Welcome to the Viking Therapeutics VK2735 Maintenance Study Top Line Data conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a question and answer session. To ask a question at that time, please press star key, followed by one on your touch-tone phone. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this conference call is being recorded today, September 22nd, 2026. I would now like to turn the conference over to Viking's Manager of Investor Relations, Stephanie Diaz. Please go ahead, Stephanie.
Hello, and thank you all for participating in today's call. Joining me today is Brian Lian, Viking's President and CEO, Hubert Chen, Viking's Chief Medical Officer, Greg Zante, Viking's CFO, and Dr. Lou Aronne, former President of The Obesity Society and a renowned investigator and KOL in the field of weight loss therapeutics. Before we begin, I'd like to caution that comments made during this conference call today, September 22nd, 2026, will contain forward-looking statements under the Safe Harbor Provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its development activities, timelines, and milestones.
Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely, and reported results should not be considered as an indication of future performance. These forward-looking statements speak only as of today's date, and the company undertakes no obligation to revise or update any statement made today. I encourage you to review all of the company's filings to the Securities and Exchange Commission concerning these and other matters. I'll now turn the call over to Brian Lian for his initial comments.
Thanks, Stephanie, and good morning to everyone joining us on the call today. Earlier this morning, we issued a press release describing the top-line results from Viking's novel maintenance dosing study of VK2735. As a reminder, VK2735 is a dual agonist of the GLP-1 and GIP receptors in development for the potential treatment of obesity. Coactivation of these receptors has been shown to decrease glucose, reduce appetite, lower body weight, and improve insulin sensitivity in patients with obesity, type 2 diabetes, or both. Due to these two mechanisms having complementary activities, this approach has shown generally improved therapeutic benefits compared with GLP-1 mono-agonism. As we look across the development program for VK2735, as this slide shows, we have a lot of activity going on. Viking is currently conducting two phase III clinical studies with subcutaneous formulation of VK2735 called VANQUISH-1 and VANQUISH-2.
VANQUISH-1 is evaluating VK2735 for the treatment of adults with obesity, and VANQUISH-2 is evaluating the treatment of adults with obesity and type 2 diabetes. Both trials are fully enrolled, and we expect the results from the program to be available in 2027. We are also excited to be developing an oral tablet formulation of VK2735. We are planning to begin in the near future two additional phase III trials with this formulation. These two studies will mirror the subcutaneous VANQUISH studies and target patients with obesity and patients with obesity and type 2 diabetes. Today's focus will be on the right-hand side of this slide, and that is our recently completed innovative dose-ranging study designed to evaluate multiple, more convenient, less frequent dosing regimens for the long-term maintenance of weight loss.
Prior clinical and non-clinical studies with VK2735 demonstrated the compound's differentiated exposure and pharmacokinetic profile, including a slower time to peak exposure, which may mitigate gastrointestinal side effects. Additionally, VK2735 has an extended half-life that suggests the potential for more convenient and less frequent regimens for weight management. In particular, our prior phase II VENTURE study demonstrated prolonged plasma exposures at levels we believed suggested correspondingly prolonged therapeutic benefits. The totality of these prior results led us to explore the novel maintenance dosing study that we are reporting this morning. We believe providing patients with flexible dosing options will help ensure that each individual can tailor their treatment for maximal effect and convenience. Less frequent dosing regimens could represent attractive options for those patients who have achieved their weight loss goals and are seeking to maintain that weight loss moving forward.
Importantly, by using the same therapeutic agent for both the initial weight loss and for the longer-term maintenance phase of weight management, we believe patients may experience reduced side effects compared with options that require switching between different therapeutic agents. By reducing side effects, we believe adherence to treatment may be improved, allowing patients to ultimately realize the long-term benefits of weight loss, such as improved cardiovascular health, enhanced physical function, and increased quality of life. During the fourth quarter of 2025, Viking initiated a novel dose range-finding study to explore various maintenance dosing regimens. In this study, all subjects initially received weekly doses of VK2735, followed by a transition to a range of maintenance regimens, including weekly, monthly, and every other week dosing or placebo. The objectives of the study were to evaluate the safety, tolerability, and pharmacokinetic profile of VK2735 under these various regimens.
Exploratory endpoints are assessing the change in body weight from baseline, as well as the change in body weight during the maintenance portion of the study. The results from this study will help inform the selection of doses in the upcoming VANQUISH extension studies expected to begin late 2026 or early 2027. Before we discuss the results, I would like to remind everyone that we have only recently received these data. We believe we have enough information to report on certain of the study's objectives, but we have not yet received all of the data, nor have we had time to rigorously evaluate every line item in the data received. As these are top-line results, there may be differences in certain elements of the data that arise upon receipt of the final results later this year.
