Great. Thanks, Roger. Thanks to Jefferies also for the invitation. We've got a great schedule. I appreciate it. I'll make some forward-looking statements today. I refer anybody hearing this presentation to the Securities and Exchange Commission website for the most current information on Viking Therapeutics. Happy to walk through the story today. I'm Brian Lian, the founder and CEO. We're based in San Diego. We're developing small molecule therapeutics for metabolic and endocrine disorders. We have multiple programs that have demonstrated very promising clinical activity. Our metabolic disease program's highlighted by an obesity program, VK2735, which is a dual agonist of the GLP-1 and GIP receptors. We have both a sub-Q and an oral formulation of that molecule. We have a NASH program highlighted by VK2809, which is a selective thyroid receptor agonist.
Just this week, we read out some phase 2 data from that program, which I'll highlight today. We have a rare disease program as well, which is highlighted by a small molecule called VK0214, which is another selective thyroid receptor agonist that is in a phase 1b study in a rare disease called X-linked adrenoleukodystrophy. I'll talk more about our thyroid receptor agonists. First, just an overview of the thyroid hormone. These are nuclear hormone receptors, two main types. The beta receptor is the receptor we target. It's primarily localized to the liver, and we think of this as sort of a master regulator of lipid metabolism. There's another isoform called the alpha receptor that's expressed in cardiac tissue that plays a role in basal metabolic rate and is proarrhythmic.
So when you're developing something in the NASH setting or the lipid setting, you really want to have good selectivity on beta with minimal activity on the alpha, and that's what our compounds seem to do really nicely. VK2809 is a really unique compound, as you see here. It's actually dosed here as a pro drug. Following oral administration, if you go down the arrow, it's actually converted to this active thyroid agonist we call VK2809A, and that conversion is mediated by CYP3A4, which is primarily expressed in the liver. So the result is you get this truly chemically targeted delivery of drug into the tissue of greatest relevance.
What the image here shows on the right is a rodent that was dosed with radiolabeled VK2809, and you can see the radioactivity localizes in the liver relative to other tissues, and that really highlights that the drug behaves the way in which it was designed to behave. We, earlier this week, read out data from a phase 2b study called the VOYAGE study. This was a 12-month study in patients with biopsy-confirmed NASH, or MASH is the newer term for it. It was a 5-arm study for 1 year of treatment. The primary endpoint was a 3-month read on liver fat with MRI-PDFF. Patients were then dosed for the remainder of the 12-month window, and the second biopsy was then taken at 12 months and looking at histology for NASH resolution, fibrosis improvement, and that sort of thing.
Last year, we read out the primary endpoint for VOYAGE, and that was the relative change in liver fat content after 12 weeks of treatment. We saw a significant reduction in liver fat down to approximately 57% with the 10-mg cohort from 38% at the 1-mg cohort, statistically significant in the three higher arms. So very excited to have the success on the primary endpoint in this study. Patients continued on through then 52 weeks and received a second biopsy, and here are the data from the 52-week biopsy when we look at the, I'm sorry, these are the response rates after 52 weeks. It's just showing that the liver fat holds up for 52 weeks. So this is a percent of patients with at least a 30% relative reduction in liver fat at 52 weeks, and so the response rates range from 63%-88%.
So nice dose-dependent liver fat reduction and shows a sustained liver fat reduction through the 52 weeks. Now going to the biopsy data. So one of the biopsy endpoints was the NASH resolution rate without worsening of fibrosis after 52 weeks of treatment, and here we see the NASH resolution rates up to 75% in the 10-mg cohort, also statistically significant in the 1-mg cohort. We don't consider this to be sort of a reverse dose-response or anything like that. We just think this is a smaller cohort that had a couple of extra responders and had a high response rate. So overall, a very, very impressive endpoint on NASH resolution after 52 weeks.
