remain the lead during this period.

As you know we believe I'm on the minute seems have a potential to help patients.

Addressing the all time at the medical needs and treating disease. That's another let's say borne by recombinant proteins cosman when of course.

So that's something that drove him on there we believe I am on him. It just seems provider higher probability of technical success and fulfill timelines to clinical trials.

Uh huh.

Congratulations on medicine.

So believed that the manufacturing capacity and can skew of M&A. He's metairie lower rental can be no protein it'll cost of manufacturing got commercials care would be see me, though small money couldn't injectables.

We continue to focus on managing risk across the portfolio, especially thinking energy and Bourchier risk.

You look Walter we're proud to shuffle did you face when they suck up two important milestones well CMV vaccine and antibody against their chagrin whenever us develop RV.

We should that we successfully even I see when it got keep subjects with CMB and boosted syrup, we'll get to use we plan to sell the phase two study very soon there GMP material. That's already been made and the study protocol has been submitted to eat healthier.

Stphane Bancel: We plan to start the Phase II study very soon. The GMP material has already been made, and the study protocol has been submitted to the FDA. At the 3-month interim result of a phase 2 trial, we should be able to make a decision on a phase 3 dose. The team is already spending a lot of energy planning for the Phase 3 study. We believe our CME vaccine could, if approved, change the future of thousands of children around the world by preventing birth defects. Moderna owns the global commercial rights to the CMV vaccine.

At the Fremont instead, we moved out of a phase two trial, we should be able to make a decision for phase three dose.

The team is over these spending a lot of energy to plan for phase three study.

We believe of CMV vaccine <unk>, if approved change the future of thousands of children around the world by preventing belt defect.

Well done that owns the go to commercial rights to the CMV vaccine.

We also presented data from a film ever and mountain Echo that antibody in a human study.

Stphane Bancel: We also presented data from the first ever mRNA-encoded antibody in a human study. We are very proud of this major scientific achievement, and we are eager to move forward with the MMA and PA clinical studies. Both of these rare disease programs use the same delivery technology as the one in the antibody program.

Well I'm very proud of this major authentic achievements and where you got to move <unk>, we'd be EM EMEA and P. Acne course studies soon.

Both of these reddys programs that use the same that every second university as the one in the antibody program.

If we step back and we've got somebody or can you call dates out what were less freeing up yes, we have come a long way.

Stphane Bancel: If we step back and look at the body of clinical data over the last three and a half years, we have come a long way. We started 16 Phase 1 trials with those mentioned, 1,400 subjects and patients. We repeated those with up to eight doses of mRNA up to three weeks apart in our Oxford T ligand and PCV trials.

We started 16 phase one trials.

We those men fat and protein on that subject and patients.

Repeat dose if tomatoes easily amounting to five weeks about <unk> and PCB trials.

Additionally across the five modalities for which we have human data, we have cost exactly showing that the m. on him into scenes I wouldn't want everything.

Stphane Bancel: Additionally, across the five modalities for which we have human data, we have consistently shown that the mRNA medicines are well-tolerated, resulting in consistent protein expression in humans. Transcribed by https://otter.ai. These findings are very important. They show that our technology investments are paying off. We believe we are at an important inflection point in company history. Five out of the first five modalities have shown success in the community. That was not easy. Now, was it obvious that this would be the case? Two critical factors explain it for me. One is the quality of our science. 2.

Resulting cost is templeton expression in humans.

And but for protein that's a function or in your mind.

<unk> broken equipment anything to humans.

These findings are very important.

Sure that's off technology investments are paying off.

We believe we are up and importantly fiction pointing the company history.

Five out of a first five modalities upfront success in the clinic.

That's what's not easy.

Nobody overuse that these would be the case.

Two particular fructose expanded for me one the quality of a science.

To the quality of all CMC, including manufacturing technical development and quality.

Stphane Bancel: The quality of our CMC, including manufacturing, technical development, and quality. One of my mentors at Eli Lilly, the late Dr. Gus Watanabe, who was president of Lilly Research Labs, once told me, Stefan, he takes graph science to make important medicine. We work in science. Well, good luck.

One of my menthol that you'd ideally the laid up I guess with an idea what's president Obama was such labs once told me.

Stefan you fix grip science to make important medicines, we look good times well good luck.

We're very humbled to be name for with P. neuro amongst the best employees around the world by Science.

Stphane Bancel: We are very humbled to be named for the fifth year in a row among the best employers around the world by Science. To be a science, 2019 Top Employers speaks loudly of the culture we have established in our scientific team. M.R.

Yes, I asked what the 19th up I'm, probably else speaks loudly overcoat sure we have established centric teams.

Well I'm on the cut foam or drug discovery and if so process development you manufacturing.

Stphane Bancel: on the Platform, or Drug Discovery, and also Process Development in Manufacturing. We are more than ever committed to being the best MR&A company in the world. It requires the right culture. And being named to this list five years in a row by our Moderna colleagues seems to signal we are on the right path.

We are moving there, though committed to be the best amounted company in the world.

Quiet right culture.

And being named to these least five years in a row bio Madonna colleagues seems to seeking though we are on the right path.

Hi, Mom society is not easy.

Stphane Bancel: It requires great collaboration from many disciplines with the right capabilities around the table. We think that with more than 300 scientific colleagues, we have scaled. We believe it is very hard to do a great amount of science with a much smaller team.

Between choirs get collaboration from many of you see brings we have a REIT capabilities around the table.

We think that's we've not been pronto sensitive colleagues we upscale.

We believe it is very healthy great them on his science, we there's a much smaller team.

Stphane Bancel: We also recognize that great science is being done outside of our walls. As such, a key part of our strategy is to collaborate on research with leading academic and medical centers around the world. We have established over 15 collaborations in over a year. Our more recent research collaboration with Harvard is centered around developing new medicines for immunological diseases. On slide 9, you see our current development pipeline. A few important milestones if you're free to note.

We also recognized that great science is being done outside of awards.

Such a keep a strategy to collaborate on research with leading academic and ecosystem fills around the world.

We have are you establish about 15 collaborations.

Well I'm always centrally self collaboration Weve, how about you sent to other on developing new medicines for even though she called disease.

On slide nine you'll see our current Europe and pipeline.

People, then milestones into free to note. The PCB you faced randomized trial has begun.

Stphane Bancel: The PCB phase randomized trial has begun, and we reported positive CRE Phase 1 data. We reported positive results from our antibody program, and the first subject was dosed in the H-de-escalation cohort of a Phase 1b of the HMPV-PRE3 vaccine. Zika received fast-track designation by the FDA. Pia has an open IND with the FDA, and recently got fast-track designation as well. Let me now turn to Tal to review clinical progress.

We reported positive CMV phase one data.

We reported positive result from antibody program.

The fill subject has been those in the age de escalation call up a phase one be OVH MPV PRB free vaccine.

He kind of whiskey fast track designation by the of the U P hasn't opened 90 baby every year and recently got fast track designation as well.

I'll now turn to calculate your clinical progress.

Stephane Bancel: Thank you, Stphane. We're advancing our pipeline of medicines in six different modalities, so let me start with the prophylactic vaccines, where we've treated over 1,000 healthy volunteers across seven programs to date. We're pleased with the emerging consistent safety and tolerability profile and, of course, with the repeated demonstration of potent immunogenicity, which we had expected based both on the fundamentals of expressing a viral antigen using our body's own cells and the wealth of preclinical data that continue to translate well in the clinic. The CMV Phase 1 success is the latest addition here. These data have exceeded our expectations, but before I review them, let me first briefly update you on other progress.

Thank you Stephanie we're advancing our pipeline of medicines and six different modalities. So let me start with a prophylactic vaccines, where we've treated over a thousand healthy volunteers across southern programs today.

We're pleased with the emerging consistent safety and Tolerability profile and of course with the repeated demonstration of bumped into Immunogenicity, which we had expected based both on the fundamentals of expressing alvaro antigen using our bodies on cells and the wealth of preclinical data that continue to translate well in the clinic.

The seem to be phase. One success is the latest addition here these data have exceeded our expectations, but before I review them. Let me first briefly update you on the on other progress both the RSV and Zika programs continue to dose patients and their respective phase one studies.

Stephane Bancel: Both the RSV and Zika programs continue to dose patients in their respective Phase 1 studies. For Zika, we also presented preclinical data at the International Society for Vaccine Conference in late October, where vaccination with mRNA 1893 was shown to be fully protective at the lowest dose tested. I'm pleased to report that the HD Escalation Study has started with the first subject dose.

For Zika, we also presented preclinical data at the International Society for vaccine conference in late October where vaccination with M&A 18, 93 was shown to be fully protected at the lowest dose tested.

On the agent Pvp would be three program I'm pleased to report that the escalation study is to fund notice has started with the first subject. Those we also presented seven month Immunogenicity data and infectious disease week in October and finally, with our Chicken Union vaccine program. We continue to see good durability with 78.6% of the subjects your positive to chicken going.

Stephane Bancel: We also presented seven-month immunogenicity data at Infectious Disease Week in October. And finally, with our Chikungunya vaccine program, we continue to see good durability with 78.6% of the subjects seropositive for the Chikungunya virus at 12 months post-vaccination. So let's get back to CMV.

Your virus at 12 months post vaccination.

So let's get back to CMV.

Stephane Bancel: CMV is a common pathogen that is a member of the herpes family of viruses, and like other herpes viruses, it's a latent virus, which means once we're infected, it's for life. The largest unmet need associated with CMV is birth defects and disease in babies born to mothers who are infected during pregnancy. The burden of the disease is significant, with approximately 25,000 newborns being infected each year in the U.S.

CMBS a common pathogen that is a member of the herpes family of viruses. Unlike other herpes viruses, it's a latent virus, which means once were infected it's for life, the largest unmet need associated with CMBS birth defects and disease and babies born to mothers cortland affected during pregnancy, the burden of disease, a significant with approximately 25000 newborns and.

That each year in the U.S.

Stephane Bancel: Currently, there aren't any vaccines against CMV on the market, despite repeated attempts over the last 50 years. Now, we believe that a reason for prior failures has been the inadequate immunization against the pentamer complex, which the virus uses to infect epithelial cells, the cells that line body surfaces and so are the first port of entry for the virus. This pentamer is made of five distinct proteins that have to assemble inside the cell before they're transported to the membrane. So trying to make this structure one protein at a time using traditional recombinant technologies is obviously challenging. However, this challenge can be overcome with our mRNA-based vaccine because our technology enables the simultaneous translation of five components. As shown on the bottom half of this slide, mRNA1647 actually contains six mRNA sequences, five of which encode for the sphincter and one that encodes for GB.

Currently there aren't any vaccines against CMV on the market. Despite repeated attempts over the last 50 years now we believe that a reason for prior failures has been the inadequate immunization against the pen some are complex, which the virus uses to infect the fuel cells either the cells that line body surfaces and saw the first part of entry for the Vars. This pensioners made a five distinct protein.

Instead have to assemble inside the so before their transported to the membrane. So trying to make this structure one protein at a time using traditional recombinant technologies is obviously challenging.

However, the challenge can be overcome with our M&A based vaccine because our technology enables the simultaneous translation of five components as shown on the bottom half of the slide M&A 16, 47 actually contains six M&A sequences five of which and code for the spend to Merck and one that encodes for GB GB, It's a relatively simple single protein receptor.

