TBPH (2025 - Q2)

Ladies and gentlemen, good afternoon. I'd like to welcome everyone to the Theravance Biopharma Second Quarter 2025 Conference Call. [Operator Instructions] Also, today's conference is being recorded. And now I would like to turn the call over to Rick Winningham, Chief Executive Officer. Please go ahead, sir. Rick E.

Good afternoon, and welcome to Theravance Biopharma's Second Quarter 2025 Earnings Results Conference Call. On Slide 2, you'll find our forward-looking statements disclaimer, which covers certain risk factors, which could cause actual results to differ materially from any such statements we might make in today's call and which are described further in our filings with the SEC. Moving to Slide 3. I'm joined today by Rhonda Farnum, Chief Business Officer; Aine Miller, Head of Development; and Aziz Sawaf, Chief Financial Officer. And turning to Slide 4. We delivered an excellent quarter, underscored by disciplined execution across our commercial and development organizations, which drove continued momentum in both YUPELRI and ampreloxetine. In addition, we completed a high-impact strategic transaction. This performance reflects a team that's sharply focused on delivering value to our stakeholders. Starting with our commercial business, YUPELRI, our durable cash-generating product continues to perform. Net sales for the quarter reached approximately $66 million, driven by continued demand growth and favorable net pricing with strong pull-through performance in the hospital channel. In addition, YUPELRI received approval in China, triggering a $7.5 million milestone payment. We also completed the $225 million sale of our remaining royalty interest in TRELEGY to GSK, a transaction that significantly strengthens our balance sheet and represents the first major outcome from our strategic review committee's efforts to unlock shareholder value. TRELEGY's strong second quarter performance further increased the likelihood that we will receive the remaining $150 million in milestones from Royalty Pharma over the next 18 months. And turning to ampreloxetine. I'm pleased to report that the Phase III CYPRESS trial continues to progress well, designed specifically to replicate the Study 170 MSA prespecified subgroup, CYPRESS remains on track to complete enrollment in the open-label portion over the next couple of weeks, and we expect to report top line data approximately 6 months after. The quality of execution and engagement from investigators, patients and advocacy groups has been exceptional. Given that multiple system atrophy or MSA is a rare disease with no proven therapies specifically for neurogenic orthostatic hypotension or nOH, we believe this program has the potential to bring great value to patients and shareholders. We ended the quarter with approximately $340 million in cash and no debt. Our operations remain near cash neutral. Theravance has a clear and compelling profile, a strong balance sheet enhanced by visibility into significant near-term milestone payments, a growing profitable commercial asset and on top of that, the potential for a transformative near-term catalyst based on the CYPRESS data readout. We entered the second half of 2025 with clear momentum and look forward to completing enrollment in CYPRESS and sharing top line data. We're in a strong financial position. And together with the strategic review committee, we continue to evaluate a range of opportunities to enhance shareholder value and remain committed to capital discipline and returning excess capital. And with that, I'll turn the call over to Rhonda to provide additional detail on YUPELRI's performance.

