Ladies and gentlemen, good afternoon. I'd like to welcome everyone to the Theravance Biopharma Q1 2022 conference call.
During the presentation, all participants will be in a listen-only mode. A question-and-answer session will follow the company's formal remarks.
To ask a question, press the star key followed by the digit one on your phone. Again, that's star one to ask a question. If listening via webcast, please mute audio on your webcast device before asking a question over the phone.
I will repeat these instructions after management completes their prepared remarks. Also, today's conference call is being recorded.
Now I would like to turn the call over to Gail Cohen, Vice President, Corporate Communications. Please go ahead.
Good afternoon, and thank you for joining the Theravance Biopharma Q1 2022 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. I would direct your attention to slide 3. Joining us are Rick Winningham, Chief Executive Officer, followed by Rhonda Farnum, Senior Vice President, Chief Business Officer, 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 to slide four. Last September, we announced the restructuring of the company to optimize our business. Since then, we've rapidly transitioned to a focused and streamlined Theravance Biopharma. We're focused on leveraging our expertise in developing and commercializing respiratory therapeutics. We've streamlined our R&D investments to concentrate on highest value opportunities, and we're exploring strategic partnerships for our pipeline assets to unlock additional value.
All of these actions drive towards our goal of to maximize shareholder value. There are three key pillars of value creation, as highlighted on slide five, for the go-forward plan that builds on our proven record of respiratory innovations, supporting several approved medicines for COPD and asthma. These pillars include YUPELRI, which was discovered and developed by Theravance Biopharma, and is commercialized in partnership with Viatris. YUPELRI has continued quarter-over-quarter market share growth despite the respiratory pandemic.
Sell-side analysts covering Theravance Biopharma estimate YUPELRI has the 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 the study is successful, our addressable U.S. market could potentially include all patients with low peak inspiratory flow, which is estimated to be one in five patients with COPD.
The impact of this study obviously is not included in current analyst peak sales estimates. Rhonda will speak to YUPELRI's successes from this most recent quarter. Second, our pipeline, our second pillar of value creation. It includes our most advanced respiratory candidate, nezulcitinib, our dry powder inhaled JAK inhibitor program, which we have said before we'd advance a drug candidate into the clinic with a strategic partner.
It also includes ampreloxetine, an investigational Theravance Biopharma-discovered once-daily norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension or NOH. Results from a phase 3 study of ampreloxetine we reported last month showed a benefit in patients with multiple system atrophy. Rick Graham will walk through the data and the next steps for that program.
The third pillar is our economic interest in TRELEGY, a 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 the global respiratory pandemic.
At present, GSK sell-side analysts project that TRELEGY could generate global peak sales of $3.5 billion annually. Andrew will review TRELEGY's Q1 performance with 2022 as well as review Theravance financials. We continue to believe that the strong and growing cash flows of YUPELRI and TRELEGY and the expected future robust revenue performance for both, coupled with the several sources of potential upside in our development pipeline, can generate significant value creation opportunities for our shareholders.
I'll now turn the call over to Rhonda to review YUPELRI.
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 the 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 respiratory pandemic, we are encouraged by YUPELRI's growth and believe we are seeing evidence of receding pandemic impact. 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., with 65% going to Viatris and 35% to Theravance Biopharma. Looking specifically at the Theravance field sales deployment efforts on slide 8.
In Q1 of 2022, doses sold exclusively in the hospital setting represented a year-over-year increase of 73.2% from Q1 of 2021 and an increase of 4.3% from the prior quarter, demonstrating the highest quarter volume launch to date. The COVID-19 pandemic impacted the launch phase of YUPELRI's growth in 2020, but we have seen YUPELRI's hospital volume return to growth in the second half of 2021.
With the achievement of new key hospital system formulary placements and the continued addition of new purchasing accounts, we believe these wins will yield significant growth in 2022 as YUPELRI will be the first LAMA of choice in many hospital systems. Turning to slide 9, you can see that YUPELRI's share of the hospital setting increased to 11.3% in Q1 of 2022, which is up 7.8% from 7.8% in Q1 of 2021. YUPELRI's market share in the community setting increased to 23.5% through January of 2022, which is our latest data point and up from 19.7% in Q1 of 2021.
