Ladies and gentlemen, good afternoon. At this time, I'd like to welcome everyone to the Theravance Biopharma Conference Call. During the presentation, all participants will be in a listen-only mode. A question-and-answer session will follow the company's formal remarks. [Operator Instructions.] Today's conference call is being recorded. And now, I'd like to turn the call over to Mr. Alex Dobbin, Head of Investor Relations. Please go ahead.

Okay. Thank you very much, operator. Good afternoon everyone. We were just informed by the NASDAQ before we begin the NASDAQ is having technical difficulties in their operation center, so we do hope this call proceeds uninterrupted, in the event that we disconnect. I hope that you will try to reconnect. With that, thank you all for joining us for our first quarter 2017 financial results conference call and web cast. With me today, Rick Winningham, Chief Executive Officer; Renee Gala, Chief Financial Officer; and Brett Haumann, Chief Medical Officer. Following prepared remarks, we will open the call for questions. A copy of the press release and the slides accompanying this call can be downloaded from our web site, or you can call Investor Relations at 650-808-4045, and we will be happy to assist. We'd like to remind you this call will contain forward-looking statements which involve certain risks and uncertainties, including statements about our product pipeline, expected benefits of our products, the anticipated timing of trial results and regulatory filings, and expected financial results. Information concerning factors that could cause results to differ materially from our forward-looking statements are described further in the company's filings made with the Securities and Exchange Commission. And with that, I'll hand the call over to Rick.

Thanks Alex. Good afternoon everyone and thank you for joining us. 2017 is shaping up as an extraordinary year of progress for Theravance Biopharma. Building on our accomplishments in 2016, we are continuing to make important clinical gains across our key programs, with multiple clinical milestones anticipated, through the remainder of 2017 and 2018. In our call today, we will provide an update on our key programs and near term milestones. First, I will give an overview, and then Brett will share more color, then Renee will review our financial performance, then we will open the call to questions. First, our Phase 1b study of TD1473 in patients with moderate to severe ulcerative colitis is progressing. We expect data in mid 2017. 1473 is designed to be selectively active, reducing inflammation in the intestinal wall, while sparing the body from systemic immune suppression. In the Phase 1b study, we are looking for a meaningful reduction in disease activity in ulcerative colitis patients, and we want to achieve this without systemic immune suppression, consistent with the findings in the phase 1 healthy volunteer study. Data from the Phase 1b study will inform our broader clinical development plans for this compound, including potential assessments and immune checkpoint inhibitor colitis as well as Crohn's disease. Second, we anticipate completing in the middle of the year, the Phase 3 long term safety study for revefenacin, our nebulized once-daily long acting muscarinic antagonist or LAMA, for the treatment of COPD. This long term safety study, combined with the two positive pivotal Phase 3 efficacy studies reported last October, is intended to support our NDA filing, which we expect to submit to the FDA in the fourth quarter of this year. We recently initiated a Phase 3b study of revefenacin in COPD patients with low peak…

Thanks Rick. I will provide an overview of four of our key programs, all of which have clinical study readouts expected this year. Each program is the result of internal research and discovery, and we believe each could represent meaningfully differentiated therapeutic options for patients. Firstly, in our JAK inhibitor program, the goal is to develop a highly differentiated treatment for inflammatory bowel diseases, including ulcerative colitis, Crohn's disease and colitis associated with the use of immune checkpoint inhibitors. We are developing JAK inhibitors, for the design to remain localized and only act within the gut wall, thereby maximizing local anti-inflammatory efficacy and minimizing the systemic exposure that would otherwise lead to immuno suppression. Our approach has a potential to increase the therapeutic index. By improving the safety profile, seen with systemic JAK inhibitors and by increasing the potential to go to higher doses than can be achieved with systemic JAK inhibitors, to achieve even greater efficacy. It's also worth noting, that our approach allows us to leverage the broad anti-inflammatory effect of a pan-JAK inhibitor by restricting its activity to the disease organ. In contrast to the systemic JAK inhibitors that need to be more selective, in order to reduce systemic toxicity. As previously reported, we are conducting a small Phase 1b trial of 1473 in patients with active, moderate to severe ulcerative colitis. The study is designed to assess the safety and tolerability of 1473 and the effect of 1473 on a range of relevant markers of inflammation in the colon. Cellular changes and measures of endoscopic improvement and clinical benefits, including changes in Partial Mayo Score. We will also measure PK to assess whether the systemic levels of 1473 in patients match the very low level seen in healthy volunteers. The study has an adaptive design, which…