Stephane Bancel: Now, GB is a relatively simple single-protein receptor, and the important thing is that prior studies with the recombinant vaccine that only included GB already showed prevention. So, let me frame the next two data slides. Every one of us has either been infected with CMV in the past or not. And if we have it, we're lifelong carriers, and our immune system is constantly fighting this chronic infection. So we have antibodies in the serum of our blood, and that is called seropositive. If we've never been infected, we are.

And the important thing is that prior studies with the recombinant vaccine that only included GB already showed prevention of half the cases of CMV infection, which provides us with a very good starting point for demonstrating efficacy.

So let me frame. The next two data slides every one of US has either been infected with CMV in the past or not and if we have we're lifelong carriers and our immune system is constantly finding this chronic infection. So we have antibodies in the serum of our blood and that is called see are positive. If we've never been infected were a negative now both seer positive answer your negative subjects were enrolled in our phase ones.

Stephane Bancel: Now, both seropositive and seronegative subjects were enrolled in our Phase 1 study, so we'll be looking at the levels of neutralizing antibody titers for each of these subjects. mRNA-1647 encodes for the two antigens, the pentamer and the GP, that, in general, mediate the ability of the virus to infect two different cell types, epithelial cells and fibroblasts. So we will look at titers in the blood of subjects that can neutralize the virus's ability to infect either type of cell. Now this is important because we're talking about a functional readout. So, all in all, we are looking at four data sets from this trial. Let's start with the seronegative subjects on slide 13. The top half of the table shows neutralizing antibody titers against epithelial cell infection.

Study, so we'll be looking at the levels of neutralizing antibody titers for each.

Marni 16, 47 encodes for the two antigen append to mourn the GP that in general media the ability of the virus to infect two different cell types. The big deal yourselves on fiber of left so we will look at titers and the blood of subjects that can neutralize the viruses ability to infect either type of so there is important because we're talking about a functional readout.

So all in all we're looking at four dataset from this trial.

Let's start with a C or negative subjects on slide 13, the top half of the table shows neutralizing antibody titers against that we feel you also infection I'm going to draw your attention to two rose in the top half of the table. The fourth wrote down label GMT Post second vaccination, where you will see the Titan levels for placebo and each dose tested which were basically zero.

Stephane Bancel: And I'm going to draw your attention to two rows in the top half of the table. The fourth row down, labeled GMT post-second vaccination, where you will see the titer levels for placebo in each dose tested, which were basically zero for the placebo group and roughly 3,000, 15,000, and 31,000 for the 30, 90, and 180 microgram dose levels. The second row to focus on is the sixth row that shows the CMV seropositive titer level of 5588. This is the level of neutralizing titers seen in people who've been previously infected by CMV, the seropositives. The row above shows the ratio between the neutralizing antibody levels achieved with our vaccine relative to that level seen from seropositive subjects in the trial.

For the placebo group and roughly 3000 15030 1000 for the 30, 90, and 180 microgram dose levels.

The second wrote a focus on is the six throw that shows the CMV seropositive tighter level of 55 88. This is the level of neutralizing titers scene and the people who'd been previously infected by CMB. This your positives the ROE right above shows the ratio between the neutralizing antibody levels achieved with our vaccine relative to that level.

As seen from zero positive subjects in the trial at the 90 and 180 microgram doses M&A 16, 47 elicited an immune response against it we feel so infection that is 2.7 and 5.5 fold higher than what has seen its your positive subjects with natural infection.

Stephane Bancel: At the 90 and 180 microgram doses, mRNA1647 elicited an immune response against epithelial cell infection that is 2.7 and 5.5 fold higher than what is seen in seropositive subjects with natural infection. The reason why this is an important point is that because of CMV, seropositive pregnant women have been observed to have a lower rate of CMV transmission to their unborn children. So these results are striking and previous vaccines have not exceeded seropositive levels, and it demonstrates the strong immunological potency of our mRNA vaccine platform. The bottom half of the table shows a similar comparison for neutralizing antibody titers against fibroblast. Here, we see our vaccine-induced neutralizing antibody titer levels are similar to levels in seropositive subjects, so we've achieved the goal here as well.

The reason why this is an important point is that because of the CMV seropositive pregnant women have been observed to have a lower rate of CMV transmission to their unborn children. So these results are striking and that previous vaccines have not exceeded your positive levels and it demonstrates the strong immunological potency of our M&A vaccine class.

Sure.

The bottom half of the table shows a similar comparison for neutralizing antibody titers against fibroblast here, we see our vaccine induced neutralizing antibody titer levels similar to levels in zero positive subjects. So we've achieved that goal here as well taken together. These interim data shows that M&A 16, 47, effectively immunize is zero negative.

Stephane Bancel: Taken together, these interim data show that mRNA-1647 effectively immunizes seronegative subjects to levels at or well above those of seropositive individuals. Slide 14 shows the same representation of the data, only this time for the seropositive subjects in the trial. Here placebo subjects started off with neutralizing antibody titers. The average level of width, as I described, was 5588. After both the first and second vaccination, we see marked increases in neutralizing antibody titers. Thus, both vaccinations boost neutralizing antibody levels well above the baseline. And this is true for epithelial cells as well as fibroblasts. For epithelial cells, we see a 10 to 19-fold increase above the CMV0 positive benchmark. And with fibroblasts, we see a 2 to 4-fold increase.

Subjects to level at or well above zero positive individuals.

Slide 14 shows the same representation of the data only this time for the Super positive subjects in the trial here placebo subjects started off with neutralizing antibody titers. The average level with as I described was 55 88. After both the first and second vaccination, we see mark increases in neutralizing antibody titers, so both vaccination.

Runs boosting neutralizing antibody levels well above the baseline.

And this is true for it the fuel cells as well as fiberglass whether it be fuel cells. We see a tend to 19 fold increase above the CMV zero positive benchmark and with fiber glass, we see a two to four fold increase it's worth noting that this boosting gives your positive individuals has not been observed with prior vaccines.

Stephane Bancel: It's worth noting that this boosting of seropositive individuals has not been observed with prior vaccines. In terms of safety and tolerability, the vaccine was generally safe and well-tolerated, with no serious adverse events. Local adverse events included pain, redness, and swelling at the injection site, and the most common systemic adverse events were flu-like symptoms of fatigue, fever, chills, and myalgia. The adverse events seem to be more common and tend to be more severe in seropositive subjects and after more than one vaccination. In other words, they tend to correlate with the potency of this vaccine to elicit a specific immune response. That said, the adverse events are of a type that one expects to see in a healthy volunteer vaccine trial and are consistent with the safety and tolerability profile that we've seen in our other vaccine trials.

In terms of safety and Tolerability to proceed with generally safe and well tolerated with no serious adverse events local adverse events included pain redness swelling at the injection site and the most common systemic adverse events were flu like symptoms of fatigue fever, chills and lay algea. The adverse event seem to be more common and tend to be more severe and syrup positive subject and after more.

Then one vaccinations in other words, they tend to correlate with the potency of this vaccine to elicit a specific immune response.

That said the adverse events or have a type at one expects to see in a healthy volunteer vaccine trial and are consistent with the safety and Tolerability profile that we've seen in our other vaccine trials.

As a reminder, the data I've described thus far the interim data as analyzed one month. After the second dose regimen is a three dose regimen and zero two in six months in on this slide you can see preliminary results results from a small cohort of Sera negative subjects for which we have data out to a year. Following the three dose regimen. The solid Gray line is the level of.

Stephane Bancel: As a reminder, the data I've described thus far are the interim data as analyzed one month after the second dose. Our regimen is a three-dose regimen at zero, two, and six months, and on this slide, you can see preliminary results from a small cohort of seronegative subjects for which we have data out to a year following the three-dose regimen. The solid gray line is the level of seropositive neutralizing titers against epithelial cell infection, and you can see that everyone starts at zero, gets to the level I previously described by month three, and is further boosted at month six so that they remain at or above the level of seropositive at least out to a year with a relatively shallow decline over time.

Zero positive neutralizing titers against the fuel cell infection, and you can see that everyone starts at zero gets to the level I previously described by month, three and our further boosted at month six so that they remain at or above the level of your positive at least out to a year with a relatively shallow decline overtime.

Stephane Bancel: My expectation is that this durability is a function of eliciting strong T-cell help, which we know is an inherent feature of our mRNA vaccine platform. So, in summary, we're very pleased with these CMV data. We've shown seronegative subjects were successfully immunized to generate neutralizing titers while seropositive subjects were boosted to levels above their baseline, something that I don't believe the vaccine community has seen before. mRNA1647 was generally safe and well-tolerated, and we have early evidence of durability out to a year. We're excited by these results and are quickly moving to start a Phase 2 dose confirmation study. Phase 3 preparations are well underway, and importantly, FDA feedback suggests a regulatory path to approval using prevention of primary infection in a population that would include women of childbearing age as a basis for licensure, as opposed to licensure that would be based only on demonstrating the prevention of infection in newborns.

My expectation is that this durability is a function of eliciting strong T cell help which we know is an inherent feature of our marni vaccine platform.

So in summary, we're very pleased with these CMV data, we've shown serum negative subjects were successfully immunized to generate neutralizing tighter well see your positive subjects were boosted to level above their baseline something that I don't believe the vaccine community has seen before M&A 16, 47 was generally safe and well tolerated and we have early evidence of durability out.

A year.

Excitedly. These results in our quickly moving to start a phase two dose confirmation study phase three preparations are well underway and importantly, the FDA feedback suggest a regulatory path to approval using prevention of primary infection. In a population that would include women of childbearing age as a basis for licensure as opposed to licensure that would be.

Based only on demonstrating the prevention of infection in new Burns, we believe a phase III trial with this endpoint is achievable with less than 8000 subjects.

Stephane Bancel: We believe a Phase III trial with this endpoint could be achievable with less than 8,000 subjects.

Stephane Bancel: Prevention of CMV in women of childbearing age is a very significant unmet need, which we expect will translate into a large commercial opportunity. Currently, there aren't any vaccines on the market for CMV, and we're targeting a highly motivated population with clear opportunities down the road for label expansion. The sales effort should be focused on calling on OBGYNs and pediatricians, and assuming pricing similar to other innovative vaccines, one can quickly get to a multi-billion dollar annual sales potential. Moving to the cancer vaccine modality, recall that both we and NCI demonstrated at ASCO the ability of our personalized cancer vaccine to induce T-cells against the neoantigens that we encode. The NCI has now completed enrollment of five subjects in their trial.

Prevention of CMV in women of Childbearing age is a very significant unmet need which we expect will translate into a large commercial opportunity currently there aren't any vaccines on the market for CMV and we're targeting a highly motivated population with clear opportunities down the road for label expansion. The sales effort should be focused calling on Ob Gee why ends and.

Pediatricians and assuming pricing similar to other innovative exceeds when can quickly get to a multibillion dollar annual sales potential.

Moving to the cancer vaccines modality recall that both we and NCR demonstrated at ASCO the ability of our personalized cancer vaccine to induced T cells against the new antigens that we in code. The Ensco has now completed enrollment of five subjects and their trial the used our personalized cancer vaccine as a single agent in an attempt to further boost the expansion of.

