Theravance Biopharma Inc (TBPH) 2017 Q4 法說會逐字稿

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.

Good afternoon, everyone.

Thank you for joining our conference call and webcast to discuss our fourth quarter and full year 2017 financial results.

With me on the call today are Rick Winningham, Chief Executive Officer; Renée Galá, 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.

Prior to our update, we'd like to 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'd call your attention to Slide 3, and hand the call over to Rick.

Thanks, Alex.

Good afternoon, everyone, and thank you for joining us.

The last 12 months have been a period of significant progress with Theravance Biopharma, having advanced several programs within our portfolio across key milestones.

We reported important clinical results across a range of therapeutic areas and phases of development, submitted an NDA and signed a strategic partnership with Janssen Biotech.

The strategic partnership with Janssen surrounding our intestinally-restricted JAK program for inflammatory intestinal disease represents a key point in the evolution of our company.

The intestinally-restricted JAK program is the first to emerge from our research efforts to create localized medicines for localized disease.

These insights began with our work in the lung, which led to the discovery of revefenacin.

To those understandings, we had a depth in immunology as well as leveraged our knowledge in other organ systems such as the GI tract.

Key to our progress has been our growth in understanding of both metabolism and absorption and integrating all of that knowledge into chemical design.

We're excited about the evolution of our company's focus on leveraging insights into the properties of local tissue and suppression of specific cytokines in these tissues.

2018 will be an important year for Theravance Biopharma as we intensify our focus on strategic priorities, drive clinical execution and advance programs from our validated research platform towards clinical development.

With Trelegy Ellipta launched in the United States and multiple strategic partners secured to complement our internal efforts, we're well positioned to execute on the most important opportunities in our portfolio.

On our call today, we will highlight our achievements in 2017 and discuss our key upcoming events and milestones.

Before doing so, I'd like to provide an update regarding VIBATIV in the Phase III bacteremia study as it pertains to our asset allocation strategy in 2018.

Over the course of 2017, we made reductions in VIBATIV commercial spending, given the headwinds in the antibiotic market.

Alongside this, a prespecified interim analysis was recently conducted by an interim review committee on the data from our ongoing Phase III bacteremia study.

The independent review committee concluded that the study is underpowered and therefore unlikely to achieve the primary study objective without an increase in study size beyond the approximately 250 patients planned.

We do not believe investing to increase the power of the study is an appropriate allocation of our capital at this time and as a result, we are closing the study.

The interim analysis showed no new safety concerns so all existing subjects will be allowed to complete dosing, but we will not enroll new patients.

Once we finish collecting and analyzing the data generated in the study, we plan to share it with regulators and submit it for future scientific publication.

Even though we're closing the study early, the study will still be the largest randomized evaluation of MRSA bacteremia patients to date with just over 120 patients with confirmed MRSA enrolled.

VIBATIV remains a key medicine to treat serious infections in very sick patients, and we will continue to support its commercial profile commensurate with the current and expected near-term opportunity.

As we turn to the pipeline and key upcoming events, we plan to initiate the Phase II development in Crohn's and Phase IIb/III development in UC of our intestinally-restricted JAK inhibitor, TD-1473, with Janssen; advance our potential medicine for patients with symptomatic neurogenic orthostatic hypotension, TD-9855, towards a registrational program; secure approval for and launch revefenacin for our nebulized LAMA for COPD with our partner Mylan; and advance a new program into the clinic in inhaled JAK inhibitor for serious respiratory disease.

This will be the second program that has progressed out of research from our focus on localized medicines for localized disease and a focus on inhibiting JAK.

We look forward to updating you on our progress across research and development later this year in an R&D day.

As we enter 2018, we're pleased to see the continued advancement of GSK and Innoviva's Trelegy Ellipta.

Trelegy's progress is led by regulatory approvals for COPD in the U.S. and EU, positive results from the landmark IMPACT study, and more recently, submissions of that data to FDA and EMA in order to support an expanded label for the product.

Additionally, Trelegy's progress and weekly prescriptions as well as payer coverage in the week since introduction has been impressive.

Meanwhile, GSK is conducting a large Phase III study in asthma patients referred to as the CAPTAIN study with data expected in 2018.

Now I'd like to ask Brett to provide updates on our development programs.

Thanks, Rick.

I'll begin on Slide 4 with our JAK inhibitor program.

