TBPH (2021 - Q4)

Ladies and gentlemen, good afternoon. I'd like to welcome everyone to the Theravance Biopharma Fourth Quarter and Full Year 2021 Conference Call. [Operator Instructions] Also, today's conference call is being recorded. And now I would like to turn the call over to Gail Cohen, Vice President, Corporate Communications. Please go ahead. Gail Coh

Good afternoon. And thank you for joining the Theravance Biopharma fourth quarter and full year 2021 conference call to discuss our business. As always, I remind you that this call will contain forward-looking statements that involve risks and uncertainties, including statements about our development pipeline, expected benefits of our products, anticipated timing of clinical trials, regulatory filings and expected financial results. Information concerning factors that could cause results to differ materially from our forward-looking statements is described further in our filings with the SEC. Now I would direct your attention to Slide 3. Joining us are Rick Winningham, Chief Executive Officer; followed by Rhonda Farnum, Senior Vice President, Commercial and Medical Affairs; Rick Graham, Senior Vice President, Research and Development; and Andrew Hindman, Chief Financial Officer. Now I will hand the call to Rick Winningham for opening remarks.

Thanks, Gail. Turning the Slide 4 last September, we announced a restructuring of the company to optimize our business model. We immediately initiated a significant cost reduction program and have taken actions to reduce the company’s headcount by approximately 75% in estimated 270 positions. We completed most of these reductions by the end of November, with the remainder expected to be completed by the end of this month. Since then, we've rapidly transitioned to a streamlined focused Theravance Biopharma. We plan to leverage our expertise in developing and commercializing respiratory therapeutics. And we'll continue to explore strategic partnerships for our pipeline assets to unlock additional value. All of these actions drive towards our goal of maximizing shareholder value. There are three pillars of value creation highlighted on Slide 5. For the go forward plan to build on our proven track record of respiratory innovations, supporting several approved medicines for COPD and asthma. These pillars include: number one, YUPELRI, which was discovered and developed by Theravance Biopharma. It is commercialized currently in partnership with Viatris. YUPELRI’s demonstrated market share growth quarter-after-quarter despite the respiratory pandemic. Sell-side analysts covering Theravance Biopharma estimate YUPELRI has potential to generate U.S. peak sales, of approximately $400 million annually. We announced in early January the enrollment of the first patient in the YUPELRI Phase 4 PIFR-2 study. If this study is successful, we could potentially increase the addressable U.S. market from one in ten patients to one in five patients. This increase in the total addressable market obviously isn't included in current analyst peak sales estimates. Rhonda will speak to this in the YUPELRI’s summary of quarterly successes. Number two, our core respiratory pipeline, our second pillar of value creation includes our most advanced candidate, nezulcitinib, our dry powder inhaled JAK inhibitor program that we indicated would move into the clinic after securing a partnership. Rick Graham will walk through our development update. And the third pillar is our economic interest in TRELEGY, respiratory medicine developed by GlaxoSmithKline, also known as GSK in collaboration with the company's predecessor, Theravance, Inc., now known as Innoviva. TRELEGY is the first and only once-daily, single inhaler triple combination therapy approved for the treatment of COPD and asthma, and is owned, controlled and marketed globally by GSK. Given the strength of the clinical data underlying TRELEGY and its indicated uses coupled with GSK’s commercial excellence, TRELEGY continues to experience exceptional revenue growth trends, even in the face of a global respiratory pandemic. At present GSK sell side analysts project TRELEGY could generate global peak sales of $3.6 billion annually. Andrew will review TRELEGY’s fourth quarter performance, and full year 2021 performance, as well as review Theravance financials. We believe the strong growing cash flows of YUPELRI and TRELEGY and the expected future robust revenue for both coupled with the several sources of upside potential in our development pipeline to generate significant value creation opportunities for our shareholders. And now I'll turn the call over to Rhonda to review YUPELRI. Rhonda?

