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spk11: I'd like to welcome everyone to the TheraVance Biopharma third quarter 2022 conference call. During the presentation, all participants will be in a listen-only mode. A question and answer session will follow the company's formal remarks. To ask a question, please press the star key followed by the digit 1-1 on your telephone. Again, that's star 1-1 to ask a question. If listening via webcast, please mute audio on your webcast device before asking a question over the phone. I will repeat these instructions after management completes their prepared remarks. Also, today's conference call is being recorded. And now I'd like to turn the call over to Rick Winningham, Chief Executive Officer. Please go ahead.
spk09: Good afternoon, and thank you for joining the TheraVents Biopharma third quarter 2022 conference call. to discuss our business. I remind you that this call will contain forward-looking statements that involve risks and uncertainties, including statements about our development pipeline, expected benefits of our products, anticipated timing of clinical trials, regulatory filings, and expected financial results. Information concerning factors that could cause results to differ materially from our forward-looking statements is described further in our filings with the SEC. would direct your attention to slide four. Joining me today are Rhonda Farnham, Chief Business Officer, Rick Graham, Head of Research and Development, and Andrew Heinemann, the Chief Financial Officer. Now turning to slide five. Theravance Biopharma's unwavering purpose is to create medicines that make a difference. The third quarter marked another major inflection point in the company's transformation. We recognized a record quarter of upelry net sales and profitability and continue to build our intellectual property portfolio. Rhonda will review the details. Three opinion leaders in the field presented Amprolox team data demonstrating clinically meaningful and durable effectiveness in MSA patients with neurogenic orthostatic hypotension in our phase three study 170 at the opening session of the 33rd International Symposium on the autonomic nervous system. Rick will share where we are today on ampryloxetine and where we're headed. We closed the sale of our royalty interest in Trilogy Elliptid, a royalty pharma, for approximately $1.1 billion in upfront cash, $250 million in potential milestones and outer year royalties, and royalty pharma invested in the ampryloxetine program. And as a result, Of the deal with Royalty Pharma, we were able to initiate a $250 million capital return program, which included purchasing GSK's entire holdings at $9.75 a share and launching a Dutch auction tender offer for up to $95 million of the TheraVance Biopharma ordinary shares, a tender offer that's currently open. We ended the third quarter with $487 million in cash and zero debt. Andrew will review further financial details. All of these actions drive towards our goal of maximizing shareholder value. I'll now turn the call over to Rhonda to review UPelry.
spk01: Thanks, Rick. We are very pleased to share the latest performance update on UPelry, which is the first and only once daily nebulized long-acting muscarinic antagonist, or LAMA, that provides a full 24 hours of control for patients as it is indicated for the maintenance treatment of patients. with COPD. Turning to slide 7, in Q3, net sales of upelre reached another quarterly high launched to date. As a reminder, TheraVans Biopharma and Vietris co-promote in the U.S. with our combined sales infrastructure, targeting healthcare professionals who treat COPD patients suitable for upelre. TheraVans Biopharma's commercial and medical teams cover the hospital segment, and Vietris is responsible for outpatient based community healthcare professionals. From a financial perspective, we share profits and certain expenses on upelry in the U.S. with 65% going to Beatrice and 35% to TheraVance Biopharma. Slide seven shows TheraVance Biopharma's implied 35% share of net sales for upelry during the third quarter of 2022 of 18.7 million. I am also pleased to highlight that UPelry's year-over-year net sales have increased by 35%. Overall, Q3 2022 demand increased 4% from Q2 of 2022 and increased by 22% year-over-year. We are also very encouraged to see quarter-over-quarter growth in net sales given we saw a slight decline over the same time last year. We typically anticipate seasonality dips in the third quarter due to lower patient census and fewer exacerbations, et cetera. And