Thanks Renee. As we progress into mid-2017, we are on track to deliver clinical results at every stage of development in our pipeline, throughout the remainder of the year. From a personal perspective, very rarely in my career, have I ever entered a year, where I have Phase 1a, Phase 1b, Phase 2a, Phase 2b, Phase 3a, Phase 3b studies, with a potential NDA approval and an NDA filing all anticipated to occur over a 12 month period of time. But that's the opportunity that 2017 presents for Theravance Biopharma. This is an unprecedented period for the company, that underscores the depth and breadth of our portfolio. The productivity of our internal R&D engine and a robust business model. In summary, and if you reference the slide accompanying today's call, in 2017, we expect to achieve the following milestones. Data from our Phase 1b study in TD-1473 and ulcerative colitis. Data from our Phase 2b study of Velusetrag and gastroparesis. Data from the Phase 3 12 month safety study of revefenacin, followed by a planned NDA filing. Data from the Phase 2a study of TD-9855 and neurogenic orthostatic hypotension. Final data from the TOUR patient registry study with VIBATIV and data from the Phase 3b impact study, with a close triple and potential regulatory approval of the product in the U.S. and the EU for COPD. And in 2018, we expect to achieve the following milestones, data from the Phase 3b study of revefenacin in patients with low peak inspiratory flow rate, intended to support commercialization. Data from the Phase 3 registrational study of VIBATIV in bactremia followed by a planned SNDA submission in the U.S. The potential regulatory approval of revefenacin in the U.S. for COPD. The potential to start earning income from the close triple and finally, data from the Phase 3a captain study of the close triple in asthma patients, followed by a potential regulatory submissions for asthma. In closing, we are very proud of our entire team at Theravance Biopharma. All of them continue to drive our business forward. We believe that our programs represent valuable and differentiated product opportunities with the potential to have a meaningful impact on patients lives, change how serious diseases are treated and create long term value for our shareholders. And now I'd like to turn the call over the operator for questions.

Thank you, sir. I would like to apologize for the technical difficulties. We appreciate your patience. [Operator Instructions]. We will have our first question from Geoffrey Porges of Leerink Partners. Your line is open.

Thanks very much. And a few questions if I may; looking forward to all those readouts in the remainder of the year. So Rick, first, on 9855, could you explain the protocol change and the extension a little bit more clearly and whether you have seen the data, and if not, what made you to make the change? And then secondly, sort of related to 9855 and 5108, should we be assuming that both of those programs, if they are successful in the current Phase 2 trials, would be Phase 3 candidates for next year? And then related to that, are they partnering candidates or are they Theravance sort of owned full development and commercialization programs, and what, in addition to those, might be business development priorities? Sorry for the long list.

No, thanks Geoff. I will turn over our thinking on 9855 to Brett, because it has been a very exciting program for us, and I will just touch, before Brett starts on sort of how we view Velusetrag and 9855 from a partnering perspective. And clearly, 9855 is a program we can take all the way to the finish line ourselves, and given the relatively small target audience that treats neurogenic orthostatic hypotension, in fact commercialize ourselves. So that's not one where we would require a partner. In Velusetrag, we have a partner today in Europe, and number of few other countries, Alfa Wassermann. So we have rights in the United States and Japan and a number of other countries. Whether we partner Velusetrag or not, with regard to those regions that we currently own, will sort of depend on a number of factors going forward, including what is happening with other programs. But I think right now, we see a pretty significant opportunity, if the Phase 2b study is positive for Velusetrag, a fairly significant opportunity for the program in the United States and Japan, in terms of making a difference with patients and then commercial opportunity, because I think the data from the Phase 2b are such, that with good data on symptoms in the phase 2b, we could be pretty confident on success in a Phase 3 study. So 9855, we will keep ourselves. We got the ability to take that all the way ourselves. Velusetrag, we will have to see. We certainly, if things fall the right way, we could certainly develop Velusetrag ourselves, and of course, that's primarily diagnosed both in the emergency room, as well as with gastroenterologists in terms of gastroparesis. So with that, I will turn it over to Brett.