TD-1473 is a novel, potent, orally-administered and intestinally-restricted pan-JAK inhibitor, with the potential to treat a range of inflammatory intestinal diseases, including ulcerative colitis and Crohn's disease.

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 Rick mentioned, we recently executed a global collaboration agreement with Janssen for the joint development and commercialization of 1473 and related backup compounds.

As we discussed at the announcement of our agreement, this collaboration has the potential to benefit both 1473 and the company in a number of ways.

First, by immediately harnessing the expertise of Janssen, we believe we can optimize the clinical strategy and execution of 1473, which is of particular importance in this competitive field of inflammatory bowel disease.

Second, this collaboration allows us to accelerate and expand the scope of the development program, with a plan to pursue multiple indications in parallel starting this year.

And finally, our goal is to maximize the worldwide commercial opportunity for 1473 for Theravance Biopharma and our shareholders.

And we think having Janssen as our partner now in advance of our registrational programs will enhance our overall probability of success and support achievements of this objective.

We were pleased with the data from the first cohort of patients in our Phase Ib study in ulcerative colitis as it demonstrated target engagements and biological activity and provided us and Janssen with confidence in initiating the Phase IIb/III induction and maintenance study in ulcerative colitis and the Phase II induction study in Crohn's disease in the second half of 2018.

We don't view the remaining cohorts as gating our progression into these larger studies, but the results may inform those selection.

In the current Phase Ib study, enrollment is now complete, and the last remaining patients are completing their 4-week treatment period.

In recognition of our newly formed partnership with Janssen, we'll be working with them to agree on the timing and mechanism of disclosure for the remaining data from the study.

I'll now turn to Slide 5 and TD-9855, our norepinephrine serotonin reuptake inhibitor in patients with an orphan condition called symptomatic neurogenic orthostatic hypotension or nOH, which affects a proportion of patients with Parkinson's disease as well as the majority of patients with multiple system atrophy, MSA and pure autonomic failure, PAF.

Our exploratory Phase IIa study in patients with this rare syndrome is ongoing, and we continue to observe emerging signals of potential benefit for patients with symptomatic nOH in a single ascending dose portion of the study.

Patients who respond in this portion are then eligible for a repeat dose phase of up to 5 months of treatment, in which we're assessing the durability of response to 9855, with the primary assessment after 4 weeks of treatment.

It's important to note that not all patients who respond in a single ascending dose are able to complete the repeat dose portion of the study.

In some cases, their health is deteriorating rapidly due to their underlying condition of Parkinson's disease, MSA or PAF.

Sadly, in extreme cases, the patient may not live long enough to progress into the repeat dose portion.

As a result, the data we expect to report in the middle of this year will be from a limited number of patients that progress to the 4-week time point.

As this is a small exploratory study, we did not design it to demonstrate statistical significance.

We're seeking to demonstrate the durability of effect on symptoms as we believe this could lead to significant benefits over existing therapy for nOH patients.

We have learned from our exploratory study that nOH is a multifaceted disease, and a number of symptoms contribute to patient's disabling state.

While low blood pressure is fundamental to the disease, it's evident that treating symptoms and function are also meaningful in this patient population.

While the exploratory study is ongoing and recruitment is not yet complete, we're particularly interested in those patients who failed to accomplish a 10-minute standing test at baseline.

This is a population in whom standing to undertake basic chores, for example, going to the bathroom or making a cup of coffee, is impossible.

They spend the majority of their waking hours in a wheelchair or lying down.

The majority of the patients in our current study are not able to stand for 10 minutes of baseline, and these are the patients we believe will be most valuable in informing the clinical evaluation, including dose selection for 9855.

We're encouraged by what we know to date about 9855 as well as our interactions with regulatory authorities regarding the future of the program.

We'd like to be in a position to start Phase III late this year or early next year.

So stay tuned for further updates.

Turning to Slide 6 and revefenacin, our once-daily nebulized LAMA for the treatment of COPD.

Last month, we announced the FDA had accepted our NDA submission for revefenacin and provided us with a PDUFA date of November 13, 2018.

Also in this communication, the FDA stated it does not currently plan to convene an advisory committee to discuss the NDA.

Our NDA submission is supported by positive results from 2 replicate pivotal Phase III efficacy studies and a 12-month Phase III safety study.