We also plan to present the results at future medical meetings, so we may wish to preserve certain details until those presentations. With that background, we are pleased to share with you on this call an overview of the initial results, as well as key takeaways from the study. This slide summarizes the maintenance study design. This is an elegant study that could actually be viewed as four studies in one. A 21-week induction study, a 12-week monthly maintenance dosing study, a 12-week every-other-week maintenance dosing study, and a 33-week study utilizing a 17.5 mg weekly dose. 180 subjects were randomized across 11 treatment groups, and subjects were randomized to have a BMI of at least 30, but no other comorbidities. Induction doses ranged from 15 mg per week up to 22.5 mg per week or placebo, administered once weekly by subcutaneous injection for 21 weeks.
Final doses were achieved via titration that generally followed two-week dosing blocks for successively higher doses. Following the 21-week induction period, subjects were transitioned to a range of maintenance regimens, including monthly and every-other-week dosing or placebo for an additional 12 weeks. This slide shows the weight loss achieved through the initial 21 weeks of weekly dosing. Here we see a nice steep progression at all dose levels with no signs of plateau at 21 weeks for any dose. Week 21 weight loss ranged from approximately 16% to approximately 19%, compared with approximately 0% for placebo. All doses clearly separated from placebo starting at week four, with p-values at each dosing level less than 0.0001 compared with placebo. This slide shows the proportion of subjects across combined VK2735 treatment groups achieving specific weight loss thresholds.
Among treated subjects, 98% achieved 5% weight loss, 90% achieved 10%, 65% achieved 15% weight loss, and 32% achieved 20% weight loss. This compares well with the placebo cohort, for which only 13% achieved 5% weight loss and none achieved 10%, 15%, or 20% weight loss at week 21. These are very robust data and based on the trajectories shown on the prior slide, almost certainly expected to improve with continued dosing. Turning now to the maintenance portion of the study. This slide is looking at the maintenance effect when subjects were transitioned to every-other-week dosing from weekly dosing, and it shows the proportion of the initial weight loss that was retained following the transition from weekly to every-other-week dosing.
Among VK2735-treated subjects, the mean weight loss retained at week 33 ranged from 83% - 97%, compared with 61% among subjects transitioned from 17.5 mg weekly to placebo, with p-values less than 0.01 for each cohort versus placebo. Here we can see the placebo cohort demonstrating a rapid decline of weight loss benefit over the 12-week treatment window compared to each of the every-other-week dosing regimens. Given the fact that dosing was effectively reduced by up to 85% in these treatment groups, the data are particularly impressive and support the concept of less frequent dosing as a potentially viable regimen for longer-term weight management. Turning to the monthly maintenance portion of the study. Here we see the proportion of the initial weight loss that was retained following the transition from weekly to monthly dosing.
Among VK2735-treated subjects, the mean weight loss retained at week 33 ranged from 82%-90%, compared with 61% for placebo, with p-values less than 0.01 for each cohort versus placebo. As with every-other-week dosing, the fact that dosing was effectively reduced by up to 85% in these cohorts demonstrates a compelling maintenance signal and supports the concept of less frequent monthly dosing as a potentially viable regimen for longer-term weight management. When we look at the cohort of subjects who were maintained on a 17.5 mg weekly dose for the entire 33-week treatment window, this slide shows the continued weight loss trajectory for the cohort throughout the study period, reaching 21.7% weight loss from baseline and 22% placebo-adjusted. No plateau was observed, suggesting further weight loss might be expected with continued dosing. We believe these results are very encouraging.
Looking across the current treatment landscape, the currently approved GLP-1 GIP agonists have demonstrated approximately 14% placebo-adjusted weight loss at week 33. In addition, the most advanced triple agonist in development with glucagon activity demonstrated approximately 17% placebo-adjusted weight loss at the 33-week time point. These are, of course, published data using different titration methods and not head-to-head study data. Nonetheless, we understand it will be a top-of-mind question despite the significant caveats and risks in cross-trial comparisons. Turning to tolerability, this slide shows the discontinuations and GI adverse events reported for the 21-week induction period of the study. Overall, there were very few discontinuations due to adverse events.
