Pfizer Inc. (PFE) Earnings Call Transcript & Summary

Good day, everyone, and welcome to Pfizer Pflash: A Spotlight on Clostridioides difficile Vaccine Development. Today's call is being recorded. At this time, I would like to turn the call over to Francesca DeMartino, Chief Investment Relations Officer (sic) [ Chief Investor Relations Officer ] and Senior Vice President. Please go ahead, ma'am.

Thank you, and good morning, everyone. I'm Francesca DeMartino, Chief Investor Relations Officer. On behalf of the Pfizer team, thank you for joining us for our second Pfizer Pflash webcast. Today's call will be recorded and will be available for replay on our IR website at pfizer.com. As a reminder, our Pfizer Pflash series is intended to serve as an educational deep dive into our pipeline, products and leadership. Each call will spotlight a specific product, therapeutic area or growth initiative and give you an opportunity to hear from and interact with our business leaders. Today's session will begin with a short conversation followed by a live Q&A. As a reminder, this call is intended only for the investment community, including our sell-side analysts and institutional investors. If you are unable to join the entirety of the event, you can find a replay available on our IR website. I want to note that on today's call, we will be making forward-looking statements. I encourage you to view Slide 2 in our presentation and the disclosures in our SEC filings, which are all available on our IR website at pfizer.com. Forward-looking statements on the call are subject to substantial risks and uncertainties speak only as of the call's original date, and we undertake no obligation to update or revise any of the statements. With that, let's get started. As you know, vaccines are a key area of focus for Pfizer with a portfolio that seeks to address both viral and bacterial pathogens. Today, we will provide insight into a program that we believe has the potential to be a key driver of growth for our bacterial vaccine franchise. It is a privilege to have you all with us as we delve into C. diff. Before we move to the main discussion, let me take a moment to introduce our speakers. Annaliesa Anderson, Senior Vice President and Head, Vaccine Research and Development; Alejandra Gurtman, Senior Vice President and Head of Vaccine Clinical Research and Development; and Julie Skinner, Vice President, Bacterial Vaccines and Technology. And Annaliesa, Alejandra and Julie are central to our innovative work focusing on vaccines from early discovery through licensure. Annaliesa, Alejandra and Julie, welcome, and thank you so much for joining today. Can you please start by introducing yourself and giving a brief overview of your current role and experience?

Thank you, Francesca. I'm thrilled to be here today with my colleagues, Alejandra and Julie to talk about the impact of C. difficile infections and our progress in developing a potential vaccine. In my role at Pfizer as Senior Vice President and Head of Vaccine Research and Development, I'm responsible for leading the end-to-end research and development for all infectious disease vaccine programs in Pfizer's portfolio. During my time at Pfizer, I've helped to lead the strategy and execution of multiple programs leading to the licensure of numerous vaccines and therapeutics, including the 13-valent pneumococcal conjugate vaccine, PREVNAR 13, the first-ever U.S. licensed vaccine against invasive meningococcal disease caused by serogroup B, TRUMENBA, strain change and next-generation research and development for the first ever licensed mRNA-based vaccine community. The first-in-class antiviral PAXLOVID and the most complex vaccine ever marketed for both adults and pediatrics, Prevnar 20 and the first ever bivalent prefusion F RSV vaccine ABRYSVO for use in both older adults and pregnant people for the protection of newborns against RSV disease. And with that, I'll turn over to Alejandra.

Thank you, Annaliesa. I'm Alejandra Gurtman, Senior Vice President, Pfizer Vaccine Clinical Research and Development. I am responsible for early and late-stage clinical development of Pfizer's vaccine pipeline. I had to lead the RSV vaccine program resulting in approvals for adults and maternal indications in the U.S. and Europe and Pfizer's COVID-19 vaccine program supporting development and strategy and advancing the adolescent and pediatric programs for emergency use authorization. Before this role, I was a global clinical lead for the staphylococcus aureus vaccine and also led the PREVNAR 13 pediatric program. I supported the PREVNAR 13 adult program and studies in high-risk immunocompromised populations. I am trained in medicine at the University of Buenos Aires and completed my post-doctoral training at Mount Sinai School of Medicine in New York City, where I also served as an associate professor and the founder of the Travel Medicine program before coming to Pfizer nearly 20 years ago. And next, we will hear from Julie.

