September 12, 2023 ACIP Meeting - Moderna, Novavax, Pfizer-BioNTech COVID-19 Vaccine

Okay. Thank you, everyone. We're at the top of the hour. And as Dr. Daley had mentioned, we have three teams coming to present on the 2023-24 COVID-19 vaccine formulations. First is Moderna, second is Novavax, and third the team from Pfizer-BioNTech. I am going to take the chair's prerogative and just shift things around a bit in our internal schedule and just say that I'm going to ask each manufacturer if you'd be willing to present for the 10 minutes allotted each. And then we will take Q&A at the end for all three manufacturers in order to try and get us back on time. So with that, I would be delighted to turn it over to Dr. Fran Priddy from Moderna. Thank you, Dr. Lee. Can you hear me? Yes, we can. Thank you. Great. Thank you. Good afternoon. My name is Fran Priddy, and I'm executive director and clinical lead for the COVID-19 vaccine program at Moderna. Next slide, please. As the pandemic has evolved, Moderna has continued to monitor emerging variants to ensure we are prepared to develop and evaluate new COVID-19 vaccines. We are committed to generating preclinical and clinical data to share with agencies worldwide and inform vaccine update decision-making. Earlier this year, we developed an investigational XPB1.5 variant-containing vaccines and evaluated them in both preclinical and clinical studies. Today, I will share clinical data on our monovalent XPB1.5 vaccine, which was selected for the current 2023-2024 season, including an analysis of cross-neutralization data for newer variants such as BA286. Next slide, please. We performed a clinical study in which 101 participants were randomized to receive either a monovalent XPB1.5 vaccine shown in orange or a bivalent BA4.5 plus XPB1.5 vaccine shown in green. The focus of today's presentation will be on the monovalent XPB1.5 vaccine approved for this coming season. The total dose for the vaccine is 50 micrograms. All study participants had already received four doses of mRNA vaccine, a two-dose primary series, and a booster of the original vaccine, plus any mRNA BA4.5 booster vaccine three months or more prior to enrollment in the study. And all analyses from this study are descriptive. Next slide, please. Here are the characteristics of the 50 individuals who received the XPB1.5 vaccine. The median age was 55 years, and 22% of individuals were 65 years of age and above. Seen towards the bottom, the median time from the last COVID-19 vaccination was 8.2 months. And the proportion of participants with prior SARS-CoV-2 infection was 68%. Next slide, please. So I'll begin with a brief summary of safety data. Next slide, please. This figure shows local reactogenicity within seven days after receiving the current XPB1.5 vaccine in orange. For reference, the local reactions from the original booster are shown in light blue, and from the BA4.5 bivalent vaccine in dark blue. Solid bars represent grade one and two reactions, and while stripes represent grade three. The XPB1.5 vaccine was well tolerated. Pain was the most frequent local reaction, and all other reactions were very low. No grade three local reactions were reported. You can see that the local reactions for XPB1.5 were similar or lower than the previously authorized Moderna COVID-19 vaccines. Next slide, please. And here are the systemic reactions reported post-vaccination. Headache, fatigue, myalgia, and arthralgia were the most common reactions after XPB1.5. There were very few grade three reactions and no grade four reactions. Here again, the comparison with the prior vaccines in light and dark blue show that the XPB1.5 systemic reactions were similar or lower than the previously authorized Moderna COVID-19 vaccines. There have been no serious adverse events, adverse events of special interest, or AEs leading to discontinuation in the current study. Next slide, please. Now we'll turn to immunogenicity. More recently, we have evaluated the ability of this XPB1.5 vaccine to cross-neutralize newly emerging variants using clinical samples from adults vaccinated in this study. The ability to cross-neutralize new variants with significant antigenic differences from XPB1.5, such as the recently emerged BA286 strain, may be important for continued effectiveness of COVID-19 vaccines. Next slide, please. This rapid assessment of cross-neutralizing capacity was conducted using pseudoviral neutralization assays from two different labs at Duke University and Moderna. A preprint publication of most of this data is available. Both day 15 and day 29 post-vaccination samples were evaluated. Human sera were tested against prior and current strains as well as the newer strains, EG51, FL151, and BA286. As described earlier today, the BA286 sub-variant is recently emerged and is significantly antigenically different from XPB1.5. Next slide, please. This figure shows cross-neutralization after vaccination with the XPB1.5 vaccine. Pre-boost titers are shown with stripes and post-boost titers are in solid colors. On the left in orange are the neutralization responses pre and post-boost against the XPB1.5 strain contained in the vaccine. And in the middle in yellow are the titers against the closely related XPB1.16 strain. On the right