Theravance Biopharma Inc

NASDAQ:TBPH

Earnings Call Transcript 2023-Q1

[Operator]

Ladies and gentlemen, good afternoon. I’d like to welcome everyone to the Theravance Biopharma First Quarter 2023 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.

[Rick Winningham, Chief Executive Officer]

Good afternoon. And thank you for joining the Theravance Biopharma first quarter 2023 earnings conference call.

On Slide 2 I’d like to remind you to 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.

Turning your attention to Slide 3, I’m joined today by Rhonda Farnum, Chief Business Officer; Rick Graham, Senior Vice President of Research and Development; and Aziz Sawaf, Chief Financial Officer.

On Slide 4, I’d like to begin my presentation by focusing your attention on Theravance’s immediate future. Those of you who are familiar with the company recognize the tremendous work that our team and partners have done to bring the organization to this point. Through a combination of perseverance and resilience, we’re down a position to focus our energies behind two key initiatives, capitalizing on the tremendous opportunity we have to grow YUPELRI and executing on an unambiguous regulatory pathway for ampreloxetine in multiple systems atrophy patients with symptomatic NOH. These are reflected in the 2023 targets we outlined in our last quarterly call and I am pleased to share with you the progress that we’ve achieved today.

On Slide 5, beginning with YUPELRI, our team in collaboration with Viatris, turned in a solid quarter with sales up 8% year-over-year. As we previously discussed, there are many COPD patients not well controlled on their existing therapy, a good benefit from either the addition of or switching to YUPELRI. We bring a coordinated approach to reducing the barriers that prevent patients from receiving YUPELRI and or working diligently to translate this into tangible results. Importantly, we know our hospital customers comprehensively and we meet them with solutions that fit their individual needs.

This quarter, we were successful at driving growth in both the hospital and the community settings with hospital volumes up 62% and retail patient news starts up 61% year-over-year. We reached new highs in market share in both the hospital and community settings. Rhonda will go into greater detail regarding YUPELRI’s performance and new growth opportunities later in the presentation.

However, I’d remind listeners that YUPELRI demand currently doesn’t reflect any upside that we may enjoy should our PIFR-2 study be successful. Rick Graham will provide an update on PIFR-2 later in the presentation.

On Slide 6, while we’re excited about YUPELRI’s continued performance, we’re just as excited for the potential of ampreloxetine’s success in CYPRESS. We worked extremely hard to optimize a Phase 3 design in consultation with the FDA and believe the results from this study could support a full approval for MSA patients suffering from symptomatic NOH. We are pleased with the progress we’ve made having now opened the study and plan to continue to add a number of important recruitment sites in the coming weeks. We’ve also submitted a request for an orphan drug designation and expect to hear back from the FDA sometime this quarter.

As Rick Graham will discuss, ampreloxetine has the potential to offer significant efficacy, safety, and dosing advantages over existing therapies and could represent a life-changing therapy for MSA patients with symptomatic NOH. We project that enrollment in CYPRESS will be complete by the second half of 2024 and look forward to providing additional guidance around regulatory milestones and commercial plans as we move forward.

Now, turning to Slide 7, I’d like to offer a brief update on our capital allocation strategy and financial condition. Year-to-date and through the end of April, we’ve returned approximately $215 million to shareholders through our share repurchase program. We remain on track to return the $110 million that remains outstanding by the end of the year. Importantly, we are doing this from a position of financial strength. We have positioned ourselves by reducing our expense base and remain on track to reach non-GAAP profitability on an ongoing basis sometime in the second half of the year.

Finally, I’d like to publicly welcome Jim Kelly of Weiss Asset Management to our board and express my enthusiasm for the contributions that we expect from Jim, Susannah Gray and our other board members that continue to make. Jim brings a unique skillset and shareholder perspective to the board as well as remarkable energy.

With that, I will now hand the call over to Rhonda to review YUPELRI’s first quarter 2023 performance and the opportunities we see to deliver robust growth for the remainder of the year and beyond. Rhonda?