When we looked at fibrosis stage, we were actually not expecting much of a signal in fibrosis because the trial was sort of moderately sized, and we hadn't seen a robust fibrosis benefit in some of the other thyroid agonist studies. So we were really happy to see this fibrosis improvement. We saw up to 57% of patients achieving a one-stage improvement in fibrosis without worsening of NASH, and that was statistically significant at both the 5- and 10-mg cohorts. When we look at the combined endpoint of fibrosis improvement and NASH resolution, also saw very impressive data here ranging from 40% at the 2.5-mg up to 48% at the 10-mg cohort versus around 20% in the placebo group. So very impressive on the combined endpoint of fibrosis improvement and NASH resolution. Some of the other endpoints looked at lipid changes.
This shows the effect on LDL cholesterol after 52 weeks. We had previously shown after 12 weeks somewhere in the high teens for LDL reduction. So at 52 weeks, we do see a modest improvement over the 12-week endpoint, ranging from about 20%-25% placebo-adjusted, and highly significant at the top three doses. Also saw statistically significant improvement in triglycerides, apolipoprotein B, lipoprotein(a), and apolipoprotein C3. When we look at safety and tolerability in the VOYAGE study, very encouraging profile. The treatment-emergent adverse events, about 79% in placebo, a little bit higher overall in the combined treatment arms. When we look at the drug-related treatment-emergent adverse events, pretty well balanced, about 34% in placebo to 30% in the treatment. The treatment-emergent adverse events leading to discontinuation, also very well balanced, 9% placebo, 6% in the combined arms.
And then, importantly, on GI-related adverse events, overall very well balanced, 18% overall in placebo, a little bit lower in the treatment arms. So no delta really on GI-related adverse events. So overall, most AEs were mild or moderate, a really encouraging discontinuation rate related to adverse events as well. So no real delta from placebo. So the main takeaways from the VOYAGE study, we were happy to announce last year the achievement of the primary endpoint showing robust reduction in liver fat after 12 weeks. The histologic endpoints after 52 weeks showed NASH resolution, improvement in fibrosis, as well as an improvement in both the combined endpoint for NASH resolution and improvement in fibrosis.
When you look broadly at the cardiometabolic profile, we saw reductions in LDL as well as Lp(a) and ApoB and ApoC-III, really encouraging tolerability, GI side effects similar to placebo, and excellent overall safety with 94% of adverse events mild to moderate. Next steps with this program are to conduct an End-of-Phase 2 meeting with the FDA in the second half of the year, understand the current thinking for registration and approvability endpoints in NASH, and then proceed from there with the compound to make a decision on further steps. I'll now move to our obesity program. This is focused on peptides that bind to two receptors. The GLP-1 receptor, shown here in the red, distributed throughout the body.
They're produced in the peptide. GLP-1 is produced in the intestines following ingestion of nutrients and then binds to the pancreas and also the hypothalamus to stimulate insulin production and affect appetite. GIP is another receptor that's related, also expressed in the pancreas and the hypothalamus, also important for feeding behavior and insulin regulation. These receptors have shown great promise in both obesity and diabetes, and now more recently in NASH. We designed a series of compounds, peptide-based compounds that target both receptors. They're very potent at both GLP-1 and GIP, highly variable GIP activity. What we see here is the data from some of the early work we did, 14 days in a rodent model of obesity, looking at body weight change across a series of compounds. Generally, we see 15%-30% placebo-adjusted reduction in body weight after a relatively short treatment window.
Compounds have predictable PK, well-behaved. Here's just an example from a compound, I think this was VK2745, shows you a very tight PK profile in primates, so very reproducible and well-behaved. We conducted a phase 1 study with VK2735. We read these data out last year, and this was a 28-day multiple ascending dose study looking at once-weekly dosing. What this graph shows is the change in body weight after 28 days, and we saw in this study a very nice improvement in body weight, dose-dependent, ranged up to approximately 8%, 7.8% from baseline, placebo-adjusted 6% change from baseline after four weekly doses. So really nice preliminary proof of concept here. This graph shows kind of the trajectory of weight loss after 28 days.
Just looking at three doses here, so the gray is the placebo, the light blue is the lowest dose, which is 0.5 milligrams, the blue is a middle dose, 5 milligrams, and then the dark blue is the high dose, 10 milligrams. So nice lack of a plateau here at 28 days, and these data led us to believe a longer treatment window would lead to further enhancement of the weight loss signal. So following that study, we designed a longer study, a 13-week study. We called it the Venture study. This was looking at four different doses: 2.5 milligrams, 5 milligrams, 10 milligrams, and 15 milligrams, dosing weekly for 13 weeks. And what you can see here are these little triangles demonstrating where people were up-titrated.
