Theravance Biopharma Inc (TBPH) 2025 Q3 法說會逐字稿

Ladies and gentlemen, good afternoon. I'd like to welcome everyone to the Theravance Biopharma third quarter 2025 conference call. (Operator Instructions)

Also, today's conference call is being recorded. And now I'd like to turn the call over to Rick Winningham, Chief Executive Officer. Please go ahead, sir.

Good afternoon, and welcome to Theravance Biopharma's third 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 forward-looking 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.

Turning to slide 4. Theravance delivered strong results in the third quarter, reflecting continued execution across the business and notable progress toward our strategic objectives.

We achieved several key accomplishments, including solid YUPELRI net sales growth and record brand profitability, leading to the achievement of non-GAAP breakeven, underscoring the strength of our business model and commitment to financial discipline.

In parallel, we continue to advance the pivotal Phase III CYPRESS trial of ampreloxetine towards a data readout in early 2026, a milestone we believe could represent a material value inflection point for the company.

Starting with our commercial business, YUPELRI. Our durable cash-generating asset continues to deliver strong results. Net sales and importantly, profitability for the quarter reached all-time highs, driven by continued demand growth and favorable net pricing.

This performance puts YUPELRI year-to-date sales on track to trigger a $25 million milestone from Viatris. With ampreloxetine, we are excited as we approach a critical moment for Theravance. We remain on track to deliver top line results from the pivotal Phase III CYPRESS study in the first quarter of 2026.

We believe this readout has the potential to be transformational for both patients and the company as we hope ampreloxetine will become the first precision therapy for symptomatic neurogenic orthostatic hypotension in patients with multiple system atrophy, a rare debilitating disease.

In preparation for the data, we will host a KOL event for investors on December 8 to highlight the significant unmet medical need of these patients and how ampreloxetine aims to address it.

We ended the quarter with approximately $333 million in cash and no debt. And importantly, we remain on track to achieve near-term milestones totaling $75 million in the fourth quarter, $50 million for TRELEGY and $25 million for YUPELRI.

In addition, the strong growth demand trends -- strong growth trends for TRELEGY bode well for the achievement of the $100 million milestone in 2026.

Lastly, in October, we launched a new disease education campaign for health care professionals to raise awareness and deepen scientific understanding of nOH associated with MSA. This initiative reflects our continued commitment to the MSA community and to advancing education on the complex mechanisms underlying nOH and MSA.

Theravance today stands on a foundation of financial strength with significant upside opportunity, anchored by a robust balance sheet, continued cash generation from YUPELRI and highly probable near-term milestone payments.

We entered the final quarter of 2025 with confidence and growing excitement for the rapidly approaching transformational potential of the CYPRESS data readout.

With that, I'll turn the call over to Rhonda to provide additional detail on YUPELRI's performance. Rhonda?

Thanks, Rick. If you turn to slide 6, you'll see that the Theravance Viatris commercial partnership delivered a record quarter for YUPELRI. Third quarter net sales increased 15% year-over-year to $71.4 million. This was driven by two main factors. First, strong demand growth, up 6% year-over-year versus Q3 of 2024; and second, continued net price improvement due to a more favorable channel mix, which is the result of close collaboration with our partners at Viatris as exemplified by effective field sales execution with a focus on fulfillment optimization efforts.

Importantly, following these results, only $54 million of net sales are required in the fourth quarter for us to achieve the $250 million calendar-year sales threshold, required to trigger a $25 million milestone payment from Viatris.

Turning to slide 7. In addition to our solid net sales growth, YUPELRI continued to experience expanding profit margins, reaching record levels and positive momentum across both hospital and community outpatient channels.

The hospital channel continues to be a key driver of prescribing with hospital volume increasing 29% versus Q3 of 2024, illustrating our team's sustained success in securing formulary wins and implementing therapeutic interchange protocols.

This quarter, YUPELRI share in the long-acting nebulized hospital market reached a new launch to date high of approximately 21%.