[Rhonda Farnum, Chief Business Officer]

Thanks Rick. Moving to Slide 9, we are pleased to share the latest performance for YUPELRI. During the quarter, total net sales of YUPELRI reached $47 million, up 8% year-over-year. Theravance has implied 35% share of net sales for YUPELRI during the first quarter of 2023 was $16.4 million. As a reminder, Theravance and Viatris co-promote YUPELRI in the United States. Theravance’s commercial and medical teams covering the hospital segment and Viatris is responsible for outpatient based community healthcare needs and promotion for the product.

This quarter, as we expected and previously communicated, seasonal factors impacted reported YUPELRI net sales. Changes in ordering patterns, which are typical of the pharmaceutical business and often more pronounced during the first quarter, had a larger than normal effect this period. However, we remain confident that our team will deliver strong YUPELRI performance for the year based on a number of positive key performance indicators. To this end commercial – I’m sorry, customer demand once again, increased quarter-over-quarter and as well I will show later in the presentation, patient fulfillment continues to reach new highs.

As Rick mentioned in his opening comments we have formulated a winning strategy for driving YUPELRI growth in the hospital setting. We focus our efforts in a number of areas including formulary wins, clinical pathways, and discharge planning protocols, all with a goal of making YUPELRI available to COPD patients who may benefit from the only once a day long-acting nebulized LAMA.

Looking at Theravance’s hospital results on the right side of Slide 9, [indiscernible] doses sold exclusively in the hospital setting, represented an increase of 15% from the previous quarter and 62% compared to the same period a year ago, therein reaching the highest quarterly total launch to date. We have driven significant growth in the YUPELRI’s hospital business every quarter since the third quarter of 2020, the point at which our team was able to reengage more fully following the initial impact of COVID.

Launch to date, Theravance has secured 616 hospital formulary wins leading to approximately 1,350 hospital outlets purchasing YUPELRI. By comparison, we reported 580 formulary wins and approximately 1200 purchasing hospital outlets at the end of 2022.

Turning to Slide 10, YUPELRI’s share of the long-acting nebulized market in the hospital setting once again reached a new record high of 15% in Q1 of 2023. We believe these account wins and forthcoming system additions will yield continued growth through 2023 as YUPELRI will be the first LAMA of choice in many hospitals due to the growing recognition and acceptance of YUPELRI’s, clinical benefits, and once-daily value proposition.

As a key component of the joint strategy between the Theravance and Viatris teams’ data continue to show that approximately 90% of patients receiving YUPELRI in the hospital setting are discharged with a prescription to continue their treatment in the outpatient setting, allowing for continuity of YUPELRI maintenance therapy post-hospitalization. Reflecting further on the outpatient care setting, YUPELRI’s market share in the overall community setting increased to 27.7% through January of 2023, which is our latest data point.

We have also been encouraged by the growth trends seen specifically in the retail channel as Q1 total prescriptions grew quarter-over-quarter, while historically script volumes have decreased in the first quarter due to seasonal factors.

On Slide 11, we provide a snapshot of YUPELRI retail new patient starts, which during the first quarter increased a robust 61% year-over-year and 23% quarter-over-quarter. New patient starts are key to future performance and the recent exceptional growth can be attributed to the realization of new commercial initiatives, which includes concomitant use education, expansion into additional site of care channels and additional focus on fulfillment support.

Looking beyond this quarter's success, there still exists significant long-term growth opportunities for YUPELRI. Starting with the current long-acting nebulized patient population, we expect our market share to continue to grow both from switches as well as an add-on therapy with further deployment of concomitant use education. There are also many patients inappropriately using short-acting nebulized treatments for maintenance who may benefit from switching to a once-a-day long-acting therapy such as YUPELRI.

Lastly, there are even more patients on handheld maintenance regimens that remain uncontrolled due to a number of reasons, including dexterity challenges, cognitive impairment and/or low peak inspiratory flow. In total, these patients segments represent a sizable niche opportunity for YUPELRI and we've only started to scratch the surface. Given this significant remaining opportunity, we expect to be able to continue, if not accelerate the pace of YUPELRI’s adoption moving forward. One of the ways in which we plan to do so is by making available and communicating data from our Phase 4 PIFR-2 study results of which we expect later this year.