in dark green are the neutralization titers against the newer EG51 strain. And in gray are the BA286 responses. Comparing the fold rise of neutralization titers across the four strains, we see that the XPB1.5 vaccine induces a substantial fold rise in neutralization across all strains, including BA286. Next slide, please. Here's the same data separated by prior SARS-CoV-2 infection status with no prior infection across the top and prior infection on the bottom. As we've seen previously, the post-boost titers are numerically higher in the SARS-CoV-2 positive group on the bottom. Despite this, we see a robust response and evidence of cross-neutralization in both groups. The XPB1.5 vaccine provides a substantial increase in responses to both the variant in the vaccine and cross-neutralization of newer variants, and this is regardless of prior infection status. Next slide, please. Using our research assay at Moderna, we were able to quickly assess neutralization responses against recently emerging variants, including BA286, in a randomly selected subset of 20 participants who received the XPB1.5 vaccine in the current study. In this analysis, the XPB1.5 vaccine elicited similar and robust neutralizing antibody titers against all five variants shown here, further confirming the ability of the monovalent XPB1.5 vaccine to cross-neutralize multiple emerging variants. Next slide, please. And here again are the same data for these five variants, now separated by prior SARS-CoV-2 infection status, with no prior infection on the top and prior infection on the bottom. The same trend is seen here with numerically higher titers for baseline positive participants, and we see cross-neutralization demonstrated in both groups, regardless of prior SARS-CoV-2 status. Overall, this analysis confirms that administration of the XPB1.5 vaccine provides a substantial increase in responses, both to the variant in the vaccine, as well as cross-neutralization of newer variants, including BA286, and this occurs regardless of prior infection status. Next slide, please. And finally, for comparison, we assess neutralizing responses against these newer variants in participants vaccinated with the previous BA45-containing bivalent vaccine. Here we see, shown in this figure from left to right, are the neutralizing responses to the ancestral strain in light blue and the BA45 variant in dark blue, followed by newer variants, including XPB1.5, XPB1.16, XPB232, and EG5. While the bivalent, the BA45 bivalent vaccine resulted in an increase in antibody levels for the newer variants, the mean titers were relatively low. Together, the data we have presented here support the use of the newly approved, updated XPB1.5 vaccine that results in robust responses to newer variants. Next slide, please. So, in summary, we have shared clinical data on the safety and immunogenicity of the Moderna COVID-19 vaccine 2023-2024 formula. The safety profile of the XPB1.5 vaccine is consistent, as shown, with the previously authorized vaccines, and we've been able to demonstrate in a clinical study that robust neutralizing antibody titers are induced against XPB1.5, closely related variants such as XPB1.16, and more distant variants, including EG51, FL151, and BA286. The XPB1.5 vaccine is anticipated to be effective against current SARS-CoV-2 variants. After the approval by the FDA yesterday, Moderna is now in the process of supplying the XPB1.5 vaccine for fall 2023, and we will continue our ongoing variant monitoring and risk assessment of emerging variants using both preclinical and clinical data. Next slide, please. Thanks so much for your attention, and we'd like to thank all the investigators and study collaborators for our studies, including study site personnel, lab personnel, and most importantly, the individuals who participated in the trials. Thank you. Thank you very much, and thank you for keeping to time. Next, we have Dr. Philip Dubofsky from Novavax. Good afternoon. My name is Philip Dubofsky. I'm the President of Research and Development at Novavax. Today, I'll present data generated by our scientists and collaborators that support the use of our XPB1.5 vaccine for the 23-24 vaccination campaign, but first, because we're different, I want to review the Novavax vaccine technology platform. Next slide, please. The Novavax vaccine includes a full-length recombinant spike protein shown in red, presented in its native primary conformation. The antigens form particles around a polysorbate core shown here in blue, which improves antigen uptake and processing, and we manufacture the antigen in insect cells, which have truncated glycans compared to mammalian cells, and we hypothesize the smaller glycans facilitate epitope exposure to the immune system. The antigen is co-formulated with our saponin-based adjuvant matrix M, which is known to facilitate the induction of broad B-cell and T-cell responses, and is responsible for the vaccine's unique immunophenotype. And the combination of these factors resulted in very high levels of efficacy in our phase 3 studies against a prototype strain, as well as against variants that circulated at that time. Okay, let's look at some of the vaccine's attributes that it takes to use. Next slide, please. So, the Novavax vaccine