Thank you, Alejandra. In my role as Pfizer's Vice President of Bacterial Vaccines and Technology. I am responsible for leading Pfizer's portfolio of bacterial vaccines and early discovery through development. This includes leadership and oversight of our C. difficile vaccine program. Prior to joining Pfizer, I completed postdoctoral training at the CDC before moving to vaccine development with roles at the biotechnology company, Intercell, followed by 15 years at Merck, leading their bacterial vaccine programs. including work leading to the approvals of the pneumococcal vaccines, VAXNEUVANCE and CAPVAXIVE. I am thrilled to have joined Pfizer and have the opportunity to lead our bacterial vaccine programs. With that, I will bring it back to Francesca.

Thank you all for your introductions. Lisa, can you briefly speak to Pfizer's overall strategy in developing bacterial vaccines?

Yes, of course. As we all know, vaccines are one of the greatest public health advancements of all time, resulting in the control, elimination or near elimination of numerous infectious diseases that were once pervasive and often fatal. Today, more people are benefiting from safe and efficacious vaccines to help prevent infectious diseases than ever before, and vaccines provide an essential health benefit at all ages from maternal and infant populations to seniors. However, our work is not done, given the many infectious diseases remaining with high unmet medical need that cause a significant burden to society. At Pfizer, we're focused on 3 pillars to target emerging health threats and drive potential for long-term growth. Speaking to only our bacterial programs, we are enhancing our core pneumococcal franchise. Our fourth-generation pneumococcal conjugate vaccine or PCV candidate is in Phase II for adults and pediatrics after demonstrating encouraging immunogenicity and an acceptable safety and tolerability profile in first-in-human Phase I study. As a reminder, our fourth-generation PCV candidate covers 25 serotypes, including potentially improved immunogenicity for serotype 3, which is one of the largest remaining contributors of disease. Our second pillar is focused on executing on our mid- to late-stage pipeline portfolio. Today, we will spotlight C. difficile. Lastly, we're focused on growing our pipeline. We have some very exciting preclinical programs targeting both bacterial and viral pathogens, and I look forward to providing an update on these in the future.

Great. Thank you. So diving in, could you please give us a little background on C. diff and why it would be so important to have a vaccine against this disease?

Of course. Clostridioides difficile is a gram-positive aerobic spore-forming bacillus. We also call it C. diff, and it causes -- it produces 2 virulence toxins that are responsible for the illness known as Clostridioides difficile infection or CDI for short. These toxins are called toxin A and toxin B. C. diff colonization is often enabled by disruption in the normal gut flora due to factors such as antibiotic use, age and recent hospital stays being additional common risk factors for the disease. We have a slide here that provides a visual of how CDI happens. If C. diff colonizes the gut and releases its toxins, they can cause severe damage. CDI causes inflammation in the bowel and manifestations range from asymptomatic or mild to more serious complications such as severe diarrhea, toxic megacolon, intestinal perforation and other life-threatening complications. Unfortunately, individuals contracting an initial case of C. difficile are frequently susceptible to recurrent infection with the CDC estimating that approximately 1 in 6 will be recurrent in the subsequent 2 to 8 weeks. In recent years, C. diff has emerged as a major cause of infectious diarrhea. In fact, it is estimated that there are nearly 500,000 infections a year in the U.S. 1 in 11 people over the age of 65 is diagnosed with health care-associated CDI will die within 1 month. In 2019, C. difficile was categorized by the U.S. Centers for Disease Control and Prevention as an urgent public health threat, its highest infectious disease threat designation. Patients with C. diff requiring medical intervention are typically treated with antibiotics such as vancomycin, Fidaxomicin, though in some instances, surgical or fecal microbiota transplantation techniques may be employed. In addition, orally or rectally administered fecal microbiota products are approved to prevent recurrence of CDI, though not for protecting against a first infection. Treating and managing patients with CDI places a substantial burden on the health care system with prior peer-reviewed publications estimating the annual U.S. health care cost at approximately $5 billion to $6 billion. Given the current landscape, there is a pressing unmet medical need for a vaccine that can prevent primary or recurrent CDI to reduce C. diff-associated health care burden with our development program. We aim to address this need and deliver the first such vaccine to providers and patients.

