All right. Welcome everyone to Jefferies Healthcare London Conference. My name is Roger Song, one of the senior analysts covering biotech in the U.S. It is my pleasure to introduce our presenting company, Viking Therapeutics, CEO Brian Lian.
Thanks, Roger. Thanks to Jefferies for the invitation to present. I really have a great schedule today, so I really appreciate it. I'll make some forward-looking statements today. I'd encourage anybody hearing this presentation to refer to the Securities and Exchange Commission website for the most current information on Viking Therapeutics. I'll walk you through the story today. I'm Brian Lian. I'm the founder and CEO. We're a San Diego-based company. We've got about 55 employees. We are focused on metabolic and endocrine disorders. We think our clinical programs have demonstrated best-in-class efficacy data. We'll talk a lot today about our metabolic disease programs. VK2735 is a GLP-1, GIP dual agonist that we're developing for obesity. It's currently in a phase III program. We call it the VANQUISH program. We have an oral formulation of the same molecule that recently completed the phase II study.
I'll walk through some of those data today as well. And then we have an amylin agonist that is approaching the clinic, and we expect to file an IND in the first quarter. We have additional programs focused on the thyroid receptor beta, the two agonists, one VK2809 that's been through a phase II-B study in NASH, and one VK0214 that's been through a phase I-B study in X-linked adrenoleukodystrophy. We're not actively developing those programs. Here's a graphical representation of the pipeline here. You can see the VK2735 in phase III with the subQ formulation, and then the oral formulation just completed a phase II study. And then the amylin moving toward the clinic. The additional programs are not being actively developed right now at the NASH program and the X-ALD program.
With the peptide hormone agonist program, we started working on these molecules back in 2019. We looked at the GLP-1 monoagonists, and then dual agonists where GIP activity is added, and then triple agonists where glucagon activity is added on top of those. We prioritized the dual agonist mechanism because they just seemed to work the best. When we added glucagon, there was not any incremental benefits. We focused on the dual GLP-1, GIP coagonists. VK2735 was selected as the lead development compound. We have two follow-ons that are IND ready today. The injectable formulation completed the SAD/MAD study in the first half of 2023. Subsequently, we took it into phase III, called the VANQUISH-2 phase III programs, studies.
The oral formulation has been through a similarly a phase I SAD/MAD and also a phase II study with the most recent data reported in the third quarter of last year. I'll move to the oral formulation. It's a little bit earlier stage than the subQ, but it's where we have the most recent data. These are some data from a 28-day study we conducted with the tablet formulation. This is once daily dosing. With this formulation, after 28 days, we saw a nice dose response. You can see up to around 8% from baseline at 100 mg, placebo adjusted, around 7%. Very nice overall dose response. This shows the trajectory of a weight change following 28 days of dosing. What was interesting in this graph is when you—it's most obvious in that red line, the top dose, 100 mg.
You can see the dotted line there showing where treatment was stopped. For the following 57 days, we saw pretty good maintenance effect that lasted four weeks after that last dose. Actually, we had 8.3% after 57 days and 8.2% after 28 days. Really held on nicely. It suggested, in our view, that maybe once someone has attained some degree of weight loss, the maintenance could be feasible with a low dose for a longer period of time. When we look at the GI tolerability summary from the phase I study, very, very encouraging tolerability and very, very little titration in these. Most of the cohorts started at the top dose from the prior cohort and just went at that top dose for a week and then went to the target dose for three weeks.
For example, the 80 mg cohort started at 60 for a week and then went to 80 for three weeks. Despite that accelerated titration, we saw very nice tolerability. The phase I takeaways here from the 28-day study: up to 8.2% body weight reduction after 28 days of dosing. Progressive effect in most cohorts suggested that further weight loss likely to occur with longer treatment. The majority of the weight loss was maintained four weeks after the final dose. We saw in this study excellent tolerability through 100 mg with the vast majority of adverse events being characterized as mild or moderate. We saw low rates of vomiting, diarrhea, and constipation in the higher dose cohorts.
