Good day everyone, welcome to Pfizer's Analyst and Investor Call to discuss data from an ongoing phase I/II study of mRNA-based vaccine candidate against SARS-CoV-2. Today's call is being recorded. At this time, I would like to turn the call over to Mr. Chuck Triano, Senior Vice President of Investor Relations. Please go ahead, sir.
Thank you, operator. Good afternoon, everyone, and thanks for joining us today on short notice to review initial clinical data from our U.S. phase I/II study for our most advanced COVID-19 vaccine candidate. I'm joined this afternoon by Mikael Dolsten, Chief Scientific Officer and President of Pfizer Worldwide Research and Development, and Kathrin Jansen, our Senior Vice President and Head of Vaccine Research and Development. Before we start, I want to remind everybody that we will be making forward-looking statements on today's call, and actual results may differ from those statements. The forward-looking statements speak only as of the original date of this presentation, and we undertake no obligation to update or revise any of these statements. For the flow of the call, Mikael and Kathrin will make opening remarks, and then we will move into a Q&A session. I'll now turn the call over to Mikael Dolsten. Mikael?
Thank you, Chuck. Good afternoon, everyone. I'm pleased to be talking to you today about Pfizer and BioNTech's early positive data from the most advanced of our four investigational vaccine candidates from our BNT162 mRNA-based vaccine program against SARS-CoV-2. Before we go into the data deeper, a brief mention that Pfizer has a rich vaccine history with six approved vaccines currently in over 160 countries. We have committed that experience and knowledge to the fight against COVID-19. Beyond the vaccine that we're discussing today, Pfizer has identified antiviral protease inhibitor compounds that may have potential to address COVID-19, one of which we hope to have in the clinic by August or September. We're also exploring the potential utility of certain existing Pfizer pipeline assets, none of which are currently approved for COVID-19. Now, going back to our vaccine and today's discussion. Next slide, please.
The data we're presenting today was gathered from the U.S. phase I/II placebo-controlled observer blinded clinical trial we initiated in May and from one of the vaccine candidates on the investigation, specifically the nucleoside-modified mRNA vaccine candidate BNT162b1, expressing the SARS-CoV-2 receptor binding domain, in short RBD, that's being evaluated in 45 subjects. It's important to note that the preliminary clinical data from this ongoing study is available on an online preprint manuscript server, medRxiv, and have been submitted for potential publication in a peer-reviewed journal. The data we're sharing today is in collaboration with our partner, BioNTech. Pfizer and BioNTech started working together in 2018, exploring a potential influenza vaccine using BioNTech's proprietary mRNA vaccine platform.
By combining BioNTech's leading mRNA platform with Pfizer's proven expertise across vaccine research and development, regulatory affairs, global manufacturing, and distribution, we hope to make an important contribution to help combat this COVID-19 pandemic. Slide, please. I think it's important to briefly explain why we believe that an mRNA platform could help us deliver a vaccine against COVID-19. We are guided by a sense of urgency to deliver a safe and effective vaccine as quickly as possible. Our BNT162 program is based on BioNTech's proprietary mRNA-based technology, a novel tech platform that provides efficiency and flexibility, which is apparent by the pace of vaccine development and the unprecedented trial design that it supports. The mRNA platform has several key advantages uniquely suited to this crisis. First, mRNA vaccine technology uses the cell's own machinery trained to stimulate an immune response, including the production of T cells and utilizing antibodies.
If shown to be safe and effective, mRNA vaccines have the potential to help prevent SARS-CoV-2 infection and its associated COVID-19. It's a fast platform. mRNA-based vaccines have shown the potential to elicit neutralizing antibody responses and T cell responses with a T helper cell 1 phenotype. This is a combination of immune characteristics believed to potentially maximize the probability of protection and minimize potential for disease enhancement. Disease enhancement is a phenomenon in which a T helper cell 2 phenotype response leads to an exaggerated inflammatory response to infection or the binding of antibodies to a virus enhances its entry into host cells and sometimes also its replication and infectivity in the environment. Hence, our platform has a favorable characteristic for protective versus any possible negative immune response. The potential mRNA vaccine deliver the RNA to the cell by protein-free lipid nanoparticles, in short, LNPs.
BioNTech's mRNA-based vaccine candidates have elicited immune response in multiple pre-clinical and ongoing clinical studies for vaccination against cancer. BioNTech's mRNA vaccine technology is expected to enable rapid development and quick production scaling, which is critical for bringing a COVID-19 vaccine to market to address the urgent medical need brought by this pandemic. The novel design of our vaccine trial allows Pfizer and BioNTech to evaluate four different potential vaccine candidates with combination of two different antigens and three different types of mRNA, unmodified mRNA, nucleoside-modified mRNA, and self-amplifying RNA. The largest spike sequence is included in two of the vaccine candidates as antigen and a smaller portion, the active component of spike, the optimized receptor-binding domain of the spike protein, is included in the other two candidates active for receptor-binding.
