Good day, everyone, and welcome to Pfizer Flash Live from ADA, spotlighting berobenatide, an investigational potential first-in-class monthly GLP-1 receptor agonist peptide. Today's event is being recorded. At this time, I would like to turn the call over to Francesca DeMartino, Chief Investor Relations Officer and Senior Vice President. Please go ahead, ma'am. Thank you, good morning, everyone, both here in New Orleans and on the web. I'm Francesca DeMartino, chief investor relations officer. On behalf of the Pfizer team, thank you so much for joining us. Today's event will be recorded and available for replay on our IR website at pfizer.com. As a reminder, our Pfizer Flash series is intended to serve as an educational deep dive into our pipeline, products, and people. Each event spotlights a specific product, therapeutic, or growth initiative and gives you an opportunity to hear from our business leaders. Today's session will begin with a presentation, followed by live Q&A. As a reminder, this call is intended only for the investment community, including our sell-side analysts and institutional investors. I want to note that on today's call, we'll be making forward-looking statements. I encourage you to view slide two in our presentation and the disclosures in our SEC filings, all of which are 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. Obesity is a key area of focus for Pfizer. Last November, we completed our acquisition of Metsera and are now advancing a differentiated, diverse pipeline anchored by the investigational ultra-long-acting GLP-1 receptor agonist berobenatide, formerly known as MET-097 or PF-3944. Earlier today, key opinion leaders presented new data from three phase IIb trials of berobenatide at the American Diabetes Association Scientific Sessions. Today's presentation will build off of that symposium. In the room, I'm joined by Pfizer's R&D leader, Jim List. Jim, who is our Chief Internal Medicine Officer, will review highlights of the new data, as well as berobenatide's development plan and target profile. I'm also joined by Navin Katyal, who leads Pfizer's U.S. Primary Care, including responsibility for translating Pfizer's global obesity commercial opportunity from strategy to launch. In addition to obesity, his portfolio also includes ELIQUIS, NURTEC, PAXLOVID, and vaccines. From Navin, you'll hear about what berobenatide's projected profile could mean for its market potential. With that, I will hand it over to Jim. Thank you, Francesca. It's a pleasure to be here. Let me start with the key takeaways from the ADA expert symposium that you just saw. We believe berobenatide has the potential to be the first monthly GLP-1 peptide approved for obesity and related comorbidities. Based on our Phase IIb data, berobenatide has the potential to combine efficacy on par with tirzepatide with favorable GI tolerability in a patient-friendly presentation that provides convenience and scalability advantages. Informed by these Phase IIb data, we're executing an extensive pivotal program. 10 Phase III studies are expected to advance this year, and I'm going to review these later in the presentation. Through these, we aim to develop berobenatide into a foundational metabolic medicine, both as a monotherapy and as the backbone for combination peptide therapy. Now, a reminder of the purpose of Phase II. The objectives in phase II were to identify the right doses for phase III, to test titration schemes, and to test both weekly and monthly dosing. We have positive results across all three of these objectives. I'm going to go over the efficacy and the tolerability before handing it to Navin to highlight berobenatide's positioning, if approved, with our target profile of a first-in-class monthly peptide delivered with a simple subcutaneous auto-injector. I'll go over next steps in our development strategy before we open it up for Q&A. Given that we just came from the ADA symposium, I won't rehash the entire phase II data package. For anyone interested or who missed the symposium, on-demand viewing will be available through ADA's website starting on June 10th, and details from VESPER-1, VESPER-2, and VESPER-3 will be available as an appendix to our Pfizer Flash slides. Turning to efficacy, we believe monthly berobenatide can deliver weight loss that is on par with weekly tirzepatide and potentially superior to semaglutide. Supporting that belief are our phase IIb results viewed alongside data from approved weekly therapies, with the caveat that cross-trial comparisons have inherent limitations that preclude one from drawing definitive conclusions. A key point to make before discussing the comparisons, it's critical that these be made at matched time points and across relevant doses. When we look at 4.8 milligrams of monthly berobenatide, which is our medium phase III dose, it's viewed alongside the medium approved doses of semaglutide and tirzepatide, which are 2.4 milligrams and 10 milligrams respectively. Even there, it's not quite apples to apples because we're talking about half of our top phase III dose compared to two-thirds of the top tirzepatide dose. When we do this, here's what we see. For placebo-corrected weight change at week 28, berobenatide at the medium Phase III monthly dose of 4.8 milligrams delivered 12.3% and 12.0% weight loss across the two VESPER-3 arms. semaglutide 2.4 milligrams weekly in STEP 1 gave approximately 9%. Tirzepatide 10 milligrams weekly in SURMOUNT-1 gave approximately 12.5%. Again, that's looking at half the top Phase III dose of tirzepatide, but two-thirds of the top dose of tirzepatide. Just a moment, I'll show you the first clinical data at our top Phase III dose. VESPER-2 is our Phase IIb trial of weekly tirzepatide in participants with obesity