filing is under active review by the FDA, so this slide includes some forward-looking statements pending final authorization. We understand our vaccine will be indicated for individuals 12 years of age and older, consistent with the age indication of last year's vaccine. The vaccine will be distributed in two vials per carton, with five doses per vial, so each carton contains 10 doses, and the dosage volume is 0.5 mils per dose, the same dose is used in all authorized age groups. Our product is ready to use, requiring no reconstitution, and can be administered with standard needles and syringes, routinely stocked in vaccine clinics. And the vaccine is shipped and stored at standard refrigerated temperature, and currently has a nine-month shelf life, and is to be used within 12 hours of initial puncture of the vial. In discussion with the FDA, we understand a single dose will be indicated for people who have been previously vaccinated, irrespective of which vaccine they received, and a two-day series, 21 days apart, is to be used for those who have not been previously vaccinated. Okay, I'll now review some non-clinical data that supports the use of our XPB1.5 vaccine, including immune responses against more recently emerged XPB sub-variants. First, I want to present data from non-human primates that demonstrates our vaccine technology induces broad neutralizing antibodies with primary vaccination. Displayed here are neutralizing responses after two doses of XPB1.5 vaccine in rhesus macaques. In the dark blue bar, second from the left, is a homologous response against XPB1.5, and as we have previously shown within the limitations of the sample size, the responses are generally consistent for XPB2.3 and 1.16. On the far right-hand side of the slide, shaded in yellow, are the responses to more recently emerging variants, 1.16.6, PT.5.1, and FL.1.5.1, all of which share the same common 4.5.6L mutation in the receptor binding domain. According to the data from CDC we saw this morning, these three variants account for approximately 45 percent of sequences collected in the U.S., and they're increasing in frequency compared to the previous sub-variants of XPB1.5 and 1.16. And the responses of these recently emerging variants are comparable to the magnitude of the homologous response induced by XPB1.5. Next slide. Okay, now let's look at some neutralizing responses after boosting with XPB1.5. These responses are probably more relevant to the situation today because the vast majority of the U.S. population has already been primed with serial vaccination and or serial infections. Therefore, these booster responses in primed animals may more closely mimic what we will see when vaccinating the general population. Next slide, please. Here we're looking at data from macaques that were primed with a bivalent vaccine containing prototype NbA5. Shown on the left-hand side of the slide are the neutralizing responses approximately seven months after primary vaccination and five weeks before being boosted. As expected, the responses to the prototype strain in the vaccine are better than the responses against the XPB sub-variants, which are fairly low. On the right-hand side of the slide are neutralizing responses after single boost with XPB1.5. As in the previous slide, the neutral responses against all XPB sub-variants are robust, achieving levels comparable to the homologous XPB1.5 response. For the recently emerging sub-variants, marked here in yellow, we see a greater than 150-fold increase compared to prior to boosting. Therefore, the data from the two experiments I've shown you after either primary vaccination or boosting provides strong evidence that our XPB1.5 vaccine is capable of inducing robust and relevant neutralizing responses to the variants that are causing disease in the U.S. today. Next slide. So cellular immune responses are thought to be important for limiting severe disease and hospitalizations. The data I will show next demonstrates a consistent cellular immune response against XPB sub-variants. Next slide, please. Displayed here are results from intercellular cytokine staining of CD4 cells after vaccinating macaques with two doses of XPB1.5. On the left side of the panel are Th1 cytokines, interferon gamma, IL-2, and TNF-alpha. On the right-hand side are two model Th2 cytokines, IL-5, and IL-13. You can see that within the limitations of the sample size, the XPB1.5 vaccine induces comparable responses to the homologous variant as well as to the recently emerging XPB1.16 and EG5.1 variants. This breadth of immune response has been previously shown by us and others for the cellular side of the house, and it's consistent with conservation of T cell epitopes across many different strains. You can also see the magnitude of the Th1 signal is greater than the Th2 signal, indicating the preservation of a Th1 bias in the cellular immune response. Okay, let's move to my last slide for a quick summary. So Novavax's XPB1.5 vaccine will be the only protein-based COVID vaccine available in the U.S. Based on data we've gathered on the performance of our vaccine against currently circulating sub-variants, we believe our vaccine has an important role to play in offering protection from COVID in the 2023-24 season. Providing