Thanks, Rick. If you turn to Slide 6, you'll see that the Theravance Viatris commercial partnership delivered another strong quarter of YUPELRI performance. Second quarter net sales increased 22% year-over-year to $66.3 million, our highest Q2 result since launch. That growth was driven by 3 key elements: First, solid demand growth, up 4% versus Q2 of 2024 and 5% sequentially from Q1 of 2025. Second, continued net price improvement, supported by pricing discipline and a favorable channel mix. And third, a onetime favorable adjustment to net pricing in the quarter. It's worth noting that even without the nonrecurring pricing benefit, we would have still delivered a mid-teen year-over-year net sales growth in Q2, underscoring the product's strong and sustained growth trajectory. Importantly, these results increase our confidence in achieving the $250 million calendar year sales threshold required to trigger a $25 million milestone payment. Turning to Slide 7. In addition to the strong net sales growth in the quarter, YUPELRI continued to experience expanding profit margins and strong momentum across both hospital and community outpatient channels. The hospital channel remains a critical differentiator and a key driver of prescribing for the brand. Notably, hospital volume increased 31% versus Q2 of 2024, reflecting our team's sustained success in securing formulary wins and implementing therapeutic interchange protocols. In Q2, YUPELRI's long-acting nebulized market share in the hospital reached a new launch to date high of approximately 20%. Hospital performance continues to serve as a foundational component of our strategy, functioning as a key entry point for transitioning patients to community outpatient maintenance therapy care. I would also like to call attention to the recent approval of YUPELRI by China's National Medical Products Administration in June. The approval triggered a $7.5 million milestone payment. And importantly, Viatris will lead launch and commercialization efforts, meaning Theravance will incur no commercial cost. Given the recent approval and that Viatris is still finalizing the commercialization plan, we will not be providing guidance on formal launch timing at this stage. We'll share additional updates in future calls as Viatris' plans continue to take shape. Looking ahead, market research continues to point to a sizable remaining addressable patient population in the U.S. Our aligned strategies with Viatris, promoting concomitant use with nebulized LABAs and converting appropriate handheld patients are gaining traction. Enhancements in fulfillment, adherence and persistency further reinforce YUPELRI's durable growth profile. With the prospect of a $25 million near-term U.S. sales milestone for achieving $250 million in calendar year net sales and patent protection into 2039, we believe YUPELRI is well positioned to deliver long-term sustainable value for Theravance and our shareholders. With that, I'll turn the call over to Aine to provide an update on the ampreloxetine development program. Aine?

Thanks, Rhonda. Let me begin with an update on the CYPRESS Phase III study. We are now very close to completing enrollment. With strong traction across our study sites over the last quarter, we are wrapping up screening activities and will close enrollment to the open-label portion of the study in the next couple of weeks. This milestone will mark a pivotal moment in our development program, and we are incredibly encouraged by the high-quality execution that has brought us here. As we approach the end of enrollment, we are energized by the momentum we have built and are optimistic about the potential of this trial to deliver a meaningful outcome for patients with multiple system atrophy or MSA. This optimism is rooted in 2 core strengths: firstly, the precision of ampreloxetine's mechanism of action; and secondly, how we have designed and are executing this study. Moving to Slide 9. I want to remind you why we believe this molecule is particularly well matched to the pathophysiology observed in patients with MSA who experience neurogenic orthostatic hypotension, or nOH. Generally, these patients with autonomic dysfunction have a distinct profile. While their central autonomic pathways are impaired, their peripheral neurons remain relatively intact. Ampreloxetine is a highly selective norepinephrine reuptake inhibitor designed to increase synaptic norepinephrine concentrations. By leveraging preserved peripheral sympathetic function, it is intended to enhance vasoconstriction, improve blood pressure and alleviate symptoms of nOH. This tailored mechanism has been supported in our previous trials. In the prespecified MSA subgroup analysis from our earlier REDWOOD study, also known as Study 170, patients on ampreloxetine demonstrated durable improvements in symptom burden and daily function. While those withdrawn to placebo experienced a clear loss of benefit, including a drop in standing blood pressure and worsening of symptoms. Importantly, ampreloxetine was not associated with worsening of supine hypertension, potentially a key differentiator versus existing therapies, thanks to its targeted and physiologically attuned mechanism. Moving now to Slide 10. CYPRESS was designed in collaboration with FDA to confirm the benefits observed in Study 170 in a larger population of patients with MSA. Like Study 170, CYPRESS uses a randomized withdrawal design and intentionally includes an enrichment strategy, allowing us to identify patients who show clear symptom benefit during the open-label phase and progress only those individuals to the critical randomized withdrawal phase. This gives us high confidence that we are measuring the drug's sustained efficacy in a population most likely to benefit and therefore, optimize our ability to detect worsening of symptoms when they are taken off ampreloxetine. We applied key learnings from Study 170 to refine the design of CYPRESS while ensuring consistency in enrollment and enrichment criteria in both studies. As a result, we believe we have optimized the probability of success for the CYPRESS study. We also remain focused on strong and high-quality execution. We partner closely with leading MSA centers of excellence and academic institutions known for their high-touch approach to care and best equipped to manage patients through our study. Our teams have maintained an unwavering focus on ensuring we enroll the right patients at the right sites. As with Study 170, we are utilizing an external enrollment committee comprised of the same clinical neurologists to review every patient enrolled. This continuity ensures consistent application of the enrollment criteria across both studies and provides an independent review of the diagnosis of MSA. Also, by managing this study directly, we are uniquely positioned to apply real-time operational oversight and foster high levels of engagement with our sites. Additionally, we have taken a proactive approach to educate our sites about patient retention strategies through the randomized withdrawal period and managing variability throughout the duration of the study. Looking ahead now on Slide 11. We are also executing on NDA readiness in parallel. With modules already in advanced stages of drafting, we are preparing for an expedited submission should the readout be positive. At filing, we intend to submit an application to support a full approval and also intend to request priority review to further accelerate potential approval and access. In summary, we believe CYPRESS is positioned well to deliver through its smart design, high-quality execution and a mechanism of action biologically tailored to MSA, we are advancing what we believe could be the first precision therapy in autonomic neurology for a community with high unmet need. I will now hand the call back over to Rhonda to discuss the commercial opportunity for ampreloxetine. Rhonda?

