Theravance Biopharma, Inc.
Q3 2017 Earnings Call Transcript

Published: 8 Nov 2017

[Operator:]

Ladies and gentlemen, good afternoon. At this time, I'd like to welcome everyone to the Theravance Biopharma Conference Call. [Operator Instructions] Today's conference call is being recorded. And now I would like to turn the call over to Alex Dobbin, Head of Investor Relations. Please go ahead.

[Alex Dobbin:]

Thank you, Operator. Good afternoon, everyone. Thank you for joining our third quarter 2017 financial results conference call and webcast. With me on the call today are Rick Winningham, Chief Executive Officer; Renee Gala, Chief Financial Officer; and Brett Haumann, Chief Medical Officer. Following our prepared remarks, we'll open the call for questions. A copy of the press release and the slides accompanying this call can be downloaded from our website, or you can call Investor Relations at 650-808-4045, and we'll be happy to assist you. Before we get started, I’ll direct your attention to Slide 2, of the deck and remind you that this conference 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 now I call your attention to Slide 3 of the deck and hand the call over to Rick.

[Rick Winningham:]

Thanks, Alex. Good afternoon, everyone, and thank you for joining us. Theravance Biopharma continues to demonstrate the potential of our portfolio with encouraging clinical data across multiple programs. Looking forward, we are positioned to achieve numerous clinical and regulatory milestones with the plan deliver on the promise of developing differentiated medicines for patients in need. On our call today, we'll provide an update on our key development programs and discuss recent progress with Trelegy Ellipta, formerly known as the Closed Triple, where we have an important economic interest. As has been our practice, I'll provide an overview of our recent progress, Brett will provide additional detail on our clinical programs and Renee will review our financial performance, and then we'll open the call to questions. I'll start with 1473, our intestinally restricted JAK inhibitor for inflammatory bowel disease, including ulcerative colitis. In August, we were excited to announce the results of the first cohort of our Phase 1b study TD-1473 in patients with moderate to severe ulcerative colitis. Data from the first cohort demonstrated a favorable target product profile for 1473. We saw consistent biological evidence of localized target engagement, improvements in measurements of disease severity without evidence of systemic exposure and a favorable exposure and a favorable tolerability profile. These results are consistent with the properties we designed into the molecule to maximize local anti-inflammatory efficacy and minimize side effects in order to optimize therapeutic index. The encouraging evidence we have seen to date has given us confidence to move forward in planning and conducting a large multidose induction and maintenance study in patients with ulcerative colitis, and we're on track to start that study in 2018. For TD-9855, our dual norepinephrine and serotonin reuptake inhibitor, the Phase 2a study in neurogenic orthostatic hypotension or nOH is ongoing. Our objective with 9855 is to restore function in patients with this debilitating condition. We are excited by our progress in this key program, which Brett will describe shortly. Last quarter, we reviewed promising top line data from the Phase 2b study of velusetrag, our highly selective 5-HT4 agonist. This was the first clinical evaluation of velusetrag's effect on the symptoms of gastroparesis, and the results from the study provided us with encouraging evidence of the effects of velusetrag at low dose. With only one approved treatment for gastroparesis in the last 35 years and safety risks associated with the approved treatment's use, this condition represents a significant unmet medical need. We and our partner, Alfasigma, are preparing for meetings with regulators to discuss the next phase of development. Finally, I'll mention revefenacin, our investigational long-acting muscarinic antagonist, or LAMA, in development as a once-daily nebulized bronchodilator for COPD. We're on track to file an NDA before the end of this year, and this stands to be a major achievement. While we prepare for our NDA submission, the Phase 3b study in COPD patients with low peak inspiratory flow rate, or PIFR, is ongoing, and completion of the study is anticipated in the first quarter of 2018. The PIFR study is intended to support the commercialization of revefenacin and is not required for NDA submission. Before I turn the call over to Brett, a few comments on VIBATIV. We remain focused on strategies to optimize our operational effectiveness in our acute care commercial organization. Additionally, our patient registry study, or TOUR, is providing valuable information about the use of VIBATIV in real-world clinical settings. We've presented 17 TOUR-related abstracts and posters at conferences to date, including last month at the Annual CHEST Meeting, and we're planning additional publications in 2018. With the potential launch of revefenacin in sight, we see the acute care setting as an important inflection point for identifying the right patients for nebulized therapy, and we look forward to the opportunity to leverage our existing organization to support the success of this product. I'll now turn the call over to Brett for further updates on our clinical programs. Brett?