So these bottom doses started at 2.5 mg, the 5-mg dose up-titrated to 5 mg after 3 weeks, the 10-mg up-titrated to 10 mg after titrating to 5 mg, 7.5 mg, and then starting at 10 mg. Then the 15 was a little bit different. It started at 5 mg and then up-titrated to 7.5, and then 10 mg, and then 15 mg here. So overall, everybody reached their top dose for a minimum of 4 weeks. When we look at the primary endpoint of this study, it was change in body weight after 13 weeks of weekly dosing, and we saw a significant reduction in body weight after 13 weeks, approximately 15% from baseline, 13.1% placebo-adjusted, and highly significant at each dose level. So very encouraging overall 13-week readout on body weight change.
This graph shows the trajectory of weight loss through the 13-week treatment window, and you can see here at the first week, there was a separation from placebo, and each arm was statistically significant after just one week, and then it became further progressive through the course of the treatment window. You can see nice dose-dependent reduction from 9% at the 2.5-mg dose up to 14.7% at the high dose, and no real evidence of a plateau here. So we believe that further extension of dosing window should lead to a further emergence of additional weight loss. When we look at GI tolerability from this study, pretty encouraging overall. What you typically see with GLP-1 activation is this nausea induced by GLP-1 agonism, but so we did see that.
So primarily mild to moderate nausea that came up a little bit in a dose-dependent fashion, very limited amount of vomiting overall, and then really no separation on the other abdominal pain and diarrhea, not a huge delta versus placebo. So we were very satisfied with the GI tolerability given that we were titrating a little bit more aggressively at a 3-week cadence. This is a combined cohort analysis of just GI adverse events through 13 weeks. And so what you can see here, constipation in green, diarrhea in blue, nausea in the purple, and then vomiting in the gold. And what we thought was interesting about this was that you can see that most of these AEs tend to predominate in the first week of treatment and then really asymptotically approach 0 through 13 weeks. So it suggests that these are all pretty early.
They're on the first exposure to the drug, and then they moderate over time without any interruption in dosing or down titration or anything like that. So the Venture study takeaways here, we saw up to 14.7% weight loss from baseline after 13 weeks, very promising tolerability. Let me go back here. Promising tolerability with over 90% of the drug-related treatment-emergent adverse events, mild to moderate. Majority of the GI AEs occurred early in treatment and then resolved with continued treatment. And then we're still waiting on the final, final data from this study looking at PK and clinical chemistry, and we should receive that very shortly. The next steps, as I said, we expect the final Venture data this month sometime.
We have submitted a request to the FDA for a Type C meeting, and that request was accepted, and we expect to receive the written responses to the Type C meeting this quarter. Then we'll make a decision on what the next clinical study will be based on that feedback. We expect to move into the next clinical study, whether that's a phase 2b or a phase 3, toward the end of this year. We've also been working with an oral formulation of VK2735, and I will highlight that here. Same molecule, but in a tablet formulation. We're still conducting a multiple ascending dose study with this formulation. This is the study design outlined here. It's a single-site placebo-controlled extension of the multiple ascending dose study that was conducted with the sub-Q formulation.
Primary objectives, safety and tolerability, but body weight and glucose are really what people are most interested in, body weight in particular. Here is the titration scheme. So starting at 2.5 mg daily for 28 days, then there's a dose-level review team that meets and discusses the data and makes a recommendation to go up. So the cohorts that have been completed thus far have been 2.5 mg daily, 5 mg daily, 10 mg daily, 20 mg daily, and then a 40 mg daily cohort. And we're currently in a 60-mg daily cohort. When we look at the data thus far after 28 days of daily dosing, we reported these a couple of months ago. What we see here is a pretty nice dose response.