Moving forward, our goal is to continue to secure institutional access and further expand the hospital channel as a foundational component of our brand strategy, functioning as a critical entry point for transitioning patients to community outpatient maintenance therapy.

Beyond the encouraging growth trends in Q3 with net sales demand and hospital volume, YUPELRI is positioned for continued expansion with a sizable addressable population remaining in the US.

Our aligned strategies with Viatris continue to deliver strong results, specifically the adoption of concomitant use with LABA therapies and switches from handheld-only regimens as well as further diversification of product fulfillment.

We were also excited to share two analyses presented at the recent 2025 CHEST meeting. First, we presented new post-hoc analyses from a Phase III safety study showing that patients treated with YUPELRI experienced a lower incidence and severity of moderate to severe exacerbations compared to those taking tiotropium.

The second presentation was a new retrospective cohort study of claims data, which demonstrated that following hospital discharge, patients adherent to YUPELRI, experienced significantly fewer and less severe exacerbations and lower health system costs than nonadherent patients.

These findings reinforce YUPELRI's differentiated clinical profile and highlight its potential to improve both clinical and economic outcomes for appropriate COPD patients, further reinforcing the scientific foundation of YUPELRI.

In summary, YUPELRI's profit margin continues to expand, supported by disciplined execution and patent protection in the US into 2039. As a result, we are confident that YUPELRI will continue to deliver long-term sustainable value for Theravance and its shareholders.

With that, I'll turn the call over to Aine to provide an update on the ampreloxetine development program. Aine?

Thanks, Rhonda. Turning to slide 9. Before providing an update on the CYPRESS study, I'd like to highlight some recent ampreloxetine publications and presentations.

First, we submitted a manuscript detailing the results of the prior Phase III REDWOOD study in the MSA subgroup, where ampreloxetine demonstrated durable improvement in symptoms of nOH. I will take the opportunity to provide a quick recap of this data shortly as it reinforces our confidence in ampreloxetine's mechanism of action and its potential to deliver meaningful benefit to patients with MSA, a community that remains underserved by current treatment options.

A preprint version of this manuscript has been posted online to medRxiv. Second, a publication establishing the minimally clinically important difference for the orthostatic hypotension questionnaire was published in a peer-reviewed journal, Clinical Autonomic Research, an important tool to support interpretation of clinical benefit as we head into the Phase III CYPRESS readout.

Additionally, we had a strong presence at the recent International Symposium of Autonomic Nervous System organized by the American Autonomic Society or AAS, where we had one platform presentation and three posters.

The platform presentation highlighted the results from the prior Phase III REDWOOD study in the MSA subgroup analysis, along with a poster reviewing the impact of ampreloxetine on supine hypertension in the Phase III SEQUOIA study, which showed no worsening of supine hypertension, an important potential differentiator for the product.

The two other poster presentations detail the rigorous recruitment and retention methodologies used to address challenges in conducting a trial in rare disease with severely [ill] patients.

By applying these insights to the CYPRESS study, we were well positioned to successfully address the executional challenges associated with clinical studies in rare and severe neurodegenerative diseases. As I mentioned earlier, I'd like to recap the results from the subgroup analysis of patients with MSA from the REDWOOD study shown here on slide 10.

The top graph shows the standing systolic blood pressure throughout the REDWOOD trial, where a pressure effect was observed in the open-label phase of the trial with blood pressure at three minutes of standing increasing compared to baseline.

At the end of the randomized withdrawal compared to the open label, blood pressure at three minutes of standing dropped in the group withdrawn to placebo while remaining stable in patients that stayed on ampreloxetine.

This increase in standing blood pressure observed with ampreloxetine translated to a meaningful impact on patient symptoms and daily activities.

However, the benefit seen in symptoms and short-term daily living activities shown in the two bottom graphs were only maintained in patients who remained on ampreloxetine in the randomized withdrawal portion, but worsened in those withdrawn to placebo.