[Brett Haumann:]

Thanks, Rick. Turning to Slide 4. I'll start with our JAK inhibitor program. Our goal is to develop a highly differentiated treatment option for inflammatory bowel diseases, including ulcerative colitis. Our lead molecule, 1473, is designed 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 immunosuppression. As reported in August, we achieved a wide set of objectives in the first cohort of our Phase 1b study, a number of which are particularly meaningful given the study's treatment period of only four weeks. In the Phase 1b study, we've sought to evaluate PK properties, target engagement, biological activity and tolerability in patients? Results from the first cohort at 80 milligrams were highly encouraging. Firstly, we were able to confirm that patients with active disease had the same very low concentrations of drug in the blood that we've previously seen with healthy volunteers, despite these patients having an inflamed and disrupted gut wall. This was an extremely important finding, confirming that patients with active disease did not have high levels of drug in the blood. Second, we saw clear evidence of biological activity, not only in terms of reduced inflammatory biomarkers, but also in terms of clinical responses, such as reduced rectal bleeding, evidence of evidence of mucosal healing and evidence of clinical response using total Mayo and partial Mayo scores. We were particularly pleased to see evidence of clinical improvements in this four week study. These findings provide a wealth of information they confirm 1473 is having an affect on inflamed tissue and behaving in patients as designed. And these data provide a strong foundation for proceeding to design a large multidose induction and maintenance study while we complete the two additional cohorts of the Phase 1b study. These two additional cohorts have been run in parallel with doses intended to bookend the 80-milligram dose, with 20 milligrams at the low end and 270 milligrams at the high end. Recall that in our Phase 1 study in healthy volunteers, we dosed 1473 as high as 1,000 milligrams as a single dose and up to 300 milligrams once daily in the multiple dose study and saw no evidence of immunosuppression. In the completion of the Phase 1b study, we're building confidence around what doses to take into the induction and maintenance study. We expect data from the low-and high-dose cohorts in the first half of 2018, but we're not waiting on this data to mobilize our planning for the next study, which we plan to initiate in 2018. Our intent for the next study is to conduct an eight week induction phase followed by a maintenance phase, evaluating several doses for both efficacy and safety. Moving on to 9855 on Slide 5, nOH is a disorder of the autonomic nervous system characterized by the inability to regulate blood pressure when moving from a lying to a sitting or standing position. It's an often condition affecting fewer than 200,000 patients in the U.S. and includes patient with multiple system atrophy, Parkinson's disease and pure autonomic failure. The condition is very debilitating and often confines patients to their beds, severely impacting mobility and quality of life. As we've outlined on Slide 6, the current approved treatment for nOH are droxidopa and midodrine, both of which are exogenous analogs of norepinephrine. They essentially saturate the nerve endings in the autonomic nervous system with exogenous norepinephrine in order to increase blood pressure and reduce symptoms. That approach can, for a short period of time, maintain blood pressure while patients are active during the day. But the benefit is short-lived, requiring dosing three times a day. And in addition, patients cannot take these therapies after about 3

[Renee Gala:]