or overweight and with type 2 diabetes. The trial, we observed placebo-corrected reductions in weight of up to 9.5% and placebo-corrected reductions of HbA1c of up to 2.0%, both at week 28. Those results were achieved with a maintenance dose of 1.6 milligrams weekly. This time, we're talking about two-thirds of our top phase III dose. Again, there's potential headroom above this dose where the results were generated, and we look forward to seeing our phase III results. On a cross-trial basis, this compares well to both the 10 and 15-milligram doses of tirzepatide when you look at the same time point within their pivotal SURMOUNT-2 trial in the type 2 diabetes population, and those results are noted on this slide. VESPER-2 and VESPER-3 were only partially up the dose-response curve for efficacy, and neither study went up to the high phase III dose of tirzepatide, which is 2.4 milligrams weekly or 9.6 milligrams monthly. Our first clinical data with the high dose came in the extension of our phase II VESPER-1 study. As shown here, participants who escalated from placebo to the high dose of 2.4 milligrams tirzepatide weekly had substantial weight loss, with a mean change of approximately 16% at 32 weeks. The curve continued its steep downward trajectory throughout the entire time period, suggesting, as you would expect, a greater magnitude of weight loss will be seen with a higher dose. This first glimpse of high-dose data conforms to our expectations. Based on modeling, we expect the high dose to drive meaningfully greater weight loss than the mid or low doses. Perhaps the best way to make cross-trial comparisons in light of their limitations is to leverage as much data as are available and build a model-based meta-analysis, and that's exactly what we've done here. We integrated a dataset of 69 weight loss trials incorporating aggregated data from over 32,000 patients. This approach integrates all the available data using a mathematical model that accounts for pharmacology and describes the weight loss trajectory over time and the dose-response relationship. Now, using this approach, we predicted weight loss at 72 weeks for tirzepatide's high monthly phase III dose compared to the highest approved doses of tirzepatide and semaglutide. The modeling suggests tirzepatide can deliver weight loss similar to tirzepatide, with point estimates less than 1% apart, and potentially better than semaglutide. That prediction holds whether we're talking about weekly or monthly dosing, which generate equivalent average exposure over the dosing interval. At the bottom of the chart, you'll see we also predicted 72-week weight loss for monthly berobenatide. It's honestly very hard to say very much there because there's limited data publicly available, and that's reflected in the wide confidence interval. What gives us a lot of confidence is that the data we generated with the 2.4-milligram high dose in the VESPER-1 extension align extremely well with the model's predictions. It validates our approach, it validates our expectations for Phase III. Turning now to tolerability. Remember, one of the purposes of Phase II is to understand the relationship between tolerability, dose, and titration. That's the lens to keep in mind through the next few slides. We're quite pleased with what we've seen. In the VESPER-1 extension, evaluating weekly, every other week, and monthly dosing intervals, we observed excellent GI tolerability. 96% of participants reported no key GI treatment emergent adverse events or only mild ones, that's nausea, vomiting, diarrhea, constipation. In the arm that went from placebo up to our high dose in the extension, the vomiting rate was under 20%. Notably in the extension, there were no treatment discontinuations due to treatment emergent GI adverse events in any of the arms. In VESPER-3, tirzepatide was also well-tolerated. 83% of participants experienced no or only mild key GI treatment emergent adverse events, with vomiting rates in the low to mid-20s across active arms. Fewer than 10% of participants in the tirzepatide groups discontinued treatment due to treatment emergent adverse events, and that's across the 215 participants who were randomized to tirzepatide. Importantly, really importantly, these results were achieved in trials where down-titration was not permitted. If a patient experienced GI tolerability issues, they couldn't lower their dose. They had to muscle through it, or they had to discontinue. Even though the data show a good tolerability profile here, in Phase III, because we allow for down-titration, we expect to see an even better tolerability profile. With our learnings from phase II, we expect our phase III titration scheme, again, should yield an even better tolerability profile than the already very good profile that we've seen in phase II. This slide breaks down vomiting events in the VESPER-1 extension. All the events are shown here by week, with severity color-coded, mild events in green, moderate in yellow, and severe in red. The top two rows are participants who entered the extension after receiving tirzepatide weekly for 28 weeks in part A of the study. They continued at the same weekly dose for the first eight weeks of the extension, and then transitioned to monthly dosing for 24 weeks. The data shown here are for the 3.2 and 4.8 milligram dose groups, again, our low and medium phase III doses. This gives us insight into the expected tolerability profile of monthly tirzepatide in participants switching from weekly to monthly treatment. The vast majority of events were mild, none were severe, and while there was a mild transient increase at the point of the monthly transition, it rapidly improved with continued dosing. This, along with the VESPER-3 data, provides the