The RBD-based candidates contain the piece of the spike that we think is most important for eliciting neutralizing antibodies for inactivation of the virus. The flexible and rapid design of our phase I/II trial permits decisions to add or subtract vaccine candidates, doses, or regimens based on early clinical data. This highly streamlined study design is expected to generate safety, tolerability, immunogenicity, and potentially efficacy data, and allow us to select the most promising vaccine candidates for further development based on both pre-clinical and clinical data, rather than committing early to a specific candidate based only on pre-clinical information. As I mentioned, the preliminary clinical data we're discussing today is from the nucleoside-modified messenger RNA, modRNA, BNT162b1, which encodes an optimized SARS-CoV-2 receptor-binding domain, the RBD antigen.
Let me now transition to Kathrin Jansen to discuss the clinical plan and share more details around the important early preliminary and encouraging clinical data we shared today. Kathrin.
Thank you very much, Mikael. It's a pleasure to be here today discussing our initial clinical data. Could I have the next slide, please? As you can see, we have made an enormous progress in our quest to develop the COVID-19 vaccine. We are working with regulatory authorities in an effort to compress stages that have historically taken years or months into much shorter time frames, ensuring a safe and responsible way of conducting our development program. Safety is our number one priority in all human clinical trials, no matter how fast we are trying to progress our COVID-19 vaccine. As you can see, the genetic sequence of the SARS-CoV-2 virus was made available only in January, we were able to start our human trials for this vaccine candidate in only five short months.
Pending agreement with regulatory authorities, we hope to start our pivotal phase IIb/III study as early as July, expanding our trials to enroll up to 30,000 healthy participants. Could I please have the next slide? We are sharing with you now the preliminary data of our U.S. phase I/II study with the vaccine candidate BNT162b1. Could I have the next slide, please? Shown here is the enrollment in our phase I/II study. What you see is that we have interim data from an ongoing placebo-controlled observer blinded dose escalated study among healthy adults 18 to 55 years of age. What you see here, that 76 participants were screened and 45 healthy adults were enrolled in our phase I/II study. There were 15 participants in each dose level cohort. 12 received vaccine, and three received placebo in each cohort.
The 12 participants in each cohort were either immunized with 30, 10, 30 micrograms of BNT162b1 on day one and 21, so that was a two-dose series. 12 participants received 100 microgram dose on day one. The study began on May 4th, 2020. By June 19th, 2020, as I said, 76 subjects were screened and 45 participants were randomized and vaccinated. What you will see in the following, that overall, the initial data demonstrated that BNT162b1 could be administered at a dose level that was well-tolerated and generated dose-level dependent and dose-dependent immunogenicity as measured by a receptor-binding domain, binding IgG antibody assay, and by an authentic SARS-CoV-2 neutralizing antibody assay. Both of those assays are our go-forward clinical assays, and they have been qualified. Could I have the next slide, please? Let me first lay out the slide for you.
Here we show our receptor-binding domain, IgG antibody data. What you have on the Y-axis, which by the way is a logarithmic scale, it shows the RBD IgG antibody concentrations. What you see on the X-axis is the days of immunization. You see in the color code, placebo recipients in gray. You see the 30 micrograms in light green, the 10 microgram in light green, 30 micrograms in darker green, and in the much darker green, you see the 100-microgram dose level. This data illustrates the significant elevated RBD binding IgG antibody concentration observed in all 24 subjects who received two vaccinations at 10 microgram and 30 microgram dose levels of the BNT162b1 candidate.
At day 28, which is seven days after the second immunization, the geometric mean concentrations or GMCs observed are approximate eight times and 50 times the GMCs of the 602 units per ml of a panel of sera from 38 subjects who had contracted SARS-CoV-2. The relevance of the human convalescent panel is as follows. There is evidence that individuals who contract SARS-CoV-2 are immune from disease, at least for a short period of time. We believe that it's a good guidepost to compare our vaccine-induced antibody responses to this human convalescent serum panel. I like to just summarize three points to make here. Number one, we see already substantial RBD binding antibodies after a single dose that then is substantially boosted after a second dose.
The responses, if you look at the individual dots in the bars, you see that the responses of the vaccinees are very consistent, and the overall responses are very tight. The antibodies are consistently higher two weeks after the second dose. I also would like to say a few words about the human convalescent serum panel. There were 38 subjects in the panel, and each of the individuals had PCR-confirmed SARS-CoV-2 infection. 34 had symptomatic COVID-19 disease, and one individual was hospitalized. This distribution is clearly between the less severe disease that we see in young people and the more severe distribution that we see for older adults. If I could have the next slide, please. This panel describes our virus-neutralizing antibody responses. Again, I like to stress that what we are measuring here is real authentic SARS-CoV-2 virus neutralization.
Again, the slide is set up in a similar way. On the Y-axis, you do see the 50% neutralization titer, which is a common way how viral neutralization is measured. Again, it is a log scale. On the X-axis, you see the days of immunization. Again, the green bar reflects the various dose levels, and the black bar is representative of this human convalescent serum panel that I just described. After a single dose of BNT162b1, we see already modest virus-neutralizing antibody titers. The important point is, though, that after a second dose, we see 13 times and 10 times higher neutralizing titers observed compared to the first dose. Why is this important? These increases are very important, given that higher virus-neutralizing antibody titers ensure longer persistence of that neutralizing antibody. This also highlights an advantage of our technology that Mikael Dolsten described earlier.
