Earnings Call Transcript - TBPH Q3 2021

Operator, Operator

Ladies and gentlemen, good afternoon. I would like to welcome everyone to the Theravance Biopharma Third Quarter 2021 Conference Call. Today's conference call is being recorded. I would now like to turn the call over to Gail Cohen, Vice President of Corporate Communications. Please go ahead.

Gail Cohen, Vice President, Corporate Communications

Good afternoon and thank you for joining the Theravance Biopharma third quarter 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.

Rick Winningham, CEO

Thanks, Gail. In mid-September, we announced the decision to restructure the company in order to optimize our business model. This decision followed a complete scenario planning exercise led by the board and management with the assistance of outside advisors. Since the announcement, we have made our rapid transition to a streamlined respiratory-focused Theravance Biopharma. We immediately initiated a significant cost reduction program. We have taken action to reduce the company’s headcount by approximately 75%, estimated at 270 positions, and we are on track to complete the large majority of these reductions by the end of this month, with the remainder to be completed in February of 2022. We are focused on leveraging expertise in developing and commercializing respiratory therapeutics and streamlining our future R&D investments to focus solely on the highest value respiratory assets. We will continue to explore strategic partnerships for both core and non-core assets to unlock value. All of these actions drive toward our goal to maximize shareholder value. Moving to Slide 5, there are three key pillars of value creation for the go-forward plan to build on our track record of respiratory innovation leading to several approved medicines for COPD and asthma. This includes TRELEGY, our respiratory medicine developed by Glaxo Group in collaboration with the company’s predecessor, Theravance Inc., and YUPELRI, which was discovered and developed by Theravance Biopharma, launched in 2019, and is now commercialized in the U.S. in partnership with Viatris. TRELEGY is experiencing exceptional growth with its dual indication for COPD and asthma driving higher demand in the U.S., and GSK has obtained approval for the asthma indication in 10 additional markets. TRELEGY is currently expected to generate global peak sales of approximately $3 billion annually. YUPELRI remains early in its product lifecycle and has demonstrated market share growth quarter-over-quarter despite the respiratory pandemic. We believe it’s got the potential to generate U.S. peak sales exceeding $400 million. We believe the strong and growing cash flows of TRELEGY and YUPELRI and expected future robust revenue performance for both would generate significant value creation opportunities for shareholders. It’s my pleasure to have Rhonda Farnum, now SVP, Commercial and Medical Affairs, join us on the call today. Rhonda has been a part of the Theravance leadership team since joining the company in July 2018 as Vice President, Sales and Marketing, where she was responsible for the commercial execution of branded products, including sales, marketing, and managed markets. Her deep commercial expertise and success steered the team well. In a new role, with expanded responsibility including Medical Affairs, I am confident our progress will accelerate. Rhonda will provide an update on the strong and growing cash flows from YUPELRI and speak to the overall COPD market dynamics. COVID-19 continues to impact COPD patient visits, diagnoses, and new starts. Despite this dynamic, both YUPELRI and TRELEGY, thanks to GSK’s efforts, continue to grow market share and provide significant value to shareholders. Rick Graham will update you on where we are with the highest valued core respiratory programs in the rest of the pipeline. Moving to Slide 6, as we stay with the announcement regarding our strategic actions, significant operating expense reductions to drive sustainable cash flow generation, beginning in the second half of 2022, are critical, and we have provided preliminary 2022 financial guidance. Andrew Hindman will follow with the highlights of GSK’s TRELEGY performance and an overview of our third quarter financials. I will now turn the call over to Rhonda, who will share our commercial team’s progress with YUPELRI and speak to the COPD marketplace dynamics.