Alejandra, a question for you. Who would be the target population for a C. diff vaccine?

Well, CDI incidence increases dramatically after the age of 50 and a significant proportion of the burden of disease is in individuals aged 65 and older. Moreover, prolonged exposure to health care settings can increase the risk of CDI and individuals are 7 to 10x more likely to get CDI while they are on antibiotics and during the months following. Our CV vaccine candidate trials are focused on adults that are 50 years of age or older. While we cannot speculate on decisions of regulatory agencies or recommending bodies, potential populations could include those who are 50 years of age or older. As we get older, our risk factors increase, and so it could potentially be a good strategy to be vaccinated before the risk period starts when it may be too late to get a vaccine.

Pfizer had a first-generation C. diff vaccine candidate that advanced their Phase III testing. Alejandra, can you give us a little background on that?

Well, happy to. Our first-generation candidate is a genetically and chemically toxify investigational vaccine formulated with modified C. diff toxin A and B antigens. It received FDA Fast Track designation in 2014. Phase I and II data indicated that 3 doses of this vaccine candidate were well tolerated and elicited robust neutralizing antibody activity against toxins A and B for up to 4 years in adults aged 50 to 85.

And can you tell us about the Phase III trial?

Of course. Based on the Phase I and II data I just mentioned, we then evaluated the safety and efficacy of our first-generation C. diff vaccine candidate. In the Phase III CLOVER trial, an overview of which you can see on the slide. CLOVER was an important innovative study. The trial began in 2017 and [ span the height ] of the COVID-19 pandemic with top line data being announced in the first quarter of 2022. I have a schematic here that summarizes the trial. We randomized more than 17,000 adults aged 50 and older who are at increased risk of C. diff infection. Participants received 3 doses of investigational vaccine or placebo over a 6-month period. The first and second primary endpoints of the trial tracked the first C. diff infection episode that took place 14 days or more days after the participant had taken the third dose or the second dose of the vaccine, respectively. Given the innovative nature of the CLOVER study, we worked with regulators such as the FDA and the EMA as well as key infectious diseases experts to align on a clear definition of a primary C. diff case. In the middle of the slide, I am showing you the trial uses single rigid criteria that demanded specific clinical symptoms and lab confirmation that the participant was positive for C. diff toxin. Notably, this definition did not distinguish between mild self-limiting cases and more severe cases that require medical attention. Data from the trial showed that the primary endpoint was not met as the lower bound of the vaccine efficacy 96.4 confidence interval fell below the prespecified cut of 20% However, when looking at secondary endpoints and additional analysis, we saw encouraging signals of efficacy that highlighted our candidates' potential to lower C. diff-associated health care burden.

Can you tell us more about the secondary and additional analysis and how they give you confidence in the C. diff program going forward?

Sure. This analysis showed the vaccination with our first-generation candidate led to reductions in medically attended CDI and the duration of infection. Starting with the table on the left, the first row shows data on the primary endpoint, which I just mentioned was not met. However, looking at the second and third rows, you will notice that none of the C. diff infections reported in vaccinated participants in the relevant per protocol population require medical attention or antibiotic intervention. This is indicative of 100% vaccine efficacy for these post-hoc endpoints. And looking on the right, you can see that the median C. diff infection duration dropped from 4 days with the placebo to only 1 day with vaccination. Taken together, these results suggest that our first-generation vaccine candidate may have alleviated CDI severity from moderate to severe cases to mild self-limited disease. Furthermore, by showing 100% efficacy against medically attended CDI, they suggest that the vaccine, including our toxin A and toxin B antigens may have the potential to play an important role in protecting at-risk patients and reducing the health care burden of this potentially fatal disease.