Thank you, Brett. Turning to Slide 11, our third quarter financial results were within our expectations and guidance. Revenue for the third quarter of 2017 was $4.3 million, primarily related to U.S. net product sales of VIBATIV. Research and development expenses for the third quarter were $39.3 million as compared to $32 million for the same period in 2016. The increase in R&D expenses is primarily attributed to costs associated with the progression of our key programs as well as employee-related costs. Third quarter R&D expense includes $5 million in noncash share-based compensation expense. Selling, general and administrative expenses for the third quarter were $20.9 million as compared to $20.3 million for the same period in 2016. The increase in expense is primarily due to employee-related costs and noncash share-based compensation, partially offset by a reduction in external expenses related to commercialization activities. Third quarter SG&A expense includes $5.7 million in noncash share-based compensation expense. Third quarter operating loss was $57 million or $46.3 million excluding share-based compensation, which is in line with our full year guidance of $205 million to $215 million. Cash, cash equivalents and marketable securities at the end of the third quarter totaled $434.4 million, placing us in a well-capitalized position as we prepared to enter 2018. Now turning to Slide 12. We are incredibly excited by the recent progress of Trelegy Ellipta, a product in which we hold a economic interest. This product is the first and only once-daily triple therapy in a single device comprised of a LABA, ICS and LAMA. Over the last two months, GSK and Innoviva have announced multiple important milestones with this program, including FDA approval and plans to launch in U.S. in the middle of this month; a positive opinion from the European Medicines Agency recommending marketing authorization in the EU; and results from the Phase 3 IMPACT study, which met both its primary endpoint and all prespecified key secondary endpoints. In this study of over 10,000 COPD patients, Trelegy Ellipta was compared to the dual therapies of Anoro Ellipta and Relvar/Breo Ellipta. Trelegy showed reductions in the rate of moderate to severe COPD exacerbations of 25% compared to Anoro and 15% compared to Relvar/Breo. Trelegy also demonstrated improvements in lung function, time to first exacerbation and quality of life compared to both Anoro and Relvar/Breo. We were delighted to see these impressive results, and we expect GSK to begin regulatory filings with the IMPACT data in 2018. In addition to the COPD program, GSK is conducting a large Phase 3 study in asthma patients referred to as the CAPTAIN Study. CAPTAIN is expected to read out in 2018 and if positive, would be followed by regulatory filings in this indication. Theravance Biopharma holds an economic interest in Trelegy Ellipta that equates to upward tiering royalties of approximately 5.5% to 8.5% of worldwide net sales. We expect to begin receiving these cash flows in the quarter following the launch of the product, and we will recognize this income below the operating line as other income. The economic interest in Trelegy represents an important strategic asset to the company as a future contributor of growth and an alternative source of funding for the pipeline. Now I'll turn the call back over to Rick.

[Rick Winningham:]

Thanks, Renee. Turning to our list of expected upcoming milestones on Slide 13. In 2017, filing our NDA for revefenacin and GSK's launch of Trelegy in the U.S. and potential regulatory approval in the EU for COPD; and in 2018, data from the remaining cohorts of the Phase 1b study of 1473 in ulcerative colitis; data from the Phase 2a study of 9855 in neurogenic orthostatic hypotension patients; data from the Phase 3b study of revefenacin in patients with low peak inspiratory flow rate; potential approval of revefenacin in the U.S. for COPD; additional data presentations from the TOUR patient registry study on VIBATIV; and Phase 3 VIBATIV study results in bacteremia in 2018 or 2019; and finally, the data from the Phase 3 CAPTAIN study of Trelegy Ellipta in asthma patients. And as I noted in my opening comments, we believe that we're in an extraordinary period of progress and maturation as a company. We have what we believe is a rich and broad portfolio of therapeutically differentiated product opportunities and a very productive internal R&D engine and a diversified business model to enable us to optimize the commercial potential of our portfolio. We are confident in our prospects as we advance multiple key programs to the clinic, and we're excited by our anticipated milestones over the next six to 12 months. And now I'd like to turn the call over to the operator for questions.

[Operator:]

Thank you, sir. [Operator Instructions] We'll have our first question from Geoffrey Porges with Leerink Partners.

[Brad Canino:]

Hi, this is Brad Canino on for Geoff. Thanks for taking the question. On the JAK, you plan to initiate a larger induction and maintenance trial in 2018. But there will also be two other JAKs with full Phase 2 data and other oral and biologic mechanisms also recruiting Phase 3 induction and maintenance trials in that period. That will probably require thousands of UC patients. So do you believe you have enough data with the Phase 1b cohorts, which is only about 30 patients, to compete for a trial recruitment in that disease?