Moving to slide 11. We continue to make strong progress towards our pivotal Phase III CYPRESS readout. At this stage, the open-label portion of the study is now complete and a small subset of patients are now completing the randomized withdrawal portion, an important step towards completion of the trial.

The team continues to demonstrate excellent operational execution, and we are highly encouraged by the level of engagement across our study sites and the broader MSA community.

We remain on track to deliver top line results in the first quarter of 2026, and we view this as a significant milestone for Theravance as we advance our efforts to bring ampreloxetine to patients with MSA-related nOH.

We've also made substantial progress on NDA preparation, particularly across the nonclinical, CMC and clinical pharmacology components of the application.

Much of this work has already been completed, positioning us to incorporate the CYPRESS data quickly once available and move efficiently towards an expedited NDA submission should the results be positive. We also intend to request priority review if the data are supportive.

Lastly, in preparation for the upcoming readout, we will host a virtual KOL event for investors on December 8, which will feature Dr. Horacio Kaufmann, Professor and Director of the Dysautonomia Center at NYU, one of the world's leading experts in autonomic disorders.

During this event, Dr. Kaufmann will provide an overview of the unmet need for patients with MSA-related nOH and will highlight why we believe ampreloxetine is uniquely positioned to address this rare and debilitating condition.

In addition, we will review the ongoing CYPRESS study and outline the commercial opportunity for ampreloxetine as a potential new treatment option. We are excited and well prepared as we approach the CYPRESS data readout in the first quarter of 2026.

With that, I'll turn the call over to Aziz to walk you through the financials. Aziz?

Thanks, Aine. Turning to slide 13, I'll start with an update on our TRELEGY milestones. GSK reported $1 billion in sales for the quarter, ahead of consensus and $2.9 billion year-to-date. Given the $3.4 billion threshold required to trigger the $50 million milestone in 2025, we need only $470 million in Q4 sales to hit this milestone, which is roughly 50% below the current run rate.

Looking ahead, the $100 million milestone in 2026 is also well within reach with a $3.5 billion sales requirement, a level that both current run rate and consensus comfortably exceed.

With TRELEGY continuing to post strong above-expectation performance, we have clear visibility into achieving these milestones, which together represent $150 million in expected cash inflow over the next 15 months, further strengthening our financial position.

Turning to slide 17, I'll summarize our Q3 financial performance, where we delivered another strong quarter. Collaboration revenue increased to $20 million, up 19% year-over-year, reflecting YUPELRI's strong operating leverage, which drove record brand level profitability.

Operating expenses, excluding share-based comp, were $22 million as R&D costs began to decline following completion of CYPRESS enrollment while we progress towards data readout in the first quarter of next year.

Share-based comp decreased 8% year-over-year, reflecting continued cost discipline. Our GAAP net income was positive in the quarter, aided by a nonrecurring benefit due to a favorable true-up related to taxes from the TRELEGY royalty sale in Q2.

However, driven by YUPELRI's profit contribution and continued expense discipline, we also achieved non-GAAP profit breakeven in the quarter. Given that this metric excludes onetime items such as the income tax benefit, it more accurately reflects the underlying performance of our operations. We ended the quarter with $333 million of cash and no debt.

Lastly, turning to slide 18, I'll cover our 2025 financial guidance. First, we are reiterating all expense guidance ranges. Second, given that we achieved breakeven on a non-GAAP basis in Q3, again, excluding onetime items, we now expect results to remain broadly consistent in Q4, though there can always be normal quarterly variability. This guidance reflects our continued focus on operating leverage and cost discipline.

Importantly, this outlook excludes the $75 million of milestones expected to be earned in Q4, $25 million for YUPELRI, which will be recognized as revenue and $50 million for TRELEGY, which will be recognized as other income, not revenue.

Note that while we expect these milestones will be earned in Q4, we will receive the cash in Q1 of 2026. In summary, Q3 was another step forward for Theravance. We delivered record YUPELRI performance, achieved breakeven on a non-GAAP basis and further strengthened our balance sheet, setting the stage for a potentially transformational 2026 with continued financial discipline and a clear focus on value creation.