Both Rick and Aine have emphasized, we're approaching a pivotal moment for Theravance as we anticipate the upcoming CYPRESS results. From a commercial perspective, our excitement comes not only from the potential impact of the data, but also from the substantial market opportunity with prelaunch activities already underway. We believe there is a meaningful commercial opportunity for ampreloxetine to stand apart in the space with high unmet need. Today, no approved treatments offer both meaningful efficacy and durable benefit for nOH in patients with MSA. In fact, 65% of patients remain symptomatic despite currently available treatments such as midodrine and droxidopa, which are often limited by a short duration of action, frequent dosing requirements and box warnings for supine hypertension. Ampreloxetine is uniquely positioned to address these limitations, offering the potential for once-daily oral dosing, durable symptom relief and a well-tolerated safety profile as demonstrated in the REDWOOD study and now being further evaluated in the ongoing CYPRESS study. We estimate an addressable population of approximately 40,000 patients in the U.S. with a clear need for better options. In parallel with study completion, we're advancing key activities across stakeholder engagement, market access and launch readiness. With focused execution across key commercial and medical work streams, we are preparing to deliver a transformational therapy for this patient community. And with that, I'll turn the call over to Aziz to walk through the financials. Aziz?

Thanks, Rhonda. Starting on Slide 14, I'll begin with an update on our TRELEGY milestones. With GSK delivering another strong quarter, our outlook on achieving these milestones is stronger than ever. In Q2, GSK reported an all-time high of $1.1 billion in sales, exceeding consensus and bringing year-to-date sales to approximately $2 billion, an 8% increase year-over-year. This performance puts us firmly on track to exceed the $3.4 billion annual sales threshold in 2025, which would trigger a $50 million milestone payment. With the brand's annualized run rate now above $4 billion, we remain confident in achieving this milestone as well as the additional $100 million milestone in 2026 or $3.5 billion in annual sales is required. In total, that represents $150 million in high probability milestones over the next 18 months, further strengthening our financial profile. Turning to Slide 18 and our Q2 financial highlights, where we came in favorable to expectations. Collaboration revenue grew 31% year-over-year, driven by continued YUPELRI net sales growth, leading to improved brand level profit margins. Note that even excluding the onetime benefit to pricing that Rhonda mentioned, collaboration revenue would have been over $17 million, still favorable to consensus. We also recognized as part of license revenue, a onetime $7.5 million milestone following YUPELRI's regulatory approval in China. R&D and SG&A operating expenses were in line with expectations. R&D reflected near complete CYPRESS enrollment and NDA-related activities. SG&A increases were tied to ampreloxetine prelaunch commercial and medical affairs activities. Share-based comp decreased 16% year-over-year, reflecting continued cost discipline. Related to the TRELEGY royalty sale, we recognized $75 million of other income. Note that under our accounting guidelines, the total $225 million upfront was reduced by approximately $145 million, which was already recognized in prior periods. Non-GAAP losses improved to $4.2 million compared to $6.3 million in prior year, excluding onetime items. We ended the quarter with approximately $340 million in cash. Excluding large onetime items, cash burn for the quarter was approximately $3 million, highlighting strong cash management. Looking ahead, we expect to pay approximately $27 million in taxes related to the TRELEGY royalty sale in the second half of the year. These taxes were fully accrued in Q2 and will not impact the P&L going forward. On Slide 19, we are reaffirming all elements of our 2025 financial guidance. That said, excluding the impact of onetime milestones and taxes, in other words, focusing on recurring operations, we expect both non-GAAP losses and cash burn to improve in the second half compared to 2024. This reflects improvements in underlying business performance and continued cost discipline. To summarize, we delivered a strong quarter of financial results and now anticipate a stronger second half than previously expected, creating a solid financial foundation as we approach the upcoming CYPRESS data readout. With that, I'll turn it back to Rick to conclude. Rick?

