Good afternoon. My name is Brandi and I'll be your conference operator today. At this time, I would like to welcome everyone to the Enanta Pharmaceuticals fourth quarter financial results conference call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions]. Thank you. Miss Carol Miceli, you may begin your conference.

Thank you, Brandi, and welcome to Enanta Pharmaceuticals conference call to review fiscal fourth quarter and year ended September 30, 2017 financial results. The news release with our financial results was issued this afternoon and is available on our website at Enanta.com. On the call today is Dr. Jay Luly, President and Chief Executive Officer; Paul Mellett, our Chief Financial Officer; and other members of Enanta's senior management team. Before we begin with our formal remarks, we want to remind you that we will be making forward-looking statements, including plans and expectations with respect to our product candidates and financial projections, all of which involve certain assumptions, risks and uncertainties that are beyond our control and could cause our actual developments and results to differ materially from these statements. A description of these results and uncertainties is in our most recent Form 10-K and other periodic reports filed with the SEC. In addition, Enanta does not undertake any obligation to update any forward-looking statements made during this call. I'd now like to turn the call over to Dr. Jay Luly, President and CEO.

Thank you, Carol. Good afternoon, everyone, and thank you for joining us today. I'm happy to report that at the end of our fourth fiscal year as a public company, Enanta has executed well on its planned goals and has achieved many financial and clinical milestones. Enanta ended of the year with approximately $294 million in cash and marketable securities. Our successful partnering strategy has provided Enanta with the funding necessary to support our business operations and to advance our internal pipeline. Enanta is on track this quarter to earn the final regulatory milestone in our 11-year HCV collaboration with AbbVie, which would mean we have successfully earned all clinical and regulatory milestones under the collaboration. Total cash from AbbVie under the collaboration through this fiscal year ended – totaled approximately $500 million. These resources have allowed us to discover and develop our wholly-owned programs in NASH, PBC, RSV and HBV and will allow us to continue to advance them and gives us the latitude to look for new opportunities. Among our wholly-owned assets, the most advanced is EDP-305, our FXR agonist for NASH and PBC. EDP-305 is a highly selective and potent FXR agonist that successfully completed the Phase I a/b study recently. The objective of this double-blind, placebo-controlled study in adult healthy volunteers and in subjects with presumed non-alcoholic fatty liver disease was to evaluate the safety, tolerability, and pharmacokinetics of single ascending dose and multiple ascending dose levels of EDP-305. Pharmacodynamic markers of FXR activity, namely FGF19 and C4 and other parameters such as lipids were measured in all dose groups. Last month, we were pleased to announce positive results from this study, indicating EDP-305 was generally safe and well tolerated over a broad range of single and multiple doses, with PK data supporting once daily oral…

Thank you, Jay. I'd like to remind everyone that Enanta reports on a fiscal year schedule. Our fiscal year ended September 30 and today we are reporting results for our fourth fiscal quarter and year ended September 30, 2017. Enanta ended the quarter with approximately $294 million in cash and marketable securities as compared to $242 million at our September 30, 2016 fiscal year-end. We expect that these cash resources and our future revenue streams from our AbbVie agreement will be sufficient to meet our anticipated cash requirements for the foreseeable future. For the three months ended September 30, 2017, revenue was $75.9 million compared to $12.8 million for the same period in 2016. The increase in revenue in the current quarter was primarily due to $65 million in milestone payments earned in the US and EU approvals of MAVIRET. Our revenue in the current quarter included $10.9 million in royalty revenue under our collaboration agreement with AbbVie. Milestone and royalty revenues have varied significantly from period to period and we expect that variability to continue in the future. Moving on to our expenses, for the three months ended September 30, 2017, research and development expenses were $16.5 million compared to $11.5 million for the same period in 2016. The increase in research and development expense was primarily due to increased preclinical and clinical costs associated with the progression of our wholly-owned R&D programs in NASH, PBC, RSV and HBV. General and administrative expense was $5.1 million for the quarter ended September 30, 2017 and $4.4 million for the comparable quarter in 2016. The increase in these expenses was primarily due to increases in compensation expense, driven by increased headcount. Enanta recorded income tax expense for the three months ended September 30, 2017 of $18.4 million compared to an income tax benefit of $0.8 million for the same period in 2016, primarily due to the net income in the 2017 quarter. The company's effective tax rate for fiscal 2017 was approximately 34%. Net income for the three months ended September 30, 2017 was $36.5 million or $1.86 per diluted common share compared to a net loss of $1.8 million or $0.09 per diluted common share for the same period in 2016. As stated in our earnings release, our financial guidance for our fiscal year ended September 30, 2018 is as follows. We expect our research and development expenses to be between $90 million and $110 million and our general and administrative expenses are expected to be between $22 million and $28 million. Further financial details are available in our press release and will be available in our Form 10-K. I'd now like to turn the call back to the operator and open the lines up for Q&A. Operator?