[Brett Haumann:]

Thanks for your question. This is Brett. We are certainly aware of the competitive landscape, and you're right, there are a number of alternative therapies. One of the opportunities here, I think, though, which shouldn't be underestimated is the value of offering a therapy which is localized. Clearly, other therapies that are coming forward remain systemic, and the challenge with those therapies is to titrate the dose so that you are balancing the efficacy and safety. Now that is also our responsibility, but one of the compelling elements and certainly supported by the current evidence that we have is that we appear to be remaining localized. We're not seeing evidence of systemic immunosuppression, and that is a distinct and separate observation from what may have been seen in other programs, particularly other JAK inhibitor programs that even if they are focused on individual isoforms of JAK do run the risk of immunosuppression. Rick?

[Rick Winningham:]

Yes, I think, Brett, that's a key point. We're offering an opportunity here for patients to enroll in a study where we have evidence, that we'll have – at that point in time, evidence of efficacy in the condition with no systemic immunosuppression. We thought that was an important element of initiating the program and research, and we remain convinced of that even today. I think you've seen a continual readout of data from systemic immunomodulators that highlight, in fact, the shortcomings of that approach. Now – and I think we remain very optimistic and confident that we've got a terrific opportunity here with 1473 to develop a medicine that's got a targeted – with targeted approach into the inflamed tissue in the colon without systemic immunosuppression.

[Brad Canino:]

Great. And are you considering using different doses for the induction and maintenance portions dose than some suggestion that with some mechanisms using a higher dose in the induction phase result in better data?

[Brett Haumann:]

So, excellent question. And certainly, the next study would include multiple doses to be evaluated because we are really wanting in a larger study a lot more akin to what you may have seen with historic programs like tofacitinib and the like in that larger study to use clinical endpoints to determine the optimal dose. So the short answer to question is yes, there would be multiple doses in that study.

[Rick Winningham:]

But I think the continue – the purpose of the Ib program to date was to collect data from a wide – relatively wide range of doses, importantly, not simply endpoint data with endoscopies and understanding the level of wound healing within the colon, but also the concentration of the JAK inhibitor in tissue to guide us in the dose range that we would use in the Phase 2b study. It's likely that the induction and maintenance phase of the – of this maintenance study will have the same dosing in the induction phase as in the maintenance phase. Brett, anything else?

[Brett Haumann:]

That's accurate. Actually, I think, in reflecting on your question, you may have been asking about titration of dose after induction. Because we are localized and because we are aiming to achieve a really optimal therapeutic benefit and because we're not being forced to titrate down to avoid safety risks in the long-term, that does allow us more flexibility than may have been seen in other programs where dose titration is often to avoid systemic liability in the long-term. So it is as Rick has described, our purpose here would be to evaluate multiple doses but to keep the same dose between induction and maintenance.

[Brad Canino:]

Great, that’s helpful. Thank you.

[Operator:]

Our next quarter comes from the line of Josh Schimmer with Evercore. Your line is now open.

[Josh Schimmer:]

Great, thanks for taking the question. Hopefully, you can hear me, actually, two questions. First, given the success of revefenacin and Trelegy now, can you talk about the feasibility and path forward for potential nebulized triple [indiscernible]?

[Brett Haumann:]

Josh, you break up a little bit at the end there. I'm not sure if you're still with us, but I think your question was about the feasibility of a nebulized to triple therapy, is that correct? So our focus really with revefenacin has been to focus on the introduction of the inspection study [indiscernible]. The purpose here is very much to focus on using a nebulized LAMA for which there’d be no treatment alternatives. One of the important things to acknowledge in our program is that at the encouragement of the agency working with the FDA, they did allow for the assessment of LAMA being used alongside other therapies, whether they were nebulized or inhaled. And certainly, that included the assessment of concomitant LABA and LABA/ICS. So we have a representation of patients in our current program for whom triple-based therapy is not only a possibility, it was evaluated in the program. That isn’t to say that it was a fixed-dose combination. This was only to support concomitant therapy. But really, our focus very much at this stage is to bring that standard of care, that LAMA monotherapy to the markets so that patients who use nebulized therapy really benefit from the standard of care that the majority of patients in the handheld space benefit from.