Tumor infiltrating lymphocytes that they have given to a heavily pre treated patient population.

Stephane Bancel: They used our personalized cancer vaccine as a single agent in an attempt to further boost the expansion of tumor-infiltrating lymphocytes that they had given to a heavily pretreated patient population. However, they have not seen any responses to the vaccine as a single agent in these five patients. In contrast, our PCV program is designed primarily to test the ability of a personalized cancer vaccine to work in synergy with a PD-1 inhibitor and in earlier stages of disease. To that end, we're actively enrolling patients with melanoma in a randomized phase 2 trial, where we will compare our personalized cancer vaccine in combination with Keytruda versus Keytruda alone for the treatment of patients in the adjuvant The phase 1 PCV trial also continues to enroll patients. And finally, KRAS as a target is getting a lot of attention these days, and our approach is to use the four most prevalent KRAS mutations for the cancer vaccine.

They have not seen any responses to the vaccine as a single agent and these fives patients.

In contrast, our PCB program is designed primarily towards testing the ability of a personalized cancer vaccine to work in synergy with a PD one inhibitor and an earlier stages of disease and to that end, we're actively enrolling patients with melanoma and the randomized phase two trial, where we will compare our personalized cancer vaccine in combination with keytruda versus.

Trudeau loan for the treatment of patients in the adamant setting.

The phase one PCB trial also continues to enroll and finally came to us as a target is getting a lot of attention. These days and our approach is to use the for most prevalent KRS mutations as a cancer vaccine the trial for our cancer vaccine for our KRS mixing in combination with Keytruda is being run by our partner Merck and the phase one targeting pancreatic colorectal in lung cancer.

As is ongoing.

Moving to the intra tumoral modality, we have three programs in this sphere with Oxford, you look into triplet and interleukin 12, starting with M&A, 20, 416, which encodes oxforty ligand potent co stimulator of immune activation. The phase one is completing the monotherapy arm and currently dosing patients with the combination of.

Stephane Bancel: The trial for our KRAS vaccine in combination with Keytruda is being run by our partner Merck, and phase 1 targeting pancreatic, colorectal, and lung cancers is ongoing. Moving to the intratumoral modality, we have three programs in this sphere with OX4D ligand, the triplet, and interleukin-12, starting with mRNA-2416, which encodes OX4D ligand, a potent co-stimulator of immune activation. The phase one trial is completing the monotherapy arm and currently dosing patients with a combination of OX4D ligand and drivalumab. We're no longer moving forward with just monotherapy of the OX4D ligand, but we'll focus our efforts on the combination with drivalumab, which we intend to move into a phase two cohort in patients with advanced ovarian cancer once the dose escalation and confirmation cohort is complete.

Oxforty ligand and drove Allomap, we're no longer moving forward with just monotherapy of ox 40 ligand, but we'll focus our efforts on the combination with Durvalumab, which we intend to move into a phase two cohort in patients with advanced ovarian cancer once the dose escalation in confirmation covert is complete.

The phase one trial for M&A, 20, 752, which encodes for Oxforty ligand and to pro inflammatory cytokines idle 23 in all three to six gamma is ongoing we intend to test the combination of this trip with with Durvalumab in several tumor specific cohorts. Finally, our aisle 12 program partnered with Astra Zeneca based on the similar rationale.

Well as also ongoing.

In our localized regenerative modality the phase two vegetative trial is ongoing recall that our partner Astrazeneca has opened additional sites in Europe with the goal of increasing enrollment here.

Stephane Bancel: The Phase 1 trial for mRNA-2752, which encodes for OX4D ligand and two pro-inflammatory cytokines, IL-23 and IL-36 gamma, is ongoing. We intend to test the combination of this triplet with Dervalomeb in several tumor-specific cohorts. Finally, our Aisle 12 program partnered with AstraZeneca based on a similar rationale is also ongoing. In our localized regenerative modality, the Phase II VEGF trial is ongoing. Recall that our partner AstraZeneca has opened additional sites in Europe with the goal of increasing enrollment.

So let me spend the last few minutes on our systemic therapeutic starting with recent data we shared at the R&D day.

As a reminder, M&A 1944 encodes for an antibody against you can give you a virus antibodies are complex proteins consistent both of the heavy in the late chain that come together. So M&A 1944 includes two M. earnings one that includes for the heavy Jane and one that it goes for the life change once formed we would expect the antibody to be secreted in the bloodstream, where we can.

Measured.

So here are the phase one data.

We saw translation of Jakafi 24, the antibody in a dose dependent matter, meaning the more M&A 1944, you gave the more chicory 24 anti body was made.

Stephane Bancel: So let me spend the last few minutes on our systemic therapeutics, starting with recent data we shared on R&D day. As a reminder, mRNA-1944 encodes for an antibody against the Chikungunya virus. Antibodies are complex proteins consisting of both a heavy and a light chain that come together. So mRNA-1944 includes two mRNAs, one that encodes for the heavy chain and one that encodes for the light chain. Once formed, we would expect the antibody to be secreted into the bloodstream, where we can measure it. So, here are the phase one data. We saw translation of CHIKV-24, the antibody, in a dose-dependent manner, meaning the more mRNA-1944 you gave, the more CHIKV-24 antibody was made. Administering mRNA-1944 at the middle and high doses showed protein production well in excess of the 1 microgram per ml level that we had pre-specified as the level predicted to be protective against the Chikungunya virus. And the half-life behavior of the protein is exactly as predicted, such that the amount of antibody is expected to stay above the 1 microgram level for at least 4 months at the 0.3 mg per kg dose.

Administrating the M&A 1944 at the Middle and high doses show protein production well in excess of the one microgram per mill.

Level that we had pre specified as the level predicted to be protective against that you can get new buyers and the half life behavior of the protein is exactly as predicted such that the amount of antibody is expected to stay above the one microgram level for at least four month at the 0.3 make for kick dose.

As you can see in the inset protein production starts within hours. This is relevant as we think of using this delivered technology to directed synthesis of interest solar enzymes in liver cells of children born with rare genetic disease as is the case and metal melodic SDN propionic acid.

The final point to make on this slide is the remarkably low inter subject variability as measured by the coefficient of variants in the range of 20% to 40%. This is similar to what is seen with recombinant proteins. In other words are delivered technology can direct protein expression without a parent increase in the variability between subject.

Which is important as it relates to our ability to define a dose response relationship not just within a given subject, but within the population as a whole.

Stephane Bancel: As you can see in the inset, protein products...

Stephane Bancel: This is relevant as we think of using this delivery technology to direct the synthesis of intracellular enzymes in liver cells of children born with rare genetic diseases, as is the case in methylmalonic acidemia and propionic acidemia. The final point to make on this slide is the remarkably low inter-subject variability, as measured by the coefficient of variance in the range of 20 to 40 percent.

We also showed that the anybody made using M&A 944 as active as expected.

Here are the antibody is collected from the serum of subjects and tested against the virus in an essay and it is shown here is the proportion of patients in whom you can dilute the blood at least 100 fold and still be able to neutralize the virus.

Let me review the safety information.

Based on the preclinical toxicology, we were able to test them or 1944 without steward pre medications. They of course, the investigator had the option of using steroids if needed for the low end middle doses, we could not distinguish a difference between the drug arm and placebo as it relates to safety and recall that at the middle dose, we reached potentially therapeutic levels of protein.

Stephane Bancel: This is similar to what is seen with recombinant proteins. In other words, our delivered technology can direct protein expression without an apparent increase in variability between subjects, which is important as it relates to our ability to define a dose-response relationship, not just within a given subject but within the population as a whole. We also showed that the antibody made using mRNA-1944 is active as expected. Here, the antibody is collected from the serum of subjects and tested against the virus in an assay. And this is shown here as the proportion of patients in whom you can dilute the blood at least 100-fold and still be able to neutralize the virus. Now, let me review the safety information.

And at the high dose we started to see infusion related reactions that are typically associated with lipid nanoparticles and in fact with recombinant proteins at large.

These were anticipated in the protocol they occurred within hours of the infusion we're clinically resolved by the time to subsequent to sleeper got up in the morning and did not require medical intervention.

We did not see any serious adverse events and we did not see changes in liver kidney function tests.

To understand the performance of our technology I'd ask our clinical pharmacology theme, Tom modeled lead exposure that we would expect in humans based on the preclinical animal model experience. So here in the shaded area as you can see the 90% confidence intervals for where we would expect human protein levels to fall at each dose level and the solid darts are the individual clinic.

Stephane Bancel: Based on preclinical toxicology, we were able to test mRNA-1944 without steroid premedications, though of course, the investigator had the option of using steroids if needed. For the low and middle doses, we could not distinguish a difference between the drug arm and placebo as it relates to safety. And recall that at the middle dose, we reached potentially therapeutic levels of protein. At the high dose, we started to see infusion-related reactions that are typically associated with lipid nanoparticles and, in fact, with recombinant proteins at large. These were anticipated in the protocol. They occurred within hours of the infusion, were clinically resolved by the time the subject went to sleep or got up in the morning, and did not require medical intervention.

Well data lending exactly where expected.

Our delivery technology in other words translates from preclinical species to human with no loss of potency and this is important because it increases our confidence our confidence in the predicted activity of the zero point to make for kick dose level for may our first rare disease program because it is using the same delivery lippitt nanoparticle.

Given that we explicitly did not include steward communication in the first part of the study. The question is whether we can add stewards to the 0.6 Mig for kick dose and further reduce or completely eliminate the infusion related reactions that we've seen so we're continuing to explore the pharmacology of emerging 1944, 0.6 make perfect dose level and then tend to do so.

With both the inclusion of steward communication as well as by splitting the dose and giving two doses of 0.3 make for keurig, one week apart without steroids. So I look forward to continue to show the data as it emerges from this trial.

In summary, we're really happy with the results of our Chicken Guinea antibody program and morning, 1944, we saw a dose dependent increasing levels of antibodies against the chicken going you borrowers. The antibodies were functional with a predictive translation profile from species to species and no loss of potency when we bring into humans. M&A 1944 was also will total.

Stephane Bancel: We did not see any serious adverse events, and we did not see any changes in liver or kidney function tests. To understand the performance of our technology, I would ask our clinical pharmacology team to model the exposure that we would expect in humans based on the preclinical animal model experience. So here in the shaded areas, you can see the 90% confidence intervals for where we would expect human protein levels to fall at each dose level, and the solid dots are the individual clinical data landing exactly where expected.

Rather than a healthy volunteer population at a dose where we saw therapeutic levels of antibodies being produced.

And importantly, these results bode well for a rare disease programs like may that use the same LMP delivery technology as M&A 1944.

So this brings me to the intra cellular therapeutics and then this modality. Let me provide you a quick update on M&A in PA. These are similar diseases caused by inborn errors of protein metabolism, and our caused by mutations and deficiency or PCC deficiency, both of which act interest similarly.