Thank you, Alejandra. Julie, following the CLOVER results, what were the next steps for the program? And what is its current status?

Looking at the totality of CLOVER data, we came away from the trial encouraged. Though we were, of course, disappointed to miss the primary endpoint, we saw a clear signal suggesting our vaccine candidate may protect against medically attended and more severe forms of infection, which is a critical piece for reducing disease burden. And as the CLOVER study was ongoing, we had actually already began working on an updated C. diff vaccine formulation that could simplify the dosing schedule. Specifically, we wanted to develop a formulation that would induce a robust and durable immune response with a 2-dose regimen. Compared to the 3-dose regimen evaluated in CLOVER, we believe a 2-dose vaccine could improve completion of the dosing series and enable us to help protect more patients. So following the CLOVER readout, we continue to focus on developing this updated formulation and designing a clinical program to demonstrate our candidate's ability to meaningfully reduce C. diff disease burden. A key early step in this process was assessing the potential of our updated formulation to induce immune responses against toxin A and toxin B similar to or better than that displayed by our first-generation candidate, but faster and with less doses. This would provide an early indication of the new formulation's potential to protect against medically attended and/or severe C. diff infection. To pursue our objectives, we advanced 3 updated formulations of our vaccine candidate into a Phase I/II trial in the first half of 2023. Based on safety and immunogenicity data from the Phase I portion of the study, we selected a preferred formulation to bring into Phase II. The Phase II portion of the study remains ongoing and is exploring multiple dosing schedules. We expect data from the trial in 2025 and pending positive results and alignment on a regulatory path with agencies, we would aim to potentially start a Phase III trial in late 2025.

Thanks, Julie. Alejandra, one final question for you. If we get the results we're hoping for in a Phase II, what would the planned Phase III trial look like?

It's too early to speak to the specifics of the potential Phase III trial design, but this would be informed by both the Phase II findings as well as regulatory interactions.

Okay. And thank you all for a great discussion. So in summary, our C. diff program targets an urgent and serious public health threat with no vaccines approved to protect against C. diff infection. This highlights a pressing unmet need with 1 in 11 people over the age of 65 diagnosed with healthcare-associated CDI passing away within 1 month. With our first-generation vaccine candidate, we saw reductions in disease duration and medically attended cases in Phase III, demonstrating its potential to reduce C. diff associated health care burden. We are now building on these prior results by advancing an updated formulation of our investigational vaccine that has the potential to be administered as a 2-dose regimen. This updated formulation displayed encouraging safety and immunogenicity in Phase I and is now advancing through a Phase II proof-of-concept trial. Pending positive Phase II data and alignment on a regulatory path forward with agencies, we would aim to potentially start a Phase III trial in late 2025. We'll now begin the Q&A session with Lisa, Alejandra and Julie. As a reminder, our Pfizer Pflash series is designed as an educational deep dive into our pipeline programs. I'll therefore kindly ask participants to keep questions focused on the C. diff vaccine development program discussed today and to avoid those that would require us to provide forward-looking financial projections. While we're happy to clarify any information shared during the presentation, we will not be offering estimates beyond what has already been communicated. We will do our best to provide as much clarity as possible within these guidelines and thank you for your understanding. With that, we're ready to take the first question. Operator, if you could please assemble the queue.

[Operator Instructions]. We'll go first to Evan Seigerman with BMO Capital Markets.

So as you think about kind of the unmet need in C. diff, I know there's clearly -- it's clearly a big issue for seniors. I guess how do you envision this product actually -- how do you envision this product being used in the real world? Is it for a specific type of at-risk senior? Is it for a broad population? And secondarily to that, what would the potential uptake curve look like knowing that -- assuming that the Phase III trial for this is successful?

