Welcome to the Viking Therapeutics oral VK 2735 phase 1 Data Review Conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ask a question at that time, please press the star key followed by 1 on your touch-tone phone. If anyone has any difficulty hearing the conference, please press star, then 0 for operator assistance. As a reminder, this conference call is being recorded today, March 26, 2024. I would now like to turn the conference over to Viking's manager of investor relations, Stephanie Diaz. Stephanie, please go ahead.
Hello and thank you all for participating in today's call. Joining me today is Brian Lian, Viking's president and CEO, Marianne Mancini, the company's chief operating officer, and Greg Zante, Viking's chief financial officer. Before we begin, I'd like to caution that comments made during this conference call today, March 26, 2024, 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 with 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 initial results from our phase 1 clinical trial evaluating an oral tablet formulation of VK2735, our dual agonist of the glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptors, in healthy volunteers with a minimum body mass index of 30. We are pleased to share with you on this call an overview of the initial data and key takeaways from the study at this point. Following my prepared comments, we'll open the line for questions. Before reviewing the results, I'd like to remind everyone that we have only recently received these data. As indicated in today's press release, based on a review of the encouraging data collected to date, we have decided to continue with dose escalation beyond the levels reported today.
As such, we will not have the final results from all subjects in this study until after completion of subsequent cohorts, and as a result, there may be differences in certain elements of the data that arise upon receipt of final results later this year. In particular, additional placebo subjects may impact the final determination of placebo-adjusted effects. We would not anticipate these potential differences to have a significant impact on the changes from baseline or the majority of the safety and tolerability results we are reporting today. As additional data become available, we'll provide further updates. We also may wish to present the results at future medical meetings and may reserve certain details until those presentations. As a reminder, VK2735 is a dual agonist of the GLP-1 and GIP receptors in development for the potential treatment of obesity.
Activation of the glucagon-like peptide 1 receptor has been shown to decrease glucose, reduce appetite, lower body weight, and improve insulin sensitivity in patients with type 2 diabetes, obesity, or both. Multiple GLP-1 receptor agonists are currently approved for use in the United States. More recently, research efforts have explored the potential co-activation of the glucose-dependent insulinotropic polypeptide, or GIP, receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation. Because these two mechanisms demonstrate complementary activities, this approach has shown generally improved therapeutic benefits compared with GLP-1 alone. During the first quarter of 2023, Viking announced positive results from a phase 1 single ascending dose and multiple ascending dose clinical trial of VK2735 in healthy volunteers.
In the multiple ascending dose portion of the study, VK2735 demonstrated encouraging safety and tolerability and positive signs of clinical activity following 28 days of weekly dosing as a subcutaneous injection. All cohorts receiving VK2735 experienced reductions in mean body weight from baseline, ranging up to 7.8%. VK2735 also demonstrated encouraging safety and tolerability following repeated subcutaneous dosing, with the majority of adverse events reported as mild or moderate. These results were featured in an oral presentation at Obesity Week in October 2023. Following the completion of the phase 1 study of the subcutaneous formulation of VK2735, Viking initiated a phase 2 study, which we called the VENTURE Study , to evaluate the efficacy, safety, and tolerability of VK2735 dosed weekly for 13 weeks. Last month, we reported the top-line results from the VENTURE Study . This trial successfully achieved its primary and all secondary endpoints.
Patients receiving VK2735 demonstrated statistically significant reductions in body weight from baseline, ranging up to 14.7%. In addition, up to 88% of patients in VK2735 treated cohorts experienced at least a 10% reduction in body weight compared with 4% of patients receiving placebo. The top-line results also showed that treatment with VK2735 was safe and well-tolerated through 13 weeks of weekly subcutaneous dosing, with the majority of reported adverse events characterized as mild or moderate. As weight loss in all VK2735 treated cohorts appeared to be progressive throughout the VENTURE Study with no plateaus, we believe that further benefits could be achieved through extended dosing beyond the study's 13-week treatment period, and we plan to conduct a longer-term study following a review of our plans with the regulatory authorities.
In parallel with the development of a subcutaneous formulation of VK2735, Viking has also been developing an oral tablet formulation of this compound. We believe a tablet formulation could represent an attractive treatment option for patients with obesity and see this as an important potential expansion of the overall opportunity for this program. Last year, we initiated an extension of the subcutaneous phase 1 study to evaluate a novel oral formulation. The oral portion of this study is a randomized, double-blind, placebo-controlled study in healthy adults with a minimum body mass index of 30 kilograms per meter squared. The primary objective is to evaluate the safety and tolerability of VK2735 administered as a tablet once daily for 28 days. Secondary and exploratory objectives include an evaluation of the pharmacokinetics of orally administered VK2735, as well as various pharmacodynamic measures, including changes in body weight and other metrics.