Stephane Bancel: Our delivery technology, in other words, translates from preclinical species to humans with no loss of potential. And this is important because it increases our confidence in the predicted activity of the 0.2 mg per kg dose level for MMA, our first rare disease program, because it is using the same delivery lipid nanoparticles. Given that we explicitly did not include steroid premedication in the first part of the study, the question is whether we can add steroids to the 0.6 mg per kg dose and further reduce or completely eliminate the infusion-related reactions that we've seen. So we're continuing to explore the pharmacology of mRNA-1944 at the 0.6 mg per kg dose level and intend to do so with both the inclusion of steroid premedication as well So I look forward to continuing to share the data as it emerges from this trial. In summary, we're really happy with the results of our chicken guinea antibody program, mRNA-1944. We saw a dose-dependent increase in levels of antibodies against the chicken guinea virus.

Our M&A impeded programs aimed to replace these proteins and bring the protein metabolism and the associated SDDP levels closer to normal.

From a regulatory standpoint, and we're in a 37 know for an M&A 30, 927 have similar to dig nations. Both compounds have FDA orphan drug designation M- orphan disease status FDA fast track status and the FDA rare pediatric disease designation, which upon approval will qualify the two programs for rare pediatric disease vouchers.

The phase one study for M&A is currently active recruiting patients and the period program recently had its R&D open we're preparing to start a phase one two trial there shortly.

Now regarding M&A. The initial cohort was limited by FDA to adolescence between the ages of 12 in 18 and during the summer we had gone back to the agency and they allowed for the expansion of this age bracket to include patient older than eight while we're continuing the dialogue with FDA regarding further modification to the enrollment criteria in the past few weeks. This amended protocol has been ups.

By the Arby's of the first few institutions. So I look forward to updating you on our progress soon.

Teekay has a similar design and similar initial age restrictions and following the opening of the Indian subsequent fast track designation, we have begun startup activities at the leading academic centers.

Stephane Bancel: The antibodies were functional with a predicted translation profile from species to species and no loss of potency when we introduced them into humans. mRNA-1944 was also well-tolerated in a healthy volunteer population at a dose where we saw therapeutic levels of antibodies being produced. And importantly, these results bode well for our rare disease programs like MMA that use the same LNP delivery technology as mRNA-1944. So this brings me to intracellular therapeutics. And in this mode, let me provide you with a quick update on MMA and PA. These are similar diseases caused by inborn errors of protein metabolism and are caused by mute enzyme deficiency or PCC deficiency, both of which act intracellularly. Our MMA and PA programs aim to replace these proteins and bring the protein metabolism and the associated acidemia levels closer to normal. From a regulatory standpoint, mRNA 3704 and

Let me close with slide 32, which lists the anticipated next steps and then an upcoming clinical catalyst and I'll focus you on the CMV face to start as well as the eventual readout and on the M&A in key a phase one two trials with that let me turn the call over to Lawrence. Thank you Tom.

In today's press release, we report our third quarter 2018 financial results. Please note. These results are unaudited.

We ended Q3 2900 cash cash equivalents investments of $1.34 billion. This compares to $1.69 billion at the end of 2018.

Net cash used in operating activities was $363 million for the first nine months of 2019 compared to $240 million in 2018.

Cash used for purchases of property and equipment was $25 million for the first nine months of 2019 compared to $92 million in 2018, which was the first year that we put our Nora manufacturing facility into service.

Now recall that on January 1st 2019, we adopted the mandated revenue recognition standard DSE six of six using the modified retrospective transition method applied to this contract to true not completed as of January Onest 2019.

Stephane Bancel: University

Lawrence Kim: [inaudible] The Phase I study for MMA is currently active recruiting patients, and the PA program recently had its ID open. We're preparing to start a Phase I-II trial there shortly. Now regarding MMA, the initial cohort was limited by FDA to adolescents between the ages of 12 and 18, and during the summer, we had gone back to the agency, and they allowed for the expansion of this age bracket to include patients older than 8. While we're continuing the dialogue with FDA regarding further modification to the enrollment criteria, in the past few weeks, this amended protocol has been approved by the IRBs of the first few institutions, so I look forward to updating you on our PA has a similar design and similar initial age restrictions, and following the opening of the IND and subsequent Fast Track designations, we have begun startup activities at the leading academic centers. Let me close with slide 32, which lists the anticipated next steps and an upcoming clinical catalyst. And I'll focus you on the CMV Phase 2 start, as well as the eventual readout, and on the MMA and TA Phase 1-2 trials. With that, I'll turn the call over to Lawrence. Thank you, Tom.

So the deep decreases in total revenue for Q3 and for the first nine months of 2019 compared to 2018 from mainly attributable to the adoption of this new revenue standard.

Let me for Q3, 2019 was $17 million as compared to 42 million for Q3 of 18 and for the first nine months between 19 revenue was 46 million compared to 100 million in 2018.

Total revenue under the previous revenue recognition standard would've been 25 million for Q3.

2019, and $80 million for the first nine months by 19.

R&D expenses for Q3, 2019 were $120 million compared to $109 million for Q3 2018.

First nine months of 2019, R&D expenses were 379 million compared to 304 million in 2018, the increase in Q3 and for the first nine months of 20 and 19 compared to prior year was mainly driven by an increase in personnel related costs, including stock based compensation with additional increases for the first nine months of 2019 being driven by higher.

Clinical trial manufacturing costs, an increase in last platinum materials in an increase in consulting and outside services.

In expenses for Q3, 2019, or approximately $28 million compared to $19 million in Q3 2018 and for the first nine months of 2019 expenses were 84 million compared to $56 million in 2018.

Lawrence Kim: Hall. In today's press release, we report our third quarter 2019 financial results. Please note these results are unaudited. We ended Q3 2019 with cash, cash equivalents, and investments of $1.34 billion. This compares to $1.69 billion at the end of 2018. Net cash used in operating activities was $363 million for the first nine months of 2019, compared to $240 million in 2018. And cash used for purchases of property and equipment was $25 million for the first nine months of 2019 compared to $92 million in 2018, which was the first year that we put our Norwood manufacturing facility into service. Now 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, and so the decreases in total revenue for Q Revenue for Q3 2019 was $17 million, as compared to $42 million for Q3 of 2018. And for the first nine months of 2019, revenue was $46 million, compared to $100 million in 2018. Total revenue under the previous revenue recognition standard would have been $25 million for Q3 2019 and $80 million for the first nine months of 2019.

The increase increases in Q3 in the first nine months of 2019 comparing to prior year, mainly due to the additional cost of operating as a publicly traded company, including an increase in personnel related costs and stock based compensation consulting and outside services legal and insurance costs.

Let me now drill down on our balance sheet strength. We ended Q3 as I mentioned with cash cash equivalents in investments of $1.34 billion that balance sheet as augmented by our access to a number of grants. We are fortunate to have established strategic alliances with government sponsored and private organizations, including Darva BARDA in the Bill and Melinda Gates Foundation.

So as of September Thirtyth 2019, we recognize $59 million in revenue to date, while we have a total additional available funding of $187 million comprising 99 million of committed funding and another 88 million of non diluted funding that we can tap into.

I will turn out to where we expect to end 2019.

We ended 2018 on 1.69 billion in cash cash equivalent in investments and early this year, we got into a yearend 2019 cash balance of $1.15 billion to $1.20 billion. We've reiterated that guidance on subsequent quarterly calls and today, we are guiding the yearend cash at the high end of that range that is we expect to have approximately 1.2 billion at the end.

2019.

This works out to a change in cash of less than $500 million for 2019.

I also want to highlight two specific cash flow line items, our cash used in operating activities and purchases of property and equipment by quarter. In Q1, we used $152 million of cash in these two items that number included $22 million of in licensing payments, but we have no further in lessons and payment obligations to these entities going forward and then you can see the decline in our quarter over quarter.

Lawrence Kim: R&D expenses for Q3 2019 were $120 million compared to $109 million for Q3 2018. For the first nine months of 2019, R&D expenses were $379 million compared to $304 million in 2018. The increase in Q3 and for the first nine months of 2019 compared to the prior year was mainly driven by an increase in personnel-related costs, including stock-based compensation, with additional increases for the first nine months of 2019 being driven by higher clinical trial manufacturing costs, an increase in lab supplies, materials, and an increase in consulting and outside services. G&A expenses for Q3 2019 were approximately $28 million compared to $19 million in Q3 2018. And for the first nine months of 2019, G&A expenses were $84 million compared to $56 million. The increases in Q3 in the first nine months of 2019 compared to the prior year 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, legal, and insurance costs.

Cash used for these items in a year to date number $388 million.

So when you look ahead to the full year on these cash flow metrics. We can expect 2019 net cash used in operating activities and purchases of property and equipment to total approximately $500 million as we've said in the past. This reflects our ongoing focus and allocation of our shareholders' capital toward value driving investments in our portfolio and platform.

Lastly, as we look at 2020, we are issuing guidance now for next year around the same cash flow metrics I'll start by noting that we actually expect that trend to be relatively flat year over year. This trend is really due to a combination of factors firstly, a nonrecurring costs such as a 2000 $18 million in licensing payments in 2019.

Also at this time with Norwood operating well our need for significant new facilities and associated capital expenditures is limited and our pipeline, while advancing well, it's actually not burdened with very large trials in 2020 for instance, while we are planning for a substantial phase three CMV vaccine study at program only requires pre investment in 2020.

And lastly, I'll note that our partners fund significant development cost or programs, such as RSV Ziggo K Ras aisle 12 that Jeff and should continue antibody and so for these reasons, we do not expect growth in our cash needs for next year, while being able to fund significant pipeline advancement and ongoing platform development.

Lawrence Kim: Let me now drill down on our balance sheet strength. We ended Q3, as I mentioned, with cash-cash equivalents and investments of $1.34 billion. That balance sheet is augmented by our access to a number of grants. We are fortunate to have established strategic alliances with government-sponsored and private organizations, including DARPA, BARDA, and the Bill & Melinda Gates Foundation.

As a result, our guidance is that we now expect net cash used in operating activities under purchases of property equipment to totaled $490 million to $510 million for 2020, very similar to where we will end 2019.

As I hand, it back it's just testified I'll close again with our pipeline, which reiterated my last point on a number of programs as we've highlighted that our partner funded.

Lawrence Kim: And so as of September 30, 2019, we've recognized $59 million in revenue to date, while we have a total additional available funding of $187 million, comprising $99 million of committed funding and another $88 million of non-committed funding that we can tap into. Now, I'll turn now to where we expect to end 2019. We ended 2018 with $1.69 billion in cash, cash equivalents, and investments. Early this year, we guided to a year-end 2019 cash balance of $1.15 to $1.20 billion. We've reiterated that guidance on subsequent quarterly calls, and today we are guiding to year-end cash at the high end of that range, that is, we expect to have approximately $1.2 billion at the end of 2019. This works out to a change in cash of less than $500 million for 2019.

Thanks.

So close I wouldn't spend as capital maintenance on the if you've opened product and why we're so excited about them and whether caring for patients that thoughts we've all in about the vaccine.

We now have in clinical studies falling for thinking about the vaccine.

CMV vaccine and as the vaccine.

Combo MPV NPV free vaccine and this is Kevin.

Yes, no approved vaccines to protect two months from these five ounces.

The morbidity and mortality calls around the world by these five ROTC understating.

We believe CMV RSV and actually MPV, obviously combo, each multibillion dollar annual except as opportunities and decades as several hundred million that all annual Dicks said opportunity.

We know that all vaccine phosphates, whether from quick and equal more those two phase one data.

Anything is well documented in the pharmaceutical industry that vaccines. Once official are positive phase will have a highest priority to launch across any for uptick area.