Rhonda Farnum, Senior Vice President, Commercial and Medical Affairs

Thanks, Rick. I appreciate the opportunity to participate and provide this quarter’s update. Turning to Slide 8, YUPELRI 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 as a result of the global pandemic, we are encouraged by the growth of YUPELRI total prescriptions from Q2 to Q3, as well as the addition of new hospital accounts that are ordering each week. As a reminder, Theravance Biopharma and Viatris co-promote in the United States with our combined sales infrastructure, targeting healthcare professionals who treat COPD patients suitable for YUPELRI. Theravance Biopharma's commercial and medical field teams cover the hospital segment of healthcare providers, and Viatris covers community healthcare professionals. Also, remember, the Viatris and Theravance Biopharma commercial partnership is a 65:35 profit share split. Slide 9 shows Theravance Biopharma’s implied 35% share of net sales for YUPELRI during the third quarter of 2021 of $13.8 million. YUPELRI year-over-year net sales are up by 7% for Q3 2021 versus Q3 2020. The brand also continues to show quarter-by-quarter market share growth. Demand doses increased 1% in the third quarter over the second quarter of 2021 and 21% year-over-year. While institutions in some parts of the country are allowing more in-person access, in-person engagements remain below pre-pandemic levels. Total prescription volumes continue to grow across most specialties, with volumes heading toward parity with 2020. However, prescription volumes within pulmonology especially remain below pre-pandemic levels. Turning to Slide 10, you can see that YUPELRI share continues to grow both in the hospital and in the community retail settings. As we have noted previously, many patients with COPD experienced an acute respiratory episode serious enough to require a trip to the hospital. The hospital becomes a key point to assess a person with COPD and convert or switch them from their current medication to YUPELRI. Data shows that many patients who received 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 effectively and collaboratively using multiple tools and tactics in coordination to convert appropriate patients from competitive products to YUPELRI during the hospital to outpatient transition experience. Over the course of Q3 2021, approximately 33% of all COPD-targeted hospitals were physically accessible to our field colleagues, which was a natural decline from 62% the previous quarter. Despite the evolving institutional and outpatient clinic access, we have been encouraged with the growth in total prescriptions from Q2 to Q3. The native brand prescriptions have remained stable over the same time period. In addition, new hospital purchasing accounts are being added weekly. Looking specifically at the Theravance field sales deployment efforts in Q3 of 2021, doses sold exclusively in the hospital setting represented an 11.7% increase from the previous quarter. September YUPELRI hospital volume hit a new launch-to-date high and we saw a 43.5% year-over-year growth from September in 2020. Looking ahead, it is important to understand that according to the Gold guidelines, LAMA or long-acting muscarinic antagonist is foundational to COPD maintenance care. The execution of our tactical plan will continue to leverage these guidelines and appropriate patient types, while we continue to optimize the marketing mix through rigorous and continued measurement of tactics. We will be initiating a Phase 4 PIPER clinical study, which is aimed at helping to better inform decisions when physicians are designing a personalized COPD treatment plan with patients. This study will compare improvements in lung function in adults with severe to very severe COPD and sub-optimal inspiratory flow rates following once-daily treatment with either YUPELRI delivered via a standard jet nebulizer or tiotropium delivered via a dry powder inhaler. Findings from this study are intended to provide data to support a possible label update and help to better inform physicians as they are working with their patients to design COPD maintenance treatment plans, and we expect the study to initiate later this year or early January 2022. Moving to Slide 11, let’s take a more macro look at the overall COPD retail market. If you take a rolling view over the past 12 months of both nebulizers and handhelds, again, in the face of a respiratory pandemic, YUPELRI and GSK’s TRELEGY demonstrate resilience to many of the external factors. As a reminder, TRELEGY owned and marketed by GSK is the first and only once-daily single inhaler triple combination therapy approved for the treatment of COPD and asthma. I am not specifically highlighting BREZTRI’s growth because of its recent launch timing, but let’s take a closer look and move to Slide 12. As a result of BREZTRI’s entrance to the market and the addition of the asthma indication for TRELEGY in September of 2020, the overall close triple market has grown as expected and is also demonstrated on Slide 13. GSK mentioned during their Q3 earnings last week that the dual indication is driving higher demand in the U.S. The slide also reconfirms the challenges pulmonologists experienced in the third quarter and throughout the pandemic when treating COPD patients, which includes a decrease in in-person patient visit volume and a limited ability for healthcare professionals to diagnose and reassess the patients without pulmonary function tests, respirometry, which cannot be performed via telemedicine visits. Those factors contributing to a reduction in prescriber confidence and fewer prescriptions. The pandemic has also led to increased insurance changes, which include Medicare patients migrating from fee-for-service Medicare to Medicare Advantage plans, which could result in higher patient co-pays and create greater concerns of affordability associated with prescription fulfillment. We expect as more people are vaccinated, boosters are given, and pulmonologists’ ability to return to seeing more patients face-to-face in their offices grows, there will be a rise in sales for TRELEGY and YUPELRI in the coming quarter in 2022. I will now turn the call over to Rick Graham.