critical insight that guides our phase III strategy for the transition to monthly dosing. Specifically, smaller increments in dose than were used in phase II should help address any tolerability concerns that happen at the weekly to monthly transition. At the bottom, we see the placebo switch group escalating to the high dose. Again, the vast majority of events were mild and none were severe. Similarly for our placebo-controlled VESPER-3 trial, which evaluated the switch from weekly to monthly maintenance dosing, we saw a slight transient increase in events at the monthly transition, which rapidly improved with continued dosing. As we look ahead to phase III, as I said, we learned from phase II and implemented designs for phase III that should help ensure a smooth dose and PK transition to optimized tolerability at the point of the switch from weekly to monthly dosing. I'll talk more about phase III shortly, first, let me hand it to Navin to talk about what tirzepatide's projected profile could mean in the obesity landscape. Navin? Right. Thank you, Jim. As Jim has covered, we've seen a competitive efficacy and tolerability profile with tirzepatide. Combined with its convenient monthly dosing, we're very excited about the commercial opportunity this sets up for us. I'm now going to spend a few minutes on what signals we have about the desire for a monthly product, where we think tirzepatide could fit in a patient's journey, and the commercial principles guiding our build. Starting with the market, it's clear that the prevailing focus in this category is on who's leading, but I think what gets less attention is how much of it has yet to be served. The fact is that most eligible patients still are not on therapy at all, and most who are starting don't stay on. That's why we believe the commercial opportunity for tirzepatide is so significant. It has a highly competitive profile, as Jim just outlined. It's designed for scale. There's a large and growing monthly market. It's well-positioned across the full patient journey. We have the commercial capabilities to serve this market from day one. Starting with the molecule itself, simply put, tirzepatide is built to be supplied at scale with notable COGS advantages. The API requirements, as you can see here, is 125 milligrams per patient per year, which is significantly lower than the other monthly programs in development. Monthly dosing also means a lot less device, a lot less packaging, a lot less cold chain or waste than weekly therapies. Ultimately, that means we need a lot less manufacturing capacity to serve the same patient population and that we can distribute it more efficiently. I think importantly, the 0.5 ML injection volume lets us deliver it in a familiar auto-injector that patients and providers are very familiar with and very, trust. Taking together, tirzepatide is expected to be available in formats people already know, already trust. That, of course, is really crucial in a massive growing category. Turning to the market, we've actually done a lot of research with both providers and patients to understand what a profile like tirzepatide's, with competitive efficacy and tolerability, but in a monthly regimen, would mean for them. I think what's clear is that upon seeing that profile, that value proposition becomes super intuitive to them. We see that 51% of treatment-naive patients prefer monthly as their long-term destination when comparing it against the existing injectable and oral options. On the provider side, 86% of those surveyed said they would be more likely to switch their patients to monthly tirzepatide when shown hypothetical positive switch trial data. That projected switching intent rises 1.7 times. Ultimately, we believe tirzepatide is going to have two distinct shots on goal. First, for new patients who want a highly effective therapy and who know these therapies are not a one and done and want something with less long-term burden. Second, for existing patients on weekly GLPs who want something that feels more sustainable than dosing every single week or every single day, for example, on the orals, to maintain what they've achieved. We've built phase III trials designed to generate evidence to serve both, Jim is going to walk through that shortly. In addition to starting or switching, another substantial part of this opportunity, and a critical need I would add, is keeping people on therapy for the long term. Today, about 65% of people without type 2 diabetes who initiate a weekly GLP-1 discontinue within a year. There's real consequences of that, as we all know. In fact, two-thirds of the weight patients lost in the pivotal semaglutide trial was regained within a year of stopping. We also know about this market and are encouraged by that the vast majority of lapsed users say they would consider coming back. I think what is missing right now is a regimen built for sustainable long-term use, and that's exactly what we believe monthly is built for. What we've seen time and time again is that less frequent dosing has driven adherence improvements across multiple chronic conditions. When we put all of this together, we expect tirzepatide to compete across the entire patient journey. In a market expected to reach well over $100 billion, where there's fewer than 10% of eligible adults on therapy today, we're super excited about the potential to unlock real growth by bringing more patients in who haven't been willing to start, by serving those who want to switch to something more sustainable, and of course, keeping people on therapy longer. Finally, just a note about our commercial model. There's a number of principles that guide how we're approaching this. There's three that I'm going to pull out today. First is our integrated