If approved, revefenacin will be well-positioned as the first once-daily nebulized LAMA for COPD patients.

Our launch readiness activities in partnership with Mylan are ongoing, and we are pleased with the progress of our collaborative efforts.

We recently completed our revefenacin Phase IIIb study in approximately 200 COPD patients with suboptimal peak inspiratory flow rates or PIFR, the first prospective study of this nature ever conducted.

The purpose of the PIFR study was to support commercialization of revefenacin.

The study is not required for NDA approval.

The study was designed to assist potential superiority of nebulized revefenacin versus handheld tiotropium delivered by the Handihaler device in a broad population of COPD patients with suboptimal PIFR.

The primary endpoint in the study was improvement in lung function as measured by trough FEV1 after 4 weeks of treatment.

We saw numerical improvements for revefenacin over tiotropium in the overall population of moderate to very severe that is GOLD stage 2, 3 and 4 patients.

But these improvements with revefenacin were not statistically significant.

And as a result, the study failed to meet the predefined thresholds for superiority.

Importantly, in the prespecified subgroup of severe and very severe COPD patients -- these are the GOLD 3 and 4 patients, which make up approximately 80% of the patients in the study, revefenacin demonstrated nominally statistically significant and clinically relevant improvements versus tiotropium.

This data provide very important insights to both informed future studies of revefenacin in COPD patients with suboptimal PIFR and direct our future efforts in identifying those patients that may benefit most from nebulized therapy.

Revefenacin was well tolerated in this study with no new safety issues identified.

Data from the Phase IIIb study will be submitted to the FDA to support our overall safety package, although as previously mentioned, the study itself is not required for product approval.

We plan to publish data from this study at a future medical meeting or conference closer to the time we expect revefenacin to be approved and on the market.

Finally, on Slide 7, I'll touch on velusetrag, our 5HT4 agonist, which completed a Phase IIb study in gastroparesis last year.

On this program, we've been in active dialogue with regulators regarding the Phase III requirements for gastroparesis.

These discussions include agencies in the U.S. and Europe, including a separate division in the U.S. FDA that provides guidance specific to patient-reported outcome tools.

We expect to provide an update regarding the next steps for velusetrag in the first half of this year.

As a reminder, our partner for velusetrag outside the U.S. is Alfasigma.

Under the collaboration agreement, Alfasigma paid for the majority of the Phase II program in gastroparesis and is now entitled to exercise an option to further develop and potentially commercialize velusetrag in the EU and certain other markets.

The timing of this option period is, of course, linked to the time required to complete the necessary regulatory interactions.

So we would also expect to provide an update on Alfasigma's intent with velusetrag sometime in the first half of 2018.

Should Alfasigma decide to opt in, this will result in a $10 million opt-in payment to Theravance Biopharma and rights to certain -- and rights to receive certain future milestones and royalties.

Now I'll pass the call over to Renée.

Thank you, Brett.

I'll start with our financial results, then cover our 2018 financial guidance and close out with a quick update on our economic interests related to Trelegy Ellipta.

Revenue for the fourth quarter and full year of 2017 was $4.5 million and $15.4 million respectively, primarily related to U.S. net product sales of VIBATIV.

R&D expenses for the fourth quarter of 2017 were $51.1 million, representing an increase of $9 million compared to the same period in 2016.

The increase is primarily due to increases in employee-related costs, share-based compensation and other expenses.

Full year R&D expenses were $173.9 million or $151.2 million, excluding share-based compensation expense.

SG&A expenses for the fourth quarter of 2017 were $29.5 million, representing an increase of $9.2 million compared to the same period in 2016.

The increase is primarily due to increases in employee-related costs and share-based compensation.

Full year SG&A expenses were $95.6 million or $69.1 million excluding share-based compensation expense.

Full year 2017 operating loss was $260.1 million or $211 million, excluding share-based compensation.

We entered 2018 in a well-capitalized position with just over $390 million in cash, cash equivalents and marketable securities.

This amount excludes the $100 million upfront payment received earlier this month from the recently announced global collaboration with Janssen.

Now I'll move on to our financial guidance.

For the full year of 2017, we incurred an operating loss, excluding share-based compensation, of approximately $211 million, which is within our stated guidance of $205 million to $215 million.

In 2018, we expect full year operating loss, excluding share-based compensation, will be lower in the range of $180 million to $200 million.