With the RNA technology, we have the opportunity to boost our immune response, so that the antibody responses, as you saw, both for RBD-binding antibody as well as neutralizing antibody, can be enhanced, in this case, as I said, 13 times and 10 times, without an issue of an attenuation of the immune response that we often see using other technologies, such as viral vectors, that actually do induce an anti-vector response even after a first dose, which then limits or attenuates subsequent booster responses. In summary, what you see here is that the virus neutralizing geometric mean titers induced by BNT162b1 after 10 and 30 microgram dose level after two doses, are actually 1.8 to 2.8-fold higher than the GMTs of the convalescent serum panel.
It is also noteworthy that the 100 microgram dose level, those individuals received only a single immunization, was not better than the 30 microgram dose level. We believe that based on those data, the dose level that will likely move forward will be somewhere between 10 to 30 micrograms. Could I have the next slide, please? Now I'd like to summarize our safety and tolerability data from this first cohort. Individuals were reporting local reactions for seven days after each immunization. What you see here on the graph is that the most commonly reported local reaction was injection site pain, which was generally mild to moderate, except in one of the 12 subjects who received 100 microgram dose level, where we saw one severe event of pain. Reactions including fever were more common after the second dose than the first dose.
Following dose two, about 8% of participants who received the 10 microgram dose and 75% of participants who received the 30 microgram dose reported fever. Fevers generally resolved within one day of onset. There were no serious adverse events reported. Let me now go to the systemic events. Here displayed are the systemic events seven days after vaccination one. What you see in general is that the systemic events after the first dose, the highest ones were really chills, fatigue, and headache. Again, you see a dose-level dependency. In general, we saw mild to moderate reactogenicity. If you could go forward to the next slide, please. This now shows the systemic events after the second immunization. Here you only see the individuals that received the 10 and 30 microgram dose level.
The reason for this is that because of the immunogenicity data that I showed you earlier, looking particularly at the neutralizing antibody titers, we didn't see an advantage of the 100 microgram dose. As you saw from the local tolerability as well as the systemic events for the 100 microgram dose level, we saw more reactogenicity associated with the 100 microgram dose level. Therefore, based on immunogenicity and the tolerability profile, we made the decision not to immunize the 100 microgram dose level and give those individuals a second dose. Again, in summary, you see that we have a mild to moderate systemic tolerability profile after administration of 10 and 30 microgram, both after the first as well as the second dose, with our BNT162b1 candidate. Could I have the next slide, please? I think here I reach over back to, I think, Mikael.
Thank you very much, Kathrin. I want to briefly mention how we're ramping up manufacturing capacity and investing $ hundreds of millions at risk in preparation for potential COVID-19 vaccine supplies. We are planning for a cumulative vaccine supply goal of up to 100 million doses in 2020, and more than 1 billion doses in 2021. We are jointly leveraging our extensive global infrastructure across this partnership. Pfizer is a proven, reliable global vaccine producer, supplying vaccines to over 165 countries. We have distributed over 1 billion doses of Prevnar 13, our pneumococcal conjugate vaccine, with unprecedented reliability since 2010. This is one of the largest scale sterile manufacturing operations in the industry, producing 1.5 billion sterile units per year. Next slide, please. In closing, I wanted to share a few key takeaways.
Preliminary data demonstrated that BNT162b1 could be administered in a dose that was well-tolerated and generated dose-dependent immunogenicity as measured by RBD binding IgG concentration and SARS-CoV-2-neutralizing antibody titers, as Kathrin discussed with you thoroughly. Early positive data shows that BNT162b1 can be administered at a low effective dose of 10 micrograms and provide neutralizing titers at or above human convalescent plasma as early as four weeks after vaccination. Local reaction and systemic events of immunization with 10 and 30 micrograms of BNT162b1 were dose dependent, generally mild to moderate, and transient. No serious adverse events were reported. Data from the ongoing phase I/II clinical trial are expected to enable selection of a single lead candidate and dose level for a potential large global phase II/III safety and efficacy study that may begin as early as July 2020, subject to regulatory approval.
Efforts to manufacture the leading candidate at risk are gearing up. If the safety and efficacy study is successful and the vaccine receives regulatory approval, the companies are currently expecting to manufacture up to 100 million doses by the end of this year, 2020, and potentially more than 1.2 billion doses by the end of 2021. We look forward to answering your questions.
Great. Thanks, Mikael and Kathrin, for those remarks. Operator, can we please set up call for questions at this time?
At this time, if you would like to ask a question, please press star one on your telephone keypad. Once again, that's star followed by the number one on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Umer Raffat of Evercore.