direct-to-consumer experience, which will be in market and ready from the start, building on our PfizerForAll platform that today connects patients with treatments for migraine, vaccines, appointments, and more. Second, we're building a model that serves both reimbursed and cash channels, and importantly, we're going to be set up to compete in cash from day one. Third, we're designing for persistence, building for the long-term patient experience, not just for initiation. Behind all of this is, of course, the Pfizer primary care engine, a primary care field force that's been ranked number 1 for seven years running in the industry, existing relationships across more than two-thirds of the providers writing meaningful prescriptions today in the GLP class, and of course, deep experience engaging hundreds of millions of people in large audience primary care markets. Finally, I'm going to note that we've been here before. We didn't invent the statin. LIPITOR was not the first. ELIQUIS was not the first oral anticoagulant. PREVNAR was not the first pneumococcal vaccine. In each case, we built the evidence, we built the commercial model, and we built the franchise that came to set a new standard. We're really confident in our ability to make a significant impact in the market with our obesity franchise as well. With that, Jim, I'll turn it back to you to discuss our next steps. Thank you. Thanks, Navin. Let's talk about the phase III program now. We have two phase III studies of weekly berobenatide already underway, randomized patients, and recruiting really, really well. VESPER-4 and VESPER-5. Both enroll participants with overweight or obesity. VESPER-4 excludes participants with type 2 diabetes. VESPER-5 enrolls participants with type 2 diabetes. The primary endpoint for both is% change from baseline and body weight at week 64. One design point worth flagging, VESPER-4 and VESPER-5 use a simple dose escalation scheme with one, two, or three titration steps to reach the low, medium, or high maintenance dose. That compares favorably to currently approved weekly chronic weight management therapies, which require five steps to reach the top maintenance dose. We're evaluating a streamlined path for getting to maintenance dose, making it easier for patients, while, as I said, incorporating the option to deescalate for GI adverse events. VESPER-6 is the pivotal trial for monthly berobenatide. The study is now up on clinicaltrials.gov and open for enrollment. VESPER-6 includes two cohorts, a main cohort without type 2 diabetes, and a parallel cohort with type 2 diabetes, and the primary endpoint is the percentage change in body weight at week 72 in the main cohort. The initiation of monthly dosing in VESPER-6 incorporates the learnings from phase II. Going back to phase II in VESPER-3, participants moved directly from a weekly dose to a four-fold higher monthly dose. For example, from a 1.2 milligram weekly dose directly to a 4.8 milligram monthly dose. We saw good tolerability with that approach. A detailed analysis of the data suggests that we can potentially do better. We can expect to decrease that small and transient increment in GI adverse events that we saw at the weekly to monthly transition point by decreasing the size of the dose step-up. In VESPER-6, the evaluated weekly to monthly step-ups will range from 2-2.7-fold as opposed to 4-fold. That's a much more gradual transition by design. You'll notice it's three simple titration steps to get to monthly dosing and five steps in total to reach the top monthly dose of 9.6 mg with flexibility in how you get there. Again, in phase III, we're allowing dose deescalation in response to GI adverse events. We expect this combination, smaller upward titration steps, plus allowing for down titration if needed, will make our really good tolerability profile that we saw in phase II even better in phase III. As you can see, VESPER-4, VESPER-5, and VESPER-6 are just the start. We're planning to advance a total of 10 berobenatide phase III trials this year, that includes a SWITCH study to look at transitioning patients from approved weekly therapies directly to monthly berobenatide. We're targeting a series of potential approvals, beginning with weekly dosing in 2028, with an approval for monthly berobenatide as a fast follow to that. Our pivotal program also targets obstructive sleep apnea and knee osteoarthritis, two comorbidities where other GLP-1s have shown clinical success and where berobenatide has the potential to uniquely bring a monthly dosing option for patients. As we've shown you, berobenatide has a potentially compelling profile as a single agent by itself. It's the driver behind which we're building out our research and development pipeline and metabolism. We're also really excited about berobenatide as a foundational partner to evaluate combination therapy with other monthly peptides that we're developing. The most advanced of these combinations is berobenatide plus our investigational ultra-long-acting amylin analog 3945, formerly known as MET-233i. 3945 has a very similar half-life to berobenatide. Its solubility profile supports combining it with berobenatide. We expect to report early data on our ultra-long-acting amylin analog and on the combination with berobenatide later this year. We see the potential for this combination to deliver category-leading weight loss with the convenience of well-tolerated monthly dosing. The Phase IIb study evaluating this combination, SOLIS-1, is open for enrollment. It's up on clinicaltrials.gov. Looking beyond berobenatide programs, we recognize that not every obesity medicine will be right for every patient, and that's why we're building a differentiated pipeline with multiple mechanisms and modalities, injectables