total prescriptions within the overall maintenance COPD market also decreased slightly in Q3 of 2022 versus Q2 of the prior year. Looking specifically at the TheraVans hospital segment deployment efforts on the right side of slide seven, in Q3 of 2022, Doses sold exclusively in the hospital setting represented a year-over-year increase of 45% and an increase of 5.2% from the previous quarter, demonstrating the highest hospital volume launched to date. As we have previously stated, the respiratory pandemic impacted the launch phase for UPelry's growth in 2020, particularly in the hospital setting. Since the second half of 2021, we have continued to see significant progress in UCellary's hospital business growth each quarter throughout 2022. Contributing to that growth has been the team's ability to continue to achieve new key hospital system formulary placements with a total of 605 formulary placements launched to date, which have led to now over 1,200 purchasing accounts, and the account number continues to increase weekly. We believe these wins and forthcoming additional system successes will yield continued growth through the remainder of 2022 and beyond as upelary will be the first llama of choice in many hospital systems due to the growing recognition and acceptance of upelary's once daily value proposition and clinical benefits. Turning to slide eight. you can see that UPelry's share of the hospital setting increased to 13.4% in Q3 of 2022, up from 11.7% in the previous quarter. UPelry's quarterly market share in the community setting also increased to 26.3% through August of 2022, which is our latest data point, up from 25.6% in Q2. As we have noted previously, many patients with COPD experience an acute respiratory episode serious enough to require a trip to the hospital, and therefore, the hospital becomes a key point to assess patients and convert or switch them from their current medicine to upelry. Data shows that approximately 90% of patients who receive upelry in the hospital setting are discharged with a prescription to continue their treatment in the community allowing for continuity of upelry maintenance therapy post-hospitalization. The TheraVance Biopharma and Viatris teams continue to work collaboratively and effectively to convert appropriate patients to upelry during their hospital visit, provide support through discharge, and enable them to be maintained on upelry after their return home. Understanding the upillary opportunity in the community or outpatient setting, we have also been encouraged by the growth trends seen in the retail script data where total prescriptions in Q3 have increased 21% year over year, and new-to-brand prescriptions have increased 26.9% over Q3 of 2021, with both metrics once again reaching new quarterly highs launched to date. As a reminder, While these script data only include the retail channel, they do serve as a useful proxy for the total community use, which includes retail plus the DME, or durable medical equipment fulfillment channel, which represents the majority of UPOL REIT community sales volume. We continue to see the impact of the pandemic on our business for SEED, which we believe is leading to improved demand patterns and will continue growth acceleration throughout the remainder of the year as the team continues to execute against our strategy, which leverages a hybrid mix of in-person, virtual and digital education, and promotional efforts that effectively communicate the core benefits of UPelRI. Turning to slide nine, recognizing there is a sizable niche for UPelRI within the addressable COPD patient population, which actually represent an opportunity well beyond those patients receiving upelri today. We do believe there is significant upside for the brand beyond 2022. Looking to upelri's longer-term commercial potential, we are pleased to share that it has been further enhanced by another recently issued U.S. patent that covers a method of use of revifinicin in treating COPD. This new patent expires in 2039 and is now listed in the orange book. Lastly, turning to slide 10, the phase 4 PIFR2 study comparing improvements in lung function in adults with severe to very severe COPD and suboptimal inspiratory flow rates following once-daily treatment with either revifinicin delivered via a standard jet nebulizer or teatropium delivered via a dry powder inhaler continues to actively enroll patients. Their advance is responsible for 35% of the cost of this study and are guiding to top-line results the second half of 2023. I'll now turn the call over to Rick Graham.