Thanks, Aziz. In summary, Theravance enters the second half of the year with clear momentum approaching a transformational catalyst in the CYPRESS data readout. We're operating from a position of financial strength and executing at a high level across both our R&D and commercial organizations. YUPELRI continues its profitable growth. The sale of our remaining TRELEGY royalty interest significantly bolstered our financial position and with up to $175 million in potential milestones remaining between TRELEGY and YUPELRI, we continue to see substantial value ahead. Ampreloxetine remains our most important driver of potential upside, and we are now a couple of weeks away from completing enrollment in the open-label portion of the CYPRESS study. We are confident that CYPRESS is well positioned to confirm the meaningful benefit observed in the prespecified MSA subgroup of our prior REDWOOD study. This program has been executed with discipline, quality and conviction. And if successful, we believe ampreloxetine could redefine standard of care in this rare neurogenic condition where no proven therapies exist today for patients with nOH and MSA. In summary, Theravance is focused, well capitalized and advancing towards a pivotal inflection point with a profitable commercial business, a strong balance sheet and a late-stage rare disease neurology-focused development program that is nearing a critical milestone. We're excited and well positioned to drive meaningful value for patients and shareholders in the months ahead. With that, we'll open the line for questions. Operator?

[Operator Instructions] Our first question is going to come from the line of Douglas Tsao with H.C. Wainwright.

On the progress. I guess starting with YUPELRI, I guess, Rhonda, there were comments about sort of better pull-through this quarter. I'm just curious what you attribute that to? And then also on YUPELRI, I'm just curious, we've obviously made some progress in terms of sort of optimizing or improving the channel mix to improve pricing. I'm just curious, if you think about what sort of a realistic optimal channel mix, how far away are you from that? And how -- is it realistic to get there? And how long might that take to get?

Thanks for the question, Doug. On the first note of continuing to improve the pull-through, that certainly is related to that move of volume that continues to move over to specialty pharmacy. And with that, I would say why that continues to help the support of the pull-through is certainly driven by 2 aspects. One, the pricing in that channel, but more importantly, the persistency and the support patients receive. So not only is fulfillment improved, but also persistency is much greater when fulfillment occurs in that space. As far as how much more to move and how quickly, we still continue to believe it's very important to ensure patients and health care providers have whatever option they feel is best for their individual needs. So keeping that open network still remains a strategic focus. However, ensuring that there's proper education to help clinicians make the best decision based on the patient needs, that will be, first and foremost, the priority.

And Rhonda, I guess, in terms of the specialty pharmacy and that sort of persistence, is that just sort of the typical services that specialty pharmacies provide in terms of reminders on refills and so forth?

Yes. and dedicated outreach, dedicated personnel for follow-up. So as you can imagine, that certainly is far better served relative to conventional retail pharmacy.

Just to kind of finalize Rhonda's comments, which I also think that the transition of care work, hospital to home is also improving. And certainly, channel mix, specialty pharmacy facilitate some of that work as well as the ability for patients to choose what works best for them. So...

Our next question comes from the line of Julian Harrison with BTIG.

On all the recent progress. On YUPELRI in China, I'm curious if you could talk about the outlook for near-term growth. And can you remind us of the longer-term market opportunity there as well? And regarding CYPRESS, are you able to comment now on how U.S. versus ex U.S. enrollment has been trending? And when open- label enrollment is expected to be confirmed later this summer, should we expect any disclosure of baseline characteristics around that time? Or is that something being saved for top line disclosure?

Rhonda, do you want to take YUPELRI and then we'll come back to Aine on the CYPRESS questions from Julian.

Yes. Thanks, Julian. As I highlighted in the earlier commentary, with Viatris taking the lead and frankly, the ownership of the China market, we're going to leave the additional comments based on the market plan, the full launch plan itself to when they unveil that. So my comments are really limited at this stage.