with the potential for monthly or even longer dosing intervals, oral agents, and combinations. Our goal is to address the many needs of patients across weight management profiles and dosing preferences with our long-term commitment to obesity and to metabolic health. With that, I'll turn it back to Francesca. Thanks, Jim, and thanks, Navin. To summarize, our Phase IIb data provide proof of concept for berobenatide as a potential first-in-class monthly GLP-1 receptor agonist peptide that we believe can deliver weight loss similar to tirzepatide and potentially better than semaglutide. Alongside robust efficacy, we aim to pair favorable tolerability and convenient monthly delivery to develop a foundational metabolic medicine as a single agent and backbone for future combination therapies. With berobenatide scalability, Pfizer's leading primary care field force, and a carefully designed commercial model, we believe we are well-positioned to have a substantial impact on obesity and metabolic health, subject to clinical success and regulatory approval. With that, we will begin the Q&A session with Jim and Navin. As a reminder, our Pfizer Flash series is designed as an educational deep dive into our pipeline programs. I'll therefore kindly ask that participants keep questions focused only on berobenatide's program covered today. Please avoid questions 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, and I appreciate your understanding on that. We're ready to take the first question, starting with those in the room. Please raise your hand, wait for the microphone, and introduce yourself prior to asking your question. Thank you. Chris Schott, let's start with you, J.P. Morgan. Great. Thanks so much. I just wanted to talk a little bit about the higher dose that you're going to be looking at in the phase III. How do you think about the tolerability profile there? I know you're trying to improve on the lower doses, but we were in that low 20% vomit rate. I'm just wondering with that bigger step up to that higher dose, what's your modeling suggesting what that profile could look like? Maybe just more holistically, it seems like one of the themes from this conference is this idea of not necessarily fully maximizing weight loss, but getting this balance of tolerability and acceptable weight loss, and I'm just looking as you think about the three doses you're moving forward. How important is that to the program versus some of the ones we already are seeing at the lower side? Thank you. Why don't I start with that? I think it's also, in part, a question about the need for the flexibility and multiple doses on the market too. Maybe Navin can follow me. From a tolerability standpoint, the data are the data. The data that we have are from going up to 2.4 milligrams weekly. We don't have data right now on the 9.6 monthly. What we did see in the 2.4 milligrams weekly is there really was great tolerability there. It doesn't seem that the dose per se is what drives tolerability, and that might actually be because once you get up to a certain dose with this potent of a GLP-1, with this long a half-life, and these pharmacokinetic properties, you might be essentially tonically saturating the GLP-1 receptor so that it doesn't really give you any more tolerability issues once your body has gotten used to that. The question is, how do you get up there? I will say, just a note, the reason we have a dose that's four times the weekly dose in monthly isn't just by multiplying by four. It is actually based on very complex pharmacokinetic calculations to get the same average exposure over the time duration. It turns out to be exactly four times the dose, which is convenient for us. The trick is, what we have realized through both VESPER-1 extension and VESPER-3 is that when you make the step up to monthly, if you're making that step up as a big jump, a four-fold jump, you get some tolerability signal. Not terrible, but you do get a little bit of a signal there. That's where going up to that 9.6, it's a gradual titration scheme up. There's two different schemes depending on if you already titrated up to 2.4 milligrams and you're happy at that high dose, and you decide, "Hey, I want to switch to monthly," there's one titration scheme for that. There's another one if you say, "I want to get to monthly as fast as I can, and we'll see how high I want to go with that," and you can titrate up to 9.6 that way. In both cases, it's a gradual titration scheme. The phase III data will tell the answer, but for what we know now and the data we have, I think it's very promising to be very well titrated, and very well tolerated. Now, do patients need all of this weight loss? As you know, the drugs on the market now, most patients don't get the 15 milligrams of tirzepatide. Part of that's probably because they don't tolerate it, and part of that is probably because they don't want that much weight loss or need that much weight loss. We may see a very different dynamic when it's more convenient to give it monthly and when it's very well-tolerated. There's a lot of different needs for different patients, and so I think the low and medium doses are going to be very important as well. On the market, Navin? Yeah. I think that's spot on. I think the thing I would add is, to your point, there's efficacy, there's tolerability. The two things I would also add in terms of dimensions that are part of the considerations that are convenience and flexibility. Right? If you think about the profile that's kind of emerging here from a clinical profile, as Jim highlighted, we've got a very competitive efficacy and obviously tolerability profile that we described today that's just as good as the leading agent. On the sort of flexibility and on the convenience