While this range of guidance is broader than we would normally provide, we think it is appropriate given a number of factors.

We have 2 large studies with 1473 that will be initiated in the second half of 2018 and timing of those studies will impact 2018 expense.

Also, based on the new revenue standard that went into effect recently, the amount of revenue we will recognize in 2018 related to the Janssen collaboration agreement is partially linked to these clinical timelines.

We currently expect to recognize less than $25 million of the $100 million upfront payment in 2018.

In addition, the timing of our ongoing development at 9855 will influence our 2018 operating loss.

Specifically, we'd like to start a registrational program with 9855 before the end of the year, but we need durability data from the current Phase IIa study and to complete certain dialogues with the FDA in order to finalize our plans and timelines.

As a reminder, our guidance does not include income related to sales of Trelegy Ellipta.

We'll recognize income related to our economic interest in Trelegy below the operating line as other income.

So for 2018, these amounts are not included as part of our financial guidance of operating loss, excluding share-based compensation.

I'll close with a brief update on our economic interest in Trelegy, the first once-daily closed triple treatment for COPD.

As Rick mentioned previously, in late 2017, Trelegy Ellipta gained approval in the U.S. and EU for the treatment of appropriate patients with COPD.

Additionally, GSK and Innoviva have submitted an sNDA to expand the Trelegy label with data from the landmark IMPACT study.

With FULFIL and now the IMPACT study, the data showed superiority of triple therapy over dual therapy with significant reductions in exacerbations against Breo, Anoro and Symbicort.

As reported by GSK, promotion of Trelegy Ellipta began in mid-November to 8,500 pulmonologists in the U.S., prior to expansion to primary care doctors, in order to drive longer-term success.

Earlier this month, GSK communicated they have made good progress on AXA with commercial and Medicare Part D coverage secured at several of the top national payers.

Theravance Biopharma holds an economic interest in Trelegy that equates to upward tiering royalties of approximately 5.5% to 8.5% of worldwide net sales in Trelegy.

This economic interest represents an important strategic asset to the company as both a future contributor of growth and an alternative source of funding for our pipeline.

Now I'll turn the call back over to Rick.

Thanks, Renée.

We are pleased with the progress across our pipeline the last 12 months, and we're very proud of the entire Theravance Biopharma team for their achievements this past year.

2018, as I said, will be an important year for the company as we intensify our focus on strategic priorities; drive clinical execution; and advance programs from our validated research platform towards clinical development.

We're well-positioned to execute on the most important opportunities for value creation as shown on Slide 8. These priorities include optimizing the development of 1473 with Janssen, where we plan to initiate a large Phase IIb/III study in ulcerative colitis and a Phase II study in Crohn's in the second half of 2018.

As both Renée and Brett mentioned, advancing TD-9855 towards registrational program in patients with symptomatic nOH, following the results from our exploratory Phase IIa study expected late in the first half of this year.

In partnership with Mylan, the potential approval and launch of revefenacin with an assigned PDUFA date of November 13 this year.

And finally, progressing our inhaled JAK inhibitor for serious respiratory disease into the clinic in late 2018 or early 2019.

This is the next program from our research platform aimed at discovering localized medicines.

Before I close our remarks, I'd like to spend a few moments expanding on our research, which underpins our progress and development since our entire pipeline is internally discovered.

Currently, the research efforts at Theravance Biopharma are focused in the areas of inflammation and immunology.

Our goal in research is to create localized medicines to target diseased tissues without systemic exposure in order to enhance the therapeutic index beyond systemically available treatment options.

Through our revefenacin and 1473 programs, we've developed a deep expertise in medicinal chemistry, tissue absorption and drug metabolism.

And we've leveraged those learnings in building a research platform targeting localized therapy for localized disease.

This platform and our growing foundation of expertise in immunology have given rise to a portfolio of JAK inhibitors in research, including our inhaled program for serious respiratory disease that we intend to bring into clinical development in late '18 or early 2019.

In 2018, we'll spend more time talking about the programs we're advancing towards development and how we see those programs contributing to our purpose of creating medicines that help improve the lives of patients suffering from serious illness.

Now I'd like to turn the call over to the operator for questions.

(Operator Instructions) And our first question comes from Geoffrey Porges with Leerink Capital.

And our next question comes from Josh Schimmer of Evercore ISI.

Two of them, if I may.