Aine, Cyprus?

Julian, so to your first question in terms of ex U.S. versus U.S. split, we have many of the same sites that we've included in the previous 170 study. So overall, we expect the split and the profile to look very similar. And with regard to disclosure in advance of top line readout, obviously, the pivotal data is on the endpoint is at the end of that randomized withdrawal period. So our plan at the moment is to disclose all data at top line readout.

Julian we will issue a press release when we reach the full enrollment of the open-label portion of the study.

Our next question comes from the line of Debanjana Chatterjee with Jones.

On the quarter. I had a question regarding on how you would think about pricing ampreloxetine. I know we're still a little far from the top line data, but it would be helpful if you could share your thoughts on the pricing of the drug and if Northera and its usage, it's a good benchmark.

Rhonda, you want to take that?

Thank you for the question, and it's a very important one. To your point, it's still a little bit early to really reflect on a very narrow view on what the price will be. But I will say and harkening back to some commentary from our last opinion leader event for ampreloxetine. We did an analysis looking at rare neuro drug launches and across the average of the most recent 10 launches to try to gauge what an average price would be, and that was roughly $380,000 per year. So that can give you a sense of what is occurring in the rare disease space. As a reference to droxidopa and looking at their higher strength costs on an annual basis, that is roughly $280,000 a year. So hopefully, that can help you appreciate some of the dynamics that will be taken into consideration for our pricing work that will occur once we have data from the CYPRESS study.

That's very helpful. And I had a quick follow-up. On the U.S. or ex U.S. dynamics, in terms of reimbursement and payer perspective, are there any differences between U.S. and ex U.S.? And do you expect any pushback given there are generics out there, although less effective and with clear side effects?

Rhonda, do you want to take that?

Sure. I'll comment more so on -- there are vast differences and to really even say U.S. versus ex U.S., I think that's even too broad. So I'll focus on U.S. given that's where our launch focus is. We are already actively engaging payers, and I think it's very important to ensure they appreciate the value of being educated about the disease itself as well as the very high unmet need, and they've reacted very enthusiastically to wanting to learn about this important underserved patient population. What's important to them is appreciating the data once we have the data and really what the durability will be offered for these patients given that is an unmet need currently with existing therapies as well as the safety profile, which will be critically important.

And the other point I would add to Rhonda's points are simply the endpoint that we're using here, which is the OHSA composite score, which is an overall endpoint containing a number of different symptoms on the overall well-being of patients. And I think this is quite important for describing the impact that the product has on the overall life -- quality of life of the patient and the patient's ability to interact and quite honestly, live a life that's not restricted or as restricted by bad time and bed. So we're very excited by the early perspectives of payers. And then also, it's important to underscore the endpoint here being the OHSA composite score as being very distinct from something like dizziness alone.

Our next question comes from the line of Ellen Horste with TD Cowen.

Congrats on the quarter. I'm wondering if you can speak to the pace of SG&A increases that you expect would be associated with ampreloxetine sales build-out between both now and the data and then how that might change on the back end of the data if the data is positive.

Yes, sure. I can take it. So I think if you're talking about this year, if you look into the second half relative to Q1 and Q2, I don't expect the SG&A number to increase at all. It should be pretty stable versus at least Q2 and even Q1. So we have been spending a little bit on prelaunch commercial and medical affairs related activities, as Rhonda was previously describing. Not a whole lot, but a little bit. We expect that to be kind of stable throughout the year. So you will not see a meaningful increase in SG&A between now and the CYPRESS data readout. We are maintaining as much conservatism as possible while still pushing as much value into the brand as possible prior to the data readout. So stable through now until the data readout. Post data readout, we're still working through what that would look like. Obviously, we don't provide guidance until next year. So you'll have to stay tuned in terms of the exact numbers. But obviously, if positive, there's going to be a big value inflection point, and we will be increasing SG&A spend through next year into launch. In terms of magnitude, as Rhonda and Rick have mentioned previously, we are still -- we are looking at a targeted launch. So you're not talking about huge levels of incremental spend, but there will be incremental spend as part of the launch preparation.