a choice of vaccine platforms for both vaccine recipients and healthcare providers is important for driving vaccine acceptability and use. Today I've shared data from how our vaccine induces a broad neutralizing antibody response against XPB sub-variants, including against newly emerging variants such as EG5.1, XPB1.16.6, and FL1.5.1. And this is true when used both as a primary or secondary boosting response. Next advance please. The vaccine also induces a Th1 bias CD4 cellular response against these sub-variants. And one more advance and I'll sum up. The vaccine's presentation facilitates ease of use and may minimize medication errors. It's ready to use straight from the vial and a 0.5 mL IM injection can be administered with standard needles and syringe. We anticipate the same 0.5 mL dose will be indicated for all individuals aged 12 years and older. The vaccine's been manufactured and has been pre-positioned in our U.S. distribution hub awaiting EUA and the start of the fall campaign. Thank you. This concludes my presentation. Thank you, Dr. Ptabovsky. Next we'll move on to the Pfizer-BioNTech team. Dr. Majarid. Good afternoon. My name is Keivan Majarid. I'm the executive director of viral vaccines R&D at Pfizer. Next slide please. On behalf of Pfizer and BioNTech, it's my pleasure to share recent data on our COVID-19 vaccine updated to the monovalent XBB1.5 composition for the upcoming fall-winter season per the FDA's recommendation following the June 2023 VRBPAC. Today I'll briefly review the current state of SARS-CoV-2 variant epidemiology, the approval pathway for updated COVID-19 vaccines, followed by a review of the ongoing preclinical and clinical evaluation of our monovalent XBB1.5 vaccine. Next slide. As you heard earlier today, Omicron XBB sublineages have overtaken the COVID-19 epidemiologic landscape in the last year. The emergence and rise of XBB1.5 has now shifted to related sublineages such as EG51, which has rapidly increased in prevalence in the U.S. and globally over the past few months. Despite the current dominance of these sublineages, new more phylogenetically and antigenically distant variants continue to emerge, the most notable example being the VA-286 variant under monitoring by the WHO and being closely tracked by the CDC, as you heard earlier today. Although its prevalence is still less than 1%, it has raised concern because it contains about three dozen mutations in the spike protein relative to XBB1.5, many in areas targeted by neutralizing antibodies. We have previously shown that the monovalent XBB1.5 adapted vaccine effectively neutralizes XBB sublineages. Today I'll provide an update on our continuing evaluation of new strains, specifically the predominant EG51 and more recently emerged VA-286. But first, I'll review the steps that have led us here today. Next slide. COVID-19 vaccine updates will continue to require perpetual surveillance and preclinical evaluation, as well as at-risk development on the part of manufacturers in advance of strain selections. According to FDA guidance, this will trigger the regulatory submission of a non-clinical and CMC data package akin to the model that has been a longstanding cornerstone of annual updates to influenza vaccines. This model is also applicable to COVID-19 vaccine updates because of valuable information gained over the past three years. Next slide. As presented in the June VRBPAC, we have built a robust data set for four variant adapted vaccines that has supported a consistent alignment of preclinical and clinical data. And a preclinical data package, along with learnings from prior clinical and real-world experience with our COVID-19 vaccines, supported the 2022 authorization of the bivalent Omicron BA45 vaccine and approval of our current monovalent XBB15 vaccine. Next slide. I'll now share preclinical immunogenicity data on our monovalent XBB15 vaccine as compared to the bivalent Omicron BA45 vaccine, given as both a booster and primary series. First, for the booster evaluation, the vaccines were given as a fourth dose in mice that had previously received two doses of the original vaccine and one dose of the bivalent BA45 vaccine. Next slide. Here you'll see the two vaccine groups along the horizontal axis. Pseudovirus neutralizing titers indicated on the vertical axis were measured at one month after the last boost. The colored bars represent the different strains tested. A monovalent XBB15 booster elicited substantially higher neutralizing antibody titers against XBB15, EG51, and BA286 as compared to the bivalent BA45 vaccine. There was no statistically significant difference in responses across the three strains. Next slide. Here we see that the increase in the XBB15 monovalent vaccine group relative to the bivalent BA45 group is several fold higher for the XBB strains, consistent with data shown at the VRBPAC for related strains as well, XBB116 and XBB23, but also three-fold higher for the more distant strain, BA286. Next slide. In the primary series evaluation, two doses of XBB15 monovalent vaccine were administered three weeks apart. Serum neutralizing activity was assessed one month after the second dose. Next slide. Similar to results of the booster study, we see that the monovalent XBB15 vaccine elicited