We're really starting to get into the meat of the signal here at the 20- and 40-mg doses, where we see up to 5% weight loss from baseline, 3.3% placebo-adjusted. The placebo response was a little bit larger than we expected. We expect this to kind of retrace a little bit in a larger or longer study, but we saw 2.1% for the combined placebo in these cohorts. When we look at day 34, this is one week after the last dose was administered, the half-life of the drug's over a week. So it was of interest to look out one week. And we see most of the weight loss in the two top doses retained, 3.1% and 5.2% from baseline. And you see the placebo now start to retrace a little bit from 2.1% to 1.6%.
So encouraging that you don't see this immediate rebound, and you see some sustained effect, at least at the higher doses. When we were looking at the data, I'll talk about in a minute, the AE profile was very clean, and it made us curious, are we really seeing a signal here or not, because there weren't any AEs really. So we started to look at these different cuts. And one of the cuts we looked at was the proportion of subjects with a 3% and a 5% relative weight loss. And what you see here is the blue shows the proportion of patients with a 3% weight loss. The gold shows the proportion with at least 5%.
You can see you see 20% at the placebo, but you can see a nice dose-dependent increase up to 86% in the 40-mg dose had at least 3% weight loss. When you look at the graph, up to 57% had at least 5% weight loss in the 40-mg dose cohort. So nice evidence of a signal that's clearly dose-dependent. Another cut we looked at, which was really interesting, was the clinical observation of increased satiety, so this feeling of satisfaction and not wanting to eat. And what this shows, the graph shows the proportion of subjects who report an increase in satiety. And so that ranged up to about 57% in the 40-mg cohort.
And when you mirror that with weight loss, it was just really interesting to see that you kind of mirror the dose response with the 40-mg dose showing the highest increase in satiety, the highest proportion with an increase in satiety, also showing the largest amount of body weight change. So another confirmation of the signal there. Looking at the trajectory of weight loss here across the oral cohorts, you can see the three lower dose cohorts here, not much separation at all from placebo. I mean, they're just really along the baseline here. But when you get to about two weeks with the 20 and the 40-mg cohort, then you can see this you start to see the efficacy really kind of emerge there. And the curve's still negative here at 28 days would suggest that extending the dosing window would lead to an improvement in weight change.
When we look at the GI tolerability here, this was much more mild than we had expected. We certainly expected to see the nausea and potentially vomiting and diarrhea that are observed with the mechanism. We really didn't see much of anything here. We did see overall 14% of subjects reporting mild nausea, nothing moderate, nothing severe, zero vomiting across all arms, abdominal pain lower than placebo, diarrhea lower than placebo. Just an overall surprising to us that it was so well tolerated, given that we did see really encouraging weight loss. So the study takeaways at this point, we saw up to 5.3% mean weight loss after 28 days of daily VK2735 treatment. The progressive effect would suggest that further weight loss is possible with longer treatment. Really excellent preliminary tolerability with all of the treatment-emergent adverse events across the study, mild to moderate, none severe.
Low rate of GI adverse events, no vomiting or constipation observed. We think the dose response and tolerability would suggest that further weight loss is possible with increased dose escalation. That's ongoing now. We're now in a 60-mg cohort that's going to be wrapping up shortly. Dose-level review team will evaluate those data and then make a recommendation as to whether to increase the dose. If we were to increase the dose, we would likely go to 80 mg. What the plan is with this oral formulation is to move into phase 2 by the end of the year. Then a quick wrap-up on the financials here. We ended the first quarter with $960 million in cash. We believe that's sufficient to support full phase 3 development of both the oral and the sub-Q formulation and sufficient runway, I think, for the next several years.
Very comfortable to be in the cash position we're in. That's the story. We're focused on novel therapeutics for metabolic and endocrine diseases. Our metabolic disease program highlighted by VK2735, the dual agonist of GLP-1 and GIP. We've read out a successful phase 2 study, the Venture study, which was successful in the primary and secondary endpoints. The oral formulation has shown a very promising phase 1 signal in healthy volunteers, and we're planning to go into phase 2 in the second half. Our thyroid agonist, VK2809, earlier this week read out positive data on histology endpoints following a year of treatment, showing NASH resolution and fibrosis improvement. Then the program we didn't mention in the presentation is our orphan disease program, VK0214, in a phase 1B trial in X-linked adrenoleukodystrophy.
We plan to read out data from that study around the middle of the year. So I will stop there. Thanks very much for your attention.