Dose levels that have been evaluated to date have ranged from 2.5 milligrams to 40 milligrams once daily. For doses above 2.5 milligrams, titration was used with increasing dose level applied in successive weeks until the target dose was reached. Today, we are happy to report the initial data generated from this study. With respect to safety and tolerability, oral VK2735 was shown to be safe and well-tolerated following once-daily dosing for up to 28 days at doses that were titrated up to 40 milligrams. Among subjects receiving oral VK2735, all treatment-emergent adverse events were reported as mild or moderate in severity, with the majority, 76%, reported as mild. Similarly, all gastrointestinal adverse events reported in this study were reported as mild or moderate. The majority of gastrointestinal adverse events, 79%, were also mild. Mild nausea was reported in 14% of subjects receiving VK2735.
No vomiting was reported among subjects receiving VK2735. Diarrhea was reported in 3% of VK2735 treated subjects compared with 20% of subjects receiving placebo. Overall, no clinically meaningful differences were reported for gastrointestinal adverse events among subjects treated with VK2735 compared with placebo. Importantly, to date, no serious adverse events have been reported in this study. As mentioned earlier, an exploratory assessment of change in body weight was also conducted. Subjects receiving oral VK2735 demonstrated dose-dependent reductions in body weight ranging up to 5.3% from baseline. Placebo-adjusted reductions in body weight reached up to 3.3% from baseline. Body weight reductions compared with baseline and placebo were statistically significant at the highest dose evaluated. Weight loss in the 28-day window of this study was progressive at the 20 milligram and 40 milligram dose levels, with no plateaus observed.
An exploratory assessment evaluated the proportion of subjects achieving at least 3% or 5% weight loss after 28 days of treatment. Cohorts receiving VK2735 at doses of 10 milligrams and above demonstrated higher proportions of subjects achieving 3% weight loss relative to placebo. The proportion of VK2735 treated subjects with at least 3% weight loss ranged up to 86% compared with 20% for placebo. In addition, the proportion of VK2735 treated subjects achieving 5% weight loss ranged up to 57% compared with 0% for placebo. These differences were statistically significant. Given the promising weight loss signal being reported today, along with the excellent tolerability profile observed thus far, we have decided to pursue further dose escalation in this study and recently commenced dosing in an additional cohort.
Decisions on future dose escalation will be made pending a review of the safety and tolerability data generated from completed cohorts. In addition, based on the encouraging trajectory of weight loss observed in this study and the lack of a plateau at 28 days for higher dose cohorts, we believe that further benefits might be anticipated from longer dosing periods and with potentially higher doses. To this end, we have decided to proceed with plans for a phase 2 trial in patients with obesity. We plan to initiate this study later this year. Details on study design, including dose levels, will be provided as we get closer to study initiation. In summary, we're very pleased with the results generated thus far in this study, and we believe they provide support for advancing the tablet formulation of VK2735 into phase 2 development for the potential treatment of obesity.
The promising early weight loss, combined with a potentially best-in-class tolerability profile, suggests that VK2735 could represent an important potential future treatment option for patients with obesity. We expect to commence a phase 2 trial in obesity later this year. In the interim, we plan to continue dose escalation in the current study and will provide further details as available. Finally, I'd like to thank everyone who has continued to diligently work on this study at the clinical site, at our CRO, and here at Viking for their outstanding work on the study. Thanks for joining us today, and I'll stop here and open the line for questions. We will now begin the question-and-answer session. To ask a question, you may press star, then 1 on your telephone keypad. If you are using a speakerphone today, please pick up your handset before pressing the keys.
To withdraw your question, you may press star, then 2. We will pause momentarily to assemble our roster. Today's first question comes from Steve Seedhouse with Raymond James. Please go ahead. Thanks so much. Good morning, and thanks for hosting the call and taking the questions. Brian, do you have PK data yet from these patients, and do you know the type of exposure that you're getting versus the sub-Q formulation? And is there a linear dose-exposure relationship? Basically, what's that data telling you about where you can dose to and what that might yield at 60 or 80 milligrams? Yeah. Thanks, Steve. We have PK data from the earlier cohorts, not from the later cohorts, and we do see a dose-proportional increase that's fairly predictable.