much higher neutralizing titers against XBB strains, here XBB15 and EG51, compared to the bivalent BA45 vaccine. Data on BA286 from this study are currently being generated. Next slide. Relative to the bivalent BA45 vaccine, the response in a naive background was even higher than observed in the booster study. Although SARS-CoV-2 continues to affect adult populations disproportionately, the primary series data remain relevant for the youngest pediatric populations that do not yet have experience with SARS-CoV-2 infection. Next slide. We are also generating clinical data on our monovalent XBB15 vaccine in an ongoing study in individuals 12 years of age and older. The vaccine is being evaluated as a single dose booster in people who have had at least three doses of an authorized COVID-19 vaccine, with the last one being the bivalent BA45 vaccine at least five months prior to enrollment. Standard safety information and blood for serum antibody testing will be collected through six months of follow-up. We expect to have safety and immunogenicity data, including against XBB15, EG51, and BA286 later this year. We will also be conducting clinical studies in pediatric populations six months to 11 years of age. Next slide. To summarize, XBB sublineages continue to dominate the current epidemiologic landscape, despite the emergence of new variants like BA286. The preclinical data show that the Pfizer-BioNTech monovalent XBB15 adapted vaccine administered as a booster elicits equally robust neutralizing responses against XBB15, EG51, and BA286. We see a similar trend for XBB15 and EG51 when the vaccine is given as a primary series. This shows the immunologic principle holds that variant adapted vaccines will elicit optimal immune responses against antigenically matched and related strains, thus giving us confidence that the vaccine will confer protection against the most prevalent circulating strains. Finally, the data we've shown today is part of an overall preclinical CMC package for a monovalent XBB15 adapted COVID-19 vaccine that has fulfilled licensure criteria. Next slide. I and my Pfizer and BioNTech colleagues thank all the participants in our clinical studies and their families, the site investigators and staff, our CRO collaborators, and many other partners, and especially the CDC and members of the ACIP. Thank you for your time and attention today. My colleagues and I are happy to answer your questions. Thank you for your presentation. And with that, our three presentations are open for questions. Dr. Poehling. So I want to say thank you to each of you for presenting the data and sharing and all the work that goes behind us. It's very important. I have a question for each of you. For Dr. Priddy, my question is, is there any plans to study the XBB.1.5 vaccine in children? And if so, when? Yeah, thank you for the question. We do have a significant amount of data accumulated in children on our platform, the Moderna COVID-19 mRNA vaccine platform, over 16,000 children from ages six months to 18 years. We've studied in clinical trials. So we don't have immediate plans to test this updated vaccine in that age group. But as I've shown today, we think that the characteristics of this vaccine, in particular reactogenicity, are very consistent with the prior variant-containing booster and our original vaccine. And we expect the safety profile, we anticipate that safety profile to be carried forward across all age groups. Okay, thank you. Dr. Dabas, for Novavax, I very much appreciated your presentation. Could you talk about the safety of the Novavax vaccine? Yeah, I mean, the safety is very well described from the experience we had during our clinical development program. And in general, it's exactly what's described in the label, right? So there's reactogenicity, which is largely pain and tenderness, as well as some fatigue and malaise. And then there's the sporadic symptoms that are described in the label and the warnings and precautions section. Okay, thank you. And then for Dr. Majard, could you please tell us when the data for the clinical trials would be available? And when the six-month to 11-year-old studies plan? Thank you. Thank you for that question. For the study that I presented in adults or those ages 12 years and older, they'll be available in the fourth quarter of this year. And then I will turn over to my colleague, Dr. Charu Sabharwal, to address the question about the pediatric study. So thank you so much for that question. This is Charu Sabharwal from Pfizer Vaccines, the pediatric COVID-19 lead. In terms of your question, we actually have a phase one trial in six months to less than five that will initiate XBB 1.5 starting this month. And additional ongoing trials are projected to start in fourth quarter. And we are under discussion with the FDA on those protocols. Thank you so much. Thank you. Dr. Sodeos? Thank you. This question is for Dr. Dubovsky. Do you have any data on neutralizing responses against BA286? No, those data are being developed now, but I think we saw from the academic publications as well as the data presented by the other sponsors, the neutralizing responses hold against 286. I guess the other point is there's some indication from the academic press or publications that