We did a—I didn't have it in the slides here, but an exploratory, transition cohort where people were titrated up to 80 mg daily for the first two weeks, and then they transitioned to an every other day regimen. These people also continued to demonstrate weight loss. It suggested that, again, you might be able to transition people to a lower daily dose and continue to see weight loss. Following this study, we conducted a phase II study, called the VENTURE-Oral Dosing Study. This was a dose ranging study, went from 15 mg up to 120 mg daily.
The green cohort at the bottom of the diagram there was an experimental cohort where people were titrated very quickly up to 90 mg and then down titrated to 30 mg for the final seven weeks of the study. That was to further explore this maintenance concept. These are the weight change data. These data were reported back in August. We saw a really nice dose response here, up to a little over 12% after 13 weeks of daily dosing. Every dose cohort showed a successively greater impact on weight loss. We were very happy with the efficacy profile here. When we look at the likely target doses moving forward, we're expecting to really focus on that 20 mg-75 mg range in future studies.
We feel that the profile, the weight loss profile here is very competitive after 13 weeks. This shows the trajectory of weight loss through 13 weeks, showing up to 12%, so 7%-12%, progressive, in every cohort, and statistically significant versus placebo at every time point after the first week for every cohort above 15 mg. When we look at the follow-up data here, here's some data that we received later on in October. We can see in this range that we're really interested in, that 20 mg-75 mg range, a nice maintenance of weight loss for the three weeks following completion of dosing. This further supports this concept of durability that we see. Here are the results from that exploratory maintenance cohort.
The gold line here shows the cohort that was just titrated up to 90 mg and held there through the 13-week window and showed around 11% weight loss. The green line here is that cohort that was transitioned from 90 mg to 30 mg. At week six, these people were down titrated back to 30 mg and held there for the following seven weeks. We were gratified to see that they had lost 8.1% after the first six weeks. Then after the transition to 30 mg, they continued to lose weight very gradually and ended with 8.2%. It suggested to us that this concept of a lower maintenance dose is very promising. When we look at discontinuations here and treatment emergent adverse events, really, not a lot of difference.
When you go to the far right on that 120 mg cohort, you do see an uptick in discontinuations and overall treatment emergent adverse events. When we look at the range that we're expecting to focus on in future studies, really not a great deal of difference between the treated cohorts and the placebo cohorts. Majority of the treatment emergent adverse events were mild to moderate, and discontinuations, probably due to this accelerated titration rate here. We, based on the phase I data, we had used two-week titration blocks, and we started at 30 mg. I think in future studies, we'd probably start a little lower and extend the titration block to four weeks. Most of the treatment emergent adverse events that led to discontinuation were GI related.
When we look specifically at the GI tolerability summary, again, a little bit higher as you go to the far right of the table, relative to placebo. Overall, when we focus on the dose range that we're most likely to utilize in future studies, really no significant difference from placebo on nausea or other GI adverse events. A little bit of an uptick in vomiting, but we think that starting low and going slow is likely to address that. Again, most of these mild. This is an interesting histogram that shows the time course of GI adverse events. This is consistent with what I'll show in a few minutes from the subQ experience.
That is that, usually when GI adverse events are observed, the most common occurrence is in that first week of treatment when people are first exposed to the mechanism. The second most common window of GI adverse events is in the first step in up titration. You can see that here. Week one was the initiation of treatment. Week three is your first step up, and that's where you see the highest rate of nausea, in blue. Following that, after you get to week four and beyond, really, very little difference from baseline and background rates on constipation, diarrhea, and vomiting. The phase II study takeaways and next steps, we saw up to 12.2% reduction in body weight after 13 weeks of oral dosing. Progressive, dose dependent weight loss across all treatment cohorts.
The maintenance cohort, it was exploratory, but it was very promising. It showed a, a proof of concept there. After you transition to a lower dose, you continue to see some weight loss. We thought excellent tolerability through the 120 mg dose with the majority of treatment emergent adverse events characterized as mild to moderate. We think that starting low, you know, 10 mg-15 mg starting dose and then four-week titration blocks are likely to greatly improve the tolerability profile observed here. The majority of the GI adverse events also were mild to moderate. I'll talk in a few minutes about a study that we have ongoing today, which is a transition study where people start with a subQ dosing regimen and then transition to oral, daily, a low dose oral, daily regimen. That study's ongoing.