Thanks so much for taking my question. First of all, I just want to say congratulations on the data. I have three questions, if I may. Mikael, I want to hear your thoughts on whether the other constructs for the Pfizer-BioNTech collaboration, perhaps in particular your b2 construct, which is the mRNA against full spike, or the c2 construct, which is a self-amplifying mRNA, will outperform the data reported today. I'm curious what your take is on that. Secondly, on neutralizing antibody titers, one thing I'm very confused about is that the sampling of those 38 patients you guys showed us appears to be low or materially lower than similar sampling for neutralizing antibody titers we've seen in convalescent patients in other studies. I'm curious your take on that.
Finally, on lymphocyte count reductions, one thing I noticed was the baseline lymphocyte counts were about 1.5-2, and I totally acknowledge it was transient, but in older COVID-19 patients, they often have baseline lymphocyte counts of 0.5-1 to begin with. If we're going to have a lot of reduction in lymphocytes early on, could they end up in more like grade 4 lymphocyte count reductions in older patients? Maybe you could speak to your early observations in older patients. Thank you very much.
Yeah. Let me say a few words about the first and the last, and I'll ask Kathrin to speak about the neutralizing antibody titers in our convalescent plasma. We are very excited by the data we've shared today on RBD that we think show a very promising profile for a vaccine with the potential to be protective. We still have an opportunity, as we say, to compare over the next days to a couple of weeks or so to a second candidate, as was alluded in our transcript. This includes Spike. This gives us an unprecedented opportunity to really cherry-pick dose and construct. Clearly today, we think we have very encouraging data for a promising vaccine to act against SARS-CoV-2 to prevent potential disease.
When you alluded to lymphocytes and how that may be depleted in patients as part of the disease, of course, we are particularly here focusing on vaccinating participants, and in the future, that are not infected with SARS-CoV-2. We are not thinking about vaccinating during an active infection. Normal participants, in general, do have an immune response that can give both a B and a T cell response and be protected from getting severe depletion, as you alluded to. That includes, of course, us having older patients with comorbidities continuing now in our study. I hope I got your question right. My answer was related to that we will prevent, we hope, that the aspiration of vaccine development of low lymphocyte counts. I'll ask Kathrin to specifically address the second question, and if you have anything to fill in on my other comments, please be welcome.
Yes. Thank you, Mikael. I think the one point that I want to make, that it was very important for us to assess multiple RNA platforms and constructs, as Mikael alluded to. The phase I/II trial was designed to, as I call it, quickly weed out the candidates that did not give us the desired profile. We were aiming for high neutralizing antibody, the lowest possible dose, and the most benign tolerability profile. I'd now like to speak about the neutralization question that you had. One of the problems that we have in comparing multiple candidates that have been evaluated with multiple assays. There's a number of different assays that are being run currently in the scientific arena. It is actually not possible to compare the results from one study run in one assay with the results from another study run in another assay.
This is why we put that convalescent serum panel together to have a guidepost that would allow us to see which of our constructs and dose levels would give us the better and higher neutralizing antibody responses. I like to also note that we do use an authentic neutralization assay, not a pseudo-neutralization assay, in which the serum from immunized participants is diluted and mixed with authentic infectious SARS-CoV-2. Using this authentic assay makes actually interpretation of the results also more certain. I think all of this is important to take into consideration when one looks at the data that are being described or published by others.
Thank you, Kathrin. I just wanted to add, since you also asked about the self-amplifying. With the goal of progressing rapidly to have the potential for a vaccine available this fall, we, after some initial experiences, felt the modified mRNA with these two options, RBD and spike, are best fit for that aggressive timeline. We do continue to learn from additional constructs, such as self-amplified, that could enable after the pandemic phase to offer unique life cycle management opportunities, but not with the speed of the current formats that we think also demonstrate very promising profile by themselves. As you have noted, a dose that is encouragingly low, 10 to 30 micrograms. Thank you. Next question.
Your next question comes from the line of Vamil Divan of Mizuho Securities.
Great. Thanks for taking my question. One question just in terms of the patient population in this trial. I'm trying to get a better sense of what you're doing to ensure maybe an older population or more diverse population in the other trials. Just the mean age was fairly young here, and 82% of patients were listed as being white. Given older patients and African American, Hispanic patients seem to be disproportionately affected by COVID-19, just curious what you're doing there. One other question, just more again, sort of looking forward. In terms of potentially commercializing a vaccine in this environment, I think there's been a lot of discussion about since these vaccines are moving quickly, relatively historically what we've seen.
Is there more you think you would need to do to convince people that you've gone through the proper steps to show they're safe and effective in order for enough people to be comfortable taking the product, assuming it gets approved down the road? Thanks.
Thank you for the two questions. Kathrin, if you respond to the first one related to the initial patient population versus additional population studies, I can comment on the vaccine, the standards.
Happy to do so, Mikael. Talking about the population, let me just give you a little bit of context of the choice of the population that we describe to you today. When we were getting ready to start our clinical development program, and I'm speaking here in particular about the U.S. clinical trial, we had extensive discussions with the FDA how to bring forward these candidates into human clinical evaluation. Based on those discussions, we agreed that it would be most proven to first start with a younger population, 18 to 55, we saw the data today, before using the vaccine in an older population of 65 to 85. That was done on purpose.