Thanks Rick.

Geoff, you had asked about the sort of Phase 3 readiness for those two assets, because with Velusetrag, the intent with the current Phase 2b study was exactly that, to inform a pivotal registrational program as the next step, for the classic Phase 3. With 9855, of course, it's an orphan condition, and so what we deem to be Phase 3 may look quite different. The pivotal registrational program for an orphan designation may look quite different from Velusetrag. It is our intent though, to use the current study to inform the next steps and interactions with agencies, particularly in the setting of an orphan designation. You had asked about the protocol changes with 9855, and I think without going into too much of the specifics, I wanted to reassure you and others that, it's on the basis of encouraging positive data, as opposed to concerns about the single ascending dose. So we have seen evidence of effect in some patients, who were exposed to the single doses. And so on that basis, we'd like to explore the durability. The sustained treatment effect in those patients for longer durations of therapy. We touched on it in the scripts, but we do acknowledge that existing therapies really have no evidence to support their long term use, and it's our intent to see, whether this current therapy, 9855 could demonstrate efficacy over the longer term. So it is a value added dimension to the protocol, and that was the basis of extending it.

And just to add to that and the words that Brett used in his section, describing 9855 was -- we saw responses in a majority of patients. So that's really what gave us the energy and the motivation to take the product from single ascending dose and extend the dosing out to as long as 20 weeks.

Great. Thanks very much Rick.

Our next question comes from Brian Skorney of Robert W. Baird. Your line is now open.

Hi. This is Neena on for Brian. Thanks for taking the question. I just had a question about the NEP inhibitors. I know you said that you are currently kind of looking at different options for how to take those two forward. Could you just talk a little bit more about what options you are looking at, whether or not you'd consider partnering, and what kinds of studies you might consider moving them into? Thanks.

Yeah. Brett, do you want to address that?

Sure. So I think one of the elements of we being really preoccupied with on our NEP inhibitor program, was the focus on drugs that were not [indiscernible]. And that's a distinct advantage over, even in Entresto, the only other NEP inhibitor in the class at the moment. That one approved, in combination with an ARB [ph]. But sacubitril, which is a NEP inhibitor in that product, had 60% of elimination, dependent on kidney functions. So 60% excreted through the kidney. Although that may be favorable in a healthy person, people with heart failure often have secondary kidney dysfunction and failure, because you need a good heart and a good profusion in order to make the kidney optimally performing. So we have been focused on drugs that are not [indiscernible] cleared, accepting that that maybe better suited to patients, either with heart failure, so chronic heart failure is still an opportunity we are considering. But we also recognize a broader spectrum of disease opportunities, including patients who may have underlying renal dysfunction. So either its primary heart failure with secondary kidney failure, with the possibility of considering a chronic kidney disease as well. Diabetic nephropathy for example, has a considerable unmet need. And we do recognize that for those, those are sizable developments, commitments, and really, I think it would be fair to say, and we are fairly overt about this, but those are likely to require partnership discussions. We do recognize, that there are also opportunities for narrower spectrum development opportunities, and we are considering those. So I think there is a spectrum that we are considering. Our purpose was really to get the assets to this point, to be able to characterize each of them and then consider differential development programs for each.

Great. Thank you.

Thank you.

Our next question comes from Umer Raffat of Evercore ISI. Your line is open.