Looking at the common GI adverse events of nausea, vomiting, diarrhea, and constipation, we see a profile very consistent with what was observed in our prior phase II VENTURE study, with maybe slightly lower rates of nausea and slightly higher rates of vomiting. Overall, very consistent with what was observed previously. This is really quite interesting, as these subjects were titrated faster every two weeks, compared with the three-week schedule used in the phase II study. Overall, no surprises here, and a consistent profile despite accelerated titration. Turning to tolerability under an every-other-week dosing regimen, here we see a very clean profile. Treatment-emergent adverse events were similar to placebo, and GI-related adverse events were generally low and no different from placebo. This is very encouraging and indicates no incremental change in adverse events versus placebo when dosing under an every-other-week schedule.
Even more impressive are the adverse events under the monthly dosing schedule. Here again, we see a clean overall profile with minimal GI-related adverse events. As this table shows, overall rates of nausea, vomiting, diarrhea, and constipation were not meaningfully different from placebo, suggesting excellent tolerability under a monthly dosing regimen. In addition to the impressive weight maintenance effects discussed a minute ago, this is an equally exciting result from this study. When we started this study, we were cautiously optimistic that the tolerability profile that might be observed when subjects extend their dosing intervals to four weeks would be close to that observed under the standard weekly schedule used for titration. These data suggest that despite a gap of four weeks between doses, these individuals did not resensitize to GI adverse events such as nausea or vomiting.
This supports our view that VK2735's differentiated PK profile with an extended half-life and excellent long-term exposures may provide for greater flexibility in dosing compared with existing options. In summary, we are extremely pleased with the outcome of this study, as we believe it demonstrates a credible maintenance effect, which was a key objective going in. We observed a high rate of weight loss maintenance, up to 97%, following transition to every-other-week dosing from weekly induction. The trial also demonstrated up to 90% weight loss maintenance following transition to monthly dosing, suggesting the potential viability of both regimens in the setting of maintenance dosing. We also saw a highly competitive weight loss of 22% among subjects titrated to 17.5 mg weekly for 33 weeks, and no evidence of a plateau at that point, which suggests there may be more to go.
Finally, under both maintenance regimens, we observed tolerability that was not meaningfully different from placebo. This again suggests the viability of less frequent dosing without incremental worsening of common adverse events. More work is needed, but we're certainly happy with the results. I'll close by reiterating that we believe long-term weight management will not follow a standard one-size-fits-all approach. Individuals pursuing sustainable weight loss will seek a range of treatment options that allow them to personalize their weight loss journey at every stage. We believe offering flexibility and optionality to patients will lead to improved adherence to treatment, allowing patients a greater opportunity to realize the long-term benefits of weight loss, such as improved cardiovascular health, enhanced physical function, and increased quality of life.
Dr. Lou Aronne, who has unmatched experience in developing and prescribing GLP-1 and dual GLP-1 GIP agonists, is also joining us on this call and can share his perspectives in the Q&A session on what these promising findings mean for patients. This concludes our prepared comments for today. Thanks for joining us, and we'll now open the call for questions. Operator?
We will now begin the question and answer session. To ask a question, you may press star then one on your touch tone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. Please note that we have a large number of participants in the queue. The company will do its best to answer as many questions as possible. Thank you. At this time, we will pause momentarily to assemble our roster.
[Betsy], hey, this is Brian Lian here. While we're compiling the queue, maybe I'll take the first question and just ask Dr. Aronne if he can share any thoughts on the data and what it might mean for patients. Dr. Aronne?
Thank you very much, Brian, for letting me see the data and inviting me to participate. What I can say is that based on my 35 years of experience doing this, I think it's pretty clear that VK2735 is highly effective. It's among the best that we've seen for available drugs at 22% weight loss over 33 weeks. One of the things that we're learning is that maximum efficacy is maybe not the most important thing these days now that we've gotten such good efficacy, but that treatment persistence is actually key. Having simpler and less frequent treatment regimens would make sense as a better way to use these. We're actually seeing that clinically. Our patients, once they hit a plateau, are starting to use the drugs that are currently available less frequently.
One of the interesting things is that here, lower doses seem to be effective and quite tolerable for maintenance. The full dose, if someone's taking 17.5 mg weekly, you don't need to use 70 mg monthly in order to maintain. Significantly lower doses appear to be maintaining the maximal weight loss or something close to that. Another interesting aspect to this trial is how well-tolerated the drug is. It appears to me to be at least as well-tolerated as the currently available options, despite the rapid titration scheme. That's usually when we see most of the side effects, and the fact that it's tolerable, even though it was about twice as fast as we would normally titrate, I think speaks to its tolerability. It looks like 17.5 mg is the best balance.