[Operator Instructions]. Our first question comes from the line of Jessica Fye with J.P. Morgan.

Thank you for taking my questions. A couple. Just digging into that R&D guidance for fiscal 2018, hoping you could sort of outline some of the pushes and pulls that would put your R&D spend at the upper or the lower end of that range. And then, ideally, is there any kind of proportion you could give us for sort of how much of that is devoted to advancing 305 versus RSV versus additional preclinical work? Thank you.

Hi, Jessica. It's Paul. I would say that the bulk of the increase is tied in with the fact we'll be running three clinical trials in 2018, one in NASH, one in PBC, and one in RSV, and that's really the driver. That, associated with the associated CMC costs that go along with those types of trials. In terms of the breakdown, we don't really have any comment on the splits between them at this point.

It will be more heavily weighted. This is Jay. It will be more heavily weighted, obviously, to EDP-305 because two of those three studies are Phase IIs using EDP-305. So, they are necessarily going to be a little bulkier than the Phase I for RSV.

Understood. And is there anything you can kind of tell us about what would put you closer to the 110 versus closer to the 90?

Well, I think it’s really probably – I'd say the variation there has more to do with other things in our pipeline, some of the other pipeline programs and the rate at which they proceed. HBV is hanging out there as one that we're really hoping to be bringing in forward pretty soon, and depending upon the ramp of that, when manufacturing gets involved with that, when we start doing some of the IND enabling studies, et cetera, et cetera, same with our follow on FXR for that into that same bucket. So, it's things like that depending upon when they hit, and that's a little bit more of the variable part of the equation because when you're still doing the science part of R&D, it's just a little bit harder to legislate a specific date as to when certain things are going to happen. So, I think that's probably the bulk of the variance there.

Okay, got it. Just on MAVIRET, just at a high level, it seems like the US is probably going to convert to the 2-DAA regimen pretty quickly. How should we think about the evolution of that mix of ex-US sales from sort of the higher royalty product to the – from the lower royalty product to the higher royalty product?

Sure. So, I think it will happen pretty quickly in the United States. The care is approved in over 60, 70 countries worldwide right now. So, you can imagine that the turnover to MAVIRET is not going to be instantaneous in all of those particular countries. That said, several of the strong ones have come on in Europe and will continue to do so. So, I would expect that you would just see sort of an orderly changeover as all these various country approvals and pricing approvals take in. certainly, AbbVie is ready to roll. So, it's just a question of methodically stepping through all those territories. The good news is, in the meantime, VIEKIRA continues to sell. And as you know, VIEKIRA has sold more ex-US than in US. And so, that'll be a nice transition, I think.

Great, thanks a lot.

You're welcome.

Our next question comes from the line of Brian Abrahams with RBC Capital Markets.