front, what you get with tirzepatide is the flexibility to sort of choose your own adventure, right? You can do, if you want to stay on weekly, you can stay on weekly. If you want to escalate up to monthly, you get to escalate up on the monthly, and then there's multiple doses you can do that with. I think when we look at the research, both with consumers and the provider base, what you hear sort of over and over again in spades is you want flexibility and control, right? You can optimize that tolerability and that efficacy. When we actually put the titration schedule in front of KOLs, HCPs, et cetera, that was sort of the theme that we got over and over again is, "Okay, I'm getting flexibility, I'm getting control, and now I can optimize this for my patient and sort of get them to the right sweet spot for efficacy and also for tolerability." I think the sort of three themes that came out from that is, okay, I have now control over strength, I have control over titration schedule options, and I also have control over the frequency of the dosing. That resonates, I think, really well with both consumers and with providers. Okay. Thanks for the question. Dave Risinger from Leerink, take your question. Thanks, Francesca, and thanks for hosting this session. I have two questions. The second one is quick. Could you talk a little bit about your vision for a commercial launch as a weekly and the messaging to consumers at that time? With respect to the China-only SWITCH study, why is it China only, and can that be added to the U.S. label? Thank you. I'll take the second one then. Yeah Navin. The SWITCH study is global. We are running a China study and a China program, a Japan program. The SWITCH study is part of a global program. We see that as really important for patients. There's a lot of patients already on weekly drug. The one thing that, as Navin said, 65% of patients don't make it a year. There's going to be people who are like, "I can't do this every week." They're going to want to have that option to switch. We want to bring that broadly worldwide. Yeah. Just your question around the commercial model and the weekly. Maybe I'll just start with sort of the rhythm. As Jim described earlier, we're going to launch with the weekly. The monthly comes as a fast follow. The weekly on its own, as Jim described earlier, we see as competitive in its own right, leading efficacy aligned with sort of the top agent in the market today, and the same on the tolerability front. I think the important thing about that weekly launch, though, is it gives sort of early experience to both consumers and providers about the product, the molecule, tirzepatide. All of those folks who get onto the weekly product are now eligible with the fast follow launch of the monthly. Right? That whole base becomes a immediately eligible base to now make that decision, right, and provide that flexibility and that option to switch over. I go back to my point earlier, which is anyone who is on this product now, it's a highly differentiated product in the sense that you now have an option of doing this on a weekly basis or on a monthly basis. We expect most will move over to monthly because, again, that value proposition is so incredibly intuitive. The minute you put the profile in front of both consumers and providers, and you sort of show what the existing profiles look like from an oral perspective, from a weekly injectable perspective, there's sort of like a very intuitive light bulb that goes off. You think about the fact that, okay, this is a long-term chronic thing. If you fall off of it, you're going to regain weight again, that sort of notion of do I want to be tethered to something for 52 times a week for perpetuity? Do I want to be tethered to something 365 days a year for perpetuity, or can I do this in a sustainable way, just 13 times a year? That light bulb goes off, then they sort of develop that preference. That's sort of the way we think about the rhythm of this and the launch of this and how it'll evolve. Dave, I don't know if it was confusing that on the slide you might have looked at SWITCH and China was next to it, but just as a point of clarification, each box is its own trial. You'll see that's the 10 phase III, just for clarification. Right. Okay. All right. Vamil, let's go to you, Guggenheim. Thank you. Yeah, Vamil Divan from Guggenheim. Navin, appreciate getting your insights here today. Just building on the market research that you've done, just curious if you can share sort of how you think the market's going to evolve from here. Think about injectables, but also the orals. What% of the market do you think would be actually injectables? Yeah. five years from now. Related to that, obviously, you talked about your field force and the number 1 ranking you've had for seven years. How do you think about the commercial model? Sure from a field force perspective versus more of a direct-to-consumer that we're seeing emerging. Yeah in this space? Absolutely. In terms of the evolution of the sort of mix, it's hard to have a crystal ball and predict exactly what's going to happen. I do think that it's broadly believed that the injectables will be a larger part of the market. What we've observed about the marketplace so far, though, is, I guess, a few things. The first is, we know that ultimately people want flexibility, they want control. That's what we think are a big sweet spot and big strong suit that we have here. Obviously, you want to have a great tolerability and efficacy profile. That's also what's emerging here. There's this very big sort of differentiation, which is I have now a sustainable option, where I don't have to be tethered to something 52 times a year or 365 days a year. That's sort of like the foundation