I think it's a slow accumulation over the course of the treatment window, so you're probably not seeing the full effect of each dose at 28 days. But we don't have the final PK from the last two cohorts at this point. Okay. That's interesting, actually, given the tolerability profile too. And I mean, even when you were starting at higher doses in the titration, like 20 milligrams, it didn't create any tolerability issues. So if there's slow accumulation and given the tolerability profile, I mean, do you think you can just test flat dosing from the outset, even at higher doses, or do you still need titration, do you think? Yeah. It's a great question. I don't know the answer. It just feels like, given everything we know about the mechanism, it's probably safer to err on the side of caution and titrate.
But whether or not it's really required doesn't look like it from what we've seen so far. But I think it's just, as you continue to dose up, it's just probably better to start with the titration. Okay. And I guess it depends on maybe the number of cohorts that you're going to add. But how many placebo patients would you enroll? Is it just going to be 2 per additional dose cohort, or are you maybe going to enroll more? I'm just asking because, I mean, you might get some mean regression of that placebo group. You kind of made a comment at the start of the call. It might ultimately, when the final data are in hand, increase the placebo-adjusted effect here, depending on how many you enroll. Yeah. Yeah. So we're planning to add 2 per cohort. And you're right. The placebo effect was larger than expected.
We get hit on that. I think every one of our studies has a larger-than-expected placebo effect. And the way we at least the way I was looking at it was, since the 2.5 and 5 mg appear to be really subtherapeutic, maybe the right placebo is somewhere between those three cohorts if you blend them or something. I don't know. But 2.5 and 5 mg doesn't make you gain weight. So it just feels like that, because of the small numbers, the placebo effect was a little bit larger, and I would expect it to regress a little bit. And we do see that at 34 days, we see the placebo effect pulling back another 0.4%-0.5%. So you do see it regress following more time elapsed.
Nice. Okay. Just last question.
So the final data from this study, what's the official guidance on when you might have that, just later this year?
Yeah. It's hard to because these cohorts have been so slow to enroll, it's hard to precisely say. But we would hope later this year, yes.
Okay. Great. Well, thanks so much, and congrats on another great data update.
Thanks a lot, Steve.
Thank you. The next question is from Joon Lee with Truist Securities. Please go ahead.
Hey. Congrats on the data, and thanks for taking our questions. As you're adding additional dose cohorts, which makes a lot of sense given great tolerability, do you have a maximum dose in mind given manufacturing challenges associated with the peptide drugs? I mean, is there a dose at which COGS just don't justify oral formulation? And I have a quick follow-up.
Yeah. It's a good question.
Right now, we don't have a maximum. I think we're spending a lot of time on manufacturing approaches and understanding the cheapest, fastest, highest-yielding variation of the manufacturing approach. So as we learn more about that, that will inform us better on what is a feasible top dose. But given the tolerability and the encouraging initial trajectories here, we don't have a reason to stop at this point. All right. Now that you have some oral data, are you now able to share anything about your special formulation, or is that something that you're going to continue to keep closely guarded as sort of a trade secret?
Yeah. Thanks, Joon. We're not going to disclose anything. I think we have a competitive space we're in right now, a lot of new entrants. And I think it's best to keep this sort of thing as closely guarded as possible.
I have to try. Anyways, thank you so much, and congrats on the data again. Thanks a lot, Joon.
Thank you. The next question is from Jay Olson with Oppenheimer. Please go ahead.
Oh, hey. Thanks for taking the question. Can you talk about some of the characteristics of the side effects you've observed and how they compare to the side effects you saw for the sub-Q form of VK 2735? Thank you.
Yeah. Thanks, Jay. The side effect table, as indicated in the press release, I mean, it kind of sounds crazy, but there really don't seem to be many side effects.
Certainly, on the GI side, which is what we were expecting based on the known characteristics of the mechanism, as also our phase 1 and phase 2 data, we expected to see a little more on the GI side, and we just don't see anything different from placebo. And there aren't any other areas where you see real delta on adverse events. So maybe that will emerge over time with the higher doses, but we have not yet seen any big differences.
Okay. Great. Thanks. And then can you just talk about how you're planning to position oral with injectables since you have both formulations?
Yeah. Yeah. We've thought about this a lot. The areas where you could see an oral slotting in would be potentially as a lead-in to an injectable, more in the primary care setting.
If somebody didn't want to start with an injectable therapy, maybe they could start with an oral for some temporary period of time. And then when they see weight loss, realizing the sub-Q might generate better weight loss, it would probably reduce their resistance to transitioning to an injectable. And on the other side of that, once someone has experienced a high degree of weight loss with an injectable formulation, maybe transitioning to the oral would be a suitable maintenance strategy. Those are the two, I think, largest opportunities for an oral therapy.