This is Alejandra Gurtman. Thank you for the question. We obviously need to do the Phase III trial and expect that the vaccine will be -- will show efficacy and then be approved. And part of your question is related to how the vaccine will be recommended. And as you know, that will be part of -- in the United States ACIP recommendations. As I mentioned before, as you get older, as we all get older, the risk for disease increases and especially as we go in and out of medical care and you may be exposed to antibiotics, the risk is even higher. So ideally, again, this will be an ACIP recommendation, a vaccine that is age-based where you can get it, for example, at age 50 will hopefully be protected of those events that you may have before you are exposed to that medical care I mentioned. Did I answer your question?

Yes. I guess the follow-up is kind of the second part is who would be the best candidate for this vaccine, assuming the data is successful? Is it a wide variety of patients? Or is it going to be more focused on those who would be higher risk? And how would that be defined?

Yes. I would just say that commenting on recommendations is something that we, at this point, are not able to do. Obviously, this is an unmet medical need. But I will also ask Lisa if she wants to add to what I just said.

Thank you, Alejandra. So as we get older, one can't always predict when you're going to get -- be at risk of C. difficile disease. As when you look at the population who gets disease, it's people who are older. It's people who have frequent contact with health care facilities and it's people who have to take certain antibiotics for a period of time. And so really, when one looks at an age-based recommendation, it means that you can vaccinate before you reach those periods of risk. And again, we don't always know when we're going to fall into those periods of risk.

We'll go next to Trung Huynh with UBS.

Just 2 for me, please. So in the intro, you noted C. diff is caused by toxin A and toxin B, which is what you're targeting with your vaccine. There's actually some strains that produce a third toxin, binary toxin, which is associated with more severe infections. So does your vaccine generate any immunity to that? And if not, I'm wondering how common the third toxin is in some C. diff strains? And then secondly, you noted C. diff is common in elderly patients. I'm curious in the data that you've seen, if you're seeing any waning of efficacy as you get older, older people may not be able to mount as much of a strong immune response to vaccine. So anything there would be helpful.

Sure. Thank you for the question. So as Alejandra noted, our C. diff vaccine is a toxoid-based vaccine, and it's derived from native toxins, which have been modified and inactivated to maintain immunogenicity. Our vaccine contains toxoid A and toxoid B. It does not contain binary toxin.

And if I can add to that, it's Annaliesa here. And so yes, we acknowledge that binary toxin does cause some disease, but even in studies that have been done preclinically, vaccines that contain both the toxin A and the toxin B are effective at protecting against disease even in the presence of binary toxin.

We'll go next to Chris Schott with JPMorgan.

This is Ethan on for Chris. Just 2 for me. The first is, how do you think about the time line of the potential Phase III trial this time around given the CLOVER trial took around 5 years to be announced, but was affected by COVID? And then on the duration of the C. diff vaccine, any information you have here? It seems like this is a regimen that patients will only need to take once. Is that fair to say?

Yes. So it's Alejandra here again. Thank you for the question. So the timing of the study, as it was alluded, we're hoping to start the study in 2025. When you refer to CLOVER, most of the CLOVER, as I mentioned, study was implemented and executed during the pandemic. And as you might remember, during the pandemic, medical care really changed, right? So surgeries were -- elective surgeries were canceled, many procedures and actually medical visits were postponed and were done through telehealth. And therefore, the incidence of disease probably went down based on the fact that patients didn't have the exposure that you will need or what we were expecting to have during the study. So by the time that we conduct the next Phase III study, hopefully, we will not be in a pandemic. And this will be, again, a case accrual design, which means that you need to accumulate sufficient cases to be able to then declare efficacy. We will execute the study, and we will select the right institutions and networks to be able to do the study. And I cannot tell you the timing that we want to have this vaccine as early as possible. So we will be very diligent on how we design and who we bring into that. In terms of duration of protection, which I think was your second question, one of the good things about the CLOVER study among many of them is that we were clearly able to show that the vaccine protects during at least 4 years, right? So we expect that the new vaccine will be -- we have a duration of protection as such. And even when you design a Phase III [indiscernible] efficacy, we will be potentially be able to follow patients for longer to assess the duration. In the current Phase I and II studies, actually, we have duration of immune response for many years to start to see again, hopefully, that the vaccine actually induces antibodies that stay there for long time to be able to protect. So did I answer your question.