Lawrence Kim: I also want to highlight two specific cash flow line items, our cash use in operating activities and purchases of property and equipment by quarter. In Q1, we used $152 million of cash on these two items. That number included $22 million of in-licensing payments, but we have no further in-licensing payment obligations to these entities going forward. And then you can see the decline in our quarter-over-quarter cash use for these items and a year-to-date number of $388 million. So when we look ahead to the full year on these cash flow metrics, we can expect 2019 net cash used in operating activities and purchases of property and equipment to total approximately $500 million. As we've said in the past, this reflects our ongoing focus and allocation of our shareholders' capital toward value-driving investments in our portfolio and platform.

We have five immuno oncology programs in the clinic that these are remarkable pipeline.

For all five of course, you programs. Our aim is the same.

We had an innovative monument does seem to have commercial PD, one PDL one to improve a response rate of these patients.

Check box are wonderful medicines, but unfortunately, most patients the most responsive checkpoint inhibitors.

We believe very the lost commercial opportunity to improve accomplished response rate of checkpoint inhibitors, and we have five opportunities to try to that.

And finally in rare diseases. The tool, yes, how you pull them at it seems in development.

We have these are designed to treat the devastating disease for which we all know approvement as seen on the market may appear GST winning.

And talking about designed to improve as follow up capital patience for PK, you and pepper.

Our priorities for 2019, 20, Plenti pricing number one is to execute on our pipeline I.

Im pleased with the progress across both in 2019, especially with clinical data from all CMV vaccine and antibody against you can we have hours programs as well as our PCB per I'm now in phase two.

Lawrence Kim: Lastly, as we look to 2020, we are issuing guidance for next year around these same cash flow metrics. I'll start by noting that we actually expect this trend to be relatively flat year over year. This trend is really due to a combination of factors. First, we have non-recurring costs, such as the $22 million in licensing payments in 2019. Also, at this time, with Norwood operating well, our need for significant new facilities and associated capital expenditures is limited. And our pipeline, while it's advancing well, is actually not burdened with very large trials in 2020. For instance, while we are planning for a substantial phase 3 CMV vaccine study, that program only requires pre-investment in 2020. And lastly, I'll note that our partners fund significant development costs for programs such as RSV, Zika, KRAS, IL-12, VEGF, and chikungunya antibody.

Probably due to less named new development candidate.

Anything we'll have cities within the new DC 41, the earlier this year.

Hi, good number three is to create new development candidate in without cities.

We are continuing to make good progress in several volume will that be teas, and will follow up sharing some of data into multiplexing.

In summary, we are pleased with the pace of execution.

Yes, Thanks, a lot from Walter.

Phase one data for CMV and the antibody you guys shipping we now we have up to 1.5 billion to invest in the business between of cash balance and all grants.

We invest approximately 500 million that our company in 2019 and other so approximately 500 million underlying 2020 .

We intend to continue through new partnership with Biopharma companies and to apply for new brands.

We know that's we have a special opportunity.

Committed to delivering on the promise of science.

And we fall Walt and new vessel medicines for patients I would like to handle remarks by thinking that many people who participate in clinical studies, including patients had people don't feel that condition.

Lawrence Kim: And so, for these reasons, we do not expect growth in our cash needs for next year while being able to fund significant pipeline advancement and ongoing platform development. As a result, our guidance is that we expect net cash used in operating activities and for purchases of property equipment to total $490 to $510 million for 2020, very similar to where we will end 2019. As I hand it back to Stphane, I'll close the...

We also like to affect the great team at the Madonna working hard every day from it gives vision a reality we have that.

Occupancy pick any question Franco.

Thank you and as a reminder to ask a question you will need to press star one on your telephone to withdraw your question. Please press the pound key.

Stphane Bancel: Last point on the number of programs that we've highlighted that are partner funded. [inaudible]

Stphane Bancel: To close, I would like to spend a couple of minutes on our development products and why we are so excited about them and what they can do for patients. Let's start with our Innovative Act.

Please stand by will be composite culinary roster.

And our first question comes from the line of Matthew Harrison with Morgan Stanley . Your line is now open.

Great. Good morning. Thanks, Thanks for taking the question. Thanks for the detail on on the updates here I guess two parts for me. So first could you talk about progress in being able to enroll patients in M&A.

Stphane Bancel: We now have in clinical studies four important innovative vaccines to protect humans from this fire virus. However, there are no approved vaccines to protect humans from this fire virus. The morbidity and mortality caused around the world by these five RITs is devastating. We believe CMV, RSV, and our HMPV-PIV Free Combo are each multi-billion dollar annual pixels opportunities, and Zika is a several hundred million dollar annual pixel opportunity. We know that our vaccine translates well from preclinical models to phase one data. And it is well documented in the pharmaceutical industry that vaccines, once they show a positive phase one, have the highest probability of launch across any therapeutic area. We have five immuno-oncology programs in the clinic, which is a remarkable pipeline. For all our five oncology programs, our aim is the same. Can we add an innovative mRNA medicine to a commercial PD-1 or PD-L1 to improve the response rate of this patient? Checkpoint inhibitors are wonderful medicines, but unfortunately, most patients do not respond to checkpoint inhibitors.

I think you've had sites up and for a bit of time here and now you've been able to expand the age group, but it doesn't sound like you've enrolled the patient yet maybe just talk about.

What's going on there.

And then second on.

Chicken Goon, yet maybe just talk about when we should expect to see some information about dosing profile and you're able to drive those higher with pre medication or split dosing.

Well.

Thank you Matthew This is Paul let me address address both of your questions. You are right on M&A, we have not yet dose to our first subjects.

We.

As as noted initially FDA had requested that we limit the first three subject to ages 12 and above and before we can proceed to the children that are young as young as one year growth were the highest unmet need is.

Stphane Bancel: We believe there is a large commercial opportunity to improve the complete response rate of checkpoint inhibitors, and we have five opportunities to try to do that. And finally, in world diseases, here too, we have five important medicines in development. Three of these are designed to treat devastating diseases for which there are no approved medicines on the market, MMA, PA, GSD-1A, and two of them are designed to improve the standard of care for patients with PKU and FABRA. Our priorities for 2019-2020, priority number one is to execute on our pipeline. I am pleased with the progress across the board in 2019, especially with clinical data from our CMV vaccine and our antibody against the Chikungunya virus programs, as well as our PCB program now in place. Priority 2 was to name new development candidates in our existing modality. We named a new D.C. for D1A earlier this year. And project number three is to create new development candidates in new modalities. We are continuing to make good progress in several new modalities, and we look forward to sharing some updates in 2020.

And I think we've found in opening the sites and trying to enroll this that there are several factors that come into play.

By the time somebody gets to be an adolescent.

If their disease, it's been severe to they've often had a liver transplant in fact liver transplants.

The us our recommended between the age of the year in preschool and when the kids with them and May shows up for liver transplant. They move to the top of the Q, So theres not much waiting.

Those who don't get a liver transplant often suffer from kidney deterioration and we can do a phase one trial with.

Up really abnormal kidney function. So we had gone back in the summer as noted to discuss with FDA lowering the age Chris here. They had agreed to take it down to the ages of eight an above and while we're still in dialogue with them about that the amendment to enable us to do that.

As a just recently opened that some of the leading institutions.

And.

We look forward to enroll in the first subject soon.

Stphane Bancel: In summary, we are pleased with the pace of execution. The key allies of our first quarter are the positive Phase 1 data for CMV and the antibody against chikungunya. We have up to $1.5 billion to invest in the business between our cash, balance, and our grants. We will invest approximately $500 million in our company in 2019, and also approximately $500 million in 2020.

It is it has been a challenge for all those factors that I alluded to but I think between lowering the age and now being open at some of the selected Situtions, we should see progress soon.

Now you'd ask me about.

The chicken good.

And when do you expect to see data the.

Stphane Bancel: We intend to continue to do new partnerships with biopharma companies and to apply for new grants. We know that we have a special opportunity, and we are committed to delivering on the promise of our science and bringing forward a new class of medicine for patients. I would like to end our remarks by thanking the many people who participated in our clinical studies, including patients, healthy volunteers, and physicians. I would also like to thank the great team at Moderna, working hard every day to make this vision a reality. With that said, we are happy to take any questions. Thank you.

This is a healthy volunteer trial so.

We had gone back to the safety monitoring committee aligned with them on the next tabs and we're actively working with the site to to get the next cohorts enrolled.

So as soon as data will become available and we understand what is we have we'll be sharing it with unit.

Being at healthy volunteer trial, it should move relatively quickly.

Thank you.

Thank you and our next question comes from the line of Ted Tenthoff with Piper Jaffray. Your line is no.

Operator: Thank you. And as a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, please press the pound key.

Great. Thank you very much thanks for the update and all the great on all the great progress.

Operator: Please stand while we compile the Q&A roster, and our first question comes from the line of Matthew Harrison with Morgan Stanley. Your line is now: Great, good morning. Thanks for taking the question. Thanks for the detail on the updates here. I guess there are two parts for me.

I want to ask about the CMV vaccine really just get a little bit better clarity on what you see as the path forward here.

Appreciating a phase two.

Matthew Harrison: So first, could you just talk about progress in being able to enroll patients in MMA? You know, I think you've had sites open for a bit of time here, and now you've been able to expand the age group, but it doesn't sound like you've enrolled a patient yet. So maybe you could just talk about, What's going on there? And then, second, on chicken guna, maybe just talk about when we should expect to see some information about the dosing profile. And if you're able to drive those higher with pre-conditioning,

Dose confirmation start next year can you give us a sense of.

The size of that study and maybe how long it would take.

And then looking kind of forward. How soon do you think you could actually initiate pivotal studies in women of childbearing age. Thank you.

Thank you Ted this is Tom I'll take that question.

Hey, Tom So a couple of points.

First in terms of size and timing the phase two is about 250 subjects are so the design is really meant to confirm the dose and give us more color on both immunogenicity and safety and Tolerability. So that we're able to pick the right dose for phase three that being said.

Stephane Bancel: Thank you, Matthew. This is Tal.

Stephane Bancel: Let me address both of your questions. You're right about MMA. We have not yet dosed our first subject. As noted, initially, FDA requested that we limit the first three subjects to ages 12 and above before we can proceed to children that are as young as one-year-old, where the highest unmet need is. And I think we found in opening the sites and trying to enroll this that there are several factors that come into play. By the time somebody gets to be an adolescent, if their disease has been severe, they've often had a liver transplant. In fact, liver transplants in the U.S. are recommended between the age of a year in preschool, and when a kid with MMA shows up for a liver transplant, they move to the top of the queue, so there's not much waiting. Those who don't get a liver transplant often suffer from kidney deterioration, and we can't do a phase one trial with... really abnormal kidney function.

The time should be relatively quickly because the will make the decision based on a three month end point once everybody has been dose similar to what the interim data that we've shown in the phase. One by then we will have the further follow up post the third dose in the phase one. So we will have overall more data to be able to share in substantiate that decision.

And now the path to phase three I think the big change here for me has been the fact that if FDA has provided guidance that.

Speaks of the potential for license your based on the prevention of primary infection.

And that's that's very significant because that that means that it is eminently doable with the trial of decide that we've discussed in terms of launching that I would say that too.