With that, I will turn the presentation over to Rick Graham. Rick.

[Rick Graham]

Thanks Rhonda. In my section today, I'll be discussing the YUPELRI PIFR-2 study at a high level and we'll spend most of the time discussing the underappreciated opportunity of ampreloxetine in development for the treatment of MSA patients with symptomatic nOH. Slide 13 serves as a reminder that we conducted a prior clinical trial called PIFR-1 that served to inform the design for the ongoing PIFR-2 trial.

The left hand figure shows the results of the intent-to-treat population in PIFR-1. PIFR-1 included GOLD 2, 3, and 4 patients with a PIFR value of less than 60 liters per minute at inclusion, the left axis is least squares mean change from baseline and FEV1 at day 30. While the results demonstrated a larger change from baseline for revefenacin relative to tiotropium, this effect was not statistically significant.

Importantly, a pre-specified analysis of GOLD 3 and 4 patients shown on the right hand figure demonstrated a clear 50 milliliter and clinically relevant treatment benefit of revefenacin over tiotropium. In addition to providing confidence on the probability of technical success, the results of PIFR-1 inform the design of the PIFR-2 study.

Turning to Slide 14, the Phase 4 PIFR-2 study continues to actively enroll patients and will potentially provide even further competitive upside for YUPELRI. We continue to guide toward top line results in the second half of 2023. Transitioning to ampreloxetine, a norepinephrine reuptake inhibitor being developed for the treatment of symptomatic nOH in patients with MSA. In MSA, patients with nOH, blood pressure falls when upright owing to impaired release of norepinephrine leading to debilitating symptoms which can have a profound impact on quality of life.

Moving to Slide 16, we are pleased to announce that the Phase 3 study CYPRESS is open and actively recruiting patients. We are projecting that enrollment will be completed in the second half of 2024.

Slide 17 illustrates how we believe ampreloxetine works on a cellular tissue and patient level. The top left panel shows the untreated state where the norepinephrine reuptake transporter reduces endogenous norepinephrine levels. In the middle panel, low norepinephrine causes blood vessels to dilate leading to a decrease in blood pressure. This condition can result in syncope when a patient stands up as depicted in the far right panel.

In contrast, the bottom panel shows the effect of ampreloxetine by inhibiting the norepinephrine reuptake transporter, ampreloxetine increases norepinephrine levels leading to vasoconstriction and an increase in blood pressure. This ultimately leads to better organ perfusion and relief of symptoms for patients.

As shown on Slide 18, we believe that effective treatment with ampreloxetine requires intact peripheral nerves. This has been a longstanding hypothesis and is supported by the scientific literature. In the previous Phase 3 study, we incorporated a threshold of 40% of the study population to have MSA and we pre-specified a disease type analysis in the protocol for this very reason.

MSA is depicted on the left slide is characterized by lesions in the brain that lead to atrophy. However, the peripheral nerves that leave the brain and innovate the vasculature are generally intact. This situation facilitates the potentiation of endogenous norepinephrine in MSA patients. In contrast, patients with Parkinson's disease and pure autonomic failure tend to have degenerated peripheral nerves which hinders norepinephrine signaling to the vasculature.

Moving to Slide 19, previous clinical studies have demonstrated that ampreloxetine increased norepinephrine levels, prevented a drop in blood pressure and prevented symptom worsening in patients with MSA. The left panel of the figure shows that after four weeks of ampreloxetine treatment, norepinephrine levels increased by 57% from baseline.

In the middle panel of the figure during the randomized withdrawal period of study 170, patients who continued ampreloxetine maintain their blood pressure, whereas those who administered placebo experienced more than a 12 millimeter mercury drop in their blood pressure. As depicted in the far right panel of the figure, patients who remained on ampreloxetine during the six week randomized withdrawal period maintained symptomatic benefit as measured by the OHSA composite score. In contrast, patients administered placebo experienced a clinically meaningful one and a half point worsening of the OHSA composite score.

