Viking Therapeutics Inc (VKTX) 2019 Q4 法說會逐字稿

Good day, and welcome to the Viking Therapeutics Fourth Quarter 2019 and year-end conference call.

(Operator Instructions) Please note this event is being recorded.

I would now like to turn the conference over to Stephanie Diaz of Investor Relations.

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; and Greg Zante, Senior Vice President of Finance.

Before we begin, I'd like to caution that comments made during this conference call today, February 26, 2020, and will contain forward-looking statements within the meaning of the Securities Act of 1933 concerning the current beliefs of the company, which involve a number of assumptions, risks and uncertainties.

Actual results could differ from these statements 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.

Brian?

Thanks, Stephanie, and thanks to everyone listening on the webcast or by phone.

Today, we'll provide an overview of our fourth quarter and year-end 2019 financial results as well as an update on recent progress and developments related to our pipeline programs and operations.

2019 was a year of tremendous progress at Viking, building on the momentum that followed the successful outcomes of our completed clinical studies.

With respect to our lead program, VK2809, our novel thyroid receptor beta agonist, we completed the important work required to support a Phase IIb study in patients with biopsy-confirmed NASH, and we were pleased to announce in November the initiation of this important study.

With respect to VK0214, our second thyroid receptor beta agonist, our efforts during 2019 focused on continuing the IND-enabling work required to commence clinical studies of this molecule, and we expect to file an IND for this program in the first half of this year.

I will provide additional detail on our development activities in a few minutes, but first, we'd like to review our fourth quarter and year-end financial results.

For that, I'll turn the call over to Greg Zante, Viking's Vice -- Senior Vice President of Finance.

Greg?

Thanks, Brian.

In conjunction with my comments, I'd like to recommend that participants refer to Viking's Form 10-K filing with the Securities and Exchange Commission, which we filed after the market closed today for additional detail.

I'll first go over our financial results for the fourth quarter ended December 31, 2019.

Our research and development expenses for the 3 months ended December 31, 2019, were $6.5 million compared to $5.1 million for the same period in 2018.

The increase was primarily due to increased expenses related to clinical studies, with the initiation of the Phase IIb VOYAGE study during the quarter and manufacturing for our drug candidates, partially offset by decreased expenses related to our preclinical studies and services provided by third-party consultants.

Our general and administrative expenses for the 3 months ended December 31, 2019 were $2.4 million compared to $1.9 million for the same period in 2018.

The increase was primarily due to increased expenses related to stock-based compensation and professional fees.

For the 3 months ended December 31, 2019, Viking reported a net loss of $7.5 million or $0.10 per share compared to a net loss of $5.2 million or $0.07 per share in the corresponding period in 2018.

The increase in net loss and net loss per share for the 3 months ended December 31, 2019 was primarily due to increased research and development and general and administrative expenses noted previously, as well as decreased interest income due to the decline in interest rates throughout 2019 as compared to prevailing interest rates during the fourth quarter of 2018.

I'll now provide our financial results for the 12 months ended December 31, 2019.

Our research and development expenses for the 12 months ended December 31, 2019, were $23.6 million compared to $19 million for the same period in 2018.

The increase was primarily due to increased expenses related to manufacturing for our drug candidates, clinical studies, services provided by third-party consultants and salaries and benefits, partially offset by decreased expenses related to preclinical studies.

Our general and administrative expenses for the 12 months ended December 31, 2019 were $9.1 million compared to $7.1 million for the same period in 2018.

The increase was primarily due to increased expenses related to stock-based compensation, services provided by third party consultants, corporate insurance, legal and patent expenses and professional fees.

For the 12 months ended December 31, 2019, Viking reported a net loss of $25.8 million or $0.36 per share compared to a net loss of $22.1 million or $0.38 per share in the corresponding period of 2018.

The increase in net loss for the 12 months ended December 31, 2019, was primarily due to increased research and development and general and administrative expenses as noted previously, partially offset by increased interest income as well as the elimination of expenses related to the change in fair value of the debt conversion feature liability due to the repayment of the ligand noted May 2018.

The decrease in net loss per share for the 12 months ended December 31, 2019 was primarily driven by the additional weighted average shares outstanding at December 31, 2019, versus those outstanding at December 31, 2018, given the public equity financings that occurred during 2018.