that virus may be less fit than the XBB lineages. So it's unclear to us at all if it's going to emerge. Thank you. Ms. McNally? Thank you. I'd like to ask if any of the vaccine manufacturers are aware of the use of this monovalent vaccine in other countries. So this is Philip from Novavax. We are not authorized in any other countries right now with XBB 1.5 vaccine. Hi, this is Fran Priddy from Moderna. Was the question whether these vaccines are being authorized or approved in other countries? The monovalent vaccine, whether or not any manufacturer has authorization in other countries. Thank you. Yeah, at Moderna, we are pursuing approval in numerous other countries. Yes. Hi, this is Kevon Majered from Pfizer. We do have approval in Europe, Japan, the United Kingdom, Singapore, and the Republic of South Korea. Can Moderna and Pfizer just clarify whether it's currently being used and what the experience is in those countries? This is Moderna. We have approval in Japan and Canada, and I think the use has not started yet, and the rollout is beginning later this week. Thank you for that clarification. And here as well, in all those countries I cited, we have not had any use as of yet, but we will have a vaccine available as early as tomorrow in the U.S. in some locations. Thank you. Dr. Kotton? I was wondering if the companies could answer whether there are studies planned with this monovalent vaccine in immunocompromised patients who represent approximately 3% of the U.S. population and remain many-fold more likely to be hospitalized with severe disease. Thank you. Hi, this is Fran Priddy from Moderna. We do not have immediate plans to test the updated vaccine in immunocompromised populations, but we have conducted studies in severely immunocompromised using our prior vaccine and have shared that data publicly and with agencies. Dr. Dubofsky, go ahead. Yeah, I think our answer is pretty much the same. We have experience with our previous vaccine in immunocompromised people with different disease entities which led to their immunocompromise. We have no specific plans to initiate a study. However, not all immunocompromised is excluded from studies that we do have ongoing right now. This is Kigurama Jared from Pfizer, and our response is consistent with the other manufacturers in that we have had studies in the past in immunocompromised populations, but we do not have current plans for the updated monovalent vaccines. Dr. Sanchez? Yes, thank you for those presentations. A couple of questions. For Dr. Dubofsky with Inovavax, do you have any data on the neutralizing antibody production among those who are, I guess, in the mice who previously had received messenger RNA vaccine? Yeah, so we don't have that data in mice. What we do have is some data in human from a previous study where we use a monovalent B85 vaccine, and what we saw there is the neutral responses against 1.5 were about three to five-fold increased after that boost on top of mRNA. And do you plan to do any studies with the current monovalent? That study is fully enrolled and is maturing as we speak, and we have a companion study similar to that design on top of people, children, who have received mRNA that's enrolling right now. Thank you. And another question. So with respect to the Pfizer product, Dr. Jared, and actually, I guess, for Moderna as well, we really don't have data on any less than 12-year olds currently. And so we are in the process of trying to recommend this vaccine where the data, it's just ongoing studies at this point, right? I'm happy to start with that one. This is Fran Pree from Moderna. So we very rapidly conducted the study that I presented today in order to have clinical data for an XPV-containing vaccine to provide the most current information on immune responses, but also safety for strain selection this year. But recognizing that the study could not include all age groups, we do note that this vaccine, of course, uses the same platform as the previous Moderna COVID-19 vaccines. And that safety profile has really been extremely well-characterized with over a billion doses given worldwide. And over 50,000 adults and children evaluated safety in clinical trial setting. That includes over 16,000 children from ages six months to 18 years have received the platform vaccine, the Moderna mRNA COVID-19 vaccine in clinical trial settings. And the data I showed today, although not in children, does show a very consistent reactogenicity profile of updated vaccine compared to the prior one. So we feel that the safety profile will carry over with the updated vaccines across all age groups. Thank you. Hi, this is Kayvan Majerad from Pfizer. We have evaluated our vaccine in pediatric age groups all throughout the course of the availability of the vaccine in the original formulation, as well as the bivalent BA45 formulation. And all the data, both safety and immunogenicity, have been consistent throughout the studies with the same platform with the different formulations. And we expect that to be the case. So that is from internal data and also public data and the data that CDC has presented as well. Thank you. We'll move on to Dr. Talbot. Yes, I think Grace alluded to this earlier, pardon me, Dr. Lee. Can you all please tell me what you