Hi. Thank you so much for taking my question. Rick, I have three on the JAK inhibitor perhaps. So first one, maybe to start off, can you update us on the recruitment? Is it fully enrolled? I think clin trials implies it's still in rolling, just wanting to check in on that, number one. Number two, the study site, so how many sites are in this trial; because clin trials implies its only one center, but the site that's implied by clin trials isn't exactly -- it reads like a market research terms. I wasn't sure how many sites are participating and where they are? And then third, do you still expect close to XELJANZ, like efficacy on Partial Mayo Scores? Thank you.

So Umer, hi, this is Brett. You were fading in and out. So I just want to confirm, you were asking about the 1473 study, is that correct?

Yeah, so -- that's right.

That's fine. We don't go into the specifics of current numbers obviously, with an ongoing study, recruitment is something we don't disclose. I can't confirm it's not a single center. There are a number of centers, and in fact, we are participating in a number of countries on this program. Again, for the purposes of clinical trials or [indiscernible] often a single seminal site is listed. But there are several in this program. You asked about clinical endpoints, and I think as you will have heard us perhaps reference previously, although Partial Mayo is an endpoint in the study, it isn't the only one, and in fact, the study is not powered to be able to detect differences for a single endpoint. Our purpose here is to look at consistency in a number of different markers, including but the clinical improvements, the histological improvements, changes on endoscopy, and of course, the absence of any systemic risk, including looking at the usual suspects, white cells and so on, and the amount of drugs in the systemic circulation. So it is our purpose here to amalgamate all of that information and to provide, what we hope to be a consistent story, in order to support the localized effect of 1473. Rick?

Yeah. I think relative to expectations versus TOFA, what we are trying to do, is affect both the numerator and the denominator in the therapeutic index. I mean, clearly, the data with TOFA, certainly above some limited data in Phase 3 of the higher dose, and then the data that you -- that's in the Phase 2 program for TOFA, indicate that there is more efficacy available with higher concentrations. You just can't get there with the systemically delivered drug, because of toxicity. So we think that there is more efficacy to be had, via the pan-JAK mechanism and we hope that because our focus is on intestinal restriction with a very limited amount of drug getting into the systemic circulation, that the safety concerns will in fact be much lower than other JAK inhibitors, be they JAK selective or pan-JAK inhibitor, simply keeping the drug by and large for all purposes out of the blood stream, and having it focused into the tissue, where the inflammation occurs, and again, trying to squeeze as much efficacy as we can out of the mechanism, but in fact, keeping the drug out of the systemic circulation and because of that, creating a safer, better tolerated medicine.

Got it. So Rick, perhaps say it another way, and maybe just to build on what you just said, would the trial enable -- since it's a Phase 1 trial, are you able to simply add more arms or higher doses if you had to, if you weren't satisfied with what you guys were seeing so far?

So Umer, it is an adaptive design, and I think as you may have seen before, there is the ability to be informed from the results of one cohort, to move up or down in the dose. So I think that flexibility does exist, and certainly, would allow for characterization at different points. Bear in mind, this is not a conventional approach. Very few, in fact we are not aware of any other companies that have taken this approach this early in development. But our purpose here really is to inform a narrower dose selection, to be able to move forward into the next round of development. So that flexibility is an intrinsic part of the value, that we believe is created with this study.

Got it. Thank you very much.

Yeah Brett, you just may want to expand a little bit, with regard to how we are treating this 1b study, with regard to central evaluation, given it is a multiple site.

Thanks Rick. So a good point, and actually even for, what seems to be a fairly early and possibly a very small study, we have still applied the same rigor that would be assigned to a pivotal registrational study. So all of our endoscopy reads for example, the images that are taken during the colonoscopy are centrally overread. They are [indiscernible] by each individual investigator, in the purposes to try and reduce bias. Of course, the other important point is, that these patients are being scoped at the beginning and the end of therapy. So every patient serves as their own control, which increases our ability to detect effects over the course of treatment.

Thank you very much.

Thank you. It appears we have no further questions on the phone. I'd now like to turn the conference back to Mr. Winningham. Please go ahead, sir. [Dictation Ends Abruptly].