Good day everyone, and welcome to Pfizer's Analyst and Investor Call to review oral GLP-1 data presented at the European Association for the Study of Diabetes 2022. Today's call is being recorded. At this time, I would like to turn the call over to Mr. Ronen Tamir, Vice President, Investor Relations. Please go ahead, sir.
Thank you very much, and thank you all for joining us today. We're very happy to be presenting some exciting GLP-1 clinical data to you all. Today, we will be making forward-looking statements that are subject to substantial risks and uncertainties. I'd just like to remind you that this forward-looking statement speaks only as of the webcast original date, and we undertake no obligation to update or revise them in the future. You can find additional information on forward-looking statements in our SEC filings, including forms 10-Q and 10-K, under the sections labeled Risk Factors and Forward-looking Information and Factors That May Affect Future Results. Now allow me to introduce you to your speakers. We have Aditi Saxena, Vice President, Clinical Research, Head of Internal Medicine.
Bill Sessa, the Chief Scientific Officer of our Internal Medicine Research Unit, and Andy Schmeltz, Senior Vice President of Commercial Strategy and Innovation. For our Q&A session, Aditi, Bill, and Andy will also be joined by Jim Rusnak, Pfizer's Chief Development Officer for Internal Medicine and Hospital. With that, let me turn it over to Bill Sessa to begin.
Thank you, Ronen. Thank you all for joining us today to discuss a truly exciting area of clinical development for Pfizer. First, we wanted to remind you of the massive unmet need and market opportunity in type 2 diabetes and obesity, conditions that impact hundreds of millions of people worldwide, that's continuing to grow over the next decade. There are also significant gaps in the current treatment paradigms. For example, less than 5% of patients with obesity receive medical treatment, and only about 50% of U.S. patients with type 2 diabetes are able to get their HbA1c below treatment goals. Obesity, in particular, is a driver of comorbidities, including type 2 diabetes and over 200 health-related complications that impact every organ system in the body. The most well-characterized and obvious link to obesity is cardiovascular disease, which impacts cardiovascular outcomes, the number one cause of death worldwide.
We believe the GLP-1 receptor and GLP-1, meaning glucagon-like peptide-1 receptor, is a very promising target in obesity and type 2 diabetes, one that we think has untapped potential. We know that GLP-1 is the ligand for GLP-1 receptor, mediates insulin signaling and satiety in response to food intake. These are key drivers for both obesity and type 2 diabetes. GLP-1 receptor agonists, depicted by GLP-1 RAs, are a class of medicines that target the GLP-1 receptor, have been shown to provide clinical benefits such as decreasing appetite, delaying gastric emptying, and increasing insulin secretion, resulting in weight loss, glycemic control, and reducing cardiovascular risk. I'd like to take you through the discovery story behind Pfizer's promising GLP-1 receptor agonist candidates. They represent a tremendous tour de force on behalf of our scientists at Pfizer.
The GLP-1 receptor was a challenging target in the drug industry, plagued by failures to develop small molecule agonists. Pfizer's in-house expertise in small molecule design and medicinal chemistry enabled the discovery of a potential best-in-class oral GLP-1 agonist, danuglipron and PF-07081532, or for conventional purposes, 1532 for today's call. To overcome the challenges associated with the discovery of GLP-1 receptor agonists, we developed a sensitized screening assay that lowered the activation energy barrier for GLP-1 receptor, increasing assay sensitivity and facilitating detection of agonists. Using this high non-traditional high throughput screen, we screened close to 3 million compounds, followed by careful med chem and structure-activity relationship optimization, ultimately increasing potency over about 6 logs.
Additional optimization for pharmacologic potency, safety, and other attributes led to our two oral GLP agonist candidates, which are full agonists at the GLP receptor, similar to injectable peptides, but of course, with the convenience of oral administration. As you can see on the right side, data from phase 1 single ascending dosing studies in healthy volunteers supported twice-daily dosing for danuglipron, with a half-life between 3.4-5.7 hours. Further optimization of drug attributes yielded fifteen thirty-two, with a longer half-life of 18-21 hours, which supports once daily dosing and may provide benefits, including improved compliance that may lead to better health outcomes. Now, with this background in mind, I'd like to turn it over to Aditi Saxena, who will walk us through some of the exciting clinical data recently presented at EASD. Aditi.