We also were being asked by the regulatory agency that we made sure that the individuals that would be first enrolled in this first instance into the study did not have any underlying medical conditions. There were a lot of exclusion criteria because we wanted to be absolutely sure that we test these new vaccine candidates in a absolutely safe manner. As we move forward in our clinical development program, it is understood, and based on the safety and tolerability data that I shared with you, that are mild to moderate, that we now will move into a subject population that will also have common underlying medical conditions. As I said, that was all pre-agreed with the regulatory agency. We assume that as we go into large scale clinical trial to test the efficacy of our vaccine, that this clinical study will be much more diverse.
Because as you know, we hear reports that certain populations are preferentially or are more afflicted by COVID-19 than other populations. Since we are running an efficacy study, by default, we will have a much more diverse demographics in our phase III clinical evaluation.
Thank you. The FDA released guideline recently outlining its conditions for approving a COVID-19 vaccine. We have worked based on a long tradition closely with FDA from the onset of this program, and the guidelines are very much in line with what we expect, that FDA is setting high standards and have decided not to cut corners. This is really the way we always develop vaccines and are very agreeable to, and we think it favor experienced vaccine companies such as Pfizer, and we support that approach. We need a safe and effective vaccine. Our studies include a plan of enrolling up to 30,000 participants that will allow us, in a timely manner, to accumulate safety, immunogenicity, and vaccine efficacy in preventing disease.
We expect that you should, at the potential approval or emergency use authorization, have a convincing, safe, and effective vaccine profile that, of course, over time, in traditional post-approval commitment, can further broaden experience as you increase the number of participants that have been exposed to vaccine. That's the high-quality standard that Pfizer always adheres to, and we're very pleased to see the guidelines from FDA. Thank you. Next question.
Your next question comes from the line of Terence Flynn of Goldman Sachs.
Great. Thanks for taking the questions. Congrats on the progress. I guess two from me. Based on your preclinical and clinical data, how are you thinking about the durability of efficacy at this point, or durability of antibody levels, and could you build into the pivotal trial the ability to have a further boost down the road if that would be needed? The second question I had was just, it seems to me like the message is this is kind of your go-forward candidate here. You've looked at a lot of the other data, is there still the possibility that you could advance more than one candidate into phase III, or is the right way to think about it that this is kind of the lead that you're moving forward? Thank you.
Thank you. Let me address your questions. As Kathrin so well alluded to, we saw a very nice boost with the second dose, reaching very high RBD antibody levels and high neutralizing levels, exceeding severalfold what was seen with convalescent plasma. We do think that high antibody levels of neutralizing character bodes well for expecting reasonable to very robust durability. The beauty of this technology compared to viral technologies such as adenovirus is that you could tentatively, as you asked, boost on an annual, every two, every three years interval with this technology and expect new augmentation of the immune response. Right now, we assume that this is going to be a reasonably long-lasting immune response given the magnitude, but this technology allow you, as you follow patients, to regain strong immune responses.
Again, this was one of the reasons why we embarked on this technology, given we have experience earlier using adenovirus. I think in recent publications, you may also have seen that certain of the primate adenovirus do have cross-reactivity with human antibodies. We spent quite a lot of time thinking through this and felt that the mRNA was uniquely positioned for a pandemic, and where you need to be prepared to any outcome over years to come, whether from COVID-19 or other coronaviruses. The beauty here with our technology is that we can move so fast. We even, if there is another pandemic in a few years from another virus, quickly readjust it. Finally, I think on the go-forward candidate, we agree with you that the data today are compatible with this as a go-forward candidate with a promising profile.
We will learn more over the near couple of weeks or so. You heard Kathrin allude to that we have an option to bring a second candidate. In the end, within July, we'll select one candidate and move with regulatory dialogues into a large-scale phase II, phase III study. This is a unique property of this trial that Pfizer and BioNTech designed. Thank you. Next question.
Your next question comes from the line of Louise Chen of Cantor.
Hi. Thanks for taking my questions here. My first question for you is, what is the level of immunity do you think that's going to be required for protection in humans? How should we think about the T cell response here, CD4, CD8, with respect to the data that you saw? Last question I had is, what do you think, or how do you think vaccines will be used? Is it going to be one size fits all, or is it going to be certain vaccines for certain subpopulations or subgroups? Thank you.
Thank you. Kathrin, please discuss the level of immunity versus protection, your view on the T cell responses, and I can comment on how will vaccines be used.
Yes
for various populations.
Happy to, Mikael. The short answer to your question, Louise, is that it is not yet known what level of immunity is sufficient for protection against SARS-CoV-2 infection or COVID-19 disease. What we do know is, and that's why we use in our evaluation this panel of convalescent serum, is that individuals that contracted SARS-CoV-2 appear, at least in the short term, to be resistant from a secondary infection. While we do not know what the final levels will be, what we do know that is the immune response that we induce through vaccination with our vaccine candidate, they are very strong and mirror those that we see in individuals that have recovered from COVID-19. Now, you also asked about the T cell responses, and that is very important.