It produced the greatest weight loss, and that may be because it had fewer side effects than the higher doses. We're seeing this in other trials, where one dose seems to shine through. I think that in the long run, this is very promising for less frequent treatment regimen. I think that every other week is clearly realistic and once a month in other subjects or other patients is how this will be used. I think an important point you made is that flexibility in treatment is what's key. When people look at the fact that not everybody continues on the current medications, it's because we need more medications with slightly different mechanisms of action and slightly different ways of taking them. Thanks very much for asking me to comment on this.
Thanks very much, Dr. Aronne. We'll open the call up now for questions, Operator. Thanks.
The first question today comes from Steve Seedhouse with Cantor Fitzgerald. Please go ahead.
Good morning. Thank you. Congrats on a really nice data set. I have just a two-part question on dose selection and then one follow-up if I could. On the doses, first of all, have you decided on the maintenance dose that you would incorporate into the phase III open label extension? Is it possible that you could incorporate something like patient choice flexibility to choose their dose as you've been articulating on the call here? The press release mentioned the opportunity to evaluate additional higher doses, and I'm curious if that's referring to higher than 22.5 mg or higher than 17.5 mg in the phase III, or what that's referring to, and if you would test that in the oral maintenance study.
Yeah. Thanks, Steve. For the second question, yeah, it does mean that based on the very clean tolerability that we've seen here, it opens the possibility to explore higher doses. We just see no real impact on tolerability at all in the maintenance phase. What doses that we plan to take on in the maintenance, we haven't decided yet. We're still in the process of going through all of the data, but I think we have a reasonably good idea what that range would be. We're not prepared to announce those doses today. But I think it gives us plenty of options based on the data.
Okay. Thanks, Brian. The other question I had was just, obviously, there's sort of two factors in the induction phase here weighing on adverse events. There's the aggressive titration, but then there's that 1.25 mg mini step at the start, and obviously, you've incorporated that, in a sense, in phase III as well. I'm curious if you have the data on AEs by week and if you can basically see if that 1.25 mg step was helpful and mitigated some of the early adverse events relative to phase II.
Yeah. Thanks, Steve. It seems to help a little bit. We don't have all the per cohort data for those histograms that we like to present, but it does suggest that. First of all, I'll say across the entire induction phase if you look at the combined treatment groups, the rates of GI adverse events were always extremely low, probably in the 5% range across the induction period. But how important that 1.25 mg is, I think it's helpful. We'll have a better idea once we get the breakouts, but I do think that does help.
Great. Thank you so much.
Thanks, Steve.
The next question comes from Biren Amin with Piper Sandler. Please go ahead.
Yeah. Hi, guys. Thanks for taking my questions, and congrats on the data. Maybe on the maintenance phase of the study, Brian, could you maybe just talk about the placebo arm? I think 61% of the patients kept weight loss. Was that as expected when you designed the study, or was that higher than expected based on your original assumptions? Thanks.
Yeah. Well, the data show that the placebo cohort, the mean of the placebo cohort was a 61% retention. In other words, they rebounded by 39%, if that makes sense. That is within range from published studies. Over 12 weeks, when you withdraw therapy, you typically see anywhere from, call it, 15%-40% rebound in a 12-week period. So that 39% rebound is within range from what's been published previously.
Then maybe just one question on the 17.5 mg weekly dose for both the induction period as well as at week 33. Clearly, you're seeing progressive weight loss across both time periods. Can you just maybe talk about the nausea and vomiting rates that you saw with those doses and just read through into VANQUISH-1 based on these data, given that's the high dose that you're testing in VANQUISH-1 and VANQUISH-2?
Yeah. Very well tolerated in that maintenance period for the 17.5 mg. It seems like, and this is not unique to Viking, it just seems like the GI adverse event profile of the GLP-1 activation tends to be an early GI tolerability signal that fades over time. No real difference there. I think it is very well tolerated. As Dr. Aronne said, despite the acceleration in titration in that 21-week induction period, tolerability was really consistent with what we have seen in the phase II study.
Great. Thank you.
Thanks, Biren.
The next question comes from William Wood with B. Riley. Please go ahead.
Thank you so much for taking our questions, and congrats on the very nice data. Just thinking about for the induction period, 20 mg came out the best with 22.5 mg actually coming in slightly worse than 22.5 mg, at least on the weight loss. I was curious if you could speak to any differences in the patient population that may have been enrolled or discontinuations, or how do you think is this more towards a smaller sample size? Following the weekly to monthly transition, you actually achieved a higher percent weight maintenance with the 17.5 mg dose than the 22 mg. Just curious as to think why that may be occurring. Any thoughts on that, on those two would be very appreciated. Thank you.