Thank you, Bill. Today, I'll be providing an overview of the clinical data from studies of our oral Pfizer small molecule GLP-1 receptor agonists, which were presented at the EASD 2020 sessions.
We had 3 presentations at EASD, 2 of which covered 2 separate phase 2 studies with danuglipron and one covering the phase 1b study with our once-daily oral GLP-1 receptor agonist PF-07081532, which will be referred to as fifteen thirty-two. The first data we'll review is from the 16-week phase 2b dose-ranging study of danuglipron in participants with type 2 diabetes. This phase 2b study was a randomized, placebo-controlled, parallel group dose-ranging study to examine the effect of danuglipron over 16 weeks on the efficacy, safety, tolerability and pharmacokinetics in adults with type 2 diabetes. The primary efficacy endpoint was change from baseline in HbA1c at week 16, and key secondary endpoints were changes from baseline in fasting plasma glucose, body weight, and body weight at week 16.
This was an outpatient study conducted globally during the earliest stages of the pandemic from July 2020 to July 2021. 411 participants were randomized in dose, of whom 77% or 316 participants completed the double-blind treatment phase. The study design schema are presented here. After the screening and placebo run-in periods, participants were randomized to placebo or one of five doses of danuglipron. For participants randomized to danuglipron doses of 40 milligrams BID and above, a pre-specified dose escalation scheme was incorporated and had weekly dose escalation steps to reach the randomized target dose. For participants randomized to higher target doses of danuglipron, the target dose was reached later relative to lower doses. After dosing was completed, participants progressed to the follow-up period, which lasted approximately one month.
In this study, over 16 weeks, there were dose-responsive declines in HbA1c across all of the danuglipron arms compared with placebo, with declines up to almost 1.2% at the highest dose of danuglipron. The right panel shows the time course of the changes from baseline in HbA1c over the dosing duration. Declines in the danuglipron arm separated from the placebo arm as early as week 2 of the study and continued to increase in magnitude in a dose-dependent manner over the duration of the study. Significant reductions were also observed in fasting plasma glucose, with reductions up to approximately 32 milligrams per deciliter over 16 weeks. Similar to the pattern with HbA1c, significant reductions in fasting plasma glucose with the danuglipron arms were observed within two weeks of dosing.
Significant declines in body weight were also observed over 16 weeks at the two higher doses of danuglipron compared with placebo. Declines in body weight were observed throughout the dosing period and had not yet reached a plateau at the highest dose of danuglipron by week 16. The key takeaway here is that study participants saw a weight loss benefit even within the first few weeks, the experience of which can often help with compliance in the face of initial mild GI side effects. Now I'd like to touch very briefly on the data from our 12-week phase 2 study of danuglipron. Data from this phase 2 study were previously reported, and the full 12-week data will be available after the call and the slides posted to our website.
I do want to take a moment to highlight the HbA1c and body weight reduction seen after 12 weeks of treatment with the danuglipron in this study, which were significant compared to placebo. We conducted this study to refine our understanding of the top doses used in the 16-week study, and we believe that these data provide a better picture of danuglipron's potential efficacy at the higher dose levels. We see reductions here of up to 1.5% to 1.57% in hemoglobin A1c and 5.4 kg or 5.7% change from baseline in body weight. Now I'll provide an overview of the Phase One B study data with our once daily GLP-1 receptor agonist fifteen thirty-two.
This phase 1b study was conducted as an inpatient study at 2 clinical research unit sites in the United States. This randomized, double-blind, placebo-controlled study was the first time that multiple doses of PF-07081532 were administered, with the objectives to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating multiple oral doses of PF-07081532 in type 2 diabetes and obesity. 6 cohorts were enrolled, of which 5 cohorts were participants with type 2 diabetes and 1 cohort was non-diabetic participants with obesity. PF-07081532 or placebo were administered once daily with breakfast. Dose titration was used to achieve higher doses of PF-07081532. Dosing took place during the early stages of the COVID-19 pandemic from mid-2020 to mid-2021, and the study design is provided here.