Just to add to what Aziz has provided a nice summary as to where we are. I think it is very important to understand with 40,000 patients with MSA and nOH and the targeting that this really permits us to do of understanding where those patients are and what we need to do in the advent of a CYPRESS -- good CYPRESS data and approval to support the offices that treat and the physicians that treat these patients. And I think all the data that we have will allow us to be extremely focused on the SG&A spend with regard to the marketing of ampreloxetine.

Our next question comes from the line of David Risinger with Leerink Partners.

I have a few questions, please. And congrats on the very strong financial performance. So with respect to the Viatris collaboration, so the revenue grew 31% on a 22% YUPELRI net sales increase. Should we expect continued operating leverage in coming quarters with collaboration revenue growing higher than YUPELRI sales? So that's the first question. And then with respect to ampreloxetine, I believe the Phase III trial's primary endpoint is a longer duration primary endpoint than previously studied. If you could just talk about that and whether you think that will -- or how that may impact the results versus results that have been previously reported. Meaning, as patients stay on drug longer, do they have any tachyphylaxis? Do they -- might they improve more over an extended -- a more extended period of time? Any perspective would be helpful.

Aziz, do you want to take on the operating leverage question of YUPELRI and then we'll go to Aine for the ampreloxetine analysis.

Yes. Thanks, David, for the question. And good observation. Obviously, the collaboration revenue growth was a good amount higher than the net sales growth, 31% versus 22%. As you probably know, the difference between the collaboration revenue and simply 35% of the profit is the netting of the reimbursement between the 2 companies related to the cost. So -- but going forward, I don't expect it to kind of continue to be that significant of a gap between the collaboration revenue and the net sales growth because I think that the costs are going to be relatively stable. The costs just do sometimes bounce around quarter- to-quarter. So it just so happened this quarter was a little bit lighter. But I don't expect there to be a meaningful gap going forward between the collaboration revenue growth and the net sales growth.

David, we are able to get some leverage, as you point out on the P&L from the nature of our work and efficiency. But I think continued increases in leverage, as Aziz pointed out, is one probably shouldn't expect that. So, ampreloxetine, Aine?

Rick, just on the YUPELRI comment, what I was describing was just the difference in growth rate between the collaboration revenue and the sales. If you're talking about a profitability perspective, we do expect increased profit margin as the net sales growth because as the costs stay flat, but the net sales increase, the margin continues to expand. So from a profit margin perspective, we do -- I do expect continued increases to the profit margin as the net sales increase. Go ahead, Rick.

Aine, CYPRESS?

So, David, thanks for the question. So you're correct in terms of the primary endpoint in CYPRESS is the OHSA composite score. And durability of effect is really central to the design of CYPRESS. And what we've seen previously in 170 was a durable benefit, which is very different to what others have seen in this space in terms of benefit. So other approved drugs have not shown benefit beyond 2 weeks. So we really hope that durability is going to be a key differentiator for us. And in the CYPRESS study, what we hope to see in the randomized withdrawal and the randomized withdrawal for CYPRESS is 8 weeks long. is for the patients that stay on ampreloxetine that we continue to see stability in the benefit that we've seen over the open- label period and those then taken off ampreloxetine would worsen during that 8-week period. So that's our expectations and rightly durability being the central theme to that randomized withdrawal design.

And then, David, on your comment on tachyphylaxis, it's important to understand, as Aine sort of pointed out in terms of mechanism, ampreloxetine is a reuptake inhibitor. So we're blocking the reuptake of norepinephrine. It isn't an agonist per se. So we're not adding additional norepinephrine from an exogenous perspective into the system. We're just blocking the naturally occurring norepinephrine that occurs in the synapse. We're keeping it there longer so that, in fact, enables the exertion enables an increase in blood pressure that is measured overall by the individual symptom score of the OHSA composite.

It appears we have no further questions. I would now like to hand the conference back to Mr. Winningham. Please go ahead, sir.

Yes. Operator, thank you very much, and I'd like to thank everyone for joining us today. As we reported our second quarter results. We're obviously very excited about the performance in the second quarter, and we're very excited about what the future brings for Theravance across our portfolio. So thank you very much, and we look forward to bringing you further updates as the year progresses.

This concludes today's conference call. We thank you for participating. You may now disconnect.