Stephane Bancel: So we went back in the summer, as noted, to discuss with FDA lowering the age criteria; they agreed to take it down to the ages of eight and above. And while we're still in dialogue with them about that, the amendment to enable us to do that has just recently opened at some of the leading institutions. And I look forward to enrolling the first subject soon. It has been a challenge for all those reasons that I alluded to. But I think between lowering the age and now being open at some of the select institutions, we should see progress. Now you asked me about chikungunya and when do you expect to see data? This is a Healthy Volunteer trial, so we have gone back to the Safety and Monitoring Committee, aligned with them on the next steps, and we're actively working with the site to get the next cohorts enrolled, so as soon as data becomes available and we understand what it is we have, we'll be sharing it with you.

Gating factors I think to actually launching that study are going to be the phase two data and some regulatory discussions. This was just a very preliminary initial guidance of course before one launches a phase III trial here, we'd need to have those.

More deep discussions with FDA and other agencies to make sure. We're launching the right study now once once we get there their agreement I think the the design is fairly straight forward. One would expect an incident rate of about 1.5% a year. So hopefully with a couple of years of follow up once everybody has enrolled you good.

See the effect that you're looking for and wrap it up so that gives you a rough sense of the overall timeline here.

Great. That's super helpful. And then if I may just ask a second question appreciating that at some with Merck when could we get data from the enhanced RSV vaccine. Thanks, so much.

Stephane Bancel: Thank you. Thank you, and our next question comes from the line of Ted Tenthoff with Piper Jeffery. Your line is now open. Great, thank you very much. Thanks for the update and all of the great progress.

Yes, that's a great question.

Hi, I ask that as well.

The truth is that they are pretty efficient and running these trials they've got a long track record of running at healthy volunteer vaccine trials and of analyzing data quickly. So you know as soon as soon as they have something material to share with US we will of course.

Edward Andrew Tenthoff: I want to ask about the CMV vaccine and really just get a little bit better clarity on what you see as the path forward here. Appreciating phase two, with those confirmations starting next year, can you give us a sense of, you know, the size of that study and maybe how long it would take? And then, looking kind of forward, how soon do you think you could actually initiate pivotal studies in women of childbearing age?

Shared with you.

Thanks, so much guys.

Thank you and our next question comes on line of Salveen Richter with Goldman Sachs. Your line is now open.

Good morning, Thanks for taking my questions.

Maybe first question here and how your chicken can you have vaccine clinical development plan reflects the guidance that was provided by the FDA and then second question on the chicken Gilenya antibody program here could you just walk us through your plans for evaluating repeat dosing recognizing that you do you have this cohort study coming.

Stephane Bancel: Thank you, Ted. This is Paul.

Stephane Bancel: I'll take that question. So, a couple of points. First, in terms of size and timing, the Phase 2 study is about 250 subjects or so. The design is really meant to confirm the dose and give us more color on both immunogenicity and safety and tolerability so that we're able to pick the right dose for Phase 3. That being said, the time should be relatively quick because we'll make a decision based on a three-month endpoint once everybody has been dosed, similar to the interim data that we've shown in Phase 1. By then, we will have further follow-up after the third dose in Phase 1, so we'll have overall more data to be able to share and substantiate that decision. Now, the path to Phase 3, I think the big change here for me has been the fact that FDA has provided guidance that speaks of the potential for licensure based on the prevention of primary infection.

With two Dennis is about a week apart.

Thank you Sylvain. This is Tom will take that so the plan to develop a chicken gunia vaccine is a great question.

It's.

It's true that if FDA is giving a potential path. In fact, there is a big discussion in a couple of days time down at the FDA, where our team is presenting alongside others to flesh out what that could look like.

To date, it hasn't been clear how one could develop it and do it in a commercially viable setting to the degree that the discussions with the agency in the near term will actually paying to path, where it would be worth our capital and time to go there will obviously be looking at it.

Carefully so I don't have a clear answer because I think this is a work in progress to date, we've not seen commercial path I'm happy with the recent agency guidance and we'll see how the conversations go.

Stephane Bancel: And that's very significant because that means that it is eminently doable with a trial of the size that we've discussed. In terms of launching that, I would say the two gating factors, I think, to actually launching that study are going to be the Phase 2 data and some regulatory discussions. This was just very preliminary initial guidance, of course. Before one launches a Phase 3 trial here, we'd need to have those more deep discussions with FDA and other agencies to make sure we're launching the right study. Now, once we get their agreement, I think the design is fairly straightforward. One would expect an incident rate of about 1.5% a year, so hopefully, with a couple of years of follow-up once everybody is enrolled, you could see the effect that you're looking for and wrap it up. So that gives you a rough sense of the overall timeline here.

Your question on repeat dosing for the monoclonal antibody program the globally here is to.

Substantiate our ability to stack pharmacology in other words to show that the antibody level the protein level production of two doses given the weak part behave as expected in the clinic, we had seen that in the preclinical toxicology and the non human primate, but I think being able to show that and leveraging the fact that the.

This event profile seems to be a very quick infusion related reactions that come on quickly and come up quickly we would expect that.

There were there should not be any stacking in terms of safety, while there wouldn't be stacking in terms of pharmacology and that's the rationale of doing two doses one week apart at a dose where we actually had not seen any significant adverse events.

Stephane Bancel: Great, that's super helpful. And then, appreciating that it's with Merck, when could we get data from the enhanced RSV vaccine? Thanks so much.

Did that answer the question, yes, that's helpful. Thanks.

Stephane Bancel: Yeah, that's a great question. I asked it as well.

Thank you.

Stephane Bancel: The truth is that they're pretty efficient in running these trials. They've got a long track record of running healthy volunteer vaccine trials and of analyzing data quickly. So you know, as soon as they have something material to share with us, we'll, of course, share it with you. Thanks so much, guys.

Thank you and our next question comes from the line of Cory Kasimov with Jpmorgan. Your line is now open Hey, good morning, guys. Thanks for taking my questions. So too as well. So first is just following up on on C.M.B. and as you get the phase two sites up and running and plan for your phase three are there any additional processes are chat.

Stephane Bancel: President, Thank you.

Salveen Richter: Thank you. And our next question comes from the line of Salveen Richter, Goldman Sachs.

Salveen Richter: Your line is now open. Good morning. Thanks for taking my questions. Maybe a first question here on how your chikungunya vaccine clinical development plan reflects the guidance that was provided by the FDA. And then a second question on the chikungunya antibody program here. Could you just walk us through your plans for evaluating repeat dosing, you know, recognizing that you do have

Lunges, we should be thinking about given the new modality, you're introducing or is this something that you think you can go pretty quickly from a patient accrual point of view and then my second question is regarding your natural history studies for M.A.M.P.A., what see aimed at the age range you have there for natural history and do you think that provides any.

Stephane Bancel: Thank you, Salveen. This is Paul.

Stephane Bancel: I'll take that. So the plan to develop a chikungunya vaccine is a great question. It's It's true that FDA is giving us a potential path. In fact, there's a big discussion in a couple of days' time down at FDA where our team is presenting alongside others to flesh out what that could look like. To date, it hasn't been clear how one could develop it and do it in a commercially viable setting to the degree that the discussions with the agency in the near term will actually paint a path where it would be worth our capital and time to go there. We'll obviously be looking at it carefully. So I don't have a clear answer because I think this is a work in progress. To date, we've not seen a commercial path.

Read through to how enrollment might go once you have a broader age range introduced for your for your clinical trials 87 subjects at this stage seems like a pretty decent number for rare diseases. Thanks.

Thank you Cory this call let me take those two in sequence.

Don't first see any additional challenge for enrolling the CMV other the phase two of the phase three that our platform dependent and I'll I'll sort of give you. The two reasons for that the first is the totality of safety and Tolerability data that we've seen across the portfolio are consistent with one with what one would expect we.

Havent seen anything surprising Theres no scientific reason to expect anything untoward, and we hadn't seen anything untoward in preclinical.

Stephane Bancel: I'm happy with the recent agency guidance, and we'll see how the conversations go. If the adverse event profile seems to be a very quick infusion-related reaction that comes on quickly and comes off quickly, we would expect that there should not be any stacking in terms of safety while there would be stacking in terms of pharmacology. That's the rationale for doing two doses one week apart at a dose where we have actually not seen any significant adverse events. Did that answer the question? Yes, that was very helpful.

So.

I think this is going to be a vaccine platform that will behave as such in fact that CMV data suggests that is the more putting the vaccine is the more adverse event you get that were flu like symptoms, but the adverse event the type of adverse events. As I've noted is what you'd expect I think the other reference point is the fact that this is the platform as a platform.

No longer considered as an agile vented vaccine by the agency.

I think that is also.

Reassuring in that respect so I don't see any any hurdles that are a function of the platform to enrolling CMV.

Salveen Richter: Thanks.

Corey Kasimoff: Thank you. And our next question comes from the line of Corey Kasimoff with JP Morgan. Your line is now open. Hey, good morning, guys. Thanks for taking my questions. So, two as well.

Or getting into market frankly are your question about the natural history study is a good one year right I was pleased by the rate of enrollment on the numbers that we've gotten there to date.

The age distribution.

Is a pediatric we are seeing I think a median age of around five to eight roughly speaking looking at the.

Corey Kasimoff: So first, we're just following up on CMV. And as you get the phase two sites up and running and plan for your phase three, are there any additional processes or challenges we should be thinking about given the new modality you're introducing? Or is this something that you think you need to do?

At the totality of the data so far.

It is providing us I think good information as as it relates to the variability the biomarkers clinical endpoints all the things we've expected to saying and I think it is substantiating our sense that the older that children are at least those that are found at any given time points in terms of prevalence certainly.

Stephane Bancel: It can go pretty quickly from a patient accrual point of view. And then my second question is regarding your natural history studies for MMA and PA. What's the age range you have there for the natural history? And do you think that provides any clues as to how enrollment might go once you have a broader age range introduced for your clinical trials? 87 subjects at this stage seems like a pretty decent number for rare diseases. Thanks.

In the us.

Tend to have either undergone transplant or have deteriorated kidney function. So it all of.

It is very coherent I would say overall with.

We're seeing.

Starting up sites now in trying to enroll are the first subjects into the M&A trial.

Stephane Bancel: Thank you, Corey and Saul. Let me take those two in order. I don't foresee any additional challenge for enrolling the CMV, either the Phase II or the Phase III, that is platform dependent, and I'll sort of give you the two reasons for that. The first is that the totality of safety and tolerability data that we've seen across the portfolio is consistent with what one would expect. We haven't seen anything surprising. There's no scientific reason to expect anything untoward, and we haven't seen anything untoward in preclinical. So I think this is going to be a vaccine platform that behaves as such. In fact, the CMV data suggests that the more potent the vaccine is, the more adverse event you get, flu-like symptoms, but the type of adverse event, the type of adverse events, as I've noted, is what you'd expect.

That's helpful. Thanks So.

Thank you and our next question comes from the line of Alex Denahan with Bank of America. Your line is now open.

Hey, guys. Thanks for taking my question. So on the ongoing follow up from the phase one trial of personalized cancer vaccine.

I appreciate that the objective of the phase one is primarily to assess safety and immunogenicity.