Across cohorts 1 through 4, participants with type 2 diabetes were randomized to target doses ranging from 10 milligrams up to 120 milligrams or matching placebo with a dosing duration of 28 days. In cohort 5, type 2 diabetes participants were randomized to 180 milligrams or matching placebo with a dosing duration of 42 days. A single cohort of obesity participants were randomized to either 180 milligrams or placebo over 42 days. Here we see the pharmacokinetic profile for fifteen thirty-two, which is predictable and linear with proportional increases in Cmax and AUC across the dosing range administered and with a consistent half-life across the doses administered suitable for once daily dosing. Here we see robust declines in mean daily glucose with fifteen thirty-two across the dose range with dose-dependent reductions in mean daily glucose.
Mean daily glucose was utilized as a comprehensive assessment of glycemic control in this study. Plasma glucose was assessed over a 24-hour period, both at baseline prior to dosing and at the end of the 4- to 6-week dosing period as a pharmacodynamic biomarker for this study. These robust dose-dependent declines were observed at all doses of PF-07081532 over the 4- to 6-week dosing period in patients with type 2 diabetes, and all of the dose levels were statistically significant relative to placebo. Declines up to 99 milligrams per deciliter were observed. Based on these results for mean daily glucose, we anticipate that PF-07081532 could have very robust HbA1c lowering over a longer dosing duration. Robust declines in fasting plasma glucose were also observed with PF-07081532 over 4 to 6 weeks, with marked declines up to 86 milligrams per deciliter over the dosing duration.
This was equivalent to observed average reductions from baseline up to 79 milligrams per deciliter over 28 days and up to 102 milligrams per deciliter over 42 days. By day 28, all of the fifteen thirty-two treatment groups above 10 milligrams had an observed average fasting plasma glucose of less than or equal to 126 milligrams per deciliter, approaching non-diabetic thresholds. We also saw dose responsive declines in body weight with fifteen thirty-two over the same dosing duration relative to placebo. With higher doses of fifteen thirty-two, declines in body weight up to 5.1 kilograms were demonstrated in participants with type 2 diabetes and up to approximately 5 kilograms in non-diabetic participants with obesity over 6 weeks.
These declines were equivalent to approximately 5.5% decline in body weight in the type 2 diabetes population and a 5.2% reduction in the obesity population. Similar to danuglipron, the key takeaway here is that study participants saw weight loss benefit even within the first few weeks, the experience of which can help with compliance when experiencing mild GI side effects. In summary, administration of both danuglipron and fifteen thirty-two in clinical studies led to dose-dependent reductions in HbA1c, glucose, and body weight. Both investigational drugs demonstrated the safety and tolerability profile consistent with the GLP-1 mechanism of action, with the most common adverse events being mild in intensity and gastrointestinal in nature. Critically, unlike currently available oral treatments, study participants were not required to fast while taking danuglipron or fifteen thirty-two.
As we've discussed today, we've seen exciting data in the recently completed studies of both danuglipron and fifteen thirty-two. We believe both candidates are promising novel oral small molecule GLP-1 receptor agonists. We want to ensure we possess robust data to inform the candidate doses and profile that advances to phase 3. To do this, we expect to initiate a phase 2 program with fifteen thirty-two in the fourth quarter of 2022, and to expand our phase 2 study of danuglipron in non-diabetic patients with obesity to include a monthly titration cohort expected to complete in the second half of 2023. Our phase 2 programs will evaluate both assets in type 2 diabetes and obesity, and we have planned to advance the optimal candidate based on efficacy, tolerability, and dosing to phase 3 studies in the indications of type 2 diabetes and obesity expected to begin in 2024.
Now I'll turn it over to Andy Schmeltz.