Thanks, Rick. I am pleased to have the opportunity to share our latest performance update on YUPELRI, which is the first and only once-daily, nebulized, long-acting muscarinic antagonist that provides a full 24 hours of control for patients and is indicated for the maintenance treatment of patients with COPD. Despite the continued headwinds created because of the global pandemic, we are encouraged by the growth of YUPELRI’s performance in 2021. As a reminder, Theravance Biopharma and Viatris co-promote in the U.S. with our combined sales infrastructure, targeting healthcare professionals who treat COPD patients suitable for YUPELRI. Theravance Biopharma’s commercial and medical teams cover the hospital segment and Viatris covers outpatient-based community healthcare professionals. From a financial perspective, we share profits on YUPELRI in the U.S. 65% going to Viatris and 35% to Theravance Biopharma. Slide 8 shows Theravance Biopharma’s implied 35% share of net sales for YUPELRI during the fourth quarter 2021 of $15.3 million, which is the brand's strongest quarter-to-date. YUPELRI’s year-over-year net sales are up 13% Q4, 2021 versus Q4 2020. The implied 35% share of YUPELRI net sales for the full year 2021 was $56.7 million, which represents a 13% increase from 2020. Demand doses for YUPELRI increased 8% in the fourth quarter of over third quarter 2021 and 17% year-over-year. Total product demand for the full year 2021 was up 25% versus 2020. It was the case last quarter while institutions in some parts of the country are allowing more in-person access. In-person engagements remained below pre-pandemic levels for our team. It is also important to note that although total prescription volumes continue to demonstrate growth across most therapeutic specialties with volumes heading towards parity with 2020. Prescription volumes within the pulmonology specialty remain below pre-pandemic levels. This lag in growth is associated with the challenges the pulmonary community has experienced throughout the respiratory pandemic when treating COPD patients, which include competing time demands of COVID patients, a decrease in inpatient COPD patient visit volume and a limited ability for HCPs to diagnose and reassess their patients without pulmonary function test or spirometry, which cannot be performed via telemedicine. These factors contributing to a reduction in prescriber confidence and ultimately fewer prescriptions. Despite these challenges we have been encouraged with growth in total scripts for YUPELRI, which were up Q4 versus the prior quarter, Q3 by 7%, an increase by 32% year-over-year. New-to-brand prescriptions also increased 11% in Q4 of 2021 versus Q3 and 31% year-over-year Q4 2021 versus Q4 2020. As a reminder, these script data represent the retail setting and they serve as a proxy for overall growth but are not inclusive of the DME or durable medical equipment fulfillment channel, which represents a major of the volume of YUPELRI sales. Turning to Slide 9, you can see that YUPELRI’s share continues to grow in both the hospital and the community settings. YUPELRI’s share of the long-acting nebulized COPD market increased to 23.2% through October 2021, which is our latest data point and up from 18.2% in October of 2020. As we have noted previously many patients with COPD experience an acute respiratory episode, serious enough to require a trip to the hospital. And therefore, the hospital becomes a key point to assess a person with COPD and convert or switch them from their current medicine to YUPELRI. Data shows that many patients who receive YUPELRI in the hospital are discharged with a prescription to continue treatment, allowing for continuity of YUPELRI therapy post discharge. The Viatris and Theravance Biopharma teams continue to work effective and collaboratively using multiple tools and tactics in coordination to convert appropriate patients to YUPELRI during their hospital visits, supporting them through their discharge and enabling them to be maintained on YUPELRI after their return home. Looking specifically at the Theravance field sales deployment efforts in Q4 of 2021. Doses sold exclusively in the hospital setting represented an 18.5% increase from the previous quarter demonstrating the highest quarter volume launch to date. Slide 10 visually illustrates YUPELRI's growth trajectory in the hospital segment since launch. You can see how the unprecedented demands on pulmonologists in 2020 due to the pandemic changed the growth trajectory. Today, the YUPELRI hospital volume has returned to growth and during the fourth quarter of 2021 we achieved new key hospital account formulary placements and new purchasing accounts are being added regularly. We believe these wins will yield significant growth in 2022, as YUPELRI will be the first LAMA of choice in many hospital systems. Moving to Slide 11, the outlook for 2022 and beyond for YUPELRI is favorable. Our medical liaisons have surveyed healthcare professionals who have shared their observations on the role and use of nebulization and even with the COVID surges we saw in the fourth quarter, nebulization was reinstated. YUPELRI's once daily dosing is proving critically important to alleviate systems overwhelmed by COVID-19 in cases and healthcare provider shortages. It is important to understand that according to the evidence-based gold guidelines for COPD management, LAMA or long-acting muscarinic antagonist is foundational to COPD maintenance care. The execution of our tactical plan will continue to let these guidelines in the important role or once a day nebulized therapy like YUPELRI can offer inappropriate patient types. Looking beyond 2022 as we announced in early January Theravance Biopharma enrolled the first patient and PIFR-2 study, a Phase 4 trial evaluating the performance of YUPELRI compared to SPIRIVA in patients with low-peak inspiratory flow. If successful the PIFR-2 study will allow us to capture more of YUPELRI's addressable market and further strengthen its competitive advantage. Lastly, Viatris continues to develop YUPELRI for registration in China and if YUPELRI is marketed in China, Theravance Biopharma will receive double-digit royalties and milestones from sales in the China market. I will now turn the call over to Rick Graham.