Turning to the balance sheet.

At December 31, 2019, Viking held cash, cash equivalents and short-term investments totaling $275.6 million and had 72,413,602 shares of common stock outstanding.

This concludes my financial review, and I'll now turn the call back over to Brian.

Thanks, Greg.

I'll now provide an update on recent progress and activity with our lead program, VK2809.

As a reminder, VK2809 is an orally available, small molecule agonist of the thyroid hormone receptor that possesses selectivity for liver tissue as well as the beta-receptor subtype suggesting promising therapeutic potential in a range of metabolic disorders, including NASH.

In September 2018, we announced positive results from a 12-week Phase II trial of VK2809 in patients with hypercholesterolemia and nonalcoholic fatty liver disease.

As we have previously discussed, this trial successfully achieved both its primary and secondary endpoints, demonstrating potent reductions in liver fat content as well as improvements in plasma lipid measures.

As a brief reminder, patients receiving VK2809 experienced median relative reductions in liver fat, ranging from 54% to approximately 60%, compared with approximately 9% for placebo.

The proportion of patients experiencing at least a 30% relative reduction in liver fat ranged from 77% to 100%, with the overall average of 88% compared with 17% for placebo patients.

In addition, 70% of patients receiving VK2809 experienced at least a 50% relative reduction in liver fat content compared to baseline.

VK2809 also produced significant reductions in plasma lipids, including LDL cholesterol, triglycerides and atherogenic proteins such as apolipoprotein B and lipoprotein A. This lipid-lowering profile is a novel feature of thyroid receptor beta activation and is a particular interest in the setting of NASH as it may suggest long-term cardiovascular benefit.

In addition to the impressive efficacy observed, VK2809 has also demonstrated an encouraging safety and tolerability profile.

In the Phase II study, no serious adverse events were reported among patients receiving VK2809 or placebo, and the overall numbers of adverse events were relatively evenly distributed across treatment arms.

We believe VK2809's potent liver-specific effects, combined with its safety, tolerability and potential cardiovascular benefits, set it apart from competitive programs targeting NASH.

And we are very pleased to advance this compound into a Phase IIb study in patients with biopsy-confirmed NASH.

In preparation for this study, in 2019, we completed several additional clinical and preclinical evaluations of VK2809 to enable us to file a new IND with the FDA's division of gastroenterology and inborn errors products.

As a reminder, a new IND is required because the prior IND was directed toward hyperlipidemia and was active in the division of metabolic and endocrine products.

However, the GI division is where most NASH IND applications are reviewed.

In preparation for the NASH IND, during 2019, we completed several new studies in addition to the 12-week Phase II study I described a moment ago.

These included a Phase I study to evaluate the safety, tolerability and pharmacokinetics of VK2809 when co-administered with atorvastatin.

The results of this study confirmed previously reported data, demonstrating no meaningful interaction between VK2809 and atorvastatin.

We also conducted a Phase I study to evaluate the safety, tolerability and pharmacokinetics of VK2809 dosed in an every-other-day regimen.

These data confirmed previously reported results, demonstrating that VK2809 possesses a predictable and consistent PK profile.

We also conducted a Phase I study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VK2809 under various dosing regimens.

These data demonstrated that alternative dosing regimens may also produce improvement in measures of plasma lipids.

And finally, we completed toxicity studies of 26 and 52 weeks in duration to support chronic dosing in humans.

The results of this and prior work formed the basis of the new IND that was filed with the GI division.

Following the IND filing in November, we announced the initiation of a Phase IIb study of VK2809 in patients with NASH.

We've named this study the VOYAGE study, and we're excited to have it underway.

The VOYAGE study is a randomized, double-blind, placebo-controlled multicenter trial designed to assess the efficacy, safety and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis.

The study will target enrollment of approximately 340 patients across 5 treatment arms, including 1 milligram daily, 2.5 milligrams daily, 5 milligrams every other day, 10 milligrams every other day and placebo.

The target population includes patients with F2 and F3 fibrosis as well as up to 25% with F1 fibrosis.

F1 patients must also possess additional risk factors to be eligible for enrollment.