Yeah. Thanks, William. I think when you look at the cohorts, really all of them, I do not know, better or worse is the right characterization. They all are very good. As far as the 22.5 mg, I think it is a very small cohort, so probably the most likely explanation there is that the N was small. You do see a modest dose response when you go up from 17.5 mg to 20 mg, 15 mg, 17.5 mg to 20 mg, and then a slight downtick in the 22.5 mg. But really, that does not concern us. It is a very small cohort size there.
Got it. Maybe if I can squeeze in one more, just given the lack of tolerability, spiking it on a per month basis and now incorporating those lower doses, could you provide how are you thinking about tolerability improving even further in the VANQUISH-1 trial coming up? Thanks.
Yeah. Thanks, William. Well, we think the data support our thesis that we had after the VENTURE study, the phase II study, that it seems like the PK profile, where we have a sort of a slower onset of action, a later Tmax, it probably serves to mitigate some of the common GI adverse events that are observed. Then you couple that with the lower starting dose at 1.25 mg, and we would hope that that would mitigate some of the GI adverse events that are really common to these therapies.
Got it. Very helpful. Congrats on the data again.
Thanks, William.
The next question comes from Annabel Samimy with Stifel. Please go ahead.
Hi. Thanks for taking my question, and congratulations on the data. I have to say, you have a wide luxury of options here. I just want to go back to the question regarding what your expectations are for the open label, how you might use this data to select an actual dose range, because it seems like there's a pretty clear consistency of response anywhere between 85% and 90%, regardless of the dose. Is there a possibility to offer a physician's choice for the open label section of VANQUISH? What would the regulatory requirements be for that phase of the trial?
Yeah. Thanks, Annabel. I think what we'd like to do, we haven't made decisions on doses just yet, but what we'd like to do is incorporate probably examples of both the every other week and the monthly regimen in the extension. We do have some questions in front of the FDA right now about dose selection and dose frequency. So when we receive our responses from the FDA, we can make a better informed decision. But right now I think we have nice options, as you say, to select doses either monthly or every other week. Every other week. Yeah.
Okay. Thank you.
Thanks, Annabel.
The next question comes from Mike Ulz with Morgan Stanley. Please go ahead.
Hey, good morning. It's Avi Novick on the line for Mike. Thank you for taking our questions, and congratulations on the data. I guess, just thinking about the oral maintenance study coming up, I guess what we see is the read-through from the sub-Q to the oral. Should we expect similar tolerability and weight maintenance? Then I guess a question for Dr. Aronne is with the data on hand today, I guess how would you integrate VK2735 into your practice should it be made available? I guess also on that could you talk about the importance of having an oral option? Thanks.
I'll take the first question with the oral. The oral doses that we've selected are 17.5 mg, 27.5 mg, and 35 mg. The exposures there, since the oral has lower exposures, we expect the exposures to come down a little bit versus the sub-Q. But it's offset a little bit by the daily dose regimen. So how that actually plays out, we won't know until we see the data. But I think there's offsetting factors there that make us pretty excited about the potential for the oral maintenance option. I'll turn it over to Dr. Aronne for the second question.
Yeah. I think that having the option of every other week and once monthly dosing is going to turn out to be very useful in the long run. We need that in order to maintain persistence. If you look at the biggest threat to weight loss maintenance with the current drugs, it's that people stop taking them after a period of time. If they could take them less frequently, I firmly believe that they would do a better job of it. So to me, the fact that you could take 10 mg every other week and maintain the weight loss, that's pretty remarkable. So I can see where this fits right away.
All right. Great. Thank you for taking our questions, and congrats again.
Thank you.
The next question comes from Gregory Renza with Truist. Please go ahead.
Hi, guys. It is [Anish] on for Greg. Congrats on the data this morning and for taking our questions. Just first, in the context of retention, how do you think about the floor on maintenance exposure, and is there a dose below which the every other week construct stops holding? Second is a quick one. How durable do you see weight loss off drug, and how does that shape the commercial case for staying on a maintenance dose at all? Thanks so much.
Yeah. Thanks, [Anish]. It looks like even down to that 5 mg every other week, you see pretty effective maintenance despite coming way down in dose from that 17.5 mg per week. You do see a little bit of a dose response there. The exposures are showing up there. I would say an 80% weight loss maintenance is still very encouraging, and I think some people would gravitate to that. Where it goes from there, obviously, if you go to 2.5 mg every other week, that is probably going to give you a less effective maintenance dose. The floor looks like it is sub 5 mg, which is surprisingly good for that. What was your second question?