Thank you, Aditi. I'd like to conclude our speaking program by sharing how we believe a small molecule oral GLP-1 could be a breakthrough medicine for patients. There has been significant innovation in the type two diabetes and obesity treatment spaces with the development of the GLP-1s, which, as we've seen, offer substantial A1C lowering and weight loss. The GLP market is growing rapidly, now at $25 billion globally with 30% growth versus last year. This class growth is fueled by demonstrated cardiovascular outcomes in type two diabetes and treatment guideline updates that have moved GLP-1s earlier in the treatment paradigm. While historically, there have been reimbursement challenges for obesity medications, we've been monitoring the payer environment. Our market research with payers indicates that there's significant increase in U.S. commercial payer coverage over the past year, which we believe is here to stay.
We're seeing strong growth in the GLP-1 market and a clear patient preference for oral dosing that may lead to a significant share capture for oral GLP-1s. The data shown here come from market research with approximately 300 patients living with type 2 diabetes on the left, obesity shown on the right, or both conditions shown in the middle. About a quarter of respondents for the first two groups, patients with type 2 diabetes or both type 2 diabetes and obesity, indicated that they are currently taking an injectable GLP-1 medicine. Patients were asked about their preference for three forms of GLP-1 medication, a twice-daily oral without fasting, shown in dark blue, a once daily oral with fasting in light blue, and a once-weekly injectable shown in teal. As shown in dark blue across all patient types, the clear preference is for simple oral GLP-1 dosing without fasting restrictions.
Now note that a once daily oral without fasting wasn't provided as an option in this market research. However, that appears to be the emerging profile of PF-07081532. In summary, we're excited by danuglipron and PF-07081532, two candidates in phase 2 with the potential to offer a uniquely differentiated profile and secure significant share of the oral GLP-1 market.
The reasons to believe here are very clear. Number 1, GLP-1s are rapidly emerging as an increasingly compelling option for the treatment of type two diabetes and weight loss. Number 2, we believe an oral GLP-1 without fasting restrictions would be in a prime position, poised for class leadership. Number 3, we're particularly enthusiastic about the promise of Pfizer's two shots on goal to deliver a potential breakthrough medicine to these patients. That concludes today's prepared remarks. Let me turn it back to Ronen for the Q&A.
Thank you, Andy. Operator, you can start the Q&A.
Sure. At this time, if you would like to ask a question, please press the star and one keys on your touch tone phone. If at any time you may find that your question has been addressed, you can remove yourself from the queue by pressing star two. Once again, that is star one to ask a question. Our first question will come from Umer Raffat with Evercore ISI.
Hi, guys. Thanks for taking my question. I have three quick ones today, if I may. Perhaps first, could you lay out for us why the phase 2B has less than a 4-kilogram weight loss at week 12, but the phase 2A has 5.4 kilograms? Maybe there's something on baseline, if you could expand on that, number one. Number two, could you also get into the tolerability profile more particularly? I ask that because, when we last saw the big data updates you guys showed, there was up to 12 beats of heart rate increases, there was a real GI tolerability issue, up to 80% vomiting, 44% diarrhea.
It looked like doses above 50 milligrams BID in danuglipron were gonna be very hard, but I noticed you guys are persisting with those doses right now, not only in the trials you guys showed today, but also in the upcoming obesity study, where you're actually dialing it up to all the way up to 200 milligrams BID. I'm just trying to understand how you're threading the needle on tolerability. Finally, if you could expand on any changes in titration and whether they're actually helping so far or not.
Thank you, Umer. Aditi, why don't you start?
Yeah, I can take those. Thanks for the great questions. In terms of the weight loss differences between the phase 2B and the phase 2A studies, I think I mentioned the phase 2B study really began at the earliest stages of the pandemic. We do believe that people's background behavioral patterns were slightly different at that time relative to when our phase 2A study began, which was about six months later. They ran in parallel to each other, but they were slightly staggered, and we do believe that our phase 2A study may have represented people starting to return to their normal behavior patterns. We also explored you know multiple dosing titration schemes with those highest doses.