spk08: Thanks, Rhonda. Today, I'm going to focus on the norepinephrine reuptake inhibitor ampryloxetine in development for the treatment of symptomatic neurogenic orthostatic hypotension, in patients with multiple system atrophy, also referred to as MSA. MSA is a rare disease affecting approximately 50,000 people in the United States. In MSA patients with NOH, blood pressure falls when upright, owing to impaired release of norepinephrine, which leads to debilitating symptoms that can have a profound impact on a patient's quality of life. Neither of the two approved therapies to treat orthostatic hypotension have demonstrated durable effectiveness in mitigating the debilitating symptoms for patients with MSA. There exists a significant unmet need, and amproloxetine has the potential to markedly differentiate from other treatment options, thereby offering hope to patients with MSA. Moving to slide 12, with a unique mechanism of action, a single tablet administered once a day a durable and clinically meaningful symptom effect demonstrated in MSA patients in the Phase III Study 170, and no signal for supine hypertension, amproloxetine has a potential to differentiate from other treatment options. In the Phase III Study 170, amproloxetine was effective at treating a constellation of cardinal symptoms associated with NOH. The benefit to patients with MSA was observed in multiple endpoints in the study including a nominally statistically significant effect on the orthostatic hypotension symptom assessment score, also referred to as the OHS-A composite score. This effect on the OHS-A composite score was driven by all six symptom scores favoring ampryloctine treatment relative to placebo. These include dizziness, vision impairment, weakness, fatigue, trouble concentrating, and head and neck discomfort. The magnitude of change on the OHSA composite items was clinically meaningful, and the durability of effectiveness was maintained over the length of the 22-week study. Although we've described these data previously, I'd like to underscore the importance of demonstrating a benefit on a constellation of symptoms for these patients. By comparison, the basis for Droxidopa approval was based on a change in only one symptom, which was dizziness over a short duration. In addition to a favorable impact on symptom scores with amproloxetine treatment, items on the daily activity composite score also favored amproloxetine. The largest impact for the MSA patients was standing for a short time. For someone with MSA suffering with symptomatic NOH, even standing for a short time can have an enormous impact on their quality of life. It can mean the difference of transferring from the bed to a wheelchair. The only item that did not favor amproloxetine was walking for a long time. which isn't surprising considering that MSA is a disease with severely debilitating consequences. Amproloctine is a single 10 milligram tablet administered once per day, which is beneficial to MSA patients that may have difficulty swallowing as a result of their disease progression. This is another differentiating factor from current therapies that require multiple tablets administered several times each day. Patients with NOH are at risk for a dangerous increase in blood pressure while in the supine position. This is known as supine hypertension. The two FDA-approved therapies for NOH each have boxed warnings on the label highlighting the risk of supine hypertension. In a safety database of more than 800 patients and healthy subjects, the signal for supine hypertension has not been observed with amproloxetine treatment, offering the potential for yet another differentiating feature relative to the approved therapies. Moving to slide 13, there's an urgency to treat MSA patients suffering with NOH due to the impact on quality of life and the extreme caregiver burden. Rare diseases and conditions pose a significant economic burden. The cost burden applies to direct medical as well as indirect and non-medical costs. Having just attended the American Autonomic Society meeting and spending time with opinion leaders, clinical investigators, and patient advocacy organizations, These messages were repeatedly stated throughout the meeting. For the first time, the ampyloxetine phase three data were presented at a medical conference and was done so through oral presentations by three opinion leaders, Dr. Horatio Kaufman, Dr. Italo Biagioni, and Dr. Roy Freeman. In the presentations, the totality of the evidence from the phase three program was highlighted, supporting clinically meaningful and durable effectiveness in MSA patients with symptomatic NOH. Moving to slide 14. We're looking forward to starting a new registrational study in MSA patients with symptomatic NOH, study 197 or Cypress, in the first quarter of 2023. Study 197 is a 12-week open-label, eight-week double-blind, placebo-controlled, randomized withdrawal study with a primary endpoint of change in OHSA composite score. As a reminder, the primary endpoint was agreed upon with FDA during a Type C meeting earlier this year. We expect the $25 million investment from Royalty Pharma to fund the majority of the Phase III study costs. I'll now turn the call over to Andrew to review the financials.