The reason we chose the mRNA technology in contrast to other technology was in part our experience that came out of the oncology field. You may know that BioNTech started their work in oncology patients, from there we saw the power of the mRNA platform to really induce a very broad CD4 and CD8 T cell response, as well as innate responses. Because we did not know and still actually do not know which arms of the immunity will ultimately be needed for protection, will they all be needed? Will antibodies be sufficient? Will T cells be sufficient? It was important to us to select a vaccine platform that gives us the broadest possible immune response, that we then hope will be sufficient to protect against COVID-19.
Thank you, Kathrin. That was an excellent overview. Of course, when we compared to convalescent plasma with our immune response, we shared today that for neutralizing antibodies, we are about two to threefold higher with the two doses. As you heard from Kathrin, in addition to that, what you do not accomplish with convalescent plasma transfusion is activation of T cells. The learning from this platform in numerous studies is that you see a favorable CD4 and CD8 cell response. We're working with our German colleagues to study this and hope to shortly report back to you. We also have seen that within the CD4, it's a favorable Th1 response. Now, how will this vaccine be used in various populations? Well, as Kathrin alluded to, regulatory dialogues ask you to start with adult healthy population, hence 18 to 55 years of age.
We have generated a promising profile of the vaccine. We're now dosing 65 to 85. We are fortunate that right now the dose, as indicated, may be in the 10 to 30 microgram interval. That gives us an opportunity to select one dose that potentially works very well in older or younger adults. That's our preliminary plan, that it will be one dose, one format, given the potency we have seen of this vaccine, the antibody and the T-cell responsiveness, and those responses at the acceptable mild to moderate local and systemic events. We remain optimistic that it will be a simple dose and format for all patients, whether younger or older, whether with or without comorbidities. Next question, please.
Your next question comes from the line of Geoffrey Porges of SVB Leerink.
Thank you very much, and congratulations on this really interesting result. Kathrin, and hi. A few questions for you, if I may. First, could you talk about how you plan to establish that there isn't any risk of vaccine-related disease enhancement? Could you talk a little bit more about the clinical trial plan? It sounds as though you have a couple of phases, and in the FDA's guidance document, they suggested phase IIs should be several hundred patients. In the 30,000, is there a several hundred-patient phase II component, after which you would proceed to expand enrollment? Lastly, assuming it is 30,000 patients, how long do you think realistically it would take to enroll those patients or vaccine subjects, given all the competing trials that are now going to be going on around the world? Thanks.
Thank you. Kathrin, please respond, and I'm happy to fill in.
Yeah. Hi, Geoff. Good to hear your voice again. Let me first take your first question and talk about the theoretical concern about enhanced disease. First of all, we have done an extensive evaluation of all the available data and literature and findings pertaining to this theoretical concern of enhanced disease. Through this assessment, which by the way, we also did not just internally, but we also had support from ACTIV, which is the NIAID public-private partnership where the vaccine working group was also tasked to do an evaluation that was done by mostly academic participants in this working group. Both we ourselves, through the study of the literature and available information, as well as the academic consortium that was tasked with doing an assessment, we both came to the conclusion that indeed, antibody-enhanced disease in this particular case is really only a theoretical concern.
That said, and as I mentioned earlier, safety for us is of the utmost importance. We have discussed with the FDA, that we would put into our phase II, III clinical trial what we call a potential stopping rule. If there would be any evidence about a certain threshold that would indicate that we may have such a finding. That secures that as we enroll large numbers of subjects in our clinical trials, that we continue to ensure the safety of our participants, no matter what the findings are. You also ask about the phase II-B/III clinical trial and to get a little bit more information about this. Here, I just want to share that it is a 20,000-30,000 study. We plan to randomize the subject one-to-one to receive a placebo and vaccine. It is an endpoint-driven study.
We have, as mentioned earlier, an enormous expertise in performing large-scale vaccine clinical studies. You may remember our CAPiTA study, where we enrolled over 80,000 participants in a relatively short period of time. Here, given the urgency, we are set up to enroll those 30,000 participants, again, in a very short period of time. It could be as short as about four weeks or so. That is the plan.
Thank you, Kathrin. I just wanted to puncture a couple of things on this really good question. This particular vaccine format we reported today contains the smallest binding element to the human ACE2 receptor, the human receptor for SARS-CoV-2. As you may have noticed from reports of our German colleagues, our RBD fragment binds potently to ACE2. That was selected to optimize for binding neutralizing antibodies versus just binding. That's one favorable aspect of improving chances of good efficacy versus limiting theoretical risk of adversity that you spoke to. The second one is the Th1 versus Th2 profile that we are pretty knowledgeable about, that this platform gives preferentially Th1 with the right cytokine for preventing vaccine infection and not leading to supporting any antibody disease enhancement. Finally, there's been numerous studies in various animals exploring the risk for this with SARS-CoV-2.