It just offered more opportunity to understand what those doses could do in a relatively short period of time. Also, you know, the phase 2B was conducted globally, so across, you know, multiple regions, whereas the phase 2A was conducted in the U.S. It does speak to sort of some differences in the study population. Do believe that the phase 2A presents some very compelling data regarding the weight loss potential of the compound at the highest doses in a short duration of time. We do believe. You know, it was seen across multiple doses in that study, so we do believe that is representative of the effects of danuglipron with those doses. Coming to the tolerability profile. You remember our phase 1B data really well.
You know, that was similar to the phase 1B that we presented for PF-07081532. It was the first time that multiple doses were administered in an inpatient setting. We were pushing the dose in that phase 1B, and we had rapid titration, more rapid than what we took into our outpatient studies, where, you know, doses were being increased in our inpatient setting every two to four days. In that setting, we did see that, you know, with increased doses, there were increased incidents of GI adverse events. That was not unexpected, honestly, with this mechanism. So we did believe that slowing down the titration would improve the tolerability profile, which it did in an outpatient setting. We do believe that additional improvements will be possible with slower titration.
That has been shown across the GLP-1 class. We do believe that, you know, our agents will have a similar profile with slower titration. Then I believe the last question was how we would be changing the titration, if I'm remembering correctly. I think I spoke to it, which is we are expecting to take in slower titration schemes to our longer duration studies.
Thank you. Our next question will come from Chris Shibutani with Goldman Sachs.
Thank you very much. Also, something about the future and the commercial opportunity of this considerable range. If you had to envision how you would position these products, would you think that you're looking to displace semaglutide or are we talking about possibly some injectables as well? Realizing that you're still in a late-stage clinical data, how you see the economic scope and the positioning playing out. Thank you.
Chris, I'm sorry. I'm having a really hard time hearing you. I think that your question was about the commercial opportunity and how are we going to position it, our GLP-1 product, and I'm gonna hand it over to Andy. Operator, if you can get a clearer line so Chris may repeat his question, I will appreciate that.
Yes. No, I think you got the tone. Apologies, I'm at the airport. Yeah, looking for your perspective on the positioning and what the commercial opportunity could look like, given that the landscape will have different offerings, including presentations, oral, sub-Q, IV, et cetera.
Andy.
Sure. Thanks for the question, Chris. Let me try to frame it out. As I mentioned, the global GLP-1 class is already sizable at about $25 billion, and it's growing at a 30% rate. Yet, GLP-1 only represents about 17% and 14% of type 2 diabetes and obesity categories, respectively in the US. With continued adoption and expansion in these areas, as well as just the growing prevalence of these diseases, we could envision the GLP-1 class to be a $90 billion opportunity, perhaps over the next 10 years.
With the breakthrough potential of an oral option, such as danuglipron or PF-07081532, with compelling benefit risk vis-à-vis the alternatives and without a food effect, it's not that hard to imagine oral GLP-1s and in particular, a potential Pfizer medicine supported by our industry-leading sales, marketing, medical account management access teams, capturing a sizable share of appropriate patients across type 2 diabetes and obesity. That's kind of our current vision of how the category will evolve. The role of orals, we think is quite compelling with the right profile. Needless to say, we're very excited about the potential here that we're working on. Thanks for the question.
Thank you. Our next question comes from Louise Chen with Cantor.
Hi. Congrats on the data, and thanks for taking my questions here. Could you provide more color on what gives you confidence that payers will cover obesity as an indication, given how chronic it is for a lot of people? Secondly, would you consider advancing one of your candidates for type 2 diabetes and one for obesity, or is it either/or when you move forward with these two different molecules? Last question is what do you think is a competitive profile for HbA1c lowering and weight loss? What would you ideally like to see to be competitive in the market? Thank you.
Thanks, Louise. Andy, why don't you take the payer question, and Aditi you can take the which product we're going to advance forward and if we're gonna have one for different indication. Bill, why don't you take the last one about the profile?