of this. I think that the other thing that when we look at our research, the light bulb that goes off is, yes, there is convenience with orals, and by the way, that convenience with orals has unlocked more patients. We've seen that a big bulk of the patients that have come into this market are not switchers from injectables. They're sort of naive to GLPs. That has become a sort of a step change in unlock. We expect the same with the monthly injectable, I think the key here is the light bulb that also goes off is I can now get even more convenience because I just have to do this once a month. By the way, I don't have to make a trade-off on efficacy like I do with the orals, or a trade-off on fasting requirements like I have to do with a certain oral as well. That becomes another unlock and I think becomes part of the value proposition. It's hard to say exactly what percent of the segment will be oral versus injectable, but as more innovations like this come along, where the sort of dosing burden is a big step change reduction, we see that persisting and sort of growing the market. In terms of where we believe berobenatide is well positioned in terms of the patient journey, I think we have a lot of conviction that this is going to unlock more initiation, just like the orals did because of what I just described. We think it's going to unlock switch when people see the value proposition from that data. We think it's going to unlock maintenance because there's this existential dread a bit of being tethered to injecting yourself every single week for the rest of your life. It's going to unlock that maintenance, and perhaps even it stands to reason those who have lapsed. As I mentioned earlier, there's 74% of people who are no longer on these things who have indicated that they're likely to jump back in. If you can think about a product where you don't have to do this again every single day or every single week, that becomes super interesting to people. We think that's also going to happen. I think one last thing I'll just say in the commercial model, you asked about field force and sort of our consumer engagement. As I said, the good thing about the Pfizer primary care field force, in addition to it being ranked so highly, is that we have a really long and sort of deep relationship with these prescribers, right? Two-thirds of the prescribers that are writing meaningful GLP volume, we already know. We know them well. We call on them all the time. For example, with ELIQUIS. If you think about the tenure of our reps, the tenure of our reps in the primary care field force, 15-20 years. These are folks who have seen the entire life cycle of ELIQUIS. These are folks who have engineered the shift from ELIQUIS being sort of a cardiologist-specific play to a broad primary care play. They really know this space. They've also carried LIPITOR, right? These are people who really know this space. They're experts in cardiometabolic. We think they're going to bring a lot to the table. On the consumer side, we are a powerhouse on that side as well. If you look at the ROIs on our advertising, it's double the benchmarks. I think really important though, and beyond just sort of share of voice with engaging consumers is sort of how you bridge intent to action, and I think we've made a lot of great progress over, say, the last five to seven years in terms of how we engage consumers. You have to obviously have your DTC and all your traditional levers, but you also have to be able to intervene and not just drive awareness, but actually move people and bridge people from intent to action. If you look at, for example, what we've done in Pfizer For All, which is the sort of front door that we built a few years ago in migraine vaccines, et cetera. Not only have we had 30 million visitors to that site, but we've built really specific high engagement interactions there. For example, in the vaccines, just to give you a very quick example, we built an eligibility tool so people can figure out what vaccine they're eligible for. We've also built an end-to-end way to book a vaccine. What we've seen is a huge lift in terms of just, "Okay, I'm aware of these things, but now I'm actually bridging my intent to action," and we're going to plan to use that same sort of engagement model in obesity with Pfizer For All and all the other front doors that we build. Let's go to Geoff from Citi. Awesome. Thank you guys for doing this. A couple questions. It's good to see some new indications into the mix in your developmental slide. How are you guys thinking about combinations even beyond that, inflammation, oncology, neuropsych, et cetera? Can you take advantage of the monthly dosing in those arenas? I guess yet another commercial question. I guess the argument here is you have to compete with the weeklies to at least get people to start. How do you anticipate the differentiation on the weeklies, and then what is your assumption of the% of people that move to monthly, and the reason, is it just because they want to? Is it pure convenience? If they lose, let's say 50% of their weight, is it just that they don't want any more? They just want to maintain. I just don't know. There's just not a lot of data on that, on the folks that are averse to weekly injections, right? I mean, it's not. Well, let me just take the first part very quickly. What we've disclosed here obviously isn't our entire Phase III program because some of these trials are called undisclosed, but we have our eye on all of these possible additional indications. There's over 200 diseases that are driven by obesity. We certainly have a great interest in some of the areas you mentioned, oncology, immunology, whether it's combination approaches or even bariatric as a monotherapy for