Rick Graham, Senior Vice President, Research and Development

Thanks, Rhonda. The go-forward organization is focused on the highest value co-respiratory opportunities as outlined on Slide 14. These include YUPELRI lifecycle management, including a clinical study in partnership with Viatris. As Rhonda mentioned, success in the PIPER study would capture more of YUPELRI’s addressable market and further strengthen its competitive advantage. It will be responsible for 35% of the cost of the study, which is planned to initiate in December '21 or January of 2022. Nezulcitinib is our most advanced clinical candidate and we are finalizing the development program in the acute lung injury, building on the efficacy and safety data, including the mortality benefits seen in the Phase 2 study, which was reported in June. We are also looking to participate in externally funded platform studies, evaluating its potential role in treating hospitalized patients with severe lung inflammation. These studies could initiate in early 2022. We continue to see nezulcitinib having potential application in chronic lung inflammation, including the prevention of lung transplant rejection and fibrotic diseases of the lung. Finally, our concentrated research effort aimed at developing a dry powder inhaled form of our inhaled JAK inhibitor continues internally, and we expect to proceed into the clinic with the next-generation compound after securing a strategic partnership. Moving to Slide 15, our pipeline slide has been updated to reflect our respiratory focus and recent study results and decisions. Regarding the late-stage non-core assets, the key operational activities for all izencitinib and ampreloxetine studies will be completed by the end of the first quarter of 2022. The Phase 2 study in Crohn’s disease with izencitinib has completed enrollment, with top-line results expected in the first quarter of '22. Top-line results from the ampreloxetine Phase 3 study, REDWOOD, are also expected in the first quarter of 2022. And as a reminder, all patients in the REDWOOD study receive ampreloxetine treatment for 16 weeks, followed by a 6-week randomized withdrawal period. We plan to share top-line results and present the data from these programs at future scientific forums. I will now turn the call over to Andrew to review the financials.

Andrew Hindman, Chief Financial Officer

Thanks, Rick. Let’s first look at TRELEGY. As Rhonda mentioned, TRELEGY owned and marketed by GSK is the first and only once-daily single inhaler triple combination therapy approved for the treatment of COPD and asthma. Theravance Biopharma is entitled to receive upward tearing royalties on global net sales of TRELEGY. At present, 75% of the income from our economic interest is pledged to service principal and interest payments on our outstanding 2035 non-recourse notes, and the remaining 25% of income is retained by us. On Slide 17, we capture the most recent information GSK shared during their earnings call on October 27. They noted that TRELEGY continued to lead the market as a single inhaler triple therapy, with Q3 2021 sales growth of 77% over Q3 2020, generating global net sales of $449 million. And year-to-date in 2021, Theravance Biopharma has received $59.4 million from TRC LLC for our economic interest in TRELEGY. Moving to Theravance Biopharma’s consolidated financials on Slide 18, we provide our third quarter 2021 financial highlights compared to this third quarter 2020. R&D expenses for the third quarter of 2021 were $43.7 million compared to $67.4 million in the third quarter of 2020. SG&A expenses for the third quarter were $21.3 million compared to $27.5 million in the third quarter of 2020. As a reminder, all of these figures exclude share-based compensation, and we ended the quarter with $216.2 million of cash and cash equivalents. Regarding financial guidance for the full year 2021, we are reiterating our previously issued guidance. For R&D, we expect to invest between $180 million to $190 million relative to actual R&D investment of $230 million in 2020. For SG&A, we provided a range of $70 million to $80 million relative to actual SG&A expense of $77 million in 2020. Again, all of these figures exclude share-based compensation. And during our announcement in September, we provided preliminary 2022 financial guidance. For R&D, we guided to investing between $55 million to $65 million. And for SG&A, we provided a range of $30 million to $40 million. We plan to update the 2022 financial guidance in January 2022. And with that, I will turn the call back to Rick Winningham for closing remarks.