But do you intend to present any outcomes type data from this study beyond Immunogenicity and stay with the next six months or will we need to wait on the phase two study for this sort of analysis and then on the congrats vaccine is this something that Mark will report since they are the ones, beating the study.

Hi, Alex itself. So so yes.

Stephane Bancel: I think the other reference point is that this platform is no longer considered an adjuvanted vaccine by the agency, and I think that is also reassuring in that respect. So I don't see any hurdles that are a function of the platform for enrolling CMV. Your question about the Natural History Study is a good one, and you're right. I was pleased by the rate of enrollment and the numbers that we've gotten there to date.

Yes to both questions. The phase one PCV data, we will share that data once we've got the sort of a cogent totality of it.

Every phase one or every clinical trial that we do as a matter.

Policy and ethics and the company, we will publish and this is no different.

So at the next opportune moment, when we have a body of evidence there we will share including the totality of the clinical data and in fact I think it is the clinical data that is important to me and I think the rest of world to assess activity here in that regard recall that one of the cohorts. There is testing patients with previously refractory to PD.

One inhibitor as I think that will be meaningful data once we havent.

Stephane Bancel: VH.

Stephane Bancel: We are seeing a median age of around 5-8, roughly speaking, looking at the totality of the data so far. It is providing us, I think, good information as it relates to the variability, the biomarkers, clinical endpoints, all the things we've expected to see. And I think it is substantiating our sense that the older the children are, at least those that are found at any given time points in terms of prevalence, certainly in the U.S., tend to have either undergone a transplant or have deteriorated kidney function. So it is very coherent, I would say, overall with what we're seeing in starting up sites now and trying to enroll the first subjects into MMATRON. Okay, that's helpful.

Okay resi, you're correct Merck is running it and so Merck will be I think the party reporting out the data and I look forward to that as well.

Okay, great. Thanks, I had one more question if I may so I notice that the follow on phase one be for the H. NPV three.

The three vaccine was posted to the T. Dot Gov last week and it looks like you've dose the first station in the study.

So if your question what kind of safety metrics are required for gating between the adult and pediatric cohort.

What dose levels of the vaccine will be included in this study on how quickly do you foresee the study completing and from your conversations with the FDA and do you have a sense of potential Registrational path. Following the study thanks.

Stephane Bancel: [inaudible] Thank you. And our next question comes from the line of Alec Stranahan with Bank of America. Your line is now open.

Those are great questions, let me answer them.

Alec Warren Stranahan: Hey guys, thanks for taking my question. So on the ongoing follow-up from the phase one trial of the personalized cancer vaccine, you know, I appreciate that the objective of phase one is primarily to assess safety and immunogenicity. But do you intend to present any outcomes-type data from the study beyond immunogenicity, say within the next six months? Or will we need to wait for the phase two study for this sort of analysis? And then on the KRAS vaccine, is this something that Merck will report since they are the ones leading the study?

In turn.

The safety metrics or your typical vaccine safety metrics. So you look for safety Tolerability and we have a safety monitoring and independent safety monitoring committee that.

Reviews that and we've actually had our recent inaugural meeting with them and so it won't be just thus making that we've got some of the world's experts in this actually looking over our shoulders and helping make those decisions.

The dose level honestly on top of my mind.

I don't remember is the honest truth happy to get back to you if it's not a controlled double double check that.

The path to approval that's a great question.

Stephane Bancel: Hi Alex, it's Tolff. So yes, yes to both questions. The phase one PCV data, we will share that data once we've got sort of a cogent totality of it. Every phase one or every clinical trial that we do as a matter of policy and ethics in the company, we will publish, and this is no different. So at the next opportune moment, when we have a body of evidence there, we will share, including the totality of the clinical data. And, in fact, I think it is the clinical data that is important to me and, I think, the rest of the world, to assess activity here. In that regard, recall that one of the cohorts there is testing patients who are previously refractory to PD one inhibitor. And so I think that will be meaningful data once we have it. Kairos, you're correct, Merck is running it. And so Merck will be, I think, the party reporting out the data. And I look forward to that as well.

I think as we had as disclosed in the past we had an initial interaction with the agency we headed type C meeting in response, and we had a line of sight to the possibility to have a pivotal trial that would test both viruses together so roughly.

King the path there is demonstrate safety in the share a positive toddlers and then go onto a larger phase three study that would demonstrate efficacy in zero negative toddler, because remember we're trying to establish immunogenicity from before anybody has been exposed.

So.

I can't give you.

Clear time to completion and.

As with CMV before one goes into a phase three trial, we're going to have too.

I have more in depth discussion with regulatory authorities before we do that.

Great. Thanks for the color.

Thank you and our next question comes from the line of Hartaj Singh with Oppenheimer. Your line is now open.

Alec Warren Stranahan: Great, thanks. I had one more question, if I may. So I noticed that the follow-on phase 1B for the HMPV-PIV3 vaccine was posted to ct.gov last week, and it looks like you've dosed the first patient in the study. So, I have a few questions.

Well.

Great. Thank you for the questions I just want to ask a one question about an asset that you got the flow. This long easy the 86 year, one I know thats in partnership with Astrazeneca. The cabin study I mean, thats, including patients tall formal so about half now just any thoughts there and could read out at this stage.

Alec Warren Stranahan: What kind of safety metrics are required for gating between the adult and pediatric cohorts? What dose levels of the vaccine will be included in the study? How quickly do you foresee the study completing? And from your conversations with the FDA, do you have a sense of the potential registrational path following the study? Thanks.

To basically study could could easily move that along faster or.

Into a pivotal clinical trials any thoughts there.

A quick follow ups.

Stephane Bancel: Those are great questions. Let me answer them in turn.

Hi, This is Paul let me take that.

Stephane Bancel: The safety metrics are your typical vaccine safety metrics. So you look for safety tolerability. And we have a safety monitoring, an independent safety monitoring committee that reviews that. And we've actually had our recent inaugural meeting with them. And so it won't be just us making that. We've got some of the world's experts in this actually looking over our shoulders and helping make those decisions. The dose level, honestly, on the top of my mind, I don't remember, is the honest truth. I'm happy to get back to you. If it's not a clinical trial, I will double-check that. The path to approval, that's a great question. I think, as we have disclosed in the past, we had an initial interaction with the agency.

Two points on that trial. It is a means to give a the credit they have designed very informative pharmacology trial, because they're using sort of state of the are as you may recall oxygen labeled.

Pet imaging to really very finally map the heart and the areas at risk the challenge for them has been that they the half life without isotope is extremely short. So you have to find a hospital that basically has a cyclotron next door and so what they've done.

This past year, it's been to gone and find additional sites, where they can launch that trial. So there are now open not just in Finland, as they work, but actually in Germany and in the Netherlands and are actively looking for patients.

Good thing about that trials at the end point once enrolled subjects should be relatively quickly because its six months endpoint and the trial overall is not very large of and I think that's as much.

Stephane Bancel: We had a type C meeting and response, and we had a line of sight to the possibility of having a pivotal trial that would test both viruses together. So roughly speaking, the path there would be to demonstrate safety in seropositive toddlers and then go on to a larger phase three study that would demonstrate efficacy in seronegative toddlers. Because remember, we're trying to establish immunogenicity before anybody has been exposed. So I can't give you a... (inaudible)

Inside as I have in terms of enrollment could they move faster I think there are other ways that one could think of how you would develop a and truck harm deal we injected.

Molecule of they.

They've got a ton more expertise in this space than I do and Theyre actively thinking in working along those fronts, but.

Finally, I'd have to defer to them to give you more color on what that could look like.

Great and you had you follow ups, yes.

Alec Warren Stranahan: Great, thanks for the call. Thank you. And our next question comes from the line of Hartaj Singh with Apaname. Your line is now open.

Yes, Quicklogics mentioned them quickly I know you had mentioned that this your positive patients.

Hartaj Singh: Thank you for the questions. I just want to ask one question about an asset that you've got the furthest along, AZD8601. I know that's in partnership with AstraZeneca. The CABG study, I mean, that's been recruiting patients tall for almost about a year and a half now. Just any thoughts there? And could, with the readout of this phase two, basically a study, could AZ move that along faster or into a pivotal clinical trial? So any thoughts?

There is the data seen those the CMB trial.

That had not been seen previously other trials for your phase two in your face when you stratify, what's your positives and could those be a group that you could get approval just on their own just any thoughts there.

Yes, so a couple of thoughts I think the fact that one sees this effect on share positives I think is really scientifically interesting and I've got a deep curiosity to try and figure out whether it could translate the benefit that being said in terms of enrolling on the phase three and the eventual.

Stephane Bancel: All right, let me take that. There are two points about that trial. To give AC credit, they've designed a very informative pharmacology trial because they're using sort of state-of-the-art, as you may recall, oxygen-labeled PET imaging, to really very finely map the heart and the areas at risk. Now, the challenge for them has been that the half-life of that isotope is extremely short, and so you have to find a hospital that basically has a cyclotron next door. And so what they've done, I think, in this past year has been to go out and find additional sites where they can launch that trial. So they're now open, not just in Finland, as they were, but actually in Germany and the Netherlands and are actively looking for patients.

Label I'd make 2.1, I think the phase three will be focused on sewer negatives, because that's where you can see the obvious effective preventing infections, it's hard if not impossible to actually demonstrate a clinical benefit in this year positives. Although of course I am I remain intensely curious about that the second point to note is that if the.

Okay and their response had told us that they understand that one is not.

We expect to demonstrate the benefit into your positives, but in order for this vaccine to be viable in terms of access to patients and having an impact on the population you would need a label that would encompass both population. So the expectation is that we would demonstrate immunogens im sorry prevention of primary infection in this year negative, but we would demonstrate.

Stephane Bancel: The good thing about that trial is that the endpoint, once they enroll the subject, should be relatively quick because it's a six-month endpoint, and the trial overall is not very large. I think that's as much insight as I have in terms of enrollment. Could they move faster? I think there are other ways that one could think of how you would develop an intracardially injected molecule. They've got a ton more expertise in this space than I do, and they're actively thinking and working along those lines. But frankly, I'd have to defer to them to give you more color on what that could be.

Safety and Tolerability in the entire population that is all inclusive of Super positive.

And that could leave that into a label irrespective of seer status.

Does that.

That's great. Thank you.

Yes, great. Thank you.

Thank you and our next question comes on line of Yasmeen Rahimi with Roth Capital Partners. Your line is now open.

Hi team. Thank you for taking my question questions are all around P.A. Congrats on recently received fast track designation for the first one is for you can you tell me when you're thinking about dosing strategy <unk>.

Hartaj Singh: Great, and I think you had a few follow-up questions.

Hartaj Singh: Follow-ups, yeah.

Stephane Bancel: Yeah, I'll just mention them quickly. I know you mentioned that the seropositive patients, you know, there's data seen in those of the CMV trial that had not been seen previously in other trials. For your phase two and your phase three, will you stratify by the seropositives? And could those be a group that, you know, you could get approval just on their own? Any thoughts there?

Okay P.A., how it will differ from your strategies and three four and on when we think about sort of keep PD biomarkers.

What key biomarker in your view, who.

And then quite three of the question is what do we know from the literature in regards to what level of expression PCC, one needs to cheap to provide therapeutic patent that.