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 their treatment, allowing for continuity of YUPELRI maintenance therapy post-hospitalization.
The Theravance Biopharma and Viatris teams continue to work collaboratively and effectively to convert appropriate patients to YUPELRI during their hospital visit, providing support through discharge and enabling them to be maintained on YUPELRI after the return home. Slide 10 shows Theravance Biopharma's implied 35% of net sales for YUPELRI during the Q1 of 2022 of $15.3 million.
I'm also pleased to highlight that YUPELRI's year-over-year net sales have increased 19% comparing Q1 of 2022 versus Q1 of 2021. Demand doses for YUPELRI also increased with 23.4% year-over-year growth. As was the case last quarter, while institutions in many parts of the country are allowing increasing in-person access, in-person engagements still remain below pre-pandemic levels for our teams.
It is also important to note that although total prescription volumes continue to demonstrate growth across most therapeutic specialties, with volumes heading toward parity with 2020, prescription volumes within the pulmonary specialty continue to remain below pre-pandemic levels for the Q1 of 2022. We believe this challenging period is ending and provides upside to the brand as we move in the direction of a more normal environment for pulmonologists treating COPD patients.
Even with these lingering challenges, we have been encouraged with growth in total prescriptions, which increased by 30% year-over-year, and new-to-brand prescriptions increased 20% year-over-year.
As a reminder, these script data include only retail, but serves as a useful proxy for retail, plus the DME or durable medical equipment fulfillment channel, which represent a majority of the volume for YUPELRI sales. Lastly, although the pandemic continued to affect our business during the Q1 , in March and April, we have seen the impact recede, which we believe is leading to improved demand patterns and along with an increasing ability to engage in in-person field-facing activities, we anticipate our growth will continue to accelerate throughout 2022. I will now turn the call over to Rick Graham.
Thanks, Rhonda. Turning to slide 11. Picking up on YUPELRI. The phase 4 PIFR-2 study comparing improvements in lung function in adults with severe to very severe COPD and suboptimal inspiratory flow rates following once daily treatment with either revefenacin delivered via a standard jet nebulizer or tiotropium delivered via dry powder inhaler is actively enrolling patients. Theravance is responsible for 35% of the cost of this study, and we continue to guide to top line results within the Q1 of 2023. As Rick mentioned, we aim to unlock the value of our pipeline assets through strategic partnerships.
Today, I'm going to focus on the recently announced ampreloxetine phase 3 study results, which demonstrated a clear benefit in study patients with multiple system atrophy and symptomatic neurogenic orthostatic hypotension. Moving to slide 12. The ampreloxetine phase 3 program included three studies.
Study 169, Study 170, and the open-label extension Study 171 enrolled patients with Parkinson's disease, multiple system atrophy or MSA, and pure autonomic failure. In September of last year, we reported that the 169 study did not meet its primary endpoint, and we took actions to reorganize the company and close out the ongoing clinical studies.
Last month, we disclosed the results from Study 170 and the complete data slide set can be found on our website. Today, I'd like to focus the conversation on the benefit that ampreloxetine treatment provided to MSA patients in the study. On Slide 13, you can see the study design. Study 170 was a 22-week phase 3 study comprised of a 16-week open label period, followed by a 6-week double-blind, placebo-controlled randomized withdrawal period.
Patients entered the open label period of study 170 by either completing the 4-week efficacy study 169 or by entering 170 de novo. After receiving 10 mg of ampreloxetine once daily for 16 weeks, patients then entered the 6-week randomized withdrawal period, where they either remained on ampreloxetine or were randomized to placebo. At the end of the randomized withdrawal period, 31% of the study population was MSA patients. On Slide 14, we present the pre-specified subgroup analyses of patient-reported outcomes.
On each of the four plots, the data points to the left of the vertical line favor ampreloxetine treatment and data points to the right favor placebo. The top left panel shows the results for the primary endpoint of treatment failure, which was defined as a worsening of both OHSA item 1 and the Patient Global Impression of Severity.