Let me start with your question regarding the payer environment. We have been engaging with payers, you know, on a regular basis, conducting market research, getting their feedback in terms of reimbursement. In our most recent primary market research, you know, the feedback was that particularly in the obesity market, given the step change in efficacy that's been demonstrated now, not a 5% weight loss, but a 15% weight loss, as well as the promise, well, of potentially cardiovascular outcomes in this trial in this category in obesity on the horizon with the trial reading out, that really changes the paradigm and that, you know, the commercial plan coverage will change significantly.
That's our perspective now, and of course, as things play out, we'll continue to monitor to affirm that that's an appropriate assumption. Aditi.
Thanks, Andy. The overall plan is really to advance an agent for both type 2 diabetes and obesity. I think that was speaking to the second question, and not necessarily to dissociate the two development paths by compounds. You know, the intent is really to take forward the optimal agent dosing scheme for the 2 indications. In terms of a competitive profile, I mean, we're really seeing that an oral small molecule GLP-1 receptor agonist with all the benefits of the mechanism would really make a big difference in the care of patients with type 2 diabetes and obesity. It represents ideally a very easy to take medicine that could offer multiple benefits from glycemic control to weight loss.
I'll see if Bill or Jim maybe wanted to offer any additional comments.
Yeah, I could chime in here. I think, you know, one of the clinical profile of non-inferiority to injectables on A1C as well as weight is a beneficial profile, and we think we can be potentially best in class for orals for type 2 diabetes. That's one of the aspirational goals.
Thank you. Our next question will come from Mohit Bansal with Wells Fargo.
Great, thanks for taking my question. Questions. Two, if I may. One is, one may be related to the safety of the once-daily oral. So from the presentation, we saw that at higher doses there was higher nausea, vomiting, all those GI side effects. There was a little bit of, you know, the trial was. The dose escalation was a little bit rapid. Could you talk, speak a little bit about that, and how do you think it could pan out with a more slow dose titration? The other question, just wanted to-
Probe a little bit more on the comment you just made, non-inferior data versus injectable GLP-1. Do you think you really need that given it may be an oral? Do you think a little bit inferior data would be sufficient for an oral to become the first line treatment ahead of injectable sales? Thank you.
Aditi, why don't you start?
Sure. Thanks. I'll speak to the safety and tolerability profile of 15-32. You know, with this mechanism, it's typically expected to see dose-dependent increases in GI tolerability. That's not a surprise with the mechanism of action. We did expect that higher doses would have a higher incidence of GI side effects relative to lower doses. We do believe that with slower titration in an outpatient setting, we'll be able to optimize the tolerability of the higher doses of 15-32. At our lower doses it actually was well-tolerated. Our lowest dose had absolutely no nausea, no vomiting. Several lower doses had no vomiting at all.
I think that, you know, we really see that this profile is attractive and that with slower titration and outpatient dosing, we'll see, you know, a tolerability profile that will be very much satisfactory. Thank you. I think there was a second question too about non-inferiority. I don't know if Bill, you wanted Bill or Jim wanted to take that one.
Yeah, I could take that one, Aditi. Thanks. I think that, you know, we're very excited about the profile of these molecules. You know, clearly, you know, the data that Aditi shared around 1532 with the changes and the reductions of mean daily glucose in fasting plasma glucose is, once those are extrapolated out and measured with A1C over you know longer course trials, I think that we're going to actually have a very substantial reduction in hemoglobin A1C, and that will provide a very beneficial profile. In addition, you know, we will couple that with a you know more protracted dose escalation strategy to really optimize the benefit-risk.
Thank you. Our next question will come from Evan Seigerman with BMO Capital Markets.
Hi there, this is Connor McKay on for Evan. Thanks for taking our questions and congrats on the data. I have a couple of questions. First, would you be able to comment a bit more on how you're thinking about the phase 2 trial design for 15-32? And then also, would you consider pursuing any other indications outside of diabetes and obesity for these molecules?
Thank you. Bill, why don't you take this question?
Yeah. I think Aditi might be better. Aditi, can you take this question?