Sorry, if I could just interrupt, sorry. So just to clarify with the current Phase I/II studies, we will have the data by the time of the potential licensure. We don't have the data yet.

We'll go next to Vamil Divan with Guggenheim Securities.

So a couple of questions, if I could. So one, you shared your Phase II data over the prior vaccine Phase III data and now you mentioned you might be able to a 2-dose regimen. Can you just share a little bit more on what you've seen in terms of immunogenicity data that gives you comfort that this could be potentially a 2-dose regimen? And then my other question is maybe a broader question, this may not be fully accurate, but I feel like there's been a number of other companies that have also worked on C. diff vaccines previously that have not been successful. So I appreciate reviewing what Pfizer has done. But maybe you can just provide some broader perspective on the broader attempts that have been made here and what have been some of the challenges and why things might turn out differently this time?

Sure. Thank you for your question. So regarding the 2-dose regimen that we're looking at, we do have an ongoing Phase II trial looking at dosing. And as part of the formulation of our next-generation vaccine candidate, we have evaluated adjuvants. And we do believe that adjuvants can increase the strength or magnitude of the immune response to the vaccine. As such, if the immune response is stronger, the number of vaccinations may be able to be reduced. So if the adjuvant selected for use with our next-generation C. diff vaccine formulation proves to induce higher antibody responses to our vaccine antigens, there may be potential to reduce the number of vaccinations while still achieving optimal and impactful immune responses. And for the second part of your question, I'm going to turn to Annaliesa Anderson.

Thank you, Julie. So you appreciate we can't really comment on other people's studies and other people's programs. What we can say is in the Phase III study that we conducted, as Alejandra explained in those key secondary and investigational analysis, we were able to see very high efficacy, especially against the medically attended disease that clearly show this vaccine can have a strong clinical benefit. And we're really excited to be able to move forward with this vaccine with the new formulation to not only, yes, repeat that efficacy, but also to have a more optimized dosing schedule.

We'll go next to Geoff Meacham with Citibank.

Just have a couple of quick ones. The first one, I know it's kind of hard to assess, but just given what could be newer regulatory attitudes towards vaccines in development, what's your guys' view of whether you'll need a bigger safety database or, for example, longer follow-up versus what you normally would design, thinking just of the Phase III trial? And then on C. diff, I think when you look historically, you see outbreaks in at-risk populations like the elderly that really drive the infection rates. How does Pfizer maybe raised the bar for awareness to justify this being part of a broader kind of vaccine regimen?

Thank you for the question. It's Alejandra here. I may start and then ask my colleagues to add more. So I think that your first question was about regulatory attitude. We are engaging with regulatory authorities in the same way that we have done before. We expect that the required safety database that you asked would be similar to what we have done before. For many vaccines, the required database is about 3,000 exposed participants. This study will be larger than that. So we will be able to really have a database that will support that the vaccine is safe and well tolerated. I think that your second part -- you asked several questions was about the longer follow-up. And as I alluded, this will be a case accrual study design. And as I mentioned as well, we -- the study design, as I also shared, is a little bit too early to share at this point, but we will -- we are aware of the need for this vaccine to have longer follow-up. And so we will -- we potentially will introduce that as well to follow patients for a longer period of time. You mentioned outbreaks, I think, I was wondering if you were referring to -- maybe you can clarify if the outbreaks that you're talking are the ones that you may see in hospitals or nursing homes.

Yes. When you follow the epidemiology, that is sort of concentrated in those settings?

Yes. So as you know, unfortunately, at the current time, there is no really any vaccine or any other -- sorry, available therapies or for primary recurrent CDI. So those outbreaks are usually controlled with basic hand washing with soap and water and proper cleaning and disinfection. As you probably are aware, there is infection control practices with isolation to ensure that you can control the outbreak. We -- that will be something that will come eventually that we will be able to evaluate after the vaccine is approved, but the study design will not incorporate to look into outbreaks at this time. But maybe I will just ask my colleagues here if they have additional points that they want to call.