Thanks Rhonda. As highlighted on Slide 12, we're focused on the highest value core respiratory opportunities. As Rhonda mentioned, the PIFR-2 study is a YUPELRI Phase 4 study in partnership with Viatris, which is being conducted by Theravance Biopharma. The study will compare improvements in lung function in adults with severe to very severe COPD and suboptimal inspiratory flow rate following once-daily treatment with either revefenacin delivered via standard jet nebulizer or tiotropium delivered via a dry powder inhaler. Theravance will be responsible for 35% of the cost of this study, which is currently enrolling and with top line results expected in the first quarter of 2023. Nezulcitinib is our nebulized lung-selective JAK inhibitor in development for the treatment of acute and chronic lung diseases and as our most advanced respiratory clinical candidate. The UK COVID-19 Therapeutics Advisory Panel or UK CTAP has recommended evaluation of nezulcitinib in the REMAP-CAP Trial citing the unique inhaled formulation to block lung inflammation and tissue damage directly in the lung, while reducing potential side effects caused by systemic administration. Externally funded platform studies are an efficient way for us to generate additional clinical data with nezulcitinib in patients with COVID-19 that may be applicable to its continued development in related indications. For finalizing details of the plan platform study with REMAP-CAP, and intend to share more information when enrollment begin. Our pipeline slide, Slide 13 has been updated to reflect our respiratory focus on YUPELRI, nezulcitinib and/or inhaled JAK inhibitor program for asthma. We have economic interest in trilogy and a skin selective JAK inhibitor that is licensed to Pfizer for the treatment of dermatologic diseases. Our other pipeline assets are now considered non-core and were on track to complete study closeout for izencitinib and ampreloxetine trial by the end of the first quarter and we aim to leverage partnerships to unlock value of the non-core assets. I'll now turn the call over to Andrew for the financials.