We currently, with this formulation, plan to talk to the FDA by the end of the year and have an end of phase II meeting and then decide what the appropriate next steps are for the oral tablet. Now I'll move to the sub Q formulation. This has been through a SAD/MAD study and also a phase II, 13-week study. This is just a brief summary of the SAD/ MAD takeaways from the SAD study, single ascending dose study. We saw a TMAX of about 72 hours, which indicates a fairly gradual onset of action. Half life, 170 hours-250 hours, which we think makes the formulation amenable to weekly dosing and potentially monthly dosing. In the MAD study, we saw a dose dependent improvement in weight loss up to 7.8% after 28 days. That was in subjects with an elevated BMI.
And then we saw durable, weight loss, 21 days after the last dose. In this, in the MAD study, we also looked at liver fat. We saw up to about a 50% reduction in liver fat in the patients who received MRIs. We think that's pretty, pretty rapid effect and indicates a broad metabolic benefit from the mechanism. The really excellent exposures from weekly, suggesting that a monthly is certainly a possibility. Finally, excellent tolerability of 98% of the adverse events characterized as mild to moderate. Following the phase I, we designed and initiated this phase II study. We called it the Venture study, very similar to that oral study I just talked about, but used weekly injections, dose range from 2.5 mg up to 15 mg.
The 2.5 mg was a flat dose. The 5 mg, 10 mg, and 15 mg utilized titrations every three weeks. The primary endpoint here was, change in body weight, at week 13 versus placebo. This slide shows the, primary endpoint in that study, looking at, change in body weight after 13 weeks. Very nice dose response, ranging from 9% to approximately 15% from baseline. Statistically significant, starting at week one, and, maintaining all the way through the, the 13-week endpoint. That is shown here, the, progressive weight loss over, over 13 weeks. You can see a very nice, initiation, of weight loss and then, sustained trajectory through the entire, treatment window. No evidence in any cohort of a plateau. We think that suggests, a further improvement in body weight, with, with longer dosing.
Here is a GI tolerability summary. And, we can see here, you know, like with the oral, generally you see an increase in GI adverse events, nausea, vomiting, and diarrhea as dose increases, but it's not always purely dose dependent. You can see the, you know, for example, the 10 mg is maybe a little bit better than the 5 mg. So, general increase, but we don't think a significant issue with GI or anything that's different or unexpected from the mechanism. This is an interesting slide because it shows the time course of GI adverse events in two cohorts. The 10 mg cohort is on the left and the 15 mg cohort is on the right. The big difference in these two cohorts is that the 10 mg cohort started at 2.5 mg.
You can see in that first week, just like we saw with the oral, an elevation in nausea and a little bit of constipation there in that first week, which then declines very rapidly and then ticks up again when you hit week four, which was the first titration step. The difference between the left-hand graph and the right-hand graph is the 15 mg cohort started at twice the dose. The 15 mg cohort started at 5 mg. You can see here, a large increase in nausea. It really speaks to that mantra that everybody talks about with this mechanism, start low and go slow. When you look out on the right-hand side of that right graph, you can also see, when they were titrated to 15 mg, you see another uptick in nausea.
This was the largest uptick because people went from 10 mg to 15 mg. They skipped the 2.5 mg dose. We learned two things from this cohort. One, you want to start below 5 mg. Two, you do not want to jump more than 2.5 mg in each titration step. Very valuable learnings from this cohort. Again, to start, start low and go slow. The phase II study takeaways are summarized here, up to 14.7% mean weight loss after 13 weeks. We think very promising tolerability with over 90% of drug-related treatment emergent adverse events mild to moderate. The majority of GI-related adverse events occur early and then resolve. We see good durability here.