The primary endpoint of the study will evaluate the relative change in liver fat content as assessed by magnetic resonance imaging proton density fat fraction from baseline to week 12 in subjects treated with VK2809 as compared to placebo.

Secondary objectives include evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of dosing.

We are currently dosing patients at clinical sites in the U.S. and expect to open additional sites outside the U.S. later this year.

In addition to commencing the VOYAGE study, in the fourth quarter, we submitted an abstract describing additional data from the prior 12-week Phase II study of VK2809 for presentation at the Annual Meeting of the European Association for the Study of the Liver, or EASL.

We were recently informed that this abstract has been selected for an oral presentation on April 17.

We look forward to sharing these additional data at that time.

Given the positive results from the previous Phase II trial and the supplemental data generated in multiple studies during 2019, we continue to believe that VK2809 demonstrates a compelling efficacy and safety profile with the potential to provide benefit to the millions of patients worldwide suffering from NASH.

We look forward to sharing additional updates on VK2809 and the VOYAGE study as the trial progresses.

I'll now provide an update on our VK0214 program.

VK0214 is being evaluated as a potential treatment for X-linked adrenoleukodystrophy, or X-ALD.

X-ALD is a devastating disease for which there is no approved treatment.

The disease is caused by a defect in a peroxisomal transporter called ABCD1, This defect can result in an accumulation of very long chain fatty acids in plasma and tissue, and it is these elevated very long chain fatty acid levels that are believed to contribute to the severe cerebral and motor neuron toxicities that are characteristic of the disease.

The thyroid beta receptor is an important potential target for therapeutic intervention in X-ALD because it's believed to play a role in very long chain fatty acid metabolism.

Like VK2809, VK0214  is an orally available, small molecule bio receptor agonist that possesses selectivity for the beta receptor subtype.

To date, results from in vitro and in vivo studies have demonstrated that administration of VK0214 results in a significant increase in the expression of a compensatory transporter which is believed to result in a reduction of very long chain fatty acids in both plasma and tissue.

Given these promising results, we believe VK0214 may provide benefit to patients with X-ALD, and we are eager to move this program into the clinic.

We are currently conducting IND-enabling work for VK0214, and we expect to file the IND in the first half of this year, followed by initiation of a proof-of-concept study in humans.

With our 2 lead programs advancing in clinical development, we continue to carefully manage our balance sheet.

As Greg reported earlier, we ended 2019 with approximately $275 million in cash and equivalents.

We believe these resources provide ample runway to reach multiple clinical inflection points with both VK2809 and VK0214.

In closing, I'd like to reiterate that the important work completed in 2019 was critical to pave the way for realizing the potential of both VK2809 and VK0214.

For VK2809, the compelling data generated in both 2018 and 2019 validate our belief that it is one of the most promising candidates in development today for the treatment of NASH, and we are excited to be advancing it through the clinic.

We look forward to continued enrollment in our Phase IIb VOYAGE study.

With respect to VK0214, we continue working toward completion of the IND-enabling studies that will allow us to initiate a proof-of-concept study in humans.

It is our goal to file this IND during the first half of the year.

Finally, our balance sheet remains strong, providing the resources to execute through multiple value-creating events.

This concludes our prepared comments for today.

Thanks again for joining us, and I'd now like to open the call for questions.

Operator?

(Operator Instructions) Our first question today will come from Joon Lee of SunTrust.

And congrats on getting the podium presentation for 2809 at EASL.

In addition to the additional data from the Phase II NAFL study, will you also be sharing additional preclinical tox data as well?

And can you tell us where you are in submitting the full tox data to cover the entire 12 months?

Is that imminent, or has it already been submitted?

And I have one more follow-up.

Joon Lee, thanks for the questions.

No, as part of the presentation at EASL, we won't be disclosing any of the toxicity studies that were completed in animals.

The submission of the full 12-month data set is imminent.

And yes, it's very near term I'd say.

All the reports are completed, they're just undergoing final QC proofing.

Great.

And can you tell us a little bit about the design of the X-ALD proof-of-concept study, what that would look like and what you would hope to learn from that initial study?

Yes, no.

Great question.

So the -- it's sort of a 2-tiered clinical study.

The first portion will target healthy volunteers in, I guess it's called a stacked design, where you begin a single ascending dose study in healthy volunteers.