With that, I'll turn it back to Rick to conclude. Rick?

Thanks, Aziz. To summarize on slide 19, Theravance enters the final stretch of 2025 with strong momentum, driven by a profitable commercial business, a robust balance sheet and clear visibility into near-term milestones that will further strengthen our financial profile.

YUPELRI continues to be a key driver of that performance with sustained growth and increased profitability, highlighting the durability and long-term value of the franchise. We remain confident in the execution of the CYPRESS study and in ampreloxetine's potential to become the first precision therapy for patients with MSA who suffer from nOH.

With CYPRESS results expected in the first quarter of 2026, we are now approaching a significant moment for the company. This readout represents a transformational catalyst with meaningful upside potential while our profitable YUPELRI franchise and strong financial position provides downside protection, creating a compelling risk, reward profile as we approach the data.

As we move into 2026, we do so with focus, financial strength and confidence in the opportunities ahead. And with that, we'll open the line for questions. Operator?

(Operator Instructions)

Douglas Tsao from H.C. Wainwright.

Hi, good afternoon. Thanks for taking the question. I guess, Rick, just given sort of the continued outperformance we've seen in TRELEGY and the likelihood of some additional cash coming in, how are you thinking about, right now, you've talked about the special committee being committed to returning capital to shareholders. But how much do you potentially need to sort of keep in-house for the potential launch of ampreloxetine.

Good question, Doug. I think the -- obviously, the financial strength of the company is one of its key elements of value. We continue to view the cash on the balance sheet and the strategic review committee looks at the timing and the optimum amount of returning capital.

And if we do return capital again, how much and when. The -- obviously, ampreloxetine's launch will be a fairly efficient launch in a rare disease, not creating a substantial burden on the P&L, but nonetheless triggering up expenses.

I think for the company and the Board, what we're focused on right now because we are so close is, in fact, the execution of the CYPRESS study through the top line results and getting those top line results and then making future decisions for the company on capital and capital return, et cetera, because of the -- as was stressed in this call, the very important nature of that data.

But importantly, we're in a position of financial strength, giving us terrific opportunities going forward to return capital to shareholders if that's what the Board desires to do.

And I guess as a follow-up, when we think about the company over the last several years, you've obviously sort of narrowed your focus. Obviously, we're sort of almost sort of dual goals of maximizing the opportunity with YUPELRI as well as executing on the ampreloxetine study.

I guess when we think about the company over the long term, are there pipeline assets? I mean there were several assets, which I think some people were interesting, but sort of were put on pause.

And I guess, is that ever sort of come back into the equation, just given you noted the sort of operational or sort of the efficiency in launching ampreloxetine, and that could just bring significant capital into the company and sort of change your position?

I think that's -- again, kind of go back to my central theme, and I think the central theme for the management and the Board, which is the focus on CYPRESS and the focus on ampreloxetine clinical success that sets up a successful launch of the product.

At that point in time, once we get post ampreloxetine and post success, we'll evaluate options. I think we not only need ampreloxetine success clinically, but a pathway, which we believe we have as long as we hit a clinically meaningful result in the CYPRESS study to approval. And I think as we're going through that, we'll obviously look at the options and the alternatives to maximize shareholder value.

But again, I'd say, right now, given the relatively small organization that we've got, 110% of our focus, as you rightly point out, is on growing YUPELRI, growing YUPELRI in an effective way to drive additional profitability and finishing ampreloxetine clinical study and setting it up for commercial success.

I think once we achieve those objectives, then we have time or intellectual space to work on other things that may increase -- increase shareholder value because I do believe you're right in that ampreloxetine being a rare -- targeting a rare disease, it has the opportunity for a significant value inflection for the company.

Okay, great, thank you.

Julian Harrison, BTIG.

Hi, Congrats on the quarter. First, I'm curious to what extent that recently published manuscript detailing the MCID for the OHSA composite score informs your expectations for top line CYPRESS data first quarter of next year.