Stephane Bancel: Yeah, so a couple of thoughts. I think the fact that one sees this effect on seropositives is really scientifically interesting, and I've got a deep curiosity to try and figure out whether it could translate to benefit. That being said, in terms of enrolling in phase 3, and the Eventual Label, I'd make two points. One, I think that phase 3 will be focused on seronegatives because that's where you can see the obvious effect of preventing infection. It's hard, if not impossible, to actually demonstrate a clinical benefit in seropositives, although, of course, I remain intensely curious about that.

Thank you just mean great questions, let me take them one at a time.

Dosing strategy is roughly similar to what we expect to see an M&A. It is based on our translation of the preclinical data.

Weve.

Done long term models and animals and have use that to sort of extrapolate so far the technology as extrapolated nicely from all the preclinical species in the various modalities and so I would expect this went to be similar so I expect that dosing strategy to be once every two or every three weeks I think we're going to have to define that and see the effect we.

Stephane Bancel: We have a couple of other things that we would like to highlight. One is the importance of the vaccine. One is not expecting to demonstrate benefit in seropositives, but in order for this vaccine to be viable in terms of access to patients and having an impact on the population, you would need a label that would encompass both populations. So the expectation is that we would demonstrate prevention of primary infection in seronegatives, but we would demonstrate safety and tolerability in the entire population that is all inclusive of seropositives. And that could lead, then, to a label irrespective of serostatus.

Have on the phase one.

There's a whole slew of Biomarkers here.

That one looks at.

And I think it's premature to specify which one is going to be the one it is true I think what's your indirectly alluding to is that the biomarkers on FDA are not maybe as clear cut as they are in M&A I think that remains to be proven I think the information we hope to achieve from the natural history study.

In terms of biomarker levels were collecting it should also be informative.

Stephane Bancel: That's great. Thank you. Yeah.

So I mean, we'll continue to update that as we learn more I think our understanding of the literature and of our natural history level here is evolving in terms of the level of expression needed I think it's hard to quantify what we've seen from our preclinical models suggest that it.

Stephane Bancel: Yeah, great. Thank you. Thank you. And our next question comes from the line of Yasmeen Rahimi with Roth Capital Partners. Your line is now open.

Stephane Bancel: Hi team, thank you for taking our questions. Questions are coming from all around PA. Congratulations on recently receiving the FASTRAC designation. So the first one is for you, can you tell me when you're thinking about the dosing strategy for PA, how it will differ from your strategies in 3704? And then when we think about sort of key PD biomarkers, what key biomarker, in your view, will improve, you know, establish proof of concept? And then part three of the question is, what do we know from the literature in regards to what level of expression of PCC one needs to achieve to provide therapeutic benefit?

As a similar level that that we need of may in order to have the effect in the mice. The effect is as profound in the PPA models as it is in the May models and so we expect this similar dosing level to be required for both it maybe a little bit a higher given that in PA.

Stephane Bancel: Thank you, Yasmin. Great questions. Let me take them one at a time.

We are in coding for two proteins not one right. So.

Stephane Bancel: The dosing strategy is roughly similar to what we expect to see in MMA and is based on our translation of the preclinical data. We've done long-term models in animals and have used that to sort of extrapolate. So far, the technology has extrapolated nicely from all the preclinical species in the various modalities, and so I would expect this one to be similar. So I expect the dosing strategy to be once every two or every three weeks.

On a moeller basis, we would expect similarity ought to make for kick it may be at that higher.

But it's clearly within the same ballpark.

Thank you and then I mean, a quick follow up in regards to that everybody again.

And we're excited to see the data from the two doses.

Okay.

Stephane Bancel: I think we're going to have to define that and see the effect we have on Phase I. There's a whole slew of biomarkers here that one looks at, and I think it's premature to specify which one is going to be the one.

Hi, how are you got it.

So what are you planning to do I had regulators to.

Now.

Stephane Bancel: It is true. I think what you're indirectly alluding to is that the biomarkers on PA are not maybe as clear cut as they are in MMA. I think the information we hope to achieve from the natural history study in terms of biomarker levels where we're collecting it should also be informative. So, I mean, we'll continue to update that as we learn more. I think our understanding of the literature and of our natural history level here is evolving.

Yes.

Just to clarify the question you're asking how far out are we access are we looking at say, Mike, Yes, yes monitoring the safety since you're giving for the first two doses how far out we actually.

Patients and therefore provide for that safety.

Result.

Of several weeks I would say I don't think it's going to be much longer than that.

Stephane Bancel: In terms of the level of expression needed, I think it's hard to quantify. What we've seen from our preclinical models suggests that it is a similar level that we need of MMA in order to have the effect in the mice. The effect is as profound in the PA models as it is in the MMA models. And so, we expect a similar dosing level to be required for both. It may be a little bit higher given that in PA we are encoding for two proteins, not one, right? So, on a molar basis, we would expect similarity in Mg per kg. It may be a tad higher, but it's clearly within the same ballpark.

The reality as you've seen the adverse event profile to date. It really is a a function of the LMP as I understand that more than the protein that we make.

We'll be continuing to follow these patients.

Im sorry, the subjects for weeks, but.

I've not seen anything that leads me to expect that Theres a long term.

Challenge here I think the safety profile.

Within a week will describe what it is.

Thank you.

Thank you in our last question comes from the line of Alan Carr with Needham. Your line is now open.

Stephane Bancel: Thank you, and I may have a quick follow-up in regards to the antibody against chikungunya. And we're excited to see, you know, the data from the two doses of 0.3 mix per kg. How far out are you going to assess safety? So, you know, what are you planning to do, and what have regulators asked you to do?

Thanks for taking my questions.

Can you give us update on where the other rare disease program staying in might those be a little bit.

Stephane Bancel: Just to clarify the question, you're asking how far we are looking at safety.

Easier to enroll and then also give any update on.

Stephane Bancel: Yeah, just monitoring the safety since you're giving two doses for the first time; how far out will you actually monitor these patients and, therefore, provide us with the safety results?

These program that relaxing.

Yeah. So this is Paul let me take them.

Stephane Bancel: Several weeks, I would say. I don't think it's going to be much longer than that. The reality is, you've seen the adverse event profile.

They're in their preclinical phases once we file the R&D and we get a rolling we'll we'll update you accordingly, and I think we don't typically comment on where exactly in the in the early research space. They are I think the same holds true for relax and which is partnered with Astrazeneca.

Stephane Bancel: (inaudible) I think the safety profile within a week will describe what it is.

Stephane Bancel: Thank you. Thank you. And our last question comes from the line of Alan Carr with Needham. Your line is now open. Hi, thanks for taking my questions. Can you give us an update on where the other rare disease programs are and whether those might be a little bit, (inaudible)

Alright, and then you also mentioned Jim in the press release, some interest in partnerships and that sort of thing I was wondering if you're getting it.

Stephane Bancel: Yeah, so this is Tal. Let me take them. They're in their preclinical phases. Once we file the IND and we get rolling, we'll update you accordingly. And I think we don't typically comment on, you know, where exactly in the early research space they are. I think the same holds true for Relaxin, which is partnered with AstraZeneca.

More in terms of with academic institutions are talking about partnering programs were pleased.

With pharma and that's where anything [noise].

Yes. So thank you. This is different so I mean, if you look at the company history.

Stphane Bancel: All right, and then you also mentioned in the press release some interest in more partnerships and that sort of thing. I was wondering if you were getting at more in terms of with academic institutions or talking about partnering programs with pharma and that sort of thing.

As you know we've done there I'll stop now shape or on the Thats why Im offs, you might I hope. So we have been quite up to I think you just because we got very busy weve preparing the IPO and then.

Spending time on a role as a newly public company, but if you look at about the team has achieved than what we believe a platform can providing some of new medicines for patients.

Stphane Bancel: Thank you, this is Stephane. So, I mean, if you look at the company history, As you know, we have done a lot of partnerships. In the last 12 months, you might have noticed we have been quieter. I think it's just because we were very busy with preparing the IPO and then spending a lot of time on the road as a newly public company. But if you look at what the team has achieved and what we believe a platform can provide in terms of new medicines for patients, we have a problem of abundance, which is a wonderful problem to have in this industry. And so we think that we cannot take all the drugs that are coming from Stephen's team on the platform into the clinic by ourselves. And so we will continue to have dialogue with biopharmaceutical companies. If you look at the company history, we have raised around a quarter of our capital since the inception of the company through partnerships, and we think this is a wonderful way to tap capabilities that we don't have. [inaudible]

We have it probably will have on this which is a wonderful product too I mean does industry.

So we think Thats we cannot.

Take all of a drugs that are coming from Stephens team on the platform.

Into the clinic bile saps and so we will continue to have dialogue. We've biopharmaceutical companies. If you look at the company history with around the quality of our capital since inception of company through partnerships.

And we seem to see so we'll look for a way to tap capability that we don't have.

Wrapping up.

Capital that we don't have.

And so just increase the opportunities of getting well done as ammonia medicines to patients and to finish line and so we anticipate to continue to have new partnerships that up in the quarter obstacle.

Stphane Bancel: And what's the profile of programs that you might partner with versus keep in-house when you're looking at this?

And what's the profile of programs that you might partner versus keeping house when you're looking at this.

Stphane Bancel: So, I mean, it's bigger than what we've done before, looking at, you know, where we have expertise, looking at biological risk, so this is what we're solving for.

So I mean can you talk about what I've done before he's looking at where do we have expertise will keep but looking at biology risk.

So we see what was wondering fall.

Stphane Bancel: Great. Thanks for taking my questions. Thank you. Thank you, and this concludes today's question and answer session. I would now like to turn the call back to Stphane Bancel for any further remarks.

Great. Thanks for taking my questions.

Thank you.

Thank you in this concludes today's question and answer session I would now like turn the call back to Stephane myself for any further remarks.

Stphane Bancel: Yes, thank you very much for joining us today and for your questions. We look forward to seeing many of you in the coming weeks at the JPEM conference in January. We also wanted to share with you that we are planning to start an annual day focused on manufacturing and digital. This new Investor Day will complement Science Day, which usually happens in the spring, and R&D Day, usually in September. So the 2020 Manufacturing and Digital event will be held at the Norwood plant on the afternoon of March 4th, on the back end of a Cowen conference in Boston. Juan Andres, who leads our Technical Development, Manufacturing, and Quality, as well as Marcio Damiani, our Chief Digital Officer, will host the event. They will share with you all the progress their team has made in 2019 and the new initiatives they will implement in 2020. We hope to see many of you on the afternoon of March 4th in Norwood. Have a nice day.

Yes. Thank you very much for joining us to then for your questions. We look forward to seeing many of you in the coming weeks and at the GPM Conference in January .

I wanted to shall we viewed that's got planning to stop at an annual they focus on manufacturing and digital.

These you invest told they will complete complimentary assigned then we should really happening the spring into R&D day, usually in September so I, just want to manufacturing and do you Tony events will be head ethanol plant.

On the ethanol from off fall on the back end of Cowen Conferencing button Andress will lead saw technical development manufacturing and quality as wasn't MISO damiani, our chief dystrophy. So we hosted events.

And we shall we view of upper West of the document made in 2019, and then you initiatives that we're doing 2020.

We have to see many of you on the up them have much falloff in all would have an epic.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.