And during that, you begin dosing multiple single dosing also in healthy volunteers.

And during that then, you begin enrolling patients with X-ALD.

We would target a 28-day treatment window and look at very long chain fatty acid changes after 28 days.

And with those data then, if they're encouraging, we would then speak with the FDA about what the next steps might look like.

But that would be the proof of concept.

And when can we hope to get the top line, if at all, I mean, with the initial study?

Yes.

I would say the most likely window for that is probably going to be first half of '21.

I mean it's not impossible that it would be available later this year.

But I would say, first half of '21 is a safe bet.

Our next question will come from Steve Seedhouse of Raymond James.

My question is on one theme that's come up in the NASH field in a couple of recent Phase II studies and also at some of the recent meetings.

And that is, I was hoping you could clarify generally what the biopsy reading protocol is for the Phase IIb study, for example.

How are biopsies blinded or scrambled to the reading pathologists?

How many pathologists are there?

And are you going to be rereading baseline biopsies at the end of the study?

Or does the screening biopsy kind of serve as the time 0 comparator?

Yes, thanks, Steve.

It's a great and complex question.

I don't have the answer for all of the parts of it.

We are using 1 pathologist.

That person will be reviewing the baseline and end-of-treatment biopsy.

We will not be reshuffling and reassessing the baseline at a later date.

And I think that's about all I know on the logistics of the biopsy read procedure, but we're not going to send it out to multiple people or reshuffle and do that sort of thing.

Okay.

Those details are already helpful actually, given the variance there is between studies.

So thank you for that.

The other thing I just wanted to ask in terms of the enrollment of the Phase IIb study, are you willing to say kind of what inning you're in there or roughly how long you think it will take you to fully enroll the study?

Yes, I think it's early to say -- early innings is one way to answer that.

But we're still in the ramp-up process, opening sites, and we're, I think, moving along according to schedule there.

We will be adding 12 to 15 sites outside the U.S., and those are expected to come online in the second quarter.

And it's a little early to give guidance on completion of enrollment.

I certainly expect it to be in 2020, but tightening from there I don't -- it's hard to do right now.

Our next question will come from Derek Archila of Stifel.

Bill on for Derek.

Congrats on the progress in 2019.

So first from us.

Can you just speak to sort of what other biomarkers you're evaluating in the study?

And then what will -- which of those biomarkers you'll read out at the same time as the MRI-PDFF?

Yes.

So we're looking at the ELF panel, we're looking at PRO-C3, we're looking at TIMP1, and several others, I don't have that full list in front of me.

And I'm not sure yet if we'll read out all of that with the 12-week data.

Sometimes, those take a little longer to -- the different labs are doing those evaluations, they might take a little bit longer to receive.

But we'll play it by ear there.

But there is a whole panel of other biomarkers we're looking at.

Great.

And then can you brief -- just really briefly describe the differences between 0214 and 2809?

Yes, yes.

Different structures.

So 0214 has a slightly different substitution pattern on one of the aromatic rings.

And as a result, it has a slightly better beta selectivity and the PD profile is just a little bit different.

We always look at those guys in parallel in all of our animal studies.

And on some metrics, it's superior; on other metrics, 2809 is superior.

So I think they're both tremendously effective in the in vivo models for NASH.

But when you look at the X-ALD profile, VK0214 seems to be effective in X-ALD, and VK2809 is not very effective there.

So that was the key difference in the actual in vivo data.

Does that have to do with the liver sensitivity of 2809?

Maybe.

I don't know.

It was a surprise to us to see that the delta there since they're similar in virtually every other assay.

But it could, it could have that.

I mean, that could play a role there.

Our next question will come from Scott Henry of Roth Capital.

Just a couple of questions.

First, on the modeling for 2020, how should we think about R&D spend throughout the year?

Should we ramp it steadily?

And then as far as magnitude, perhaps relative to 2019, are we thinking double 2019 spending?

Just trying to get a sense on R&D for the year.

Yes, it's a good question.

Thanks, Scott.

It's going to be certainly higher than in 2019.

And I would say, overall, the spend will be about 50% higher, skewed a little bit -- well, it's going to be a gradual ramp.

So 4Q is going to be higher than 1Q, and 1Q is going to be higher than 4Q '19.