The second question was just on the durability of weight loss off drug. I know we're not here yet, but just a good chance to kind of give us a sense of how you're thinking about that in the commercial case for staying on a maintenance dose.
Well, we know, and I think Dr. Aronne probably has far more insight on this than I do, but we know that as you see in the placebo cohort, that withdrawing therapy leads to a pretty rapid regain. I do not know, Dr. Aronne, if you have any other comments on that.
Sure. There is tremendous variability from person to person in how long they can maintain if they do not take medication. We see some people who must continue taking it weekly or even more frequently than weekly with the current medications, and others can seemingly take a dose every 10 days, two weeks, or even once a month, even with the current meds. I think that having flexibility, being able to accommodate patients' needs is really the key to long-term persistence.
Thanks, guys.
Thanks, Greg. Or [ Anish] .
The next question comes from Ryan Deschner with Raymond James. Please go ahead.
Hi. Good morning. Congratulations on the impressive data readout. The weight loss maintenance appeared to kick up, I guess, in the maintenance in the final weeks in that week 29 to week 33. How are you thinking about what's driving this, and how do you think this might mature over subsequent time points as we'll see it in the extension for some of these cohorts? I have a follow-up. Thanks.
Yeah. Thanks, Ryan. I think you are pointing out a really interesting observation, and that is in that first little period following the transition, you see a little bit of a rebound, a little bit of decline in the maintenance effect. Then it begins to, it looks like you are seeing a resumption in the weight loss and the maintenance effect. How that plays out over time, we do not know, but all of the curves are pretty consistent and I think very encouraging for longer-term maintenance. That was a bit of a surprise to us, that you would see this uptick. But it is very consistent and it clearly looks real, so that is a really encouraging sign.
I also wanted to ask, post the transition, the safety and tolerability data is remarkably good. Does this make you more aggressive in terms of the dose selections for an expanded oral maintenance cohorts later on next year?
Yeah. It is a good question. It makes us more, I think, encouraged for both oral and sub-Q. It looks like we have good room on the tolerability side to potentially dose up. We have not made any final decisions on what additional sub-Q doses we would pursue. But having that room to dose up with good tolerability is a really nice place to be, a nice optionality.
All right. Thanks, Brian.
Thanks, Ryan.
The next question comes from Andy Hsieh with William Blair. Please go ahead.
Great. Thanks for taking our questions, and congratulations on the data. What we saw is really kind of the short-term goals of weight and maintenance. I am curious if Brian or Dr. Aronne want to comment on potential read-through to longer and perhaps most important, which is the cardiorenal protection. Any sort of extrapolation from today's data that you can extrapolate to the multi-organ protection benefits of [incretin]. Dr. Aronne, I am curious if you can comment on really kind of the third aspect of extended dosing. You mentioned about the weight maintenance, you mentioned about the improved tolerability with extended dosing, but perhaps the cost savings for patients in your clinic by extending it two times, four times, and how that would lead to better persistence. Thank you.
Sure.
I will take this— oh, go ahead, Dr. Aronne. That is fine. Go ahead.
Go ahead, Brian. You can start.
Well, I was going to say, just a global comment that it seems like the more weight loss you can maintain in these longer-term dosing periods, the more benefit you retain, whether it is better sleep apnea or cardiorenal protection. We see these cardiometabolic parameters. Once you can maintain at least 75% of that initial weight loss, those parameters would seem to be maintained as well, providing a strong suggestion of long-term benefit. I will give it to you, Dr. Aronne.
The evidence is growing that once you get to 15% weight loss or greater, you get the majority of the benefit for many of the cardiorenal, cardiometabolic complications of obesity. Once you get to 20%, you get 98%, I would like to say. There are some that are clearly weight loss dose related, like sleep apnea. The more weight you lose, the better you do. There is a mixture of these. In general, I think we are going to be targeting somewhere between 15%-20%, you are going to do great. With this compound, it looks like that is definitely in the cards. As far as the idea of taking it less frequently, many of our patients are paying out of pocket for these, and so they take it less frequently just because it is less expensive.
I think that this will be very appealing to patients, knowing that they can take it less than every single week. The idea is, you take it every week for nine months, and then you go to every other week, and then depending upon how you do, maybe you take it every month. I think that that idea would be appealing to patients, but also to payers, that the patient has to take it every single week. Now, it may be that for the maximum weight loss, you do need to take it every week. Again, it may be that that is not necessary for the average person.