spk10: Thanks, Rick. Turning to slide 16, as previously discussed, the trilogy royalty transaction with Royalty Pharma was transformational for Theravance Biopharma. The carefully structured deal that closed during the third quarter delivers three components of values. an upfront cash payment of approximately $1.1 billion in exchange for all of our units in Theravance Respiratory Company, or TRC LLC, which represented our 85% economic interest in the royalty rights on worldwide sales of GSK's Trilogy Ellipta. Secondly, the medium-term value is in the form of potential milestone payments up to an aggregate of $250 million. These milestones will be paid upon the achievement of various Trilogy revenue thresholds throughout calendar years 2023 through 2020. In 2023 specifically, we are eligible to receive a milestone payment equal to $50 million if Trilogy global net sales exceed $2.9 billion. As a recent point of reference, global net sales for the first nine months of 2022 have reached approximately $1.6 billion. an increase of 34% over sales in the first half of 2021. And finally, the third component is retained long-term value in the form of the return to Theravance Biopharma of our 85% ownership of TRC's low-season interest in the trilogy royalties. We call these the outer-year royalties, or OYRs. And the OIR period begins in 2029 for trilogy sales outside of the United States and begins in 2031 for sales within the United States. As mentioned in the deal announcement in July, this creative transaction structure monetizes our economic interest in trilogy royalties and allows Theravance Biopharma to benefit from significant near-term cash, as well as retaining medium and long-time value of the trilogy royalties. which we expect will continue to benefit from GSK's global commercial execution and lead to continued strong performance of Trilogy over time. Furthermore, this monetization also removes uncertainty with the receipt of Trilogy royalties because the outer year royalties will be paid directly from Royalty Pharma to Theravance Biopharma, and Innoviva was removed as the manager of TRC LLC. One key benefit of the Trilogy deal was that it allowed them to pay off our indebtedness with minimal equity dilution and relatively low transaction costs. At the closing of the deal, we paid down the non-recourse Trilogy notes for approximately $425 million. And by early August, we successfully retired 100% of the company's $230 million convertible notes. These two deals made Theravance Biopharma debt-free during the third quarter. while also having sufficient excess cash to design our capital return program, outlined on slide 17. In September, our board of directors authorized the $250 million capital return program with the goal of repurchasing as many shares of TBPH at attractive prices. This was an important decision by the board, and before making it, we took the time to source input from and speak directly with key shareholders and our financial advisors regarding both the quantum and the components of our capital return program. In the end, we designed a three-part program. Firstly, with approximately $95 million deployed to purchase GSK's equity stake in Theravance Biopharma, approximately 9.6 million shares at $9.75 per share. The second component is the implementation of the ongoing $95 million Dutch auction of tender offer initiated September 28th. This is an open offer, and as stated in today's press release, we are extending the length of the offer such that the offer will expire at midnight New York City time, November 17th, 2022. And for more details regarding the terms of the offer, please contact our report. Finally, the third element of the authorization by the report is to repurchase up to $60 million in Theravans biothermer shares by initiating, I think, after the close of the Dutch tender offer, an open market share repurchase program. This program has the goal to complete the share repurchases by the end of 2023. At the completion of the trilogy royalty transaction and the subsequent debt repayment and capital return program, Theravans will have strengthened its balance sheet and reduced equity share count materially. This immediately positions the company for significant future equity value creation as we focus on UBEL commercialization and AmpliLox in the phase of its execution. Moving to our third quarter financial highlights on slide 18. R&D expenses for the third quarter of 2022 were $7.2 million compared with 36.8 in the same period in 2021. SG&A expenses for the third quarter of 2022 were 11.1 million compared to 13.9 million in the same period in 2021. These quarterly figures exclude share-based compensation, one-time restructuring, and one-time transaction related expenses. We ended the third quarter of 2022 with $487 million in cash and cash equivalents. And please keep in mind that during the fourth quarter of 2022, the company will make a payment of approximately $120 million for estimated taxes due associated with the Trilogy transaction. In addition, the ongoing Dutch tender offer could utilize an additional $95 million of cash in Q4. Moving to slide 19, we are reiterating financial guidance for the full year 2022. For R&D expenses, we expect to invest between 45 to 55 million dollars relative to actuals of 168 million dollars in 2021. Of this expense range, approximately $10 million is non-recurring spending that was incurred in Q1 2022 to support the wind-down of the isensitinib and previous amproloxetine clinical programs. R&D spending in Q3 and beyond has normalized and reflects the recurring measures of strategic investments in our pipeline. For test DNA expenses, we expect to invest between $35 to $45 million relative to actuals of $71 million in 2021. And again, for operating expense guidance, we expect to invest in share-based compensation, one-time restructuring, and one-time transaction-related expenses. In closing on the financial section, I'll take a moment to reflect that Eucari's business has been profitable now for two years since Q3 of 2020. And during the third quarter of 2022, the brand realized its highest order of sales and profitability since launch. Spends during the current quarter are even stronger. As a result of the reduced spending in 2022 and the increased cash flow generation from UPelry, we expect to approach break-even cash flow on a corporate basis in 2022. With that, I'll turn the call back to Rick Winningham for closing remarks.