are planning on charging so that we can view the cost-effectiveness analysis in a more true light? Yeah, definitely. This is Fran Priddy from Moderna. I'll just start off. So the list price for our vaccine is $129 per dose. Thank you. Thank you. And thank you for being forthright. So can you hear me? This is Dr. Canet from Pfizer. Yes, we can. Please go ahead. Yes. The list price for Pfizer vaccine is $120 per dose. Thank you. John Trusino from Novavax. Please go ahead. So just a qualification, right? While we were not included in the model that Dr. Prosser presented, we do show our own pharmacoeconomic data that is consistent with that model, number one. Number two, the list and or WAC price that we refer to, ours is $130 per dose, which in industry conditions is subject to contract pricing and discounts. Also of note is that our contracted price with CDC is $72.50 per dose. Thank you. I'm going to go back to Dr. Duchin. Thank you for your patience. Thank you. Excellent questions. And this one may be for others besides the manufacturers, but I'm curious as to where we are in general with the issue of heterologous boosting. Dr. Sanchez alluded to this specifically with respect to the Novavax vaccine, but our NIH colleagues have presented to us at ACIP. Previously, there have been a number of publications that suggest superior immunogenicity with heterologous boosting. So I'd like to hear from our NIH colleagues or anyone else who can just summarize where we are with respect to the potential benefits of heterologous boosting at this point. Thank you. This is John Beigel from the NIH. So we have done, as you've said, we've done heterologous boost trials, both mix and match the original heterologous boost, and then a subsequent where we did Covail, which was a boost on top of a mixed background. I would reframe the way you said it to say that heterologous boost shows it's just as good as homologous boost. I don't think there's data to support that it is necessarily better, but in our opinion, that the data is fairly clear that heterologous boost gives a good immune response similar to homologous. And this is Philip from Novavax. We've done a number of studies looking at how our vaccine performs on top of a various number of platforms. And depending on the quality of the platform, it can make a difference. For the vaccines that are available in the US, I tend to agree with the NIH position that the immune response and magnitude is really comparable irrespective of what the priming is. There are, however, different immunophenotypes that can be imprinted depending on which vaccine was given first, and that may turn out to make a difference in the future. We just don't have that data right now. Thank you. And the last question goes to Dr. Daly. Yeah, thanks so much. So I have two different points. I think I'll make these as comments and not ask for a response based on that we're running a little bit behind. I think the first is that I have heard from small private practices about a minimum order amount, something like 200 doses. And I just think that creates barriers. So I would ask all the manufacturers to consider reducing what the minimum amount that practices need to order, just because that's a significant financial outlay, maybe $20,000, and it's for a practice who might need to buy multiple doses for multiple different age ranges, for example, a small family medicine practice, and so then that just presents a barrier. So then I want to speak to this issue about where clinical data fits in. So I think we all need to keep in mind, and this is in some ways for the listening public too, that there is quite a bit of data in populations that might be adults, that might be children, that might be immunocompromised in these platforms that precedes all of this. And then the FDA working with VRBPAC makes a decision on strain selection, and they wait because they want it to be the most updated. And so then that leaves kind of limited time to produce that clinical data. Yet the other side of the argument is that the public would just like to know that this new strain selected has some clinical data behind it. So I think there's a tension there that we all need to recognize. And I think we need to take this back to the work group, have discussion with our colleagues, including FDA colleagues, and including manufacturers to sort of figure out where that fits in. Because I think it's at this point in the program, to me, it would be reassuring to have clinical data, but I recognize that it's a challenge because of the limited time frame. And we have all of this data of the prior formulations on which to make these decisions. Thank you. Thank you. Dr. Tresino, we are at time. Do you have a really brief comment? Yes. Just to clarify our position on minimum order quantity, we're, as Dr. Dubofsky said before, 10 doses and access through all nationwide distribution. So we are not limited in the equitable distribution of vaccine across the country. Thank you. We appreciate that. You're welcome. Okay. With that, we're going to take a five minute break. Apologies to my colleagues, but I know some folks have things on the other end of the day. So five minutes and we'll return for our last session before public comment. Thank you.