Sure. You know, we are anticipating bringing in slower titration schemes to support PF-07081532's phase 2 study in type 2 diabetes and obesity. We'll have a longer duration of dosing. We are anticipating getting started later this year and hoping to have data, you know, to support phase restart in 2024. I think some of the details of the study will be forthcoming, but you know, I think in high level you'll see longer dosing durations than what we explore with danuglipron, really, to explore those slower titration schemes and get up to higher doses. Jim, did you have any additional comments?
Yeah, just that, you know, we will be starting this, you know, in the fourth quarter. It'll be a single trial. We'll be looking at both diabetes as well as non-diabetic obese patients.
Thank you. Our next question will come from David Risinger with SVB Securities.
Yes, thanks very much. Can you hear me?
Yes.
Excellent. Thank you for hosting the call. This is very helpful. I have a few questions, please. First, with respect to the next gen 1532 candidate's profile, clearly the differentiation is once daily dosing versus twice daily. But could you expand on any other differentiating features? Then, with respect to thinking about that once daily potential, is that only with 1532? Finally, the slide indicates that you're planning a phase 2b study in diabetes and obesity to initiate in the fourth quarter of 2022. Should we expect top-line results from that about 2 years later, or would you envision a different timeline to obtain top-line results? Thank you.
Thanks, David. Aditi, why don't you start and...
In terms of the profile of PF-07081532 relative to danuglipron, it is, you know, as you saw with the pharmacokinetic profile, it is suitable for once daily dosing that at this stage appears to be the primary differentiating factor. We do have a goal for bringing forward, you know, a single asset with once daily dosing. It's important to note actually that we have tested other formulations of danuglipron that did support once daily dosing as well. Those were tested in our phase 1b study. Those remain an option for the danuglipron asset as well. We do believe that PF-07081532 certainly has, you know, a PK profile at its outset that is suitable for once daily dosing.
That was, you know, what we've taken into the clinical studies and we'll be exploring in the upcoming phase 2. Perhaps I'll let Jim answer the plans for the phase 2 study.
Thanks, Aditi. With respect to our phase 2b study, as I mentioned, it will be in both type 2 diabetics as well as obese non-diabetic patients. It will be initiated in the fourth quarter of this year, and we plan to have the top line report out for that in the first quarter of 2024.
All right. Thank you. Our next question will come from Carter Gould with Barclays.
Great. Good afternoon. Thanks for hosting. This has been very helpful. I wanna ask kind of two bigger picture questions. Just given sort of the sort of arms race across diabetes and obesity, just from a franchise approach, do you think longer term, you know, having just sort of GLP-1s, albeit oral, will be enough here? Or, you know, I guess against a world where there's increasing dual and tri agonists, you know, are you gonna have to have your hand, I guess, in multiple pots there? And if there are any internal efforts at Pfizer on those fronts, could you highlight those? And then, you highlight on the slides some interest in fixed dose combinations.
As you think then about potentially rolling those out, you know, is that something you think you'd be able to do in phase 2? Just thinking about the appropriate timing for those efforts. Thank you.
Thanks, Carter. Andy, why don't you take the first question? Jim, you can take the second one.
Sure. You know, obviously, these patients are taking multiple medicines and there's a possibility for fixed dose combinations, co-formulations, and the optimal regimen choice. That's definitely right up our alley. You know, I'll let maybe Jim comment more there. I think the core of your question, which is, this is a pretty competitive environment. You refer to it as an arms race. I mean, I would just say that we're undeterred by the competition, and we really look forward to engaging in the best interest of patients to commercialize a potentially breakthrough medicine for type 2 diabetes and weight loss. We have a proven track record, competing successfully in the competitive cardiometabolic environment over the last 25 years.
We've done a pretty good job of bridging initially specialist driven therapies into a primary care setting. Our track record with Norvasc and Lipitor many years ago and more recently with Eliquis and Vyndaqel, in addition to proven success in many competitive situations across all our major therapeutic areas. We're excited to have the opportunity to engage and to demonstrate leadership in this space. Jim, do you wanna add on to the question about combinations?