We don't have the slide in this deck, but, when we look four weeks after the last administration of study drug, more than 90% of the efficacy was retained, which further suggests that, you know, possibility of a less frequent than weekly dosing. To that end, you know, the PK profile suggests that potential monthly regimen would be worth exploring. Where we are today, with the subQ formulation, we initiated two phase III studies in the second quarter. The VANQUISH-1 study is enrolling patients with obesity. The VANQUISH-2 study is enrolling patients with obesity and type 2 diabetes. Both of these studies include an extension to look at long-term safety and efficacy of 52-week extension. VANQUISH-1 , we just announced before this presentation this morning, we've completed enrollment and that was over-enrolled versus the target enrollment number there.
VANQUISH-2 , we expect to complete enrollment in the first quarter. This is a diagram of the study design, for both studies. There are three treatment arms versus placebo, 7.5 mg, 12.5 mg, and 17.5 mg. All of the cohorts started 1.25 mg. They're held there for two weeks and then they undergo four-week blocks at 2.5 mg. It takes about 26 weeks for the 17.5 mg to reach that top target dose. Once that 17.5 mg dose is reached, they're held there for 52 weeks. Primary endpoint is change in body weight from baseline and secondary endpoints look at proportions with 5%, 10%, 15%, and 20% weight loss. Finally, this is a maintenance study that we kicked off in October.
Complicated slide, it's a complicated study, but, if you focus on the top hand or the top part of this diagram, you can see cohorts are titrated on a weekly basis up to a range of weekly doses. They range from 15 mg weekly up to 22.5 mg weekly. At week 19, cohorts are transitioned to a monthly regimen. The monthly regimen ranges from 15 mg up to 22.5 mg. We have a control in there that keeps 17.5 mg weekly through the whole window. Another control that titrates up to 17.5 mg and then transitions people to placebo, and then a placebo the entire duration of the study as well as a control. The bottom hand, the bottom half of the study, of the slide, shows an oral set of cohorts here. So these cohorts are titrated up to 17.5 mg weekly.
At week 19, they're transitioned to either 17.5 mg daily oral, 27.5 mg daily oral, or 110 mg weekly oral once a week. A lot of really, really useful information will come out of this study. We expect to report the data around the middle of next year. Finally, I'll wrap up with the financial summary. We ended the third quarter with a little over $700 million in cash. We expect that to get us through the VANQUISH phase III data readouts, and really fortunate to have the runway that we have today. That's the story. We're focused on metabolic and endocrine disorders. The metabolic disease program highlighted by VK2735, that's the dual agonist for obesity, currently in the VANQUISH phase III trial program with VANQUISH-1 , completed enrollment as we announced this morning.
VANQUISH-2 , we expect to complete in the first quarter of next year. The oral formulation completed phase II. We will have an end of phase II meeting by the end of the year and then make a decision on what the next steps are with the oral formulation. I did not talk about it, but we do have an amylin agonist that is moving toward the clinic and we expect to file an IND in the first quarter of 2026. I will stop there. Thanks very much for your attention. Really appreciate it.
You wanna take a question?
Sure. Yeah.
Just one quick question. I think one of the new information I picked up is the oral formulation, the phase II, you decided to focus on the low end of the, maybe middle end of the dose cohort. Is that guided by the PK and then the GI or what, and then what's the TPP for that dose cohort?
What's the, what?
What's the target profile, product profile?
Oh, yeah. We focused on those mid-range doses. What I didn't mention is that the VENTURE-Oral study, everybody took four tablets, even the placebos. The tablets were 30 mg tablets and the 30 mg is, you know, it's a lot to put in one tablet. When we thought about doses to take forward, we wanted to, it was kind of a lot of things went into that decision. What's the right tablet size? How many tablets do people want to take? What are the margin considerations as you go up in dose? That 25-75 is really kind of the sweet spot for all of those items. That's why we decided to stay in that range. We have that weekly dose in the maintenance study.
That should be really interesting because the half-life's around eight and a half days. It's possible that, once you reach a target dose with the subQ, you could transition to that once-a-week dose and maintain body weight.
Thank you. Thank you, everyone.
Thanks.