But when you think about overall R&D and overall OpEx, it's about 50%.

Right now, we think it's going to be 50% higher.

Greg, do you have any other comment?

Yes.

No, that's right on target, I think, yes.

Okay, great.

And just one question on the trial.

I realize it's not new, but we haven't had a chance to talk about it.

When you look at the 5 doses, I was a little surprised not to see a 5-milligram daily since it was a relatively robust dose in the earlier trial.

Any thoughts on deciding which ones to go with and why you went with 5 milligrams every other day versus daily?

Yes, we definitely -- it's a great question.

So we definitely wanted to have some overlap with the Phase IIa study for comparative purposes.

We thought that going with a higher sort of a pulsatile dose might be advantageous.

I mean, I think you could argue saying 5 mg study would be advantageous based on the data.

But anyway, we chose to go 10 mg just to have that be the overlap dose and then step down from there.

We went to 5 mg every other day because we know that when we look at the last 3 doses in the Phase IIa, they all pretty much stacked on top of each other as far as efficacy.

So we were -- we felt right on the far right-hand side of the dose-response curve.

So we think that coming down as we are, we should still see efficacy.

And we have that overlap with the very effective 10 mg every other day from the Phase IIa study.

Our next question will come from Andy Hsieh of William Blair.

Great.

I think in your new slide deck, you mentioned about potential weight loss.

I know that from clinical trials phase -- so obviously, I'm talking about thousand 2809 here.

The Phase I and Phase II, unfortunately, dosing -- maximum dosing was about 12 weeks, so you probably didn't really see that.

But just maybe from nonhuman primates, did you see something like that from the compound just given the fact that it's an agonist for the thyroid pathway?

Yes.

Thanks, Andy.

I don't think we talk about that in the slide deck.

We don't see any meaningful weight changes.

When you look at vital signs across the 4 cohorts in the 12-week study, the placebo cohort was a little bit skinnier, and they gained about 1 pound, and then the treated cohorts were a little heavier and they lost about 1 pound.

So -- but there was no -- it didn't look like there was any dose response there, and we just -- we don't think there's any effect on weight from -- obvious in that study.

The thing to -- I mean, everybody wants the therapies to lose weight because that also plays a role in the signal in NASH.

But with this mechanism, it's a little bit more problematic because the weight loss might be taken as a proxy for thyroid alpha activation.

And so you really don't want to see it with a thyroid beta agonist in the early studies.

Once you can establish all the safety parameters, then maybe in a longer study.

But anyway, going back to the question, we didn't see any in the 12-week study.

Got it.

Okay.

So in terms of the EASL presentation, obviously, not compromising your ability to present, just maybe high level, what should we expect?

And what should be -- what should we be looking for, for the new data?

Yes, it's really interesting.

We had people come back at week '16 in the study.

So the endpoint was at week 12 for efficacy, and everybody came back for labs and MRI at week 16.

So we'll present those data as well as some deeper dives into some of the different subsets, patient characteristics in the study.

Okay.

That's helpful.

And so in terms of AMN for 0214, I think one of the challenges for a lot of these rare diseases is diagnosis.

And I think one of the -- so that -- so X-ALD is -- was -- well, is kind of included in the screening for newborns in 2015.

But obviously, there's a lot of adults who potentially could be carriers but do not know about that.

So just wondering from a trial enrollment or recruitment perspective, how do you identify these patients?

And what are some strategies that you can employ to maximize recruitment of this rare disease?

Yes, it's a key challenge.

Fortunately, many of these families understand that they do carry the defect.

And there are only a few treatment centers in the U.S., and most of these families are seen at one of 4 or 5 treatment centers.

We will be engaging those treatment centers in the proof-of-concept portion of the study.

And we feel like it will be a relatively small study.

We'll target adults.

They're easier to enroll than the childhood form.

And we don't think there will be any significant challenges, in the first phase of the study anyway, given the size and the availability of adults.

And it's something -- I mean it's a fair question across the board in the orphan setting, but most of these families are seen at the same treatment centers and they're -- they know that they carry the gene.

Our next question will come from Jay Olson of Oppenheimer.

This is Matt on for Jay.

We were wondering, I guess, your thoughts on the evolving competitive landscape.