Rick Winningham, CEO

Thanks, Andrew. On Slide 19, we summarized that we are creating a new respiratory-focused Theravance Biopharma. First, it’s about significant cost reduction to become sustainably cash flow positive beginning in the second half of 2022. We have already taken steps to significantly cut costs with a large majority of approximately 75% reduction in force exiting by the end of this month and the remainder by the end of February '22. Second, it’s about value creation as we reviewed the three significant levers growing YUPELRI commercial performance. The Theravance Biopharma and Viatris teams have done a great job, certainly with the COPD community, and gained market share during the pandemic. We recognized the U.S. and global opportunity to increase profit on a brand basis once the pandemic further eases, and pulmonologists returned to seeing COPD patients at the office. Realizing the potential of nezulcitinib, the first inhaled JAK inhibitor targeted directly with oral, this investigational compound has the potential of multiple indications for hyperinflammation of the lung over time and strategically designed clinical programs to maximize return on investment. We will build on our respiratory expertise from design and go forward plan. And the third level of value creation we control is leveraging partnerships to unlock the value of core and non-core assets. Another key pillar of value creation was our economic interest in TRELEGY. GSK reported year-over-year sales growth of 77% this quarter for the same period in 2020. Estimated peak sales are approximately $3 billion. The new respiratory-focused Theravance Biopharma is striving towards 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 through their tenure at the company, especially the last few months which have tested each of them personally and professionally. I am grateful for their commitment to our mission of continuing to develop medicines that make a difference, the progress of our clinical pipeline, YUPELRI, as well as the communities we serve. I also want to thank once again the investigator sites, patients, and their families across the globe who have been a part of our clinical trial programs. November is National COPD Awareness month, and with early diagnosis and treatment, people with COPD can improve their quality of life and breathe better. I thank all the advocacy groups for their educational efforts. I am hopeful that we can contain the pandemic and pulmonologists can start seeing patients with greater frequency face-to-face once again. I will now hand the call back to the operator for questions.

Operator, Operator

Thank you, sir. We have our first question from Geoffrey Porges with SVB Leerink. Your line is open.

Geoffrey Porges, Analyst

Thank you very much for taking a few questions mainly financial in nature. With first on the goal of sustainably breakeven, is that aspiration or is it your guidance that given the trajectories that you see on the plan that you have laid out that you will be sustainably breakeven in the second half? And then secondly, could you give us some sense of the expenses that are associated with your revenue from YUPELRI? So, Theravance today is YUPELRI operationally breakeven or what is the threshold for becoming breakeven? And then lastly, as you consider all these strategic alternatives, do you see the company having any assets that you could sell to generate value that you could reinvest in terms of pipeline or other complementary R&D opportunities? Thanks.