That's helpful. Thank you so much.
Thanks, Andy.
The next question comes from Jay Olson with Oppenheimer. Please go ahead.
Oh, hey. Congrats on these impressive results. Can you talk about the level of de-risking these data provide for your phase III sub-Q program? Related to that, since you've now set a really high bar for sub-Q maintenance efficacy and tolerability, what would you like to see from your oral maintenance program? Thank you.
Yeah. Thanks, Jay. It is hard to predict what the outcome of the phase III trials will be, but I think that signal we see for the 17.5 mg at both 21 weeks and 33 weeks is certainly very encouraging and very competitive with what is out there. Looks a little better than what is out there right now. I think very exciting. As far as de-risking, different studies but really a positive initial read here. As far as the oral maintenance study, we will be beginning that imminently here. I think what we see in this, especially the pattern that I think Ryan mentioned earlier, of the initial rebound, then muted, and you see a larger weight maintenance effect in months two and three. Also very promising. It will be interesting to see how that manifests with the oral dosing.
Great. Thank you. Congrats again.
Thanks, Jay.
The next question comes from Thomas Smith with Leerink Partners. Please go ahead.
Hey, guys. Good morning. This is [Brian] on for Tom. Congrats on the nice data, and thanks for taking our question. Maybe just on the oral, understanding you plan to start the phase III oral program in the fourth quarter. We do not have all the design details yet, but can you talk about your expectations on maybe the ballpark size of the studies and expected pace of enrollment relative to the VANQUISH program? Thanks so much.
Yeah. No, thanks. Good questions. The size of the study, since we will be leveraging the safety database from the sub-Q formulation in the oral data package, the size of the oral studies will be significantly smaller than the sub-Q studies. Still large studies, but quite a bit smaller and quite a bit less expensive as well. What was the second part of the question?
Pace of enrollment.
Oh, the pace of enrollment. Yeah. We had seen unusually rapid enrollment in the sub-Q studies. We see a really high level of enthusiasm for the oral, so hard to predict. But I would say we would expect those trials to enroll reasonably quickly, but really hard to predict until we get the study up and running. But a lot of enthusiasm based on the sub-Q data.
Got it. Thanks so much.
Thanks.
The next question comes from Yale Jen with Laidlaw & Co. Please go ahead.
Good morning, and thanks for taking the questions, and congrats on the great outcome. Just one question in terms of the AE. We noticed that in the 7.5 mg every other weeks, the diarrhea rate is about 15%, which is presumably higher than across the board in many others. We also noticed that there seems to be one occasion with much higher numbers here, with only two patients have that problem. I wonder whether you see this could be abnormally with a smaller patient size, or there's anything you can read from that?
Yeah. Thanks, Yale. We don't think so. It's to your point, two people had experienced diarrhea in that every other week. There's no dose response there. That's just a function of small numbers there. We don't think there's any sort of a GI issue with the 7.5 mg every other week.
Maybe as a quick follow-up, in terms of any colors you will provide for the oral maintenance in terms of dose ranging and maybe as well as duration, any colors you can share at this point? Thanks.
Yeah. Thanks, Yale. The oral maintenance will follow the same template as this study. 21 weeks of sub-Q dosing, and then we will have a 12-week period of maintenance dosing. Same overall trial design. It is under the same protocol, and doses that we talked about there are 17.5 mg, 27.5 mg, and 55 mg. No real changes. What we may do is incorporate some of these findings from this study into that second maintenance study, but still looking more at the oral cohorts in that study.
Okay, great, and congrats again.
Thanks, Yale.
The next question comes from Hardik Parikh with JPMorgan. Please go ahead.
Hey, good morning. On the data, I just had one theoretical question for both Brian and Dr. Aronne. I was thinking, how would you think these maintenance results would change if the trial was done, let's say, with patients switching from one of the currently approved injectables, such as Zepbound and Wegovy. Then same question, if patients were originally on a triple agonist as a retatrutide, how would the maintenance, do you think, potentially be different than what you saw here today?
Thanks, Hardik. I'll turn that over to Dr. Aronne for a better perspective than I have on that.
What we see both clinically and in trials, we've done switching trials now going from a dual agonist to a mono- agonist, which is oral. We see that there's some weight regain. When you take away one mechanism of action, or you give a compound that has lesser efficacy, you see weight regain. Now, the patient doesn't regain all their weight, but they tend to migrate towards the efficacy of the second compound that they're now on. But interestingly, they are somewhere in between.