First, on 9855.

If you could help frame expectations or the hurdle rate that you're looking for from this data set to support advancing into Phase III.

What kind of response rates or specific endpoint metrics you're looking for?

And then the second question, on VIBATIV, given the revenue trajectory relative to the commercial spend, is that an asset that you continue -- would continue to invest in commercially or consider a licensing just to conserve capital to invest in other development stage programs?

Okay, Josh, it was a little difficult to hear you, but I'll try and repeat the questions.

One of them was 9855, the hurdle rate that we expect to see that would -- that we believe would merit progression into Phase III.

And the second question was on VIBATIV and sort of how we look at that asset going forward.

I will -- I'll touch on VIBATIV and then make a couple of comments on 9855, and then turn it over to Brett.

VIBATIV -- we've cut back on our spending.

Clearly, if you look at the acute care organization that we have -- that sells VIBATIV, we would expect that that acute care organization would begin to transition towards the promotion of revefenacin in the hospital setting.

It's important to understand that the patients targeted with revefenacin are largely GOLD stage 3 and 4. These are patients, many of whom that unfortunately go through the hospital in their journey through the health care system.

And while in the hospital, many are placed on nebulized therapy.

And given that we have a once-a-day nebulized therapy, there are certain efficiencies in the health care systems, specifically in both acute care and long-term care to a once-a-day long-acting muscarinic antagonist.

The other obvious importance is following those patients as they go through the system and, of course, while we'll focus on the acute care setting with our organization, Mylan will focus on primary care pulmonology, et cetera, in the outpatient setting.

So we'll -- we have been and continue to monitor our investments in VIBATIV quite carefully.

And the acute care organization will be leveraged for the launch of revefenacin given the patient population that we're targeting.

Now in expectations for 9855, clearly, what we're looking for is a very, very strong signal here from the patients that we have in the IIa study and specifically, durability of effect of those patients that the drug has at 4 weeks and that developing a greater understanding of what patients, in fact, respond to 9855.

So I'll turn it over to Brett.

Thanks, Rick.

Josh, I think it's a great question.

Really, what I'd add to what Rick has already described is that we recognized, during the course of last year, that as valuable a single-dose data would be and indeed, that was the way the study was originally designed, generating this durability data, the opportunity to assess how patients are doing over time when they take this therapy is now of really central importance.

That's become, in our minds, the most important part of this study.

And that's why we extended the duration of that piece of work.

So just as a reminder, we are enrolling patients with active disease with nOH who are symptomatic.

And importantly, in this space, it's not just blood pressure that we're looking to modulate.

We are looking to improve symptoms and function in these patients.

As a reminder, the only available therapies, the alternate available to patients at the moment are a very short duration.

Midodrine is a drug which is approved only for blood pressure and droxidopa, which is the only other currently available therapy in the registration studies, was not able to demonstrate durability beyond 1 week.

And in fact, that's reflected in the current label.

Our purpose in this current study is to look at durability at least to 4 weeks and the opportunity to evaluate patients for longer if they continue to benefit.

Of course, this is all in the context of pursuing an efficient progress through development, including a rapid transition into Phase III.

We alluded to the fact in our script that we had encouraging interactions with regulatory agencies in this regard.

This is an orphan designation, and I think there is a recognition of the importance of bringing new, durable therapies to the market.

So all of those, I think, are certainly going to inform our position.

And as we mentioned, we look forward to reporting on data by the middle of this year from that durability assessment in the current study.

Got it.

And then how should we be thinking about the accounting for revefenacin in the P&L?

Good question, Josh.

So as we are in a position where the profit share is 65% Mylan, 35% Theravance Biopharma, Mylan will be booking the sales on their income statement, and they are essentially the distributor of revefenacin.

So what that means for us, as the 35% share of the profits, is if we're in a loss position, we'd expect to book that net 35% loss through operating expense.

Whereas, if we're in a profit position, once we get to a certain point in the launch, then we would expect to book that as collaboration revenue, our 35% share.

But it would not be booked as product sales since Mylan is the primary distributor here.

And our next question comes from Brian Skorney of Robert Baird.

Just to kind of follow-up a little more on the nOH data and where we should really be looking at and thinking about later this year.

I think that the Northera data, in terms of some of the symptom, data points that are focused on the OHSA Item 1, which is a measure of dizziness, maybe just comment on thoughts around that and evaluating that as one of the endpoints here.