Rick Winningham, CEO

Yes. Thanks, Geoff. Our plan that we outlined, in fact, is a plan that today we are planning to be sustainably cash flow positive after the – in the second half of next year and beyond. So, that’s the financial plan that we have put together for 2022 and beyond, and that’s the plan that we are executing against. YUPELRI as a brand has cash flow positive impact today; the financial dynamics of YUPELRI are quite attractive. That’s one of the reasons that future sales growth is critical to continuing to grow those cash flow streams to both Theravance and Mylan. So, YUPELRI is cash flow positive today, and we look forward to YUPELRI with sales growth becoming more cash flow positive in the future. Now, relative to the third question, which is asset sales, I commented in my remarks that our approach is to partner both core and non-core assets as a way to manage the financial dynamics of the company. Obviously, we have got what we think is a terrific set of core assets in respiratory, and then also exciting non-core assets that we take into a certain point in development and hold more promise and really work to optimize each of those financially as we move forward. So, they take the place of sale; they take the place in some instances of partnership to generate cash flow coming back into the company. Andrew, do you want to – yes, okay, Geoff, sorry, go ahead.

Geoffrey Porges, Analyst

Hey, just to follow-up on that though, in the case of TRELEGY, it’s really a fairly passive royalty. You don’t have any direct role in the development or commercialization of that product. So, for example, over time as TRELEGY’s revenue grows, then the amount that is paid to the bondholders as a proportion of the total will presumably come down, and the math that comes back to Theravance will go up. So, have you thought about different strategic alternatives for that royalty, for example, since it’s really – you are well into this rollout other than just being a drop box?

Rick Winningham, CEO

Yes, that’s quite well described, our passive role. And the answer to the question is yes, we think about hosting different outcomes with TRELEGY. We are, obviously as Rhonda highlighted and Andrew highlighted, we are thrilled with the performance of TRELEGY in the market, in particular, the launch of the 200 microgram dose associated with the treatment of asthma. And we will look to maximize TRELEGY’s impact on the market value of Theravance Biopharma. Andrew, any other comments?

Andrew Hindman, Chief Financial Officer

Yes, nothing further to add, but the concept that the business development corporate development activities that are at the heart of your question, Geoff, take time to complete. So, obviously, it’s not prudent to give more specificity, but other than to tell you in the street that we are actively working across that spectrum, both from a partnering process perspective for the non-core and core assets, such as the JAK program – the pulmonary JAK program for asthma and COPD and pulmonary fibrosis, as well as looking at the financial assets, which TRELEGY is effectively a financial asset, and you properly characterize the way that the royalties are paying off the debt for the 2035 non-recourse notes. And there is substantial cash flow that we believe will come up with the future royalties that will accrue to Theravance Biopharma equity holders in due course.

Geoffrey Porges, Analyst

Perfect. Thank you.

Operator, Operator

Our next question comes from Marc Frahm with Cowen & Company. Your line is open.

Marc Frahm, Analyst

Hey, thanks for taking my questions. Maybe just to follow-up on some of the YUPELRI market dynamics that you went through and thanks for all that level of detail. YUPELRI prescription volumes actually grew slightly in the quarter despite the headwinds for all markets facing, but revenue has actually declined a little bit. Is there some sort of stocking impact that we should be thinking about that was driving that, or did you have to take some sort of discounting actions to kind of maintain place as some of your competitors face generic entrants?

Rick Winningham, CEO

Well, I think relative to the financial dynamics of the net sales recognition, Mylan or Viatris, books the net sales. We have seen fairly strong pricing, and in certain markets, strong prescriptions, those were more affected by COVID. Obviously, when we think this is the difference between the asthma and COPD markets. You have seen pulmonology visits drop, and the COPD prescribing particularly involves changing a device or changing therapy. Pulmonologists like to see the patient in the office, and the lack of patient visits has had an impact on most COPD prescriptions. So, we still see reason for optimism just based on individual territory success in regions where COVID has receded already, but I will let Rhonda sort of compliment and add anything to my comments. Rhonda?

Rhonda Farnum, Senior Vice President, Commercial and Medical Affairs

Yes. Thanks, Rick for the question. And certainly building off of those external factors, where we did see certainly some challenges in access, we still were able to obtain new formulary wins and grow the business particularly in the hospital setting. So, what is absolutely key to not only where we do see success in the past quarter but certainly going forward is to ensure we are maximizing in-person HCP access. And the team is doing a great job already capitalizing on those opportunities and being mindful of the dynamics of where access is improving and where it’s not, ensuring that we are executing on hybrid communication resources and tools and ensuring that that reach and frequency is also complemented by increased investments in our digital media assets.