Hey, guys. Thanks for taking my question and congrats on the continued progress. First question is on 305. Coming out of the Phase Ib data, I'm just wondering, as you characterize the levels of – the changes in C4 and FGF19, what are some of the elements that guide the go-forward dose ranges that you're going to be looking at in Phase II?

So, those markers are two markers that were, I think, very nice and convenient and easy ones to look at in a Phase I study. Obviously, we're only taking the temperature, if you will, part of the disease. There are several other parameters to look at, things to think about. But that said, looking at FGF19 and C4, we saw a reduction in C4 and an increase in FGF19 over a broad dose range, i.e. I think the best way to think about it or at least the way we're thinking about it is there's probably a threshold level that you want to be above and you probably want to drive those markers or at least blood levels that result in those markers being driven along with a lot of other things. You probably want to pick a range where you don't either blowout FGF19 elevation or completely shut off C4 synthesis. So, the trick here is being above the threshold and below the point where you don't want to exceed. And so, I think there's a comfortable range in there. That's why we picked that 0.5 mg to 5 mg range. We do see good target engagement without seeing pruritus again, which we saw a little bit of mild to moderate pruritus, but only at the 20 mg high dose and very little, if any, at 10 mg. So, it really boils down to looking at pharmacodynamics, looking at safety, looking at the PK exposures, and feeling like you've got good coverage. That said, we're not prepared to distill it down to a single dose for our first Phase II study, and so we'll be doing some finer turning of that dose range in Phase II.

Okay, makes sense. And then, just a couple of quick questions on 938 from a mechanistic standpoint. Just wondering where you stand in terms of the characterization of the exact mechanism there. I know the mutation mapping kind of steered you to N-protein as the likely mechanism. What's sort of your level of competence there? And maybe along those lines, if you could remind us of any of the similarities or differences between other approaches with that same target in the past?

So, the N-protein, the so-called nucleoprotein, is one of the targets in the replication machinery that you can use for RSV. RSV actually has a very small viral genome. So, it's a – there is a set of interesting targets that you can approach, but I think that we've gravitated toward the N-protein based on the fact that the barrier to resistance, at least with the molecules that we've made targeting this approach, barrier to resistance is really, really quite high. We also saw, in addition to the high barrier, since we're taking on a direct acting antiviral approach where we're going directly into the viral replication machinery, we're not doing what several other folks are doing, which is the fusion inhibitor approach. Not that that's necessarily a bad approach, we just think there might be advantages of the N-inhibitor approach such that we might at least possibly be able to get away with a single agent and not have to do a combination. At least we're not as certain whether or not you'll be able to do that if you have only a fusion inhibitor. You may need some other things to back it up since fusions appear to have a fairly low barrier to resistance. So, we like N. All the studies that we've done to date point to N. And I think that the combination of the fact that we're going after the direct acting antiviral approach as opposed to fusion, mechanistically, it may allow us to still intervene with a medicine at a later stage of infection. At least from the virology work we've done in-house, we've been able to do infections and intervene at a later time with our N-inhibitor than with fusion inhibitors. So, if that translates into the clinic, that would actually be a really good advantage. Regarding other N-inhibitors out there, I think we're the only one at the development stage that I'm aware of. There was an older one many years ago that was also a member of this mechanism, but we looked at it and it actually wasn't very potent. So, we've gotten in and worked hard to try to optimize to create a pretty good molecule. So, again, 938 preclinically looks really good from a virologic perspective. It looks exceedingly good in a primate – non-human primate animal model infection and it's on track to be in our clinical study by the end of this year.

Thanks, Jay. One last question and I'll hop back in the queue. Just wondering if there's any particular pharmacodynamic measures we should be looking for in the 938 Phase I study? And I'm also wondering, how quickly you could potentially get an efficacy read out of a subsequent challenge study. I know those Phase II studies, I think, tend to move pretty rapidly in this field. Thanks.

