Okay, great. Thanks, everyone, for joining. My name is Frank Brisebois. I'm one of the biotech analysts at Oppenheimer. Our next presenting company is Theravance Biopharma. From the company, we have CEO Rick Winningham to present. And so what we'll do in terms of format, we'll do about a 20-minute presentation followed by some Q&A. So feel free to send me questions in the Q&A tab at the bottom of your screen. You can also email me questions if it's easier. With that, Rick, thank you so much for joining, and I'll let you take it away.
Yeah, thank you, everyone, for joining us here today, and Frank, thank you, and Oppenheimer for inviting us to share the Theravance Biopharma story, so if we could go to the second slide, and I will be making some forward-looking statements today in the presentation, so I encourage you to refer to our filings with the SEC. Just as another reminder, we are planning on disclosing the fourth quarter results on February 26th in our sort of year-end call, so I'll keep my comments today pretty high level, referring to previously disclosed information, so now going to the next slide. Theravance and our portfolio of revenue-generating and late-stage assets. Importantly, our product YUPELRI, which we market in the United States with our partner Viatris, a product for COPD on the market, growing.
And I'll spend some more time during the course of the presentation describing the growth opportunities for YUPELRI and the market that it serves in COPD. We also, with Viatris, have a partnership in China. Viatris is responsible for the regulatory work in China, as well as the commercial launch. They filed for approval in China in mid-2024. And we look forward to Viatris getting that product, getting our product approved in China, because, as many of you know, there's a significant opportunity in COPD in China. Then ampreloxetine. This is a phase III program, rare disease that we have underway. We're expecting to finish the open-label portion of the phase III study in the middle of this year and then have data about six months later. Again, rare disease. We have orphan drug designation. We have 100% commercial rights to the product.
Very exciting program for us and what we think we will be able to do for patients with multiple system atrophy and neurogenic orthostatic hypotension. And then finally, Trelegy, which is a passive asset for us, really dating back in the history of the company, working with GSK. And we have a series of milestones and royalties that are associated with the milestones kicking in in the very short term, based on 24 sales, 25 sales, and 26 sales. And then royalties beginning coming back to us from Royalty Pharma in 2029 and beyond. And I'll go over that a little bit later in the presentation. So if I could have the next slide, please. So, YUPELRI. This is our product that we co-market in the United States with Viatris. Our objectives here are to continue to grow YUPELRI.
We've got a significant opportunity for continued YUPELRI growth in the U.S. in 2025 and beyond. We're really continuing to just scratch the surface of the opportunity. The next potential U.S. milestone for us is a $25 million milestone in the first calendar year in which we reach $250 million in sales. This is a profit share, 65% profits to Viatris and 35% profits to Theravance. This is a product that currently is cash flow positive for the company. We look forward in future years to continuing to drive increasing brand margins as we leverage the investment that we've made historically for YUPELRI. Now, ampreloxetine. Again, as I said a moment ago, our objective is to complete enrollment in the open-label portion of our registrational phase III study called Cypress. To finish that open-label enrollment in the mid-2025.
We expect data about six months after finishing the open-label enrollment and an expedited NDA filing, assuming positive data. We will request priority review because of the unmet medical need that exists in the market. We'll use 2025 to continue to build awareness as we partner with opinion leaders and the caregiver community to educate on the disease state, as well as plan on optimizing the access strategy for the product once it's approved. Very exciting. I'll spend more time on ampreloxetine in the course of the presentation. Then finally, Trelegy, as I touched on a moment ago, $200 million in near-term milestones, $50 million being the first one, $50 million milestone based on sales of 2024. Based on GSK's call a week or so ago, their performance in 2024 strongly suggests that, in fact, we'll earn the $50 million milestone based on those 2024 sales.
We'll provide an update again on February 26th that sales, as reported by GSK, exceed the threshold necessary for the $50 million milestone in 2024. We have another potential milestone in 2025 of $50 million and then a $100 million milestone in 2026. Right now, with the growth of Trelegy, those milestones look increasingly possible and probable to us. As I mentioned, the Trelegy royalties will return to Theravance beginning in 2029 outside the United States, continuing through the mid-2030s and returning to us in the United States at the beginning of 2031. We'll have a cash flow coming back to the company coming from Trelegy royalties. I'll touch on what that is and the scale of those at the end of the presentation. From a corporate perspective, we've got a commitment to return excess capital to shareholders.
We'll issue our financial guidance when we have our February 26th call covering Q4 and 2024 results, as well as our annual results. The next slide, please. I'll cover YUPELRI. We can go to the next slide. It's a once-daily long-acting muscarinic antagonist delivered via nebulizer for patients with COPD or chronic obstructive pulmonary disease. Nebulized therapy is an important route of therapy for about one in 10 COPD patients. It's a significant market. About 1.9 million patients in the United States, we believe, could benefit from YUPELRI. Nebulization really addresses those patients who may have dexterity problems, strength problems, or have difficulty coordinating hand-to-breath activity to use a handheld inhaler. YUPELRI is reimbursed through Medicare Part B, and it's about 28% of Medicare patients with COPD currently have a nebulizer. It's a very attractive market.
YUPELRI delivers a very attractive benefit to those COPD patients as a once-daily nebulized long-acting muscarinic antagonist, which is GOLD standard therapy. Next slide, please. We currently view the opportunity in the United States, about 200,000 patients currently on long-acting nebulized therapy. These patients are on a long-acting beta-2 agonist that's helping them improve their breathing today. To that, we believe that YUPELRI can be added such that those patients that are using a nebulizer can avail themselves of really GOLD standard therapy because GOLD guidelines suggest that both category B and E patients, slightly more severe COPD patients, receive LABA/LAMA therapy, which is now possible given YUPELRI's entrance into the market. That's about 200,000 patients currently on long-acting neb therapy, of which we're working to get YUPELRI added into that regimen. There's another 200,000 patients that use short-acting nebs inappropriately for maintenance.
These short-acting nebulized therapies are used between four and six times a day. And our objective, of course, is to transition those patients from short-acting nebs to long-acting nebs that they will only have to take in the YUPELRI case only once a day. So there's a significant opportunity there. And then there's another almost million and a half symptomatic patients with reduced cognition, dexterity, or inspiratory flow issues that use handheld therapies, but using them incorrectly. And those patients can benefit from getting reliable therapy from a nebulizer. So significant opportunity exists for YUPELRI for continued growth inside the United States. Next slide, please. This describes the Theravance Viatris partnership that we're the two companies working together to drive YUPELRI growth in the US. Theravance covers the hospital and hospital patients, whereas Viatris covers the community.
Our objective inside the hospital is to get YUPELRI on formulary to be able to help patients that are hospitalized, that have COPD, and then achieve a discharge, have that hospital patient when they're discharged, have them be discharged with a prescription for YUPELRI, and then, of course, work with our partner Viatris to have those prescriptions filled in the outpatient setting and then have patients continue on YUPELRI. Our hospital starts make a sizable contribution to the overall business, and we've been able to grow the hospital business very nicely over the last several years, and I'll describe that in just a second. Next slide, please. This is YUPELRI net sales performance ending in the third quarter of 2024. As I said, we'll update the market on quarter four performance on February 26th.
But here you see in the most recent quarter that we've released, in the third quarter, growth of 7%, growth 24% over the same time in 2023