spk09: Thanks, Andrew. TheraVance Biopharma is in the midst of a strategic transformation and this quarter has been pivotal. As we noted, the key progress and continue to demonstrate a focus on our strategy. On the product and pipeline front with our partner, Vietris, the team has delivered continued sales growth for UPelri. Recently, we strengthened our intellectual property around UPelri, extending patent exclusivity until 2039. This quarter, we delved further into the ampyloxetine-dated NOH in MSA patients with the world's top opinion leaders and finalized the design for the registrational phase three trial. On the financial side, with the closing of the sale of Trilogy Royalty Interest to Royalty Pharma for over $1.5 billion in potential total value early in the quarter, we eliminated our debt and announced that we've begun to make strong progress on our capital return program. We're moving forward with focus, momentum, and determination. In closing, I'd like to thank the TheraVance Biopharma team for their resilience and their tireless efforts to meet the needs of the patient communities we serve. As we drive forward, we're well positioned to deliver medicines that make a difference in the future, as well as drive shareholder value. Thank you, everyone, for your time and participation. I'll now hand it back to the operator for questions.
spk11: Thank you, sir. Once again, if you would like to ask a question, you may do so by pressing the star key followed by the digit 1, digit 1 on your telephone. If you're listening via the webcast, please unmute the audio on your webcast device before asking your question over the phone. If you're using a speakerphone for today's call, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, that's star 11 to ask a question.
spk04: One moment for our first question. And our first question for today comes from the line of Eva Privatera from Cowan.
spk11: Your question, please.
spk00: Hi, congrats on the great quarter, and thanks for taking our questions. We noticed that IQVIA scripts had incorrectly indicated a down quarter, even though previously the trends had been fairly predictive. What do you think accounts for the discrepancy, and do you expect IQVIA to be less accurate going forward, or is it just going to vary?
spk09: Rhonda, do you want to take that?
spk01: Absolutely. One thing to certainly keep in mind, and I try to comment to the script data that's visible publicly, it is only inclusive of retail. So you have to be mindful that this is a smaller percentage, roughly 27% of our total business. So to expect that that downturn or a decrease in retail scripts is reflective of the whole business, it's not depicting the entire view.
spk00: That's really helpful. Thanks. And if I can have a second question, what's your latest estimate on the timeline for reaching cash flow positivity and what are some of the assumptions underlying that?
spk09: Yeah, so as Andrew said, on an operating basis, well, you know, our plans are to approach it in 2022. We're moving towards the, you know, cash flow positivity in 2023. We will provide more information and details on that when we give our outlook for 2023 early in the year. Andrew, anything else on that? No, that's about it.
spk00: Thank you, and congrats again.
spk11: Thank you. Thank you. Once again, if you have a question, please press star 1-1. Our next question comes from the line of Douglas Thao from HC Wainwright. Your question, please. Douglas, you might have your phone on mute.