While there was a beneficial effect of ampreloxetine in the overall study population, this benefit was largely driven by MSA patients. The benefit to MSA patients was observed in multiple endpoints, including OHSA composite, as shown in the top right panel, OHSA item number 1 on the bottom left panel, and the Orthostatic Hypotension Daily Activity Scale, or OHDAS on the bottom right. Orthostatic hypotension questionnaire composite scores, and the individual item scores from the patients with MSA are shown on Slide 15.
Starting on the top half of the slide, you can see that the symptom composite score was nominally statistically significant, with the upper bound of the 95% confidence interval to the left of zero. This effect on the OHSA composite was driven by all six items on the questionnaire favoring ampreloxetine. These include dizziness, vision, weakness, fatigue, trouble concentrating, and head and neck discomfort.
Moving to the bottom half of the slide, the daily activities composite score also favored ampreloxetine, and in this case, all but one item on the questionnaire favored ampreloxetine treatment. The largest impact for the MSA patients was standing for a short time. For someone with MSA suffering with symptomatic nOH, even standing for a short time can be an enormous impact on quality of life. It can mean the difference of transferring from the bed to a wheelchair, from the wheelchair to the restroom.
The idea that the item that slightly favored placebo was walking for a long time, which isn't surprising considering that MSA is a disease with severely debilitating consequences. Finally, the last row of the table shows the OHQ composite score, which is the integrated result of OHSA and OHDAS. The OHQ composite score favored ampreloxetine treatment, and this effect was also nominally statistically significant.
The MSA subgroup represents a patient population with nOH for which no currently approved therapy has been shown to provide sustained efficacy in mitigating the debilitating symptoms related to nOH. The MSA dataset in the current ampreloxetine program constitutes more than a third of the overall study population, and this subgroup is the largest number of MSA patients evaluated in a clinical program investigating an interventional treatment for symptomatic nOH to date.
There's an urgency to treat MSA patients suffering with nOH due to the impact on quality of life and the extreme caregiver burden. Rare diseases and conditions pose a significant economic burden, and the cost burden applies to direct medical as well as indirect and non-medical costs.
With the benefit that ampreloxetine provided to the MSA patients in the 170 study, it's important to consider why a similar result wasn't observed in study 169, the four-week efficacy study. As shown on Slide 16, longitudinal data analysis demonstrates that a treatment duration of more than four weeks with ampreloxetine is required for maximal effect.
The y-axis on the plot is the OHSA composite score, and a lower number here means that patients are feeling better. The x-axis is time by week in each period of the study. As shown on the left side of the figure, there was a minimal difference between ampreloxetine treatment in green and placebo in gray after four weeks in study 169.
However, as patients moved into the open label period of 170, the OHSA composite continued to decrease, reaching a nadir or a lowest level around week 8-12. For patients that continued on ampreloxetine, shown by the green line, into the randomized withdrawal period, the effect was durable, whereas those patients withdrawn from ampreloxetine, shown by the gray line, worsened over the next six weeks.
Again, the longitudinal data demonstrate that a treatment duration of more than 4 weeks with ampreloxetine is required for maximal effect.
Given the clear unmet need for MSA patients suffering with symptomatic NOH, coupled with the benefits that ampreloxetine provided in study 170, we will define a path forward through ongoing discussions with regulators and strategic partners. I'll now turn the call over to Andrew to review the financials.
Thanks, Rick. Turning to slide 18, we look at the performance of TRELEGY, the third pillar of our 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 non-recourse notes, and the remaining 25% of income is retained by us. On slide 18, we've captured the most recent information GSK shared during their earnings call on April 27.
GSK noted that TRELEGY continued to lead the market as a single inhaler triple therapy with year-over-year global sales growth of 33%, generating global net sales of $454 million during the Q1 of 2022. This growth is primarily driven by the continued adoption of TRELEGY in the asthma indication and strong global commercial performance by GSK's team.
Moving to our consolidated financials on slide 19, we provide our Q1 financial highlights for 2022 compared to the Q1 of 2021. R&D expenses for the Q1 of 2022 were $19 million, compared to $60 million for the Q1 of 2021. SG&A expenses for the Q1 of 2022 were $14 million, compared to $23 million in the Q1 of 2021. These quarterly figures exclude share-based compensation and one-time restructuring expenses.