improving these. We're looking at them all, but we can't do everything, obviously, and we need to be very thoughtful about where we bring differentiation. As you pointed out, a monthly is a big differentiator because just like obesity, most of these diseases are also chronic diseases that need chronic treatment, and so we have to find ways to keep patients on longer than just a year. Navin? Your point about the differentiation on the weekly piece, I think first and foremost, as we talked about earlier, we see the sort of efficacy and tolerability profile being as good as the best agent in the marketplace. In terms of the differentiation, you could choose to initiate on a weekly product where you have no option to go to monthly, like the incumbents, the products that exist today. You could choose to initiate on a weekly that gives you the optionality to go onto a monthly. I think that even for that short window of time where the weekly is on the market, because monthly will fast follow, but even for that short period of time, it's going to be very enticing, I think, for a consumer or for a provider to say, "You know what? I think I'm going to try this weekly." In just a little bit of time, I'm going to actually potentially escalate you to a monthly dose. You don't get that optionality if you start somebody on a weekly product that doesn't have this schedule. Right. [Conor- Malcolm Duo], let's go over to BMO. Hi there. Yeah, this is Conor here from Evan's team at BMO. You guys made a few comparisons today in your slides to some of the other leading agents in the space, and we were just wondering, from a strategic perspective, as you think about competing with some of these assets, what are your views on potential head-to-head studies? Thinking longer term, for your combination approach, how would you think about potentially including an active comparator arm in some of those later phase studies? Thank you. Again, we haven't disclosed the entire phase III program here, and for the combination, the next combination coming along, which is our combination with our ultra-long-acting amylin analog. We're just entering phase IIB, it's still early days there. We do anticipate that that's going to have additive efficacy because that's what we saw in phase I in a really good tolerability profile in monthly dosing. The question is what's the advantage of doing head-to-head? I'll tell you, part of the thinking here is that we have really great potential drugs here. I think with showing very good efficacy and very good tolerability, I'm not sure that there's going to necessarily be a need to do head-to-head. It might be the other people's need to do head-to-head against us because we've got, in some ways, bigger fish to fry to go after other indications where a chronic treatment with a monthly offering can really make a difference again across these many other things that are driven by obesity. Okay, we probably have time for maybe one more. Michael, you're here to represent Cowen, right? Okay, go to you. Thanks so much for the question. Mike Nedelcovych from TD Cowen. I have two, if that's all right. My first actually dovetails on something you just mentioned about the long-acting amylin. To what extent does Pfizer view amylin monotherapy as an important future category? I think the field is kind of excited about the possibility of perhaps lower efficacy, but better tolerability. On the comments you made about weekly titration and transitioning to monthly, is there a potential path to monthly dosing from the start for berobenatide or perhaps for your prodrug? If so, is that compelling or would that not be enough of an advantage to pursue? First of all, amylin monotherapy, it's early days in the sense of we're starting our phase IIb trial where we will look at weekly and monthly dosing of monotherapy and combination therapy with berobenatide, and we're going to learn a lot there. I'm not sure I would characterize it as less efficacious because what we saw in phase I with our particular amylin analog, which again is ultra long-acting, it was an incredibly high degree of efficacy for the duration that we dosed. The question is, will it fulfill a need as a monotherapy in the market? We're going to learn more about what exactly it does through phase IIb, and we'll make these decisions, as again, our sort of investment decisions of where does this embarrassment of riches of this very large pipeline that we now have meet the actual needs in the marketplace. I'm trying to remember what Oh, starting with just monthly. I'll let Navin answer it from its attractiveness commercially. From a standpoint of berobenatide itself, I think what we've worked out through phase II, that it's optimal to do weekly dosing initially for the first 12 weeks. Again, this has to do with the size of a jump that you're doing as you accumulate drug and exposure over time. For the prodrug, it's an interesting question. Prodrug is in phase I. For those who aren't aware of it's an ultra long-acting version of berobenatide. In phase I, so we need to learn a lot more about it, but there's a lot of potential advantages there to stretching out beyond monthly dosing. How you titrate there will be determined by the clinical data. Okay. In conclusion, I just want to thank my colleagues Jim and Navin for their contributions today. Also, there are numerous Pfizer employees in the room that really helped bring this all to fruition, so thank you to all of you. Last but not least, thank you so much for joining us live and on the phone. We really appreciate it, and the IR team is always available for any follow-up questions you may have. With that, I'll just ask the operator to conclude the call. Thank you
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