They don't go all the way to that weight, at least not initially, over the length of our trials, which have been generally nine months to a year. I would say that in making these switches, the maintenance would be as you expect. Going from a triagonist to a dual agonist, you might expect some weight gain. Going from a mono-agonist to a dual agonist, you would expect greater weight loss. I think that is what we are going to see. As far as going from dual agonist to dual agonist, I think that when we look at the magnitude of weight losses that we have so far, they are going to be similar.
Thank you.
Thanks, Hardik.
The next question comes from Jeet Mukherjee with BTIG. Please go ahead.
Great. Good morning. Thanks for taking the question and congrats once again on the impressive data. Two questions, if you do not mind. One for Dr. Aronne. Net-net and overall, does this weight loss and tolerability profile fall in line with approved agents and ones in development, or does it seem superior? My second question was just how do you contextualize this data today with studies such as SURMOUNT-MAINTAIN for tirzepatide or the VESPER-3 trial for Pfizer's molecule? Thank you.
What I think is it is too early to tell comparing head-to-head because this is a small phase II type trial, and those are phase III trials. You really cannot compare them. Having 12 people in a dosing arm, or 20 people in a dosing arm versus having several hundred or 1,000 in the arm are definitely different. What we have seen over time is that as the trials get larger, the weight loss is not necessarily as great as it has been. The reason we do these giant trials is really to look at safety. The important point is that this is clearly competitive. This is in the ballpark. Is it more or less? We cannot tell yet. Right now, the result we have, it is exactly on target with tirzepatide, but at an earlier point.
It is at 33 weeks where tirzepatide would not reach that for a somewhat longer period of time. Now, that could be due to the more rapid titration. There is no way to know until we do the study. We finally started doing head-to-head trials. We did a head-to-head trial we published in The New England Journal recently, showing that there is greater efficacy with the dual agonist tirzepatide. But it does not mean that any compound is not going to be used or is not going to be good.
Again, once we get to 15% weight loss, we get the majority of the health benefits. We are seeing that in these trials. Even though you may not get as much weight loss, you do get the same kind of health benefits, although the magnitude may not be as great. Remember that not everybody needs maximal efficacy. Not everyone needs that. Many people will do great and live a much longer, healthier life with somewhat lesser efficacy. But the important point is that this puts it right in the range of the most competitive compounds out there.
As we are nearing the conclusion of today's call, our final question will come from Roger Song with Jefferies. Please go ahead.
Hi, this is [Fiona] for Roger. Congrats on the data, and thanks for taking our question. The week 33 from the 17.5 mg weekly dose at 22% adjusted weight loss was very encouraging. How should we think about the translation to phase III in understanding the difference in titration scheme? Just related question for Dr. Aronne. We seem to be seeing a signal of rapid weight loss with VK2735, which seems consistent from the 13-week VENTURE study. How important do you think this kinetics of weight loss or fast onset is for patients compared to what's available on or upcoming in the treatment landscape?
I'll take the first part of the question. It's really hard to predict based on these data what the phase III readout will be. I think what we see is different titration rates and different sizes and so forth. I think we're just very encouraged by the slope being sharply negative, the slope remaining negative at both 21 and 33 weeks. It would suggest that a longer treatment window might see that further mature. But hard to really predict with confidence. But we're really encouraged by the week 33 slopes and the magnitude that we see there. I'll turn the rest over to Dr. Aronne.
As far as the rapidity of the weight loss, it's kind of a good news, bad news thing. The good news is the weight loss is rapid. But some people have suggested that if you go past a certain velocity of weight loss, you could wind up losing more lean mass. That will be investigated in future trials. But it is encouraging to have this kind of magnitude. There are people for whom this will be very appealing. There are others who will not care. It's just that the weight needs to get off because of metabolic issues, and they're going to get it off over whatever period of time. But I think there are a certain group of patient out there who really want this kind of efficacy. The thing to me that was most encouraging about the rate of weight loss was the tolerability.
I think the rate is because of the rapid titration, but the rapid titration speaks to the tolerability. I do not know what the ultimate way this will be used will be, but the fact that it could be used this way. With some of the compounds we have now, if you try to titrate it faster, the big issue is tolerability. Here, we did not seem to run into that.
Very helpful. Thank you both.
Thanks, [Fiona].
That concludes today's call and today's question and answer session. I would like to turn the conference back over for any closing remarks.
Thank you again for your participation and continued support of Viking Therapeutics. We look forward to updating you again in the coming months. Thank you.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.