Marc Frahm, Analyst

Great. Very helpful. Can you provide some details on the Phase 4 trial timeline regarding when we might expect to see data and legal updates?

Rick Winningham, CEO

Rick, do you want to take that?

Rick Graham, Senior Vice President, Research and Development

Yes, sure, Marc. Like Rhonda said, we are getting close to being able to kick that study off. Probably the best thing to do is to think back to what we have reported previously on the first PIPER study. We actually took the learnings from that and designed the second study here. We can say at this point, it’s several hundred patients that were included, revefenacin and tiotropium as Rhonda mentioned. Timing, it will start either in December or January. And then, we do expect that that will probably take around a year to enroll.

Marc Frahm, Analyst

Okay. Thanks.

Operator, Operator

Our next question comes from Liisa Bayko with Evercore ISI. Your line is open.

Liisa Bayko, Analyst

I think you just answered my question with your last response. But I guess maybe can you also characterize like how much bigger you think the market could be with the PIPER study under your belt? Thanks.

Rick Winningham, CEO

Yes. I think we have traditionally looked at patients with low-peak respiratory flow, and estimates of patients with low-peak respiratory flow represent 15% to 20% of COPD patients. Today, patients who use nebulizer therapy for maintenance represent about 9% to 10% of all COPD patients. So, I think we see a pretty significant increase in market opportunity. Obviously, tiotropium is the market leader in single-agent long-acting muscarinic antagonist. And I think this is one of the things that excites us is that when patients provide very solid FEV1 to look at our label, see those FEV1 improvements over placebo and the opportunity to refine, as Rick said, the low-PIPER population that responds the best to nebulized therapy, is a terrific opportunity to get to market growth. Rhonda, anything to add there?

Rhonda Farnum, Senior Vice President, Commercial and Medical Affairs

I am back.

Rick Winningham, CEO

So, anything to add on market opportunity?

Rhonda Farnum, Senior Vice President, Commercial and Medical Affairs

Sure. I lost her a bit, but I think I can pick up on some additional commentary there. If you think about this Phase 4 study and how it can aid the COPD clinician to understand which patients could best benefit. So, thinking about those one in five patients who have low PIPER, so which could benefit most from nebulized therapy, and then assuming a positive outcome of this study that provides us with a new data opportunity, a new data communication and educational opportunity for which our team could thereby offer to exhibit an increasing competitive advantage and add value to our overall promotional efforts.

Operator, Operator

Our next question comes from Deborah. Your line is open.

Unidentified Analyst, Analyst

Hi, good afternoon. Thanks for taking the questions. Just Rick, anything that would be helpful to understand as you sort of restructured the company, how you are thinking about resources between the existing portfolio molecules versus some of the work in terms of identifying new molecules, which is obviously as you think about the company’s success over the years has been identifying the sort of lung-specific and organ-specific targeted therapies?

Rick Winningham, CEO

Yes, that’s a great question. I think what most of our dollars and as we look forward are in development. I think we are going to capitalize on the research work that’s done historically, in a small commitment of ongoing research. And I think one of the strengths of the company is that we do have a portfolio of compounds that are near the clinic that can be leveraged in development. I will kick it over to Rick Graham.

Rick Graham, Senior Vice President, Research and Development

Yes. Not much to add. Right now, with this reorganization that we just announced six weeks ago, we have a team of people that were retained that are razor-focused on continuing development of nezulcitinib in a streamlined way, as well as continuing to work through dry powder inhaled JAK-inhibitor. And remember, we are still in the process of closing down these late-stage studies. We had hundreds of sites for izencitinib, putting them in a box team around the world. So, that’s going to be our focus for the short-term.

Unidentified Analyst, Analyst

Okay. Thank you.

Operator, Operator

Our next question comes from Vikram Purohit with Morgan Stanley. Your line is open.