Sure. Nothing fancy on the Phase I. It's not like we did with 305 where we're looking at healthies and we're looking at subjects with presumed NAFLD or some other sort of population and looking at biomarkers at every dose, every parameter. So, it's much more of a straightforward phase, Phase Ia and b, SAD/MAD study. We want to chip through that as quickly as we can, so that we can move on to what should be a very interesting and de-risking step, which is the ultimate test to get in humans against the virus. So, the good news is we know that quantifying virus is a great marker for an indication like this and we will be – at first, a challenge study will actually be in healthy volunteers, who become infected with RSV and then are subsequently treated by EDP-938. So, our goal is to get over Phase I, figure out dose ranges and exposure and tolerability ranges as quickly as we can, and then get into that challenge study later next year. We'll have more to say about the timing and the design of that next year.

Great. Thanks again.

You're welcome.

[Operator Instructions]. Our next question comes from the line of Liisa Bayko with JMP Securities.

Hi there. Just wanted to drill down a little bit more on your concept of raising the LDL receptor with respect to your FXR mechanism and what you think the potential benefits of that may be and any potential issue for seeing how comfortable you are with that – the evidence for that? And then, also just when we might hear a little bit more about your next NASH mechanism. Thank you.

Sure. So, thanks, Liisa. So, the LDL receptor is an interesting story. We and others, obviously, have thought about FXR in the context of lipids. Intercept saw LDL elevation in their study, and so we wanted to understand whether or not that would be an observation we'd have to worry about and think about how to handle going forward. So, we looked at lipids. We did a lot of interrogation preclinically and, ultimately, in our Phase I study. Preclinically, animal models are a little bit tricky. They all seem to deal with lipid regulation in different ways or at least in some of these animal models that are – it's hard to come up with perfect models in that regard. That said, when we look down at expression levels, looking at RNA and protein and then ultimately function, we did see that EDP-305 differentially versus OCA had an up-regulation of LDL receptor preferentially by EDP-305. So, for those of you who don't know, the LDL receptor is one of the proteins that's substantially responsible for reducing circulating LDL levels. So, if you have LDL receptor expression go up, you see circulating LDL go down. And that would be viewed as a good thing. So, when we saw differentially an up-regulation of LDL receptor by 305 versus OCA, we thought that was an interesting observation, but it certainly needed to be borne out clinically. Under steatotic conditions, not to make it more confusing, but under steatotic conditions, we saw no change in LDL receptor levels, but we saw that OCA reduced LDL receptor levels. So, the relative differences were preserved. So, when we went into the clinic, we looked at lipids very carefully not only in healthy volunteers across our entire dose range, but also in presumed NAFLD subjects and we didn't see any dose-related increases in LDL at all even at the highest dose of 20 mg, which we know gave better than linear pharmacokinetics, so there was a very, very large exposure in those subjects at the 20-mg dose. So, those were the observations. We saw at least – had a clinical rationale that we found preclinically. And then, at least in Phase I so far, it's borne out.

What happens to the cholesterol at that point if you're increasing the receptor? Is there anything to worry about downstream or…?

I don't think so. One of the things, if you look into PCSK9 literature, PCSK9 inhibitors work by actually preserving LDL receptor from being degraded. So, you essentially have similar net effect, which is elevation of LDL receptor versus what it would've been. And that's again a proven mechanism for reducing LDL cholesterol that's, I think, fairly well understood.

Okay, great. And then, if you could give us any sense of timing of when we might learn more about the [indiscernible]?

Sorry, timing on the other targets? Yeah, the target that we haven't yet disclosed will probably remain in that status for a while longer. I think we just want to run it out a little bit further where we've got science and assays and chemical matter and patents and all kinds of stuff going on. But we're just not quite there yet in terms of being ready to disclose what we're doing.

Okay, thank you.

You're welcome.

There appear to no further questions at this time. I will turn the call back over to Miss Carol Miceli for closing remarks.

Okay. Thank you, everyone, for joining us. If you have any additional questions, feel free to give us a call in the office. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.