[Rick Winningham:]

And just to continue briefly on Brett’s comment, I think the use of a nebulized product in particular for these patients with low peak inspiratory flow rate continues to interest us. And the – when you think about the future and progression of COPD, opportunities for nebulized therapy with one or more mechanisms, as well as nebulized therapy potentially in – to – it look like revefenacin to open the airways most completely, and then when those airways are open perhaps that facilitates better LABA/ICS therapy for – through either an MDI or a DPI. And I think we’re aware of certainly what’s happening today in the market, what might be happening in the future, and will work to position revefenacin appropriately for the evolution of the market as triple therapy likely becomes more prevalent overall. Just one final point, and that’s on the use of nebulization, I think there’s triple therapy in the market today. That’s important to understand. A significant amount of patients today in COPD are already on triple therapy. And even with the triple therapy that exists today, there remains sort of year in, year out that 9% of patients that remain on nebulized therapy with the diagnosis of COPD.

[Operator:]

And our next question comes from the line of Tazeen Ahmad with Bank of America. Your line is now open.

[Peter Stapor:]

Hi, guys. This is Peter Stapor on for Tazeen Ahmad. Just a couple of questions and one of them follows up on some of the earlier questions on the JAK program. So can you just clarify your expectations for the dose going forward? I know you talked about the Phase 2b having multiple doses, but are you planning to initiate these studies before the full data set from the high- and low-dose groups?

[Brett Haumann:]

Peter, thanks for your question. Actually, the intent here is to use the current study to bookend the range of doses that we’re planning, but we’re not waiting on the completion of that study to inform the progress into the next piece of work. So I think the planning stages are ongoing now. I think that the sense that we’ve taken from this Phase 1b study was always around biological confidence. The value of the next study in assessing multiple doses is to do the true dose ranging and to use clinical endpoints to determine that. So you’ll see, as is being done with tofacitinib and other programs, you’ll see that are being implemented in the next phase. But we certainly are building confidence using the current data set and the range of doses we’ve tested.

[Peter Stapor:]

Okay, that makes sense. And my second question is, could you provide a timeline on when you’ll have a plan to move forward with velusetrag?

[Brett Haumann:]

Thank you. Really, the focus of the team at the moment is to gain regulatory feedback, as we mentioned, in the – on the call. And that process is ongoing at the moment in both the U.S. and Europe, where we have key accountability for the U.S. registrational program and our partner is exploring the European elements. So that is a process which is ongoing and clearly, that will feed into the final planning for the next phase of development.

[Rick Winningham:]

So as we discussed and Brett discussed at the time of the data release, there are really two elements. One of them is the PRO, the patient reported outcome tool, and then the patient reported outcome tool as that fits into the Phase 3 design, we need to reach agreement with the regulatory agencies on both piece of those and that work is underway.

[Peter Stapor:]

Okay, thank you.

[Operator:]

And our next question comes from the line of Brian Skorney with Robert W. Baird. Your line is now open.

[Neena Bitritto-Garg:]

Hi. This is Neena on for Brian. Thanks for taking the question. I have a question about kind of piggybacking on some of the previous questions, just about the timeline for enrollment and the timeline for readout for the TD-1473 Phase 1b, the remaining cohort. So I know Celgene made some comments on their earnings call about pushing out the timeline on their Phase 3 readout in UC due to trouble enrolling patients. Are you seeing the same thing in your ongoing Phase 1b study and what is the current status of enrollment in the other cohorts?

[Brett Haumann:]

Thanks, Neena. So great question. I think the key element for us in the current program was obviously looking at the biological confidence. We do – as we mentioned in the earlier response, we do believe that moving to the next study, some of the impetus for enrollment and indeed some of the patient interest may come from being able to take a – or participate in a study evaluating a JAK that doesn’t carry systemic liabilities, and that would set us apart from some of the other competitors out there. Of course, some of the other programs are also looking at non-oral forms. So some of the monoclonal antibody programs would be parenteral injection-type studies, and those are carry some concerns for patients as well. So we’re hoping that the fact that we’re oral, that this is a one steady administration, that the potential for systemic risk, we believe, is managed. Although, clearly, we would need to remain vigilant through our program. But we think that those will become incentives for patients. Now you asked about the differences between that and the current study. And I think we have acknowledged this. In an environment where you try to conduct a four-week study and you’re competing for patients who could otherwise go into an induction or a maintenance or a one-year study, there’s less intensive for patients to participate, and we certainly have seen that in our four-week study. We’re not expecting that to be a concern in the next phase because the next study will offer them both induction and maintenance.