spk05: Oh, sorry. Sorry about that. I had myself on mute. Didn't realize it. Congrats on the progress, especially with UPelry. Maybe just as a question, so this is, I think, two quarters in a row where we've seen the recognized revenue a good deal below, you know, sort of the implied sales. And I know there are sort of different sort of moving parts in terms of what lets you recognize revenue. Should we see some normalization as we go into the fourth quarter?
spk10: Andrew, do you want to take that or? Yeah, well, certainly, Doug, as we've spoken about in the past, what we book is the receivable due, which nets out the collaboration expenses of the synthetic P&L behind our collaboration with Beatrice. So going forward, as we expect revenues of UPowery to continue to grow, that booked revenue line for us should also increase commensurately. There are some fluctuations based on the GAAP accounting treatment that, you know, we continue to try to provide a transparent disclosures on, but we're also a bit hampered by the collaboration accounting under GAAP. Hope that answers your question.
spk09: Just one other, yeah, Douglas, let me add one other point. I mean, one of the aspects here which changed, you know, sort of the recording was, you know, the restructuring, the removal of our costs, reduction of our costs, which cause a, as associated with the restructuring, which cause a lower level of reimbursement from Vietris to us, and therefore, us recording a lower level of revenue. It does somewhat depend on a quarter-by-quarter basis of the cost that Vietris actually incurs on their site prior to the calculation of the synthetic P&L.
spk05: Okay. That's really helpful. And I guess maybe a question for Rhonda, and I apologize if it was covered in the opening remarks. I've been jumping between a couple calls. You know, how much seasonality do you think there was in the third quarter, and should we see some seasonal strength in the fourth quarter, which, you know, historically pre-COVID typically was often the strongest period for sort of hospital-based products? And I know that Upelri is not a hospital-only product.
spk01: That's fair, Doug, and that's obviously a great question that we continue to try to understand over time with each and every year. hopefully without any pandemic impact going forward. We do anticipate that that seasonality was somewhat reflected in Q3. However, you may have missed this in the commentary, we were encouraged to still see the quarter-over-quarter growth in net sales. We did see an overall dip in sales maintenance COPD market view, which decreased a little bit in Q3 versus Q2. So, I do think the seasonality was there. And what we anticipate relative to that seasonality, you have correctly commented on that Q4 is typically where we anticipate that higher volume, whether that's due to increased patient census, but more importantly, that is, you know, the high point of flu season and obviously all that's going on around that relative to other respiratory virus impact on COPD patients and the propensity to have an increase in exacerbations.
spk05: Okay, great. Thank you so much.
spk11: Thank you. One moment for our next question. And our next question comes from the line of Joseph Stringer from Needham. Your question, please.
spk06: Hi, thanks for taking our questions. First one is on the operating cash flow breakeven. Just curious how much of the potential label expansion of upelary from the PIFR 2 trial factored into your previous guidance on breakeven operating cash flow and if the delay in the results sort of affects how you can get guidance on that. And then secondly, given the cash balance the current cash balance, understand that you have a capital return program in place. But what are your updated thoughts on any plans for bringing additional say preclinical or early stage programs into the clinic or any potential BD activity? Thank you.
spk09: Yeah, so the previous comments that we made on both 22 and 23 outlook, really didn't include any significant effect from the PIFR study. So the fact that we've, you know, increased the size of that study and pushed the data out until the end of 23, you know, has no effect on our other, on the, you know, our previous estimates. I think, you know, the fact is that the upelry is, in fact, the driver of the cash flow profile of the company. And we do expect, as Ron highlighted, obviously growth in the fourth quarter and continued growth into 23. as, you know, as both the pandemic recedes and we have greater and greater success with the positioning of UPelRI, you know, in the institutions, but also in the outpatient, also in the outpatient setting. I'm sorry, Joey, your second question.