Let's take a look at Slide 20, which outlines the unique benefits of ampreloxetine treatment that we've observed. In the Phase 3 study, 170 ampreloxetine was effective at treating a range of cardinal symptoms in MSA patients and the effect was durable over the full course of the 22 week study. Additionally, ampreloxetine improved activities of daily living that require standing or walking for a short period of time.

Ampreloxetine is a single 10 milligram tablet administered once-daily. This is especially beneficial for MSA patients with dysphagia, which is a frequent and disabling symptom of the disease. This feature sets potential ampreloxetine treatment apart from current therapies that require multiple tablets to be taken several times a day.

Patients with nOH are at risk for supine hypertension, a dangerous increase in blood pressure while in the supine position. The two FDA-approved therapies for nOH have black-box warnings and the label highlighting this risk. However, in a safety database of more than 800 patients and healthy subjects, no signal for supine hypertension has been observed with ampreloxetine treatment.

Slide 21 outlines the design of our registrational study 197, also known as CYPRESS, for the treatment of symptomatic nOH and MSA patients. The study is comprised of a 12 week open-label period followed by an eight week double-blind placebo-controlled randomized withdrawal phase. The primary endpoint is a change in OHSA composite score. Based on the strength of the prior Phase 3 study results and alignment with the FDA on the primary endpoint as well as the study design, we believe the CYPRESS study has a high probability of technical and regulatory success.

Now that the study is ongoing, our development team will begin working proactively on the new drug application. Importantly, we previously met with the FDA to align on the nonclinical pharmacology, toxicology, clinical pharmacology, and CMC strategies to support the NDA.

Let's move on to Slide 22. We estimate that the addressable patient population for ampreloxetine is between 35,000 and 45,000 and we are seeking orphan drug designation in the United States. Despite two approved therapies for orthostatic hypertension, there remains a significant unmet need.

And ampreloxetine has the potential to offer a unique treatment profile including effectiveness on multiple symptoms, durability of effect, once-daily dosing, and a favorable safety profile. As we enter a new era in treating MSA symptoms, the potential of ampreloxetine offers hope to MSA patients with symptomatic nOH.

I'll now turn the call over to Aziz to review the financials.

[Aziz Sawaf, Chief Financial Officer]

Thanks, Rick. Theravance Biopharma is a much different organization with an improved capital structure compared to where we were only a year ago. We've de-risked our balance sheet by eliminating all debt during a period of unprecedented interest rate increases, all while improving liquidity and returning significant amounts of capital to our shareholders. We've done this to focus our capital allocation behind our two most valuable assets, YUPELRI and ampreloxetine.

Skipping over to slides to our financial performance in the quarter on Slide 26, I’d draw your attention to the collaboration revenue of $10.4 million. This figure reflects our 35% share of YUPELRI net sales adjusted for expense reimbursements recognized through our partnership with Viatris.

For those modeling our earnings potential going forward, it’s important to note that while we recognize our 35% share of YUPELRI net sales within the collaboration revenue we report, we are technically entitled to 35% of YUPELRI shared profits. Thus, while quarter-to-quarter variance and shared expense recognition impacts the collaboration revenue we recognize, it is up YUPELRI’s profitability in aggregate that matters most to our earnings.

I would note that YUPELRI continue to be profitable this quarter with a similar level of shared expenses relative to past quarters, despite the seasonal effects that impacted our net sales. Given the complexity of our collaboration revenue accounting, we have added Slide 35 to the appendix of this presentation to help provide clarity on the calculation.

Shifting to expenses. We reported a combined $27 million of R&D and SG&A expense, excluding share-based comp and restructuring costs compared with $31 million in Q1 2022, a reduction of 13%. When we provided financial guidance in February, we indicated that Q1 2023 expenses should be the highest of the year, owning to the headcount reduction we made within the research organization that was completed at the end of March. During the quarter we completed the restructuring we announced in February and incurred a total of $1.6 million of restructuring costs in line with our guidance of $1 million to $2 million. We do not expect to incur any additional severance or termination costs moving forward. We ended the quarter with $260 million of cash and no debt and during the quarter we repurchased 5.2 million shares, bringing our shares outstanding to 60.5 million.