While data are not always completely convergent, I think the overall picture is that there seems to be no reason to believe anything else than a vaccine can be efficacious, while you always need to be prepared for unexpected things, as you asked us. When it comes to the enrollment, as you know, we are planning, pending finalization with FDA dialogues, to start enrolling in July. We have a large experience how to enroll fast. Kathrin exemplified enrolling for very large studies, and we have continuously multiple phase III studies ongoing, so we learn constantly. We'll have a large number of sites. We've had good epidemiological advice from internal experts, and CDC has been very collaborative in sharing their map of disease across U.S. and other regions.
We think we will be able to conclude enrollment, potentially late August, early September, to allow us have not just enough participants, but also enough events to be able, in October, file for potential approval based on safety, immunity, and vaccine efficacy. These are our plans, and we have validated them by looking at assumption of today's environment when it comes to disease % in the population. We think there is a very good probability and feasibility that our plans can materialize, and we feel optimistic about this, and we are very grateful for great advice from FDA, CDC, as well as dialogues we've had with ACTIV consortium. Thank you. Next question.
Your next question comes from Navin Jacob of UBS.
Hi, thanks for taking the question. Navin from UBS. Can you hear me okay?
Yeah.
Perfect. Just some questions around the practical front. I'm wondering, obviously COVID-19 has created an environment that's very different than an environment where traditional vaccine trials are conducted. Specifically, I'm wondering, how are you thinking about mask wearing, social distancing affecting your protocol and more importantly, the event rate that you may be seeing in the phase III? That's number one. With regards to manufacturing, you say 100 million doses by 2020, 1.2 billion doses by the end of 2021. Is that assuming 30 micrograms, 100 micrograms? Any kind of color around that would be helpful. Final question is just around the storage of the vaccine itself. Just want to understand, again, sort of the stability, what requirements are needed with regards to cold storage, and so on and so forth. Thank you so much. Congrats, by the way.
Navin, I'll respond to the first two, and Kathrin, if you discuss the storage stability and our experience with that, and feel welcome to add to my comments. Of course, it's good that there are learnings how to be, with public health actions, cautious when it comes to spreading of the vaccine virus using masks, social distancing, et cetera. Unfortunately, if you look at the situation, for example, in the U.S., there are many states where it has been either difficult to implement or insufficient, and you see rising numbers of COVID-19 cases and unfortunate poor outcomes with hospitalization and deaths. I think that's true also in other countries in Europe, various regions of the world, and we have seen dramatic outbreak of disease in Latin America, Brazil, Argentina, et cetera.
Although we applaud the use of these actions, it seems not to easily change over the next period, including when we plan to run this trial. The need for a vaccine, and we think we will be able to enroll and get events. In fact, recently, when we did a simulation about current events at the various parts of the United States and the world, we saw actually that we could easily have enough events in our trial planning to meet the requirement to demonstrate vaccine efficacy against disease. Since then, unfortunately, if anything, the disease incidence has worsened. The doses that we shared today assume a vaccine given at the dose of 10 micrograms-30 micrograms. We think these are very accurate according to the current plans in the program. Kathrin, please.
Yeah. Thank you, Mikael. I think the other question was about vaccine storage.
Yes.
Currently, our vaccine is stored at minus 80 degrees. We have generated shorter-term stability data that are still ongoing, where we evaluate storage, at least short-term storage, at other temperatures. If you think about distribution, Pfizer has a very large distribution footprint all over the world, and so we have already looked into special shipping containers that would allow to distribute the vaccine to literally wherever it needs to go, and with data associated that we can keep the storage temperature for probably about 10 days, maybe even somewhat longer than that, with those storage containers to keep the vaccine in its frozen state. Given our distribution network and given the technology that is available to us to keep the material at the appropriate temperature, we are very encouraged that we can distribute the vaccine to wherever it needs to go.
Thank you, Kathrin. As you said, our distribution logistics have been already carefully validated, and we feel that this should be within the experience and capabilities of what we have. We also hope to have, as we always do in life cycle management, a new lyophilized formulated vaccine within maybe a year after initial delivery, such as fourth quarter 2021. The lyophilized formulation could be stored in refrigerators. There are multiple opportunities from the initial first year towards life cycle management with improvements in formulations while being able to have a large amount of vaccine as soon as possible, pending conclusion of the studies with quality and consistency, and then further optimizing formulations. Next question, please.
Your next question comes from the line of Geoff Meacham of Bank of America.
Hey, guys. This is Scott on for Geoff. Thanks for taking our questions, and congrats on the early progress. Just wondering if you can provide any additional details on the specific characteristics for the 11 patients that were excluded due to eligibility criteria. Just wanted to get a better understanding of the underlying conditions in these specific patients that were deemed inappropriate to include. Thanks.
Kathrin, please.
Yes. As I mentioned earlier, we had agreed with the FDA to ensure that it had very strong exclusion criteria for the first round, so to speak, of immunizations in the 18 to 55-year-olds. The reason those individuals were excluded is because they did not meet the study inclusion criteria. For example, one of the things that we looked at, we needed to make sure that individuals that were newly infected, for example, with SARS-CoV-2 would be excluded. We wanted to exclude individuals that had previously been infected with SARS-CoV-2 and already had preexisting immune responses. That was two major reasons that led us to exclude individuals. Of course, all of those that did have underlying medical conditions that would not meet the inclusion criteria or triggered the exclusion criteria.