And also, I know the primary in the study is seated systolic blood pressure.

Are you guys measuring standing systolic?

And isn't that the primary measure of orthostasis?

And just as the final question, I know there's a lot of controversy a number of years ago around ProAmatine and lack of post-marketing studies to get a basis for full approval.

Just wondering if you guys have any insight into the regulatory path for ProAmatine and whether or not -- I know they did do some subsequent Phase IV studies and just whether there's the potential for that drug to get full approval and how you would kind of think about development if that were the case.

Thanks, Brian.

I'll take the questions in order.

I'm sure my colleagues will comment as well.

But just to pick up on the points you've raised around endpoints.

You clearly know the space well.

And absolutely, OHSA, the instrument, which has now been really confirmed by the agency as being validated in this space, is an important endpoint.

And so that's included in our assessments and we believe will play a central role, certainly, in the Phase III program as well.

But it isn't the only assessment that we're looking at.

So in addition, we've been looking at blood pressure measurements.

We're also looking at additional assessments of function.

I alluded in our script that we're looking at standing time as well.

Really, all of this is, at this stage, focused on getting an overall impression of how patients are benefiting or not from therapy and how they're able to improve on the functionality, bearing in mind that these are really patients who are completely bedridden and unable to either work or indeed, even to get around the house.

You've mentioned the seated and standing systolic blood pressure.

Both are incorporated in the current study.

But I will restate that actually our appreciation for the symptoms and the function is as important in this current piece of work.

So, although we're measuring blood pressure and indeed, it was used as a primary endpoint for the single ascending dose portion of the study, the durability assessments, the repeat-dose assessments, will include an evaluation of all of their function, including their symptoms.

So it's a much more holistic assessment.

Brett, would you just like to comment on sort of the -- a very broad brush, your regulatory approach?

Sure.

So I think you'd asked us earlier about pre versus post-marketing requirements.

And without divulging the full extent of our regulatory interactions, I think we recognize that the way in which previous therapies are being developed, whilst it may be efficient, hasn't necessarily led to full approval.

Our ambition, our goal with this program is not only to seek an efficient development program focusing on patients with the most -- the highest unmet need but also to do so in a comprehensive fashion, using the requirements of the agency, ultimately ideally to seek full approval, not conditional approval.

And of course, that's -- you'll see more of that incorporated in our Phase III strategy, which we plan to disclose as time goes on.

And our next question comes from Louise Chen of Cantor.

So first question I had here is we often get the question that now that you've partnered your JAK, what's your strategic vision for the company here?

You partner most of your major projects, and they're in different therapeutic areas.

So how do you see your business plan unfolding?

Second question I have was on your inhaled JAK that you talked about.

Maybe if you can give more color on that opportunity and who you might compete with in the space?

And then last question I had was just on some housekeeping items.

The less than $25 million that you expect to book in 2018 for J&J, is that spread evenly throughout each quarter?

And then can you talk a little bit about your R&D progression spending in 2018?

And then for revefenacin, is it that we should expect revenues to start coming in the fourth quarter of 2018?

Okay, Louise, I'm going to just start quickly on strategy and then touch for a moment on the inhaled JAK program.

Over the course of time in the evolution of the company, you will have seen us move from royalty stage -- royalty-like deals to profit share deals.

And then the likely evolution would be, at some point in time, at least from a geography perspective, retain 100% of the economics on assets, clearly, 9855 being a very, very focused product in terms of the prescriber base and a very efficient -- at least as it looks today, a very efficient Phase III pathway to market.

Clearly, that would be a product that we would retain rights to and in fact, look to sell ourselves within a -- with a very small commercial organization that would be effectively built on the back of the infrastructure we've already established to support acute care via different sales organization, but it would -- would share the infrastructure.

So I think we're clearly moving in the direction of capturing more and more of the downstream economics.

Partnerships will continue to be important to us as we proceed down the path -- the strategic path for the company but with moving to both profit shares and then 100% profit in specific geographies as we evolve.

Now the JAK program for the inhalation delivery, I think this builds both on all the work that went on -- that went into the JAK program in the gut as well as the knowledge that we've built up over time on inhalation.