Turning the Slide 27, I’ll provide an update on return of capital program. Through April 30, we have completed $215 million of our $325 million authorization at a weighted average share price of $10.38. We expect to complete the remaining $110 million of the program by end of 2023. The Board will continue to evaluate Theravance’s financial condition and progress towards the achievement of our financial targets, and in consideration of these factors, we may update the plan in the future similar to when we increased our capital return program from $250 million to $325 million earlier this year.

Finally, on Slide 28, I’ll provide updated commentary regarding our 2023 financial guidance. Based on our performance today, we are reiterating our guidance for operating expense between $35 million and $45 million for R&D and between $45 million and $55 million for SG&A, exclusive of share-based comp and one-time items. It’s worth mentioning that R&D expense at this point largely ties to our ability and intention to enroll patients in the CYPRESS study, which we expect to build over time while driving to a result for PIFR-2 during the second half of the year.

Based on our internal projections, therefore, R&D expense should be lower in Q2 compared to Q1 before building throughout the second half of the year. SG&A expense should also be lower in Q2 and then largely stable for the remaining quarters of the year. As a result of a commendable start to Q1, coupled with our expectation to drive YUPELRI sales growth, while managing expenses effectively, we continue to expect to reach profitability from a non-GAAP perspective in the second half of 2023. This is exclusive of any potential one-time milestone payment. Simultaneously, we are tracking well against our expectations for a material reduction in stock-based comp for the year. Stock-based comp in Q1 is down 34% year-over-year excluding restructuring expenses or 52% including restructuring expenses.

With that, I’ll turn the call back to Rick for closing remarks. Rick?

[Rick Winningham, Chief Executive Officer]

Thanks, Aziz. Turning the Slide 29 and summarize our commentary we’re delivering on our strategic focus for 2023. First, we’re making YUPELRI available to many individuals with COPD who are uncontrolled on their current therapy and we are simultaneously laying the foundation for added growth with potentially market moving data from PIFR-2 later this year. Second, we are working with the MSA community and treating clinicians to ensure we meet our CYPRESS milestones for ampreloxetine and advance this important potential therapy as expeditiously as possible. And third, we’ve got a robust plan in place to return capital to shareholders as appropriate for the long-term health of the company and shareholder value creation.

Thank you everyone for your time and your participation. I’ll now turn the call back over to the operator for questions.

[Operator]

[Operator Instructions] And our first question comes from the line of David Risinger from SVB Securities. Your question please.

[David Risinger, SVB Securities]

Yes. Thank you very much and thank you for all the updates. I guess, I have two key questions. First, could you provide some more color on the 8% YUPELRI net sales growth year-over-year, including, I guess anything you could say about – anything further you can say about the spending growth year-over-year, which limited Theravance’s net sales, just so that we understand a little bit more about that 8% growth.

And if you could also just comment on whether you expect better growth than that in the future or if costs could continue to grow meaningfully and hold back the Theravance book net sales relative to the end market sales growth? And then with respect to ampreloxetine and Phase 3 enrollment, could you discuss efforts to drive the enrollment given the unmet need? And obviously this is a rare disease but just want to understand if there are opportunities to potentially accelerate enrollment given the significant unmet need? Thanks very much.

[Rick Winningham, Chief Executive Officer]

Thanks David for your question. First on the financial impacts and a perspective on both expenses and the 8% net sales growth, I have Aziz comment and then have Rhonda take a few comments on expected growth for the future. Aziz?

[Aziz Sawaf, Chief Financial Officer]

Yes. Thanks David for the question. I think where you’re getting at is, is why is – when net sales is up 8%, why was the collaboration revenue slightly down year-over-year? So just as a reminder, the difference between the 35% of the sales and the collaboration revenue is the netting of the shared expenses between the two companies. So for example, in the case of this quarter, the difference was approximately $6 million. In other words, the 35% of the sales was $16.4 million, and the collaboration revenue was $10.4 million, so the delta there is $6 million.