Vikram Purohit, Analyst

Great. Thanks for taking the question. Going back to YUPELRI, I was wondering if delusion of therapy is a metric that you track and have commented on? And if so, I was wondering if you could give us any color on how that’s trended since the product you launched and through the past couple of months through the pandemic?

Rick Winningham, CEO

Yes. I think probably the only comments that we have made on duration of therapy overall is that we, with this one letter aspect of the importance of the hospital as a point of treatment initiation, is reducing longer levels of persistence with patients who will switch the medicine in the hospital. I would underscore something I think both Rhonda and I mentioned, which is we still consider ourselves relatively early in the launch of YUPELRI because of the impact of the pandemic hitting in really February and March. Rhonda, anything else?

Rhonda Farnum, Senior Vice President, Commercial and Medical Affairs

It’s certainly a metric we attempt to closely track. However, I will just comment; it’s quite difficult to assemble and recognize that those data lag from patient claims to be able to piece that together. But to answer your question specifically, have we seen a decline during the pandemic? We have not. The duration has been reasonably stable to what we were seeing in early 2020.

Vikram Purohit, Analyst

Got it. That’s helpful. Thank you. And then a follow-up question on a separate topic. On your agreement with Innoviva and TRC on the TRELEGY royalties, can you just update on where any dispute with Innoviva currently stands and if there has been any updates on your discussions with Innoviva over the past couple of months?

Rick Winningham, CEO

Yes. There was, I mean, we have received another $13 million plus of TRC. And in early October, I think we have a total of around $59 million we have received from TRC. In 2021, that’s the partnership that’s managed by Innoviva. We are not in a dispute currently with Innoviva. We continue to work with Innoviva on TRC and work to protect our rights under the agreement on the arbitration rulings that have been there, that have been held or, as I have said before, the nature of the rulings creates a degree of lumpiness in the cash flow coming out of TRC. But at the end of the day, we have received 85% of the economics out of TRC, and Innoviva receives 15%. And that’s unchanged. Andrew, anything else to comment on that?

Andrew Hindman, Chief Financial Officer

Nothing really further to add, although industries will notice that there are changes on our balance sheet for September 30, 2021, that do reflect the totality of the receivables that we are due, and we keep track of every penny of the 85% that Rick just mentioned.

Vikram Purohit, Analyst

Okay. Understood. Thank you.

Operator, Operator

Our next question comes from Brian Skorney from R.W. Baird. Your line is open.

Luke Herrmann, Analyst

Hi. This is Luke Herrmann on for Brian. We are just wondering for nezulcitinib, could you talk about the market's clinical plan and timelines of acute lung injury and fibrotic disease? And then secondly, was there any more color you could provide on the dry powder JAKs and any preclinical color that makes you optimistic?

Rick Winningham, CEO

Yes. We will get started on, I think it’s not only the preclinical work that makes us optimistic, but it’s the clinical work that makes us optimistic. This is a JAK inhibitor if you are talking about the nebulized JAK penetrates into the lung; it is a pan-JAK. And an inhibitor does reduce inflammation in the lung and affect the JAK/STAT pathway, obviously inhibiting that which has been implicated in reduction in fibrosis in a number of different models, animal models. So, that’s where we are encouraged. I think we see two different segments: one of them is the nebulized, growing nebulized JAK inhibitor, which is nezulcitinib, and the dry powder inhaler JAK program, which does require different chemical design that consolidates delivery through a dry powder inhaler. We have seen anti-inflammatory effects with the lead there and have got the lead in which is 8236 that could be improved on. And so I think we think we are just really at the, not so much at the very beginning, but early in the early stages of leveraging the JAK/STAT pathway to address hyperinflammation of the lung. Rick, maybe you want to touch a little bit more on the chronic indications.