Great. Thanks so much for taking the questions, and congrats on these results.
Thanks a lot, Jay. Thank you.
The next question is from Andy Hsieh with William Blair. Please go ahead.
Oh, great. Thanks for taking our questions. Congratulations on the data and progress. Two for us.
One is kind of looking at the landscape, looking at the semaglutide 50 milligram OASIS 1 study. They dose up to 50 milligrams. And I guess if you correct for the molecular weight, which is about 20% higher, assuming tirzepatide molecular weight for 2735, that would indicate probably in the 60 milligram. I'm just curious if that's something that would guide the maximum dose, looking at what others have done, or it's basically just a straight-up kind of a safety tolerability assessment. The second part, which has to do with tolerability, is the discontinuation. I know that you just got the data recently, but just curious if you have any information on the discontinuation rate.
Yeah. On the first one, what is guiding us really is the tolerability profile. So we haven't considered other datasets really in the dose escalation scheme.
We've just looked at our own data and decided to proceed because of the tolerability. On the discontinuation side, there were two discontinuations: one person who had a family emergency and had to leave the study, and one person who discontinued for abdominal pain. Both of those people did not complete the study. Got it. Thank you so much. Thanks, Andy.
Thank you. The next question is from Roger Song with Jefferies. Please go ahead.
Great. Congrats for the data from us. A couple of questions from me. One is understanding the discontinuation rate is pretty low, and the safety tolerability profile looks pretty clean. Can you tell us a little bit about the dose down titration? Is that allowed, and does any patient get to down titrate from the higher dose as your dose escalates?
So in terms of the efficacy measurement, how do you account for those patients with the dosing interruption in the study? I have a quick follow-up after that. Thank you.
Thanks, Roger. Yeah. On the dose adjustments and things like that, since it's a phase 1 study, it's less common to really incorporate those sorts of elements into a trial. So there was no dose adjustments allowed. If someone could not tolerate the compound, they were discontinued. The vast majority had no issues. The table in the press release speaks for itself there. What was the second question? Sorry, Roger.
The efficacy measurement for those dose adjustments, but it seems you don't have any dose adjustments. Yeah. That's right. That's right. Yep. My last question is regarding the scalability. It seems your oral looks pretty promising here.
But given this is a peptide drug, how would you think about the long-term, later-stage development and the commercialization in terms of the scalability? Understanding you're not disclosing the formulation, but how is your formulation amenable for large-scale manufacturing? Thank you.
Yeah. Thanks, Roger. And this is an area we're spending a lot of time on, is scalability. Based on the tolerability profile and the preliminary signs of weight loss that we see today, it's certainly an encouraging profile. So we are working on the best scale-up approach. We've got plenty of material on hand today to complete registration studies. But commercial is a larger demand. So we're continuing to work on it, and I think we'll get there. But it's an ongoing process. Excellent. Thank you. Thanks, Roger.
Thank you. The next question is from Annabel Samimy with Stifel. Please go ahead. Hi.
This is Jack for Annabel. Thanks for taking our questions, and congrats again on the data. So how meaningful is it that the weight loss was maintained for six days after dosing? And how has that kind of compared to the rebound that we may have seen with some of the other oral obesity programs in development?
Yeah. Thanks, Jack. It's unclear yet how durable that maintenance is. What was interesting, though, is you see the placebo start to retrace back to baseline after six days, where the treated stays pretty much at the same level they were at day 28. So that's, I think, of interest for someone who might miss a dose, might be traveling or something, and not have access to their medication. I think that's an encouraging sign that you don't necessarily have to take it every day.
But right now, it's a little early to interpret that. It looks really good, but hard to know how long that durability will last with the oral formulation. Great. And then on the PK data, so you mentioned that it seems like there's kind of a slow accumulation of effect over time. Would that potentially suggest to you at all that you may see more tolerability issues emerge with time as those maximal effects are achieved, or would the titration scheme potentially mitigate that? It's a good question. I don't think that there will emerge new tolerability issues over time because the accumulation almost serves the role of a titration. So even though we're probably not at peak exposures to 28 days in any cohort in the study, because they're gradual, you're getting acclimated to the therapy through the month.
And so it reduces the risk of some new adverse event occurring. But getting back to Steve's question earlier, could you start at higher doses and not titrate at all? And maybe you can, but we'll probably incorporate the titration element in future cohorts. Makes sense. Thank you.
Thanks, Jack.
Thank you. As a reminder, if you would like to ask a question, you may press star, then 1 on your telephone keypad. The next question is from Yale Jen with Laidlaw & Company. Please go ahead.