That $6 million difference has been pretty consistent over the last several quarters. It was $5 million in Q4, $6 million in Q3 of last year, $6 million in Q2 of last year, which means that the cost base has actually been pretty consistent the trailing four quarters. The only difference was in Q1 of last year specifically the cost base was a little bit light relative to the rest of 2022, and that was more of a timing issue. Sometimes costs couldn’t bounce around a little bit, but this obviously skewed our year-over-year collaboration revenue.

But again, the takeaway here is the cost base has been stable for pretty much the last four quarters, so it hasn’t increased really at all, except for, again, Q1 of last year, which was more timing related. So I don’t expect the cost basis to be much different from the last three or four quarters. And lastly David, I think we’ve talked about it before a couple times. Given the complexity of the collaboration revenue, we have added a new slide to the appendix of the presentation, I noted this on the prepared remarks. But it’s Slide 35 if you want to take a look that may help you and other investors digest the collaboration revenue a little bit.

[Rick Winningham, Chief Executive Officer]

Do you want to comment on the net sales and transition, Rhonda?

[Rick Graham]

Can you repeat that? The question on that one Rick for me?

[Rick Winningham, Chief Executive Officer]

Yes. David had a question on the 8% net – 8% sales growth year-over-year, any color you can...

[Rick Graham]

I'll comment on.

[Rick Winningham, Chief Executive Officer]

Yes. Sure.

[Rick Graham]

So I'll comment on kind of the seasonality aspect of it and I'll pass it over to Rhonda for a kind of demand driver. But as, as I think Rhonda and Rick Winningham have mentioned several times on previous calls, Q1 tends to be the softest quarter of the year. That was something that I think was said during the previous call in February and reiterated as latest as of the investor conference a couple weeks ago. So for a background in Q1 of 2022 we were down slightly in Q1 of 2021 we were down 5%.

So this is something we've seen consistently over the last couple years, while – and while this year's magnitude was a bit higher, the decrease was about 16%. It was well within our expectations due to the Q1 buying/ordering patterns at the wholesaler and DME levels. So this is a dynamic you've seen widely across biopharmaceutical – biopharma companies that tend to report softer Q1 sales. So ultimately this is more a timing phenomenon and we're more focused on the strong demand trends that that we're seeing that will eventually lead to higher net sales.

And I'll kind of transition the Rhonda to talk through those demand trends a little bit.

[Rhonda Farnum, Chief Business Officer]

Yes. So certainly thinking about that timing phenomenon, and I think the user's done a nice job of really explaining that and us having the expectation of stability – continuing stability in the cost basis. I think it is important to really focus on the performance metrics, all of which we highlighted in the script a few moments ago. But I think to see it in its totality from the increase in new hospital when, the number of accounts both in the outpatient setting as well as in the hospital setting that quarter-over-quarter and year-over-year growth in the hospital business. The increase in new sites of care channels specifically where the team has been focused and continuing to see the retail script increases both year-over-year and quarter-over-quarter, as well as that market share in both the outpatient and hospital setting. All of those demand trends really giving us that confidence that we will continue to reflect on increases for the remainder of the year.

[Rick Winningham, Chief Executive Officer]

And just as I transitioned to Rick on ampreloxetine, I think in particular the growth of new patients starts in the first quarter on the retail side was extremely encouraging. And I think Rhonda highlighted really three key reasons for that, that increase in new patient starts. One of them is concomitant [ph] messaging, which we rolled out last year with Viatris, and then obviously the high percentage of patients leaving the hospital now with a for prescription for YUPELRI.

So Rick, you want to touch on David's comments on ampreloxetine, Phase 3 rare disease?