spk06: Oh, yeah. In terms of given the current cash balance, I understand that you have a capital return program in place, but just curious, if you could provide your updated thoughts on the rest of the pipeline in terms of any potential BD activity or advancing internal programs into the clinic.
spk09: Well, we're extraordinarily focused on, you know, clinically on the PIFR, completion of the PIFR study and the launch and the rapid accrual of the ampryloxetine program That's really going to take a vast majority of our resources, and we really don't see any other programs right now adding to what our cash consumption profile is. But I do think all of our focus here, when we turn into 23, is going to be on the rapid execution of Amber Lockstein, and Rick can make some comments on that if you'd like.
spk08: Yeah, that's the focus of the team right now. Like I said in the prepared remarks just coming off of the American Autonomic Society meeting where we, I think through the presentation by the KOLs, created quite a bit of energy around where we're headed with this program.
spk04: So a lot of energy and effort going into that in the first quarter and the rest of 23. Great, thank you. Thank you.
spk11: One moment for our next question. And our next question comes from the line of David Reisinger from SVB Securities. Your question, please.
spk03: Yes, thanks very much. And let me add my congrats as well on all the progress. So I guess first, could you comment on the potential timeline for the ampyloxetine vaccine? Cypress trials. So obviously slide 14 is quite helpful, that it's essentially five months for each patient, but you're launching it in the first quarter of 23. When should we expect a top line readout? I'm guessing that would be in 2024, but I just don't know how you're thinking about that. So that is the first question. And then second, with respect to the trilogy target of $2.9 billion for next year, I believe that consensus GSK expectations are below $2.9 billion for 2023. So just wanted to get any additional color from you on the potential to realize that $50 million milestone. Thank you.
spk09: Yeah, thanks for the questions. Well, on ampryloxetine, I think once we roll into 2023, we've got, you know, probably 90% of the, 90, 95% of the design discussions finished with FDA. On ampryloxetine, we've got a little bit of... you know, just ticking and tying to do with them. And I think once we get that done, we'll be able to provide a better outlook as to, you know, the size of the study and then the size of the study translated into the timing for finishing the study and then filing the NDA. So, Rick, do you want to make any other comments on that?
spk08: No, that's it. That's exactly right.
spk09: Then on Trilogy, I think Trilogy, you know, the, you know, the forecast that, you know, a variety of people forecast Trilogy. There are some, obviously, some tailwinds behind Trilogy as we come out of the pandemic. I think in particular related to the kind of the COPD business for Trilogy getting back on track. That's, I'd say that's certainly something to watch. as is the continued asthma progress. And then the potential for the biologics that are built on top of controller medicines that as they continue to execute their promotional strategy, they in fact drive more patients through trilogy on the way to biologic. But, you know, I think those are sort of the factors in the market that can affect trilogy, whether, you know, whether it gets to 2.9 and we get the $50 million, we'll just have to see. I think importantly for us, is that, you know, the number that gets us $50 million in 23 is also the number that gets us 25 and 24. So, you know, if we were to come up short in 23, the trilogy were to come up short, then I think it dramatically probably increases the probability of that lower end of the 24 milestone. I don't know, Andrew, anything else on that?
spk10: The only other comment I would make is that given the outperformance versus consensus on a quarterly basis, we've seen the consensus continually increase after GSK reports their quarterly earnings. So, you know, I think you're right, David, that the current consensus for next year is just over $2.4 billion, and we expect that to continue to have upward revisions based on the performance that GSK is producing. Thank you.
spk11: Thank you. Thank you. One more moment while we have our next question. And our next question comes from the line of Vikram Prohit from Morgan Stanley. Your question, please.
spk07: Hi, this is Will on for Vikram. And congrats on the progress this quarter. We have two questions on ampryloxetine. The first is around the Cypress study. Any additional color you guys could provide on the profile of MSA patients you intend to enroll and what the expected pace of that enrollment might be would be terrific. And secondly, if you could just remind us about what the IP estate on that molecule currently is and what the duration of protection that is provided by it, that would be very helpful. Thank you.