For example, NGM just top lined their data from Phase II the other day, so if you got to take a look at that.

And any thoughts you might have there, especially your mechanism compared to the others out there?

And also, maybe as a corollary, what potential other combinations with other MOAs you could imagine being potentially helpful with yours?

Yes, thanks for the question.

I think it's better to direct the questions about another company's data set to that company.

I thought the data looked really exciting, and I've always thought that, that compound looked very promising.

I think the way we think about the competitive advantages for VK2809 are, #1, it's oral.

It's very effective on -- in animals on fibrosis, in humans on liver fat.

And a key differentiator for this mechanism is that you see a reduction across the board in plasma lipids, not just LDL but also atherogenic proteins.

And on top of that, excellent tolerability with VK2809.

There's no sort of a GI challenge or anything like that.

It's very well tolerated across the board.

So I think we feel good about the competitive profile the more we see evolving in the space.

Okay, got you.

And we were also just wondering, at EASL this year, if there's anything else, abstracts out there that you're aware of that you're looking forward to?

Well, yes, the oral session that we're in on Friday night, will have, I believe, the NGM data and several other company presentations.

So that will be a good session from -- I think it's 4:30 to 6 or 4:30 or 6:30 on Friday night.

Our next question will come from David Bautz of Zacks.

Now that you've got the Phase IIb trial underway, I'm curious if that has affected your partnering discussions at all.

It's a good question.

Not really.

I think that everybody is kind of watching everybody else right now, but it hasn't had any impact on any discussions.

Okay.

And to, I guess, follow-up on the previous question about the data that came out this week.

I guess I'm curious, in more general terms, when you talk to KOLs, what is their view about, say, an injectable drug versus an oral drug treatment for NASH?

I think, generally, all things equal, an oral is preferred.

And I think that having something that hits other lipids is generally well received in our conversations with clinicians.

But I think the FGF19 and FGF21 mechanisms are very powerful.

And they've shown really exciting data, so I'm not going to take anything away from them.

I think that there is room for a lot of different mechanisms and a lot of different combinations of different mechanisms.

And we think that we will play a really significant role in both single agent and combination settings.

Our next question will come from Mayank Mamtani of B. Riley FBR.

Congrats on the progress.

Just maybe piggybacking on the previous comments for the 16-week follow-up at EASL.

So I'm assuming, is it this PDFF?

Or will there be other markers also you'd look at?

And the reason I ask is I think there is some data where taking away the drug, the liver fat drug, actually brings back the fat and maybe other markers don't move as much.

So I'm just curious, what mechanistically could be informative to using that wear-off -- drug wear-off data at EASL?

Yes.

Thanks, Mayank.

Well, we'll look at PDFF primarily and then look at some of the other subsets at both weeks 12 and 16.

I'm not sure what you're referring to in some of the other parts of your question, but that's primarily...

Like AASLD or like...

Oh, yes, yes.

Probably have that in there as well.

I think -- yes, yes, we'll probably have that in there as well.

I was wondering if we reported that earlier, but I don't think that was at the AASLD presentation.

That's right.

Okay.

And then on the design of Phase IIb, why -- I'm just curious.

Like, what are -- like obviously, you've powered it for the primary endpoint, but you said there's obviously a lot of other markers you're looking at.

So could you maybe talk to like maybe your assumptions on how you're thinking about the placebo there on liver fat but also on the histology and then like, for the different doses, how you thought about powering the study?

Yes, yes.

We're extraordinarily well powered on liver fat with the 75, seeing what we thought and of 10 in the prior study.

We are, I think, reasonably well powered on the histology endpoints, particularly resolution of NASH.

I don't think we want to talk in more granularity about what those assumptions were.

But we -- on powering.

I think we're assuming around the 20% background rate of NASH resolution, and we're powered to show a delta over that.

Okay, great.

And just maybe one more on the -- just the background, like, what other medications are you allowing on the study as part of the protocol?

Because I mean there are different studies -- as you know, OCA is going to be available starting June.

And I mean there's GLP-1s already.

So is the protocol allowing background therapies where you can maybe learn some combination data also?

Yes.

This is another important question.

Right now, we're not allowing anything that we believe might play a role in efficacy -- an efficacy signal for NASH resolution or fibrosis.