[Neena Bitritto-Garg:]

Great, thanks.

[Operator:]

[Operator Instructions] And our next question comes from the line of Louise Chen with Cantor Fitzgerald. Your line is now open.

[Louise Chen:]

Hi, thanks for taking my questions. So first question I had was on the cash runway. Can you give an update on what that should last you through? And then second question I had was, now that your R&D engine has been validated, what areas of opportunity or unmet need do you see in the market? I know you’ve got a lot of products already in development, but just curious if there’s anything else that you’re thinking about. And then just the last question here is, on the products that you have, do you have any updated thoughts in which ones you plan to partner and which ones you plan to commercialize on your own? Thanks.

[Renee Gala:]

Great. Thanks, Louise. I’ll take the cash and then I’ll turn it over to Brett for the second question. We haven’t provided guidance for 2018 or the specific cash runway. As you would have heard on the call and seen in the press release, we ended the quarter with about $434 million in cash. So we’re in a pretty good situation. With respect to our future plans, though, and future spend, I would just remind you of the additional options that we have now with Trelegy as really serving as a cash flow vehicle for us. It enables multiple financing opportunities for us in the future to be able to fund the pipeline. So I think all in all, we’re starting out 2108 in a pretty good position. In addition to Trelegy, of course, we have a pretty full pipeline that creates business development opportunities as well. So as you know, Louise, we think about this often but also quite broadly so just stay tuned with respect to our future guidance, which we generally would give at the beginning of the year. And then I would say, keep in mind that we have multiple options now with the approval of Trelegy.

[Rick Winningham:]

Yes, just to add a point on Trelegy because I think this was quite significant for us in terms of data during the quarter. Clearly, having a number of us worked on the program over a number of years, the IMPACT study data exceeded our expectations. The reduction in exacerbations versus LABA/ICS at 15% and the reduction in exacerbations at 25% versus Anoro, very, very strong data. And I think once the IMPACT data is incorporated into the label, I think it bodes quite well for the future of Trelegy and therefore, quite well for Theravance Biopharma, given that, that loyalty flow to us really requires no cash outlay on our part. It’s just cash in the door and has Renee has highlighted both in our script and our comments, really provides a very nice base – should provide a nice base of inflow for us over the next several years. Brett, did you have another point?

[Brett Haumann:]

I think that just to respond to Louise’s second question, which is around unmet need. And Louise, I think it’s fair to say that we have really developed a set of expertise and skills within the organization that were originally built on insights that we have in the respiratory arena but now being transferred into the GI arena, where we’re focused on delivering medicines to patients where there’s an isolated organ of interest and we’re able to target that organ without exposing the rest of the body unnecessarily to therapy. And that in itself presents the opportunity to identify other patients with unmet need that would be suited to similar approaches. So I think that, that is sort of consistent with our overarching strategy, visibility to focus and lock into localized medicines for localized disease. The other element, of course, is the program that we talked with you about today, which is the unmet need in a rare condition like neurogenic orthostatic hypotension, where we believe that one of the assets in our portfolio really may have a significant opportunity to show a treatment benefit.

[Operator:]

Thank you. It appears we have no further questions on the phone. I would now like to turn the conference back to Mr. Winningham. Please go ahead, sir.

[Rick Winningham:]

Thank you very much, operator. Thanks, everyone, for participating in our conference call today. We’re very optimistic as we look towards the end of 2017 and entering 2108 with the progression of our pipeline and the progression of our company. We believe that we’ve got a number of products that, in fact, can deliver on their promise for providing benefit to patients based on a level of unmet medical need. So thank you very much, and have a great day.

[Operator:]

This concludes today’s conference call. We thank you for your participation. You may now disconnect.