spk09: Rick?
spk08: Yeah, so I'll take the first part, Rick, if you want to take the second part around IP. So with regard to the profile, Will, what we're purposefully doing is designing the Cypress study to be as close to the prior 170 study as possible. And as a reminder, which is 38 patients in the 170 study, we saw that there was a nominally statistically significant effect on OHSA composite, which will be the primary endpoint for the new study. The changes that we're making to the study are relatively minor, but they're data-driven. So for example, when you look at slide 14 of what we presented today, our open label period is 12 weeks and our randomized withdrawal period is eight weeks. In the prior study, that was 16 weeks and six. So we've just made those sorts of adjustments, but for the most part, we're targeting the same patients and with a relatively similar study design. With regard to enrollment rate, It's too early to comment on that. At this point, we're in the process of doing detailed feasibility. Now, I think one advantage for us is we have some significant experience here. We had a relatively large phase three program previously, and that allowed us to identify really top performing and top tier sites. And we've established and built relationships with those sites. So we will be going back to those sites. We've got those relationships established. We have data that seem to be compelling and interesting. More to come on the enrollment rate as we get to feasibility.
spk09: And then on IP for ampryloxetine, I think with composition of matter and patent term extension associated with it, you know, that's probably looking at 2035 and then a use patent for ampryloxetine in the treatment of MSA patients I think is 2037.
spk07: Okay, that's very helpful. Thanks.
spk09: We're also likely, obviously, because it is MSA, to pick up an orphan drug designation.
spk11: Thank you. One moment for our next question. And our next question comes from the line of Brian Scorney from Baird. Your question, please.
spk02: Oh, yeah, thank you for taking the question, guys. Just one question on the new updated Orange Book IP for your power. It's a pretty big extension opportunity. I think the latest patent after the one that's just been issued expires in 2031. So I was hoping you could talk about that 531 patent that's the basis of this extension versus the other method of use patents you have for COPD and innovative over the other ones.
spk09: Yeah, absolutely. Yeah, sorry, that's a great question, Brian. The information for the patent comes from the PEPFAR-1 study, obviously, that we did without getting into just infinite number of details, obviously addresses PIFR FEV1 and FVC, which the observations that we made in the PIFR1 study were novel and, in fact, formed the basis for the use patent. Those patients are, in fact, COPD patients, and they are sort of in our, you know, in our phase three program, such that the patent really covers an integral group that is resident in the indication section of the label.
spk02: Great. And then if we could just ask a second one. On the PIPR-2 study, can you just read the sample size increase sort of changes, those assumptions?
spk09: Rick, you want to just review the sample?
spk08: Yeah, sure. So sample size assumptions are on slide 10. And what we say is the potential to increase the sample size from 366 to 48. Now, that was based on a protocol pre-specified blinded sample size re-estimation. And the reason we did that, which, by the way, is very common to do in terms of the blinded sample size re-estimation. The reason we did that is because We had relevant information from the prior PIFR study, but it was relatively limited information. For example, the primary endpoint of that study was day 30 for FEV1, and the second study, PIFR2, the primary endpoint is change from baseline FEV1 at day 85. So where the gap was, was does the variability, which we used to estimate the sample size, translate from day 30 to day 85? Well, it turns out in a blinded fashion, the variability was a little bit higher at day 85 than we could have predicted based on the day 30 data that we have from PIPR-1. So that was the basis for the increase. Again, there's no read into the outcome of the study here. This is just simply based on factors that determine sample size.
spk02: Great. Thank you.
spk11: Thank you. There appears to be no further questions at this time. I'd like to turn the program back to Mr. Winningham for any further remarks. that we can.
spk09: Thank everyone for participating. We're very aware this is an incredibly busy time for everybody with quarterly calls. So we appreciate you joining us for our update. And if you have any questions, please reach out, contact us, and we'll answer the questions that we can. So thank you very much for your time and have a good day.
spk11: Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.
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