I think one of the questions, Jeff, if I got it correctly, was how can we increase awareness of this disease, particularly in the context of more vaccines that are available for older adults. So older adults obviously are a much more vulnerable population and vaccines are one of the most cost-effective tools that we have for preventing and mitigating serious infections. As we mentioned earlier in this call, the Centers for Disease and Control and Prevention already, highlight the importance of C. difficile on society, targeting it as the highest hazard from an infectious disease perspective. And so I think there's already acute awareness of the importance of preventing C. difficile and the potential benefit that the vaccine could have.

We'll go next to Steve Scala with TD Cowen.

I have a couple of follow-ups and then a question. So first, relative to uptake, how might uptake of a C. difficile vaccine compare to that of a pneumococcal vaccine among older people? So would you expect it to be more robust than a pneumococcal vaccine less robust? Or would it be similar? Second, did you approach regulators with the first-generation data? Pfizer thought it was provocative, but if you did approach regulators, should we assume that they didn't agree? And then lastly, my question, if C. diff is such a significant problem, then to what do you attribute the modest success of the therapeutic deficit?

Okay. I can start with this and hand over. Regarding the last question for the antibiotic with trade name, I think, Fidaxomicin, we can't comment on that. We're focusing on vaccine development. Regarding uptake and how we see a comparison of uptake of different vaccines, once we demonstrate that the vaccine is efficacious and the FDA approves it for licensure, it will then be reviewed by the ACIP, and they will look at what they call the grading process, and they will assess kind of the population who should be taking this vaccine. And so I don't think we can comment on a comparison of uptake of vaccines because there's still some more work to be done there. And then your middle question was around discussions that we have had with regulators. We conducted a Phase III study, which we call CLOVER, and we did not meet the primary endpoint. And it's important from a vaccine licenser perspective to be able to meet primary endpoints. So I think that's all we can say there.

We'll go next to Kripa Devarakonda with Truist Securities.

This is Nicole on for Kripa. On the Phase II for the next-gen vaccine, can you just remind us what the endpoints are? And what the bar for success is for the Phase II dose that you would potentially use for the Phase III?

Can we ask you to repeat the question. Your volume wasn't good for me. Thank you so much.

Sure. Sorry about that. So for the Phase II, can you remind us what the endpoints are? And what the bar is for success for the Phase II dose that you would use for the Phase III trial?

So I will start by saying the Phase II is evaluating immunogenicity and safety of the vaccine. As Julie mentioned, we had 3 candidates and we moved one to Phase II. So we are testing different doses and different regimens, and we want to ensure the vaccine is safe, well tolerated and generate immune responses that we will then -- when we have confidence and we see the results, that's when we start the Phase III. Did I answer your question?

I think I can add to that. So essentially, we reviewed with you the data that we got from CLOVER. And what we saw from that study with a 3-dose vaccine was something that could provide significant medical benefit in preventing severe C. difficile disease. And so with our second-generation program, first thing is that we want to see something that is safe and well tolerated. And secondly, we need to see immune responses with the 2-dose schedule that are going to be at least the same as what we saw in that initial Phase III study that we did.

Will you also be having the first episode of CDI also as one of the endpoints that you would be looking at to?

Not in the Phase II study. That would be something we'll assess in Phase III.

Operator, are there any more questions?

I'm showing no additional questions at this time.

Okay. Thank you again to everyone who took the time to join our call today. I would also like to offer a very special thanks to Lisa, Alejandra and Julie for sharing their insights and expertise. Our vaccines unit is an important piece of our R&D engine, and we remain committed to delivering innovative solutions to protect against harmful pathogens. We appreciate your engagement today and look forward to continuing our Pfizer Pflash series in 2025, which will resume after our Q4 call early next year. And thank you, everyone. I would like to wish everyone a happy holiday season, and we'll see you in the new year.

This does conclude today's program. Thank you for your participation. You may disconnect at any time.