[Rick Graham]

Yes, I will, and David thanks for that question. I mean, it's – I think as you're alluding to enrolling trials in a rare disease condition is a little trickier and requires a more strategic approach and thoughtful approach to make sure that we can expedite enrollment. So a few things I'll comment on. One is it really helps to have the strong headwinds that we do where we're aligned with FDA on the primary endpoint of the CYPRESS study, the study design and the ability for CYPRESS to form the basis of a full approval is positive.

We also have compelling data from our prior Phase 3 study. In addition to that, we've got good relationships with sites. Remember we ran a Phase 3 program previously, so we're going to lean into those relationships. We also have developed over the year's good relationships with advocacy organizations as well, and we've been very thoughtful about our operational infrastructure providing a mix of sites within in the United States and sites outside of the United States, and we're bringing those on every day we're adding new sites. And really for a rare disease, it's the accumulation of sites over time that drives enrollment and with small numbers of patients at each site, we have to be operationally focused on adding these high quality clinical trial sites over the course of this year.

[David Risinger, SVB Securities]

Got it. Thanks very much.

[Operator]

Thank you. One moment for our next question. And our next question comes from the line Liisa Bayko from Evercore. Your question please.

[Jingming Chen, Evercore]

Hi. Thank you for taking our question. This is Jingming Chen on for Liisa. So our question is on ampreloxetine. So could you remind us what's the powering assumption for the CYPRESS study and what is the threshold for clinical meaningfulness for OSHA composite score? Thank you.

[Rick Winningham, Chief Executive Officer]

Rick.

[Rick Graham]

Yes. Hi Jingming. Thanks for the question. We don't comment on powering of our trials, but I'll say a couple of things. One is you could generally assume that the powering for this study would be consistent with what you would expect for a registrational trial. And then two, if you look at Slide 20, the results from the 170 study and you look at the OHSA data, which is in the top swim lane there. The symptom composite score we had a nominally statistically significant result there with just 38 patients. So we're enrolling 100 patients in the open-label period of CYPRESS with the intention of getting 60 completers with the randomized withdrawal. So that should give you a sense of the powering and the sample size, okay.

And then your other question was around clinical meaningfulness. Another really good question, this is something that we've talked a lot about with our KOLs and it's generally considered on each of the symptoms in the OHSA assessment that somewhere between 0.8 and 1.0 is considered to be a clinically meaningful change. And you can see across each of our symptoms, maybe with one minor exception, we're right there within that range for clinically meaningful results.

[Jingming Chen, Evercore]

Got it. Thank you.

[Operator]

Thank you. [Operator Instructions] And our next question comes from the line Divya Rao from TD Cowen. Your question please.

[Divya Rao, TD Cowen]

Hi guys. This is Divya on for Marc Frahm. Congrats on the recorder. To understand the seasonal impacts for YUPELRI a little bit better was timing the biggest driver of this impact? Or were there any changes in in the channels that contributed that may have contributed to a potential decrease in that pricing? And then just on that – have the proportion of patients may be on therapy with Medicare versus commercial plans changed in Q1?

[Rick Winningham, Chief Executive Officer]

Rhonda.

[Rhonda Farnum, Chief Business Officer]

Rick, I can, yes, I can take that. And I'll start with that last question. There has not been a change in patient mix, so appreciate you flagging that. That is something we always obviously want to pay close attention to our commercial basis is about 8% of commercial patients within the YUPELRI business. And relative to further specifics, I mean, timing is of the essence here relative to the purchasing. So I'm not going to get into specific pricing and channel dynamics given our partner manages that in, but it really boils down to the simplicity of timing.

[Divya Rao, TD Cowen]

That's helpful. Thank you.

[Operator]

Thank you. And this does conclude the question-and-answer session of today's program. I'd like to hand the program back to Rick Winningham for any further remarks.

[Rick Winningham, Chief Executive Officer]

Thank you, operator. Thanks everyone for participating. We look forward to updating you on our progress. As we move through 2023. We're extremely excited about what we've been able to accomplish with regard to YUPELRI demand and ampreloxetine launching the CYPRESS study with ampreloxetine team. Thank you and have a good day.

[Operator]

Thank you. Ladies and gentlemen for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.