Thanks, Rick. Turning to Slide 14 we look at the performance of TRELEGY, the third pillar of our respiratory focused value creation plan. As a reminder, TRELEGY is owned and marketed globally by GSK. Through our 85% ownership interest in Theravance Respiratory Company, LLC or TRC LLC, we are entitled to receive upward-tiering royalties on global net sales of TRELEGY. At present 75% of income received from our economic interest is pledged to service principal and interest payments on our outstanding 2035 nonrecourse notes, and the remaining 25% of income is retained by us. On Slide 15 we capture the most recent information GSK shared during their earnings call on February 9. GSK noted that TRELEGY continued to lead the market as a single inhaler triple therapy, with year-over-year global sales growth of 52%, generating global net sales of $479 million during the fourth quarter of 2021 and $1.7 billion for the full-year. This growth is primarily driven by the continued adoption of TRELEGY in the asthma indication and strong global commercial performance by GSKs team. Moving to our consolidated financials on Slide 16, here we summarize our fourth quarter and full year financial highlights for 2021 compared to 2020. R&D expenses for the fourth quarter of 2021 were $28 million compared to $58 million in the fourth quarter of 2020. And for the full year 2021, they were $168 million compared to $230 million in 2020. SG&A expenses for the fourth quarter of 2021 were $16 million compared to $22 million for the fourth quarter of 2020. And the full year 2021 they were $71 million compared to $77 million in 2020. These quarterly and annual figures exclude share base compensation and the one-time restructuring expenses; we ended 2021 with $173.5 million in cash and cash equivalents. Turning to Slide 17 with respect to 2022 financial guidance; for R&D expenses we expect to invest between $45 million and $55 million relative to actual of $168 million in 2021. Of this expense range approximately $10 million is non-recurring spending that will be incurred in Q1 2022 to support the completion of izencitinib and ampreloxetine program that Rick just mentioned. R&D spending in Q2 and beyond will then normalize and reflect recurring investment in the respiratory focus portfolio. For SG&A expenses we expect to invest between $35 million to $45 million relative to actuals of about $71 million in 2021. Again, these operating expense guidance figures exclude share based compensation and the one-time restructuring expenses. As a result of our reduced spending and improved cash flow generation from YUPELRI and TRELEGY, we reiterate our expectation to become sustainably cash positive on a corporate basis in the second half of 2022. With that, I'll turn the call back to Rick Winningham for closing remarks.

Thanks Andrew. 2022 on Slide 18 effectively launched the new focus Theravance Biopharma. As we've reviewed we've got three pillars of our value creation plan returning YUPELRI's commercial performance to pre-pandemic launch mode growth trajectory, realizing the potential of our highest value R&D clinical programs led by the PIFR-2 program on YUPELRI. And the third key pillars are economic interest in TRELEGY, which is experiencing strong revenue growth based on GSK's commercial performance. The new focus Theravance Biopharma is moving toward our goal to become sustainably cash flow positive beginning in the second half of 2022, and to maximize shareholder value. In closing, I'd like to thank our internal team for their perseverance during this period of time at the company, I'm grateful for their commitment to our mission of continuing to develop medicines that make a difference in the respiratory area, the progress of our clinical pipeline in YUPELRI as well as the communities we serve. And I'll now hand the call back to the operator for questions.

Thank you, sir. [Operator Instructions] We will have our first question from Marc Frahm of Cowen. Your line is open.

Hey, thanks for taking my question and congrats on the growth with YUPELRI. Maybe looking to the PIFR-2 trial that's starting up now, what do you view as the clinically meaningful difference that you need to show there? And then assuming the trials successful and you're able to show at least that benefit. How quickly would you expect that to translate into kind of an inflection in YUPELRI sale, is the data release the inflection point or should we be looking more towards maybe a label update that might come nine months a year later?

Rick, you want to take that or...

Yes, sure. So now Marc we have – we have now put some of the details of the trial on clinicaltrials.gov. And remember it is a few hundred patients and its head-to-head YUPELRI with SPIRIVA. So we would be looking for a statistically significant difference in the trial of FEV1 at day 85. So that's what we'd be looking for. In terms of the second question, Rick, I'll hand it back to you.

Yes. I think the publication of the results is obviously one step forward. It's worth noting that in the registrational program we had low peak inspiratory flow patients in the Phase 3 program and that data is within the clinical trials, a section mixed in with high prefer patients, so low prefer patients exist as part of our – part of our label. I would see the data rolling out to fairly rapid publication and then followed by an interaction with the agency on the effects on the label. So I think without a doubt given that we are targeting YUPELRI versus the market leader increases, as Rick said in FEV1 trough is very – is important. As is overall, overall response rates and response differences in patients. So I think we're pretty encouraged by what we saw overall with the low PIFR patients in the Phase 3, and then the pilot study that we did. And we think that we can make significant headway with positive data in the PIFR-2 study because as I've mentioned in other forum we're just scratching the surface with YUPELRI. The opportunity out there for the nebulized once daily product with 24 hours of control is quite significant given approximately one in 10 patients use a nebulizer for maintenance. Many of them are using short acting nebulized therapy, that's not indicated for maintenance. So I'm pretty excited about what we might be able to deliver with PIFR-2.