Yeah. Thanks, Andy. I mean, you know, for where we are from a development perspective, it's a little bit early for us to speculate on, you know, the complete development program for GLP-1s as well as fixed dose combinations that, you know, may have, you know, very important implications into life cycle management. Obviously, you know, the opportunity to combine, you know, these oral agents with other, you know, very prominent mechanisms in this space would be highly advantageous, and I think that we can provide those updates in due course.
Thank you. Our next question will come from Geoff Meacham with Bank of America.
Hi, this is Joe Thomas on for Geoff Meacham. Thank you so much for taking my question. I just have two related questions. I was wondering if you can provide some more clarity on the titration dosing scheme and dose levels that you might move forward into the phase 3. Related to that, are you expecting to see greater magnitudes of HbA1c and weight loss in trials that go beyond 16 weeks? Thank you.
Thanks, Joe. Aditi, why don't you take that?
Sure. You know, I did present sort of the target doses that have been tested in phase 1B, and most of our titration schemes really began in that phase 1B study at 10 milligrams. We are, you know, using those clinical data to develop the titration schemes for the phase 2 study, so it's very much informed by that. There are, you know, additional steps, et cetera, that will be tested there that will really allow us to pick the optimal paradigm to take into phase 3. You know, those will be available, you know, once we have started the study.
I think that, you know, in terms of greater HbA1c and body weight loss, we know with this mechanism that, you know, you do need the longer durations to see the full effects on HbA1c and body weight, typically sort of moving out to sort of more of the 6-9-month timeframe. You know, our longer duration studies will be able to really show us what the compound can do in phase 2. I don't know, Jim, if you have any additional comments on that.
Actually, I think that you've covered that well, Aditi. Thank you.
As a reminder, that is star one to ask a question. Our next question will come from Robyn Karnauskas with Truist Securities. Robyn, your line is open. Please make sure you are unmuted.
Hello. Hi. This is Nishant. I'm on for Robyn. We have a couple of questions. Number 1 is considering PF-07081532 once daily, you know, which could have better compliance, would you consider advancing that versus danuglipron in phase 3 even if the data is, let's say, not superior to danuglipron. And second one is, you know, we are in the Inflation Reduction Act era, which is being effective in 2026. How do you take that into consideration trying to develop an oral in this environment?
I'm sorry, I do not understand the second question. Can you repeat that?
Yeah. You know, with Inflation Reduction Act, the bill passed, and, you know, it's gonna be effective in 2026. How do you take that into consideration to, you know, develop oral medication in this environment?
Thank you. Aditi, why don't you take the first question?
Sure. Yeah, we did talk about 1532's pharmacokinetic profile relative to danuglipron, and it is suitable in its standard formulation for once daily dosing. We did once daily formulation for danuglipron that's been tested in our phase 1B study. We do have an opportunity to develop that potentially if that were the compound to go forward. We don't believe that, you know, we necessarily that the decision would be made only on, you know, whether or not the compound itself is once daily. We would be able to, or we'd be hoping to bring forward a once daily profile for either one. That's the answer. I think I don't know, Ronen, if you had for the second question, who would field that one?
Andy, would you take the second question?
Sure. I think you're referring to the pricing and reimbursement environment in the US post-implementation of the Inflation Reduction Act. Certainly, you know, our eyes are wide open to the implications of that legislation going into effect. You know, we're modeling in our forecast and expectations the forward environment for pricing and certainly expect there to possibly be some downward pressure on pricing in the future. We're taking that into account and modeling. I think there's also the recognition with capping out-of-pocket costs for patients, particularly Medicare, that also has a little bit of a balancing effect as well. That's our current perspective, and of course, we'll continue. The most important thing is the profile of the medicine playing out as we continue along the development path. Thank you.
Thank you. At this time, there are no further questions, so I would like to turn it back to our speakers for any additional or closing remarks.
Thank you everybody for joining us today. As a reminder, you can find the scientific studies represented in the conference on our website in the IR section. With that, I would like to wish everybody good afternoon, good night, and have a great day.
Thank you, ladies and gentlemen. This does conclude today's teleconference and webcast. We appreciate your participation, and you may disconnect at any time.