We ended the Q1 of 2022 with $148 million in cash and cash equivalents. On slide 20, we provide our financial guidance for 2022, and for R&D expenses, we expect to invest between $45 million-$55 million relative to actual investment of $168 million in 2021. Of this expense range, approximately $10 million is non-recurring spending that was incurred in Q1 2022 to support the completion of the izencitinib and ampreloxetine clinical programs.
R&D spend in Q2 and beyond will normalize and reflect the recurring limited strategic investments in our pipeline. For SG&A expenses, we expect to invest between $35 million-$45 million relative to actuals of $71 million in 2021. Again, our operating expense guideline excludes share-based compensation and 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 flow positive on an annual basis in the second half of 2022. With that, I'll return the call back to Rick for closing remarks.
Thanks, Andrew. Turning to slide 21, Theravance Biopharma is focused and streamlined. We're executing against three pillars of value creation, maximizing the value of YUPELRI, limiting strategic investments to advance our pipeline while leveraging our internal expertise in the development of inhaled long-selected agents and pursuing strategic collaborations to optimize value. The third key pillar of value creation is our economic interest in TRELEGY, which is experiencing strong revenue growth based on GSK's commercial performance.
We continue to move towards our goal of becoming sustainably cash flow positive beginning in the second half of 2022 and to maximize shareholder value. In closing, I once again thank our internal team for their perseverance. I'm grateful to their commitment to our mission of continuing to develop medicines that make a difference, the progress in our clinical pipeline, YUPELRI, as well as the patient communities we serve.
I'll now hand the call back to the operator for questions.
Thank you, sir. Once again, if you would like to ask a question, you may do so by pressing the star key followed by the digit one on your touch tone phone. If listening via webcast, please mute audio on your webcast device before asking a question over the phone. If you are using a speakerphone for today's call, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, that's star one if you would like to ask a question, and we'll pause for a moment to assemble our roster.
Our first question will come from Eva Privitera with Cowen.
It looks like YUPELRI volumes increased 73% year-over-year in the hospital setting. From the market share data, there was a 30% year-over-year increase in the community setting. With sales increasing 19% year-over-year, is that possibly due to a decrease in mean net pricing, or how should we interpret that?
Rhonda, do you want to take that?
No, I wouldn't just attribute that to an adjustment in pricing. We're still seeing this volume kind of repair or get back to a point of pre-
Pre-pandemic, you know, growth rates. I don't know if your question is more separately relative to each channel of business or just trying to understand.
Yeah.
-the very .
I guess I'm trying to understand what's the discrepancy there and also understand, you know, what the demand trajectory is like in the community setting versus the hospital. Are there any specific challenges there in the community setting?
Go ahead, Rick.
Yeah. You know, the hospital patient, you know, we focus on the hospital because as Rhonda indicated, you know, that is a very good time to reassess the patient for the healthcare professional. If what they have been on has not been working because of the reason, you know, causing them to go in the hospital, it may, in the appropriate patient, facilitate a change to YUPELRI.
That the effect of the hospital and the growth of the hospital channel would likely be seen first, and then it would flow into the community setting.
The community setting, then we, you know, obviously, in Q1 , you have some issues generally, with community relative to payers, which is seen in many different areas as copays reset, so and cost shares reset.
That's obviously something that's happened a bit in the Q1 of this year. We certainly, as Rhonda indicated in her remarks, you know, look at the growth that we've seen in the hospital, look at the increase in face-to-face interchanges that we've had with healthcare professionals across both the Viatris and the Theravance Biopharma sales forces, you know, as a precursor to improving growth profile throughout the rest of the year. Sorry, Rhonda, go ahead.
I think the other piece to which I think is somewhat obvious is certainly the volume contribution of hospital relative to the community setting. I think everyone can appreciate the time on therapy is a different duration in hospital. Approximately 3-5 days, and then looking at the longer duration in the outpatient setting in that script fulfillment.
All right. Thank you so much.
Thank you. Our next question will come from Vikram Purohit with Morgan Stanley.