Okay. That's very helpful. And then maybe just on the cash positivity guidance, can you just remind us what kind of major variables that are going into that? Maybe what do you assume on the – in Aviva side, are you assuming there's more investment activities from them? Are you assuming royalty flows cash or maybe that you're able to start monetizing some of the investments that have been made?

Marc, the main driver of cash flow positivity is the performance. If YUPELRI and our 35% profit split of those increasingly positive cash flows here based on the U.S. performance, so it was – it's been profitable since October 2020 and we are happy that it's continued to maintain that profitability. And it's the key driver in addition to focused cost management both on R&D and SG&A expenses. As I mentioned in my prepared remarks, 75% of the cash flow is coming out of TRC LLC are pledged against the principle and interest of the notes that we have outstanding for – by the $400 million facility. So the remaining 25% of any cash disperse from TRC LLC does come to our balance sheet and income statement and cash flow statement, but it's a small driver relative to YUPELRI's performance and cash flow management.

Okay. Thank you.

Thank you. Our next question comes from Anupam Rama of J.P. Morgan. Your line is open.

Hey guys thanks so much for taking the question. On YUPELRI, are there any seasonal 1Q dynamics we should be considering just when we think about sort of quarter-over-quarter growth that you would point to? And are there any second question, maybe some timelines to better understanding the nezulcitinib development program more broadly? Thanks so much.

Rhonda, you want to touch on the seasonality of YUPELRI under the – sort of the – under the umbrella that as far as we're concerned really YUPELRI still in the launch mode, but go ahead, Rhonda.

Yes. I was going to lead off from that, 2019 being our launch year is our best baseline for looking at trying to establish any seasonality that could be associated with the product beyond what we – you would expect with COPD in general. Obviously 2020 having the disruption with COVID kind of put a stall on that ability. Looking at 2021, I think can start to mimic what we would anticipate with the seasonality with COPD. However, looking at our trajectory of return to growth it's still hard to demonstrate that there is explicit different seasonality associated with the product.

Rick?

Yes. Yes, sure. So Anupam on nezulcitinib, with regard to what we've discussed previously our focus is on acute lung injury, chronic lung injury and fibrotic diseases of the lung with nezulcitinib. So at the current time, the team is really, and this is a very focused team given restructuring is really focused on the preclinical work. So trying to understand of the acute and the chronic indications which makes the most sense scientifically from a priority standpoint and so there's a lot of preclinical work that's going on. So more to come in the future, but right now our focus is on following the science for nezulcitinib pre-clinically.

Thanks so much for taking questions.

Thank you. Our next question comes from Douglas Tsao of H.C. Wainwright. Your line is open.

Hi, good afternoon. Thanks for taking questions. Just turning to the pipeline, you talking the JAK programs that are in-house and in addition to nezulcitinib. Obviously there was the allergen study with 8236 which I know isn't a perfect proxy and there've been drugs that have been approved that have not succeeded in that. And we had seen some very promising data earlier. So just where are you with that program or is that really on pause, pending, finding a potential partner, and how far along are other sort of assets in potential development and how far along are you willing to take those without a partner or before finding a partner?

Yes, so nezulcitinib which is the nebulized JAK inhibitor, which showed proof of concept in acute lung injury due to COVID. It is lined up to go, as Rick mentioned into the REMAP-CAP program that's – that's where a significant amount of focus is for us in pushing Nez forward. Obviously as Rick said, the preclinical work going on related to understand the effect dosing duration of nezulcitinib in chronic and fibrotic – chronic and other and other diseases like fibrosis is underway. And the dry powder program, I think what we've learned quite a bit from where we were with 8236 on the necessary characteristics we think to bring forward a stronger dry powder inhaled JAK inhibitor at least said before that that program will proceed into the clinic with a partner. Rick, anything to add?