So any of the -- like, pioglitazone and PPAR agonists are excluded.

GLP-1 agonists are excluded.

Anything that might affect trigs.

We've -- maybe we do allow a little bit of trigs -- medications for trigs.

But for the most part, we're excluding anything that might modulate triglycerides, liver fat content and has shown efficacy in other prior studies.

Okay, great.

And final question on the process for -- after you submit this 12-month data?

Like, how does it work from here?

Is it just a simple review and then they respond within a 30-, 75-day time period?

Like, what's the process from hereon?

Yes.

There isn't an established process like when you file an IND or anything or an NDA.

We will be submitting the report and then circling back after an appropriate time to check the status.

But it's a little different here.

There isn't a sort of a guideline for hearing a response.

We do have a pretty wide window between the submission and when anybody would cross the 6-month treatment threshold, and we would certainly expect to understand FDA stance before anybody crosses that 6-month treatment threshold.

Great.

Oh, actually, one more for Greg.

Is there a breakdown on preclinical spend you could give 2018, 2019 and maybe 2020, like how to think about that?

Yes.

Mayank, I don't think we're -- we -- the guidance Brian gave earlier, I think, is all we're comfortable with.

We will see tick up in the spend in both preclinical and clinical, round numbers, about 50% again over last year, but I think that's about all the granularity we can give right now.

Much more heavily slanted to clinical.

Our next question will come from Thomas Smith of SVB Leerink.

Brian, can you just remind us, I know the VOYAGE trial started in November.

But when was the first patient dosed in the study?

And then I guess just following up on the last question around FDA time lines, recognizing that there's no, I guess, established process or established time line that you're looking for.

But when you do hear back from the agency, I guess, if you could just let us know how you plan to communicate this, that would be really helpful.

Yes.

Thanks, Tom.

We'll probably give those updates on quarterly calls or at conference presentations as far as meaningful communications we receive from the FDA.

But it wouldn't be a separate, stand-alone announcement.

With respect to dosing patients.

We haven't provided that sort of patient-by-patient detail.

We are actively enrolling, and that's about all the information that we're going to provide at this point.

Okay.

And then you mentioned, Brian, bringing the U.S. trial sites online.

What's your expected enrollment mix looking like between U.S. and ex-U.

S. patients?

Well, we would expect the vast majority to be in the U.S. And it's probably a 4:1 mix right now, the way we have it planned for U.S. versus ex-U.

S. sites.

But maybe the ex-U.

S. sites might outperform the U.S. if there's less competition.

But right now, we've assumed the vast majority are going to be from the U.S. sites.

Our next question will come from Julian Harrison of BTIG.

Congrats on the recent progress.

Just curious if a cardiovascular risk reduction label is in the back -- in your mind at all for 2809.

Would that be practical and maybe helpful in the long run?

Definitely understand CVADs are not small undertakings.

But it's hard to ignore that you're likely seeing more triglyceride lowering than VASCEPA: LDL-C lower comparable to bempedoic acid, great tolerability and virtually no alpha engagement on top of NASH-specific activity.

Yes, thanks.

So we're not going to do a dedicated cardiovascular outcome study unless we're asked, and there's no reason to think that we would.

But I think the overall outcomes portion of all of these NASH studies, includes a cardiovascular component, all cause mortality.

But we, at this point, won't be seeking something like this the way we sit today.

(Operator Instructions) Our next question will come from Jason McCarthy of Maxim Group.

It's Dave on the line for Jason.

I just wanted to quickly circle back to the comment you guys made regarding a potential increase in R&D and OpEx expenses.

So just for additional clarity, you guys mentioned that you believe it will be about 50% higher.

Now is that for year-end 2020 compared to year-end 2019?

Or is that more of like a quarter-by-quarter sort of basis?

It's for the full year.

And it's -- the first quarter is going to be higher than the fourth quarter.

Every quarter will be a touch higher than the prior quarter.

Okay.

But the general expectation is that OpEx and R&D will be about 50% higher for full year 2020 versus full year '19?

Yes, that's what our current estimates are, yes.

This will conclude our question-and-answer session.

At this time, I'd like to turn the conference back over to Stephanie Diaz 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.

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