Rick Graham, Senior Vice President, Research and Development

Sure. Just a little bit. I think there are a lot of opportunities here, as Rick pointed out on nezulcitinib. And just stepping back for a minute, it’s worth reminding everybody that we released results from a 200 patient, Phase 2 study in COVID-19 with nezulcitinib back in June. Our team subsequently engaged with global health authorities. And then we have been in discussions around various externally funded platform studies. So, there has been a lot of work going on with nezulcitinib. We do think that work in COVID is going to be applicable to future indications, both acute and potentially chronic indications. So, as Rick talked about, we are now focused on the streamlined R&D organization, and with nezulcitinib as our most advanced asset, we are looking forward to providing updates in the near future. With regard to chronic indications, we did talk about fibrotic diseases. And just keep in mind that fibrosis is a feature of most chronic inflammatory diseases and can affect pretty much every tissue in the body, including the lung. And when progressive, fibrosis can lead to organ malfunction and ultimately death. Importantly, the JAK/STAT pathway is known to be involved in the development of fibrotic disorders. So, like Rick said, lots of opportunities here. And we are taking a measured approach to figure this out.

Luke Herrmann, Analyst

Great. Thanks so much.

Operator, Operator

Our next question comes from Joseph Stringer with Needham & Company. Your line is open.

Joseph Stringer, Analyst

Hi, everyone. Thanks for taking my questions. Two from us on YUPELRI. Just I assume that you are co-promoting the drug in various settings, I am wondering if your guidance, your 2022 guidance sort of reflects or gives you the flexibility to sort of potentially increase investment there or increase capital in that direction just to continue to drive sales, whether it be expansion of sales force or something like that? And then secondly, more on, and sorry, if I missed this earlier, but in the past, we have given some metrics around HCP interactions and in-person interactions, but just curious if those were up Q3 relative to Q2? Thank you.

Rick Winningham, CEO

Rhonda, do you want to take the in-person interactions because you have covered part of that, so…

Rhonda Farnum, Senior Vice President, Commercial and Medical Affairs

Yes. Looking at Q3 versus Q2, they were down slightly for in-person engagement, but overall engagement, considering the team does still promote virtually, is on par there. But the in-person are what we see as the most important and greater impact.

Rick Winningham, CEO

Yes. Relative to YUPELRI’s investment and our current plan, we have that I would say that our, as Andrew highlighted, we will provide more guidance in January with regard to the spending in 2022. But under the current plan, we have got it between Mylan or Viatris and Theravance Biopharma, we have got increased investments in our plan for YUPELRI because we do think it’s a significant opportunity for the partnership.

Joseph Stringer, Analyst

Great. Thanks for taking our questions.

Operator, Operator

Our next question comes from Anupam Rama with JPMorgan. Your line is open.

Anupam Rama, Analyst

Hey, guys. Just a really quick one for me. Can you remind us of the sales cutoffs for the tiering of the royalties on the global sales of TRELEGY for that 5.5% to 8.5%? Thanks so much.

Rick Winningham, CEO

Okay. I don’t have that. We are in another tier, I don’t have that handy, that’s a – that is publicly available on the SEC website. I don’t know, Andrew, do you have?

Andrew Hindman, Chief Financial Officer

Yes, the first tier is $750 million in global net sales, and then it goes upwards from there, with the second tier off the top of my head I believe it’s $1.25 billion, and then $1.75 billion and above, but we can double-check that. I am sure I am correct off the top of my head and lead back with the schedule that’s pulled from the actual document.

Rick Winningham, CEO

Yes. So here you go, Anupam, we – up to $750 million in global sales, the royalty rate is 6.5%; from $750 million to $1.25 billion, it’s 8%; from $1.25 million to $2.25 billion, it’s 9%; and above $2.25 billion, it’s 10%. Now, that is the gross royalty rate, and then 85% is the implied royalty rate back to Theravance Biopharma.

Anupam Rama, Analyst

Thanks so much.

Operator, Operator

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

Rick Winningham, CEO

Yes. Thank you for joining us today for today’s quarterly call. We look forward to sharing the progress with you in the future of the new streamlined Theravance Biopharma. Have a great day.

Operator, Operator

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