Good morning, and thanks for taking the question, and congrats on the data. Brian mentioned that the placebo effect seems to be larger than you anticipated. What's your thought of why that might be? Do you have any thoughts or hypotheses behind that? And thanks.
Yeah. Thanks, Yale. I think primarily a function of small numbers.
One thing we did note when we look at the diarrhea signal, there were two cases of diarrhea in the placebo arm. And you can look at the weight loss trajectory in that first week. Those two subjects in placebo had diarrhea. You can see the placebo trajectory much steeper in the first week relative to the treated cohorts, and then it doesn't necessarily rebound following that first week. I don't know how much that contributes, but that was just an interesting observation when we look at the overall data tables.
Okay. Great. And again, congrats on the data.
Thanks, Yale.
Thank you. The next question is from Thomas Smith with Leerink Partners. Please go ahead.
Hey, guys. Good morning. Thanks for taking the questions, and congrats on the strong data here.
Just to follow up on the placebo response, is there anything notable in terms of the lifestyle modification and the fasting requirements that were built into the study? No. There weren't any lifestyle modifications really recommended in the study. I mean, the only thing, as I mentioned to Yale, the only thing that seemed to stick out there was the incidence of diarrhea in two people, and it led to what looked like a steeper initial trajectory in the placebo group. But I'm not sure if that's real or not, but those two things did coincide. Otherwise, I don't know. What was interesting, looking at that day 34 data, the placebo had pulled back about 0.5%. So I don't know. It was like 1.6% at 34 days, whereas the treated maintained. So the delta got a little larger. So that was really interesting. But I don't know.
When you look at the 2.5 and the 5 mg, as I said earlier, it just seems like they're clearly subtherapeutic. And so is the placebo really kind of somewhere in between those two cohorts and that 2.1%? That would correspond better with what's in the literature. But anyway, these are the data we have. Understood. That makes sense. And then was there anything notable, Brian, with respect to the food effect? And can you just remind us how patients were dosed in the phase 1?
Yeah. They were dosed in the morning following an overnight fast, which is not necessarily different from phase 1 studies in general. We asked that they not consume anything for 30 minutes after taking their dose. Whether or not that's required will determine in a real food effect study. But those are the only elements there. Got it. That's helpful. Great.
Thanks for taking the questions, Brian. I appreciate it. Thanks a lot, Tom.
Thank you. The next question is from Justin Zelin with BTIG. Please go ahead.
Thanks for taking the questions, and congrats on the strong data here. Brian, anything you could tell us on the bioavailability of the oral compound? No. We haven't really disclosed any of that. It's certainly lower than the sub-Q, but we just haven't disclosed the details around the formulation and bioavailability. Great. And just on the safety profile, this looks really clean. Do you think this could hold up over time with higher doses, having perhaps an even more safer profile than your sub-Q formulation?
Well, it seems to be extraordinarily well tolerated. And how that plays out when we get to higher dose levels, we don't know. But right now, there does not appear to be any signal.
So that's what led us to decide to continue dose escalation. We'll keep an eye on any new items that emerge. But right now, it's pretty clean. There is really no difference from what we can see in the data. There's no difference relative to placebo. No meaningful difference relative to placebo on GI in particular.
Excellent. Thanks for taking my questions.
Thanks, Justin.
Thank you. The next question is from Naz Rahman with Maxim Group. Please go ahead.
Hi, everyone. Congratulations on the data. Just a couple of questions. The first one is, did you guys measure any metabolic biomarkers like CV biomarkers in this study? And did you see any effect on those? Also, when could we see that data if you did evaluate it?
My other question is, on dose escalation, is there any thought about increasing the dosing frequency from once a day to twice a day?
On the second question, no. We're going to stick with the once a day. I don't think we need to go to a twice a day. And I'm sorry. What was the first question again? CV markers. Oh, oh, yeah. Did you measure? Yeah, yeah, yeah. On CV markers, well, we looked at lipids and glucose, insulin, those sorts of things. We just don't have those data yet. When may we see that data? Probably later in the summer when we're done with all the cohorts. We'll have all of the labs. We just don't have the labs right now. Got it. Thank you. And once again, congrats on the data. Thanks, Naz. Thank you. This concludes our question-and-answer session.
I would like to turn the call back over to Stephanie Diaz for any closing remarks.
Thank you, everyone, for joining us today. Thank you for your continued support of Viking Therapeutics. And with that, we will end the call. Thanks so much, and have a great day. The conference has now concluded. Thank you for your participation. You may now disconnect your lines.