Good day, everyone. This is Gospel on for Vikram. I was wondering, what do you think a path forward for ampreloxetine in MSA could look like in terms of an eventual trial design and the number of studies that you might need to be conducted for a potential approval? What is your current thinking on how you would support the costs associated with running any additional studies needed here? Thank you.
Yeah, thank you for the question. This is Rick Graham. I don't wanna get too far ahead of ourselves because our first step is to have a conversation with the FDA here based on the results that we have in hand that I went through today. We'll aim to have a meeting with the FDA toward mid-summer of this year. If you look at the data that I presented today, we and our KOLs are pretty impressed with the consistency in the data, the totality of the data, and the fact that we were able to see nominal significance in just 38 MSA patients looking at the OHSA composite.
Taken together, depending on the outcome of the interaction with FDA, you know, there could be a way to complete a body of work in a very, I think, streamlined and minimal way, given the data that we have in hand.
Oh, thank you.
Thank you.
Thank you.
Again, to ask a question over the telephone, that is star one. Our next question comes from Joseph Stringer with Needham & Company.
Hi, this is Ben Rickard on for Joseph Stringer . Thanks for taking our question. Assuming that the PIFR-2 trial is positive and we would see a YUPELRI label expansion, how would that change anything about the profit sharing agreement with Viatris or the division of sales marketing between the two companies?
Thank you.
No, thanks for the question. No, it wouldn't change the profit share. The profit share would remain the same. I think what it does change is it opens up a little bit more broadly the segment of the market in which YUPELRI may be able to compete very effectively versus, you know, other handhelds. Right now, as we've mentioned over time, we really are focused on a segment of the COPD market that's about 1 in 10 COPD patients who require nebulization for control of their disease. If the PIFR-2 study is successful, you know, that 1 in 10 could expand to as much as 1 in 5.
In other words, you know, today there are patients that are not getting, you know, optimal benefit from a handheld device that might benefit from therapy with YUPELRI. So that's really what the target is.
The target is, you know, expanding the rather sizable niche that YUPELRI already occupies and can participate in to facilitate longer term growth of the brand.
Rick, I just wanna add, and Ben, thanks for the question. It's one that comes up a lot about the label change. Just remember that our current indication statement for YUPELRI is already very broad and captures patients with low PIFR. The point here is that we need to do a clinical trial to better understand the impact of nebulized therapy versus dry powder inhaler on these patients with low peak inspiratory flow. If there were to be a label update, these results would go into, let's say, the clinical trial section of the label, but we aren't expecting to change the indication statement because it already captures those patients.
Great. Thank you very much.
Thank you. Our next question will come from David Risinger with SVB Securities.
Yes, thanks very much. I had three questions on the revenue, please. First, the Viatris collaboration revenue rose 3% in the March quarter year-over-year. If you could please provide some color on that. Second, the collaboration revenue declined from $3.9 million in the Q1 of 2021 to just $0.9 million in the Q1 of 2022. If you could explain that. In terms of licensing revenue, the figure was $2.5. If you could please explain that. Thank you.
Andrew, you wanna
Yeah. Hi, David. This is Andrew. So going down the list there. The collaboration agreement revenue from Viatris is essentially the receivable due from Viatris for the quarter. So there's some complex collaboration accounting behind to get to that netted out number. But that's effectively the receivable. The next line down, the collaboration revenue line.
Yes. $9,000 was booked for the Q1 of 2022, down from just under $4 million for the Q1 of 2021. This is really related to the amortization of the upfront payment received from Janssen for the collaboration we had on izencitinib.
The licensing revenue, $2.5 million for this quarter, was the first milestone payment received from Pfizer on the dermatological JAK program that we licensed to them in 2019. That payment was for the entry of the first product into the human clinical studies.
Thank you.
You're welcome.
Thank you. It appears we have no further questions on the phone. I'd now like to turn the conference back to Mr. Winningham. Please go ahead, sir.
I'd like to thank everyone for joining us today and for the questions. We look forward to updating you throughout the rest of 2022. We're very excited and encouraged about our progress to date in the year, and look forward to finishing the next three quarters quite strongly with our growth drivers. Thank you very much. Have a great day.
Ladies and gentlemen, this concludes today's conference call. We thank you for your participation, and you may disconnect at any time.