I mean, clearly what we're looking for here is prolonged lung retention but minimal plasma exposure, again, long duration of activity but broad anti-inflammatory activity affecting a number of cytokines that other products being targeted specifically to biologics simply can't affect because of their specificity but in -- and in fact, affecting those targets in the lung, achieving lung concentrations and then being cleared through first pass metabolism such that we don't -- our goal is to not see systemic immune suppression much as what the observations have been to date in the TD-1473 program.

So I think we're progressing heading into the clinic, but we're quite excited about this next program, what it might be able to deliver to patients.

And you'll hear more from that as we go forward in 2018.

Louise, I'll address your questions on the financials.

With respect to the $25 million that we expect to recognize in 2018, I would anticipate that being in the second half of 2018 primarily.

The way that the guidance works is you essentially have to allocate $100 million over what's referred to deliverables related to the collaboration.

And for us, we have a couple of clinical studies that we've referred to that we'll be conducting.

We'll spread some portion of the $100 million over the life of those studies, and they'll be some amount that is related to the delivery of the actual data for both the Phase II induction portion of UC and then the Phase II Crohn's study.

So that's how I would think about the $25 million in 2018 and then the remaining $75 million, broadly speaking.

With respect to our R&D progress, I would expect our research expenses to be fairly flat over the course of the year.

We don't generally break out research versus development.

But broadly speaking, if you translate that to activity, research is generally flat throughout the year.

And then, of course, we would expect to have higher expenses in the second half of the year related to the programs that we're conducting related to 1473.

And then we'll have to see what happens with respect to 9855.

As we noted on the call, our guidance range is a bit wider this year, given a number of moving pieces, but we're excited to have that number of opportunities to invest in over the course of 2018.

And then the last piece was your question on revenue related to revefenacin.

So we would expect to receive -- we hope, obviously, to receive approval in November, in line with the PDUFA date.

And then we're working closely with our partner, Mylan, with respect to the exact timing of launch.

Obviously, we're working diligently to prepare for commercialization.

As Rick had mentioned, our acute care sales force will be focused on that.

I wouldn't -- I certainly wouldn't expect to be in a profit position initially.

I would expect to be in a loss as we first start launching the product.

And as I've mentioned, 35% of the loss, when we're in that position, will be recognized in OpEx.

35% of the profit were in that position will be recognized as collaboration revenue.

Does that answer your question?

Yes, thank you.

Yes.

Louise, I'll just add one other comment just to frame it for people for the inhaled JAK program and in terms that you may have heard from other companies and biologics.

But the important aspect of a pan-JAK inhibitor and being able to deliver it into the lung safely is, in fact, the ability to affect both Th2 and non-Th2-driven asthma.

And I think this is particularly exciting for us as we learn and understand more about the specific cytokines and the progression of those cytokines in asthma exacerbations.

And I'd just ask Brett, since he's got quite a bit of experience in this to comment.

Thanks, Rick.

I think -- just a few things to add, of course, Rick has touched on the fact that this would still be a broad-based anti-inflammatory.

It's quite regrettable that, actually, in the markets, despite the fact that patients are in maximal inhaled therapy, there is still as many as 0.5 million U.S. citizens with severe asthma who do not have proper control of their asthma despite being on maximal doses of available therapies.

The only alternative they have at the moment is to move towards systemically available biologicals.

And those have their own side effects, in fact, analogous to what we've been talking about in the GI space.

So our vision here is to take the same building blocks as we've had before with the GI, look at the targeted approach in the lung, which would focus that broad-based anti-inflammatory effect only in the lung and avoid the systemic liabilities that some of these other biologicals may carry, for example, in the IL-5 or anti-IL-5 space, anti-IL-4 and IL-13.

So we think we have a broad-based approach, but it certainly will be building on a strong research platform that has invested heavily in looking at localized disease and targeting our medicines -- our localized medicines to treat those diseases.

And it appears we have no further questions on the phone.

I'd now like to turn the conference back over to Mr. Winningham.

Please go ahead, sir.

Great.

Thank you, operator.

I'd like to thank everyone for participating today.

We look forward to bringing you updates throughout the course of the year.

And as I mentioned earlier in my remarks, we look forward to having an R&D day where we can delve more deeply into the programs that we covered on our update today.

So have a great day, and we look forward here at Theravance Biopharma to a great 2018.

Ladies and gentlemen, this concludes today's conference call.

We thank you for your participation, and you may now disconnect.

Everyone, have a great day.