No. Nothing to add.

Okay. Great. Thank you.

Thank you. Our next question comes from Liisa Bayko of Evercore. Your line is open.

Hi there. I know you had indicated that you thought maybe the outlook for TRELEGY was – should be higher than current estimates and you kind of indicated $4 billion versus $3 billion, which is more along lines of consensus. Can you maybe just walk us through your assumptions there? And how do you think about the timing of that? I know a lot of it was driven by asthma maybe being underappreciated, but perhaps you could, just a little more detail just mathematically how we get there?

Andrew, you want to talk about the move over time with consensus?

Yes. I mean, Liisa, we're not going to go through a revenue build here on this call, happy to do it offline with you. But the comments that we've made are a general observation about the fact that the Street initially at the time of launch in 2017, valued peak sales in the COPD indication alone at $2 billion. And as of the quarterly print by GSK just put out for February 9th of this month, the Street has moved to $3.6 billion over the passage obviously over the last five years with a lot of strong commercial performance and the label indication globally in most regions for the asthma indication. So it's really based on the back of the sell-side analyst community that cover GSK that were making those comments. We of course have our own internal estimates that range around that, the Street sales estimates and could exceed $4 billion. But we're really making reference in our prepared remarks today to the sell-side analysts covering GSK, which, of course, those models are generally public. And at the end of the day, as we remarked, GSK's team globally has been doing a great job and the data set supporting its use both in COPD and in asthma as the only once-daily triple combination therapy in a dry powder inhaler is really a unique offering for patients relative to the other therapies available. So, we see it continuing to capture share across the board.

Yes. I think if you – Liisa, as you look at what's happening in the United States, with the waning of the pandemic, you are seeing more COPD prescribing. Rhonda referenced this in her comments. This is likely to affect TRELEGY in COPD as pulmonologists are seeing more patients than I think a true growth driver, and this is from third-party market research for TRELEGY. So obviously, as Andrew said, as the asthma indication, in fact getting use and prescribing from primary care in the asthma patient population with TRELEGY has been the real driver through the pandemic. And given the effectiveness of the drug overall in moderate to severe asthma patients, I don't think that there's, at least from an efficacy and safety perspective, there doesn't seem to be any sort of cap that we should continue to see growth out of both primary care and asthma, probably pulmonology and asthma and obviously pulmonology and COPD. Those are the kind of three legs of the stool, at least as we see them for TRELEGY in the U.S.

Okay. Great. And then I guess for last year, where are we with the payments, royalty payments from Innoviva for you guys? Like how much is outstanding and how much are you in receipt of on a, I guess, on a percentage basis or something?

Yes. I think we'll provide an update when we file the 10-K here shortly. It's statutorily required at the end of this month. So there will be exhaustive footnotes that will answer those questions. We did get $60 million in cash out of TRC LLC through October of last year, as we've previously noted.

Okay.

And then I think, Lisa, we'd expect the cash payments to be somewhat characterized as lumpy coming out of the LLC, but we do continue to expect to get all the cash due to us out of the LLC over time.

Yes. Okay. And then just final question for me. Can you talk about the trial design for Nezulcitinib and COVID and maybe timing?

Rick, you want to take that?

Yes. We haven't disclosed the design yet. We're still working through the details with the remap organization. But with regard to timing, we do expect in the very near future to be able to announce enrollment. So still more to come. I can't comment very much on that today, Lisa.

Okay, great. Thanks for answering my questions.

Thank you. Our next question comes from Joseph Stringer of Needham & Company. Your line is open.

Hi everyone thanks for taking our questions. Question on YUPELRI. You mentioned HCP and in-person interactions remain below pre-COVID pandemic levels. Just wondering if you could sort of quantify this a little bit more in terms of a relative percentage to prepandemic levels. How has that increased or progressed over the last couple of quarters? And you expect to reach, say, 100% of pre-pandemic levels by the end of this year? Thank you.