Thank you very much, Kathrin. As you heard, that was driven by standard FDA guidelines for this particular program, but also very much in line with typical assay procedures for any vaccine program. Thank you. Next question.
Your next question comes from the line of David Risinger of Morgan Stanley.
Yes. Hi. Thank you very much, and thank you for the comprehensive review. First, can you just discuss your view on the importance of targeting the receptor-binding domain in addition to the spike protein, given that differentiated versus some of your competitors, including Moderna?
Think you'll be able to rule out the risk of the vac-?
David, could you say the second question, rule out the risk?
I'm showing his line disconnected.
Yeah.
We'll move to the next question.
I think we can answer his first question.
Okay.
I'll ask Kathrin first to share a few words. What was the view of this program targeting the receptor-binding domain compared to the majority of other trials targeting spike, which is also included in our format. Please share some thoughts.
Yes. Thank you, Mikael. As we discussed earlier, we are testing multiple constructs of the spike protein, the receptor binding protein by itself, and of course, the full-length spike protein. The reason for this was that we wanted to see which of those constructs gives us the best immune response and also the best tolerability profile. Why we chose to look at the receptor binding domain, in contrast to many others who focus on the full-length protein, was that the receptor binding domain, of course, is the business end of the spike protein molecule. I mean, it docks to the human receptor, ACE2, with high affinity. The idea is, if one focuses the immune response to this RBD domain, in principle, one should see very powerful inhibition of the virus docking to a host cell and subsequent uptake.
Given that, we still look at those constructs, we will make decisions, as Mikael noted earlier, in the next couple of weeks, which constructs to go forward with. Again, it's all about the safety tolerability profile coupled with an optimal immune response, T-cell responses, high neutralizing antibody responses, and of course, DNA responses afforded by the platform.
Thank you, Kathrin.
Thank you.
We are the only company, to the best of my knowledge, in the clinic with this unique RBD encoded domain. There was some very elegant work done how to make it trimerize to be highly immunogenic, and I think that's what we're seeing in this study and the inquiring data reported today. We still will have an opportunity to benchmark it versus a spike over the next couple of weeks. We feel very good about this. I should say that our spike has also some unique features, among that being codon optimized for efficient expression in humans. The selection between good and good will result in us then sharing it at a final dose construct in quite a near future here. Thank you, David. Sorry you got cut off. Final question.
Your final question comes from the line of Seamus Fernandez of Guggenheim.
Great. Thanks for the question. I guess the question that I have is actually on the self-amplifying RNA. Mikael, you mentioned it sounded like there's some questions around manufacturing capabilities there, as well as maybe the construct itself. I wanted to get a better understanding. You suggested that this could be part of a second-generation opportunity. Could you talk a little bit more about what you would be looking for a self-amplifying RNA construct to achieve perhaps better than the current vaccine if you were to see that as a realistic second-generation opportunity? Thanks.
Yeah. Thank you, Seamus. I'll say a few words and then ask Kathrin to further comment. Well, the beauty of this Lightspeed program, and Kathrin alluded to that, is that we have the ability to look at multiple constructs while cherry-picking one that we move forward with. Given the good promising profile we've seen at this time point, we're at the stage now where we will select shortly a candidate with a very promising profile that then can be available pending clinical studies, regulatory dialogue as a potential for consideration for FDA in October. Now, self-amplified, originally we thought could lower the dose, maybe, and particularly that would have been important. If you need doses like 100 micrograms, that puts a significant constraint on a manufacturing network.
We were pleased to see that we are in a much lower interval, 10 to 30 micrograms, that can allow us to move quickly with a potential vaccine from approval billion of doses. You heard us say we already think we can be at 1.2 billion doses or more. Of course, self-amplified as a life cycle management could make you go even further. Of course, there may always be learnings for second-generation vaccines, and I'll ask Kathrin to speak about that. Again, I wanted to emphasize the current data today are really encouraging. We're very excited by them. It's always good to have opportunities to think not just about one product launch for a pandemic, potentially in a relatively near timeframe, but even have a platform that can help you to support pandemics over several years to come. Kathrin, please.
Yeah. I think, Mikael, you actually highlighted all the important points that Seamus was asking about. I really do not have anything to add at this point.
Thank you very much. We were very pleased to have all of you with this number of good questions. We feel certainly very enthusiastic after sharing this publication in an open source format, and we will see it later in a peer-reviewed journal. We continue to advance the program with a focus on quality, safety, and efficacy. Look forward to continue to communicate with you in relatively near term about additional data as we are able to share with them concerning T-cell activity on more patient numbers, et cetera. We certainly view this as a good day for patients and for science, and thank you for your interest.
Thank you, everyone. This will conclude our call.
Thank you for participating in today's conference. This concludes today's call. You may disconnect at this time. Presenters, please hold.