Any other comments on what you think a win on data would be, would be helpful as well. And then the YUPELRI data, CHEST looked fantastic. Thinking about that, I'm wondering if you could talk more about how these results are supportive of YUPELRI new patient starts at the hospital call point.

Hey Rhonda, do you want to take the CHEST presentations, and we'll come back to Aine and myself for ampreloxetine.

Absolutely. Thanks, Julian, for the question, and thanks for recognizing the data that were recently presented. Certainly, having data of this nature relative to both highlighting clinical outcome, which is quite meaningful as well as reduction in health care and health system costs are crucial knowledge points for the brand.

I would say the team is first focused on ensuring we get those new data into manuscript form, and then we'll be able to think about other communications and educational efforts around these data. They certainly help further substantiate what is already an element of how and why we sell into the hospital space.

So they are very nicely kind of putting a bow on top of the package we already use promotionally. So we'll see in the future if these are used in kind of more expanded fashion, if that makes sense.

So that's the exacerbation data, yeah, very important. And again, versus tiotropium to add to really the medical education efforts that we've got ongoing with YUPELRI in both the community and the hospital.

And on ampreloxetine, the minimally clinically important difference. And yes, this publication is important to us because effectively, a 1-point difference for us is -- will be in the -- composite score will be this kind of the minimally important difference that we need to see in CYPRESS. We obviously saw that in 170, and Aine can touch on the steps we've taken to make sure 170 is replicated by CYPRESS. So Aine?

Yeah. So thanks, Julian. I would encourage you to take a look at the publication. It is available online. There's open access to the article. The article was based on the data that we have previously seen in 170 and 169, looking at changes in the OHSA questionnaire, which is central obviously also to the CYPRESS study.

And really, it was based on an anchoring analysis between changes on the scale to how patients actually felt using other scales that we've included in the study, PGIC and PGIS. We've proactively built this analysis into the CYPRESS study.

And from what we have seen in our previous analysis, and you'll see in this publication, as Rick said, 1 point change on the scale is considered clinically meaningful. And our objective with the CYPRESS study is obviously to replicate the previous benefit that we had seen in the 170 study, where we did see that level of change and believe that's clinically significant.

And obviously, this information is important to the overall outcome of the study and will be part of the regulatory submission. We've also had FDA review our analysis plan around the study and this anchoring analysis and feel like we're in a really good position as we move into the CYPRESS readout in the first quarter of next year.

Very helpful. Thank you.

Ellen Horste, TD Cowen.

Hi guys. Thanks for taking the question, and congrats on the exciting quarter and the progress in the CYPRESS study. My question is about CYPRESS. So with the open-label portion complete, can you share how many patients have ultimately enrolled in the randomized withdrawal portion?

And if not, can you confirm that this number is sufficient for the powering according to the original trial design? Thank you.

So as I said in my remarks, we're really encouraged with how the study has progressed and where we've landed in terms of overall enrollment numbers.

While we're not sharing specific enrollment numbers today, I will say that we remain very confident in the operational execution and pleased with where we have landed in terms of accrual, but most importantly, also progression to the randomized withdrawal portion of the study.

We do believe that we have randomized a sufficient number of patients for us to be able to detect a treatment difference between the two arms. Just as a reminder, the study design and the analysis plan for the CYPRESS study has been aligned with FDA, and we believe that we have an adequately powered study and we'll be disclosing all the specific numbers in the context of our data readout, which is coming really soon, and we are excited about what's to come in quarter one, 2026.

And then, Ellen, just the schematics that we've outlined as part of our ongoing investor presentation on the study remains accurate relative to what we needed to achieve and what we are achieving with the study design and execution.

Thank you.

Operator, do we have any further questions? It appears that we do not have any further questions coming in from the operator. So I will just take this opportunity to thank you for joining on our call -- third quarter call. We're very pleased with the results this year to date. We look forward to a very good fourth quarter and then the exciting first quarter in 2026 headlined by the CYPRESS data.

So thank you again very much for joining, and please have a good day.