Rhonda, do you want to take that?

Sure. Well, looking at the back half of last year, they certainly increased over the immediate kind of [indiscernible] phase, thinking about Q2 of last year. And I'd say Q2 of 2020. We're still below the pre-pandemic levels. However, seeing the continued kind of variability across various regions, continue to open up access, both with in-person as well as the allowance of continued virtual engagement for promotional activities, that's continuing to grow over time. I would like to say, by the end of the year it could be closer. All of that is dependent upon what next phase we are of the pandemic or truly entering the endemic phase of COVID.

Yes. I mean so it's bounced around from – this is just general numbers, to 30%, 40% pandemic to 80%, 90%, given where you are regionally in the United States. And I think on average, our expectation, as Rhonda said, as it goes into the endemic stage is the bottom to move up and obviously get back hopefully to close to pre-pandemic levels by the end of the year. Now fortunately, we've been able to expand the number of sort of tactical considerations that we use to get in front of customers. And I think those expanded tactics are likely to continue to represent part of the calls in addition to face-to-face interactions with health care professionals.

Great. Thank you for taking our question.

[Operator Instructions] Our next question comes from Vikram Purohit of Morgan Stanley. Your line is open.

Great, thanks for taking my questions. So, two from my side, both focused on pipeline. So first on YUPELRI. Could you clarify what level of regulatory interaction that you and Viatris may have had with the FDA regarding this program? And then based on these interactions, what amount of data do you think you would need to be able to file? And what would be in the fileable package for a label update? And then second question, your pipeline page notes the skin selective JAK inhibitor for dermatology, that's partnered with Pfizer. So. I just wanted to see if you could provide us with an update on where this program stands and what the next steps here could be.

Yes, sure. On the Pfizer program, that's listed on clinicaltrials.gov as preparing to go into Phase I. So, I think you can pick it up off of there and follow the progress, both with our updates as well as progress on clin trials. I think we've had a level of interaction with the FDA on PIFR-2 and where it would go in the label. And obviously, it depends, as any regulatory interaction, it depends on the data. But I think clearly, we see a path forward for inclusion of the PIFR-2 data in the label depending on the strength and evidence that we demonstrate. So, we wouldn't have gone forward without it, so.

Thank you. Our next question comes from Douglas Tsao of H.C. Wainwright. Your line is open

Hi, thanks for taking the follow-ups. Maybe Rhonda, just in terms of YUPELRI, just curious if you could provide some color on some of the competitive dynamics. You've continued to gain some share. I think earlier in the year, midyear Brovana had some generics. So just maybe where you're gaining traction and how you might see that playing out in the coming months? Thanks.

Well, certainly seeing traction related to increased awareness in the appreciation of the role YUPELRI can offer as a once-a-day LAMA, so backing – back to the comments that Rick made earlier, we're still in launch mode. So, the ability to get the message out there and see that experience take place, that's certainly driving the utilization. There is utilization in combination with other long-acting net products like Brovana and PERFOROMIST, although we do not promote that. And also seeing – we're watching very closely how the market is playing out with the generic entries for both Brovana and PERFOROMIST. We're still watching that over time to better understand those dynamics.

Yes. I think, Doug, the benefit here with YUPELRI, and Thonda to hit on in her comments, is that LAMA is really considered foundational therapy for COPD. And for patients that – for patients that have COPD and need a nebulizer, they haven't been able to access that foundational therapy product before really at scale before YUPELRI. And so, we talk about being in launch mode, that's really true. I think we're continuing to get out there, drive awareness of YUPELRI. And then the genericization of the two twice-a-day LAMAs, we really haven't seen kind of anything but probably a net positive effect on YUPELRI from that.

Thank you.

Great, thank you.

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

Yes. Just thank you for your attendance and your interest in the company. We look forward to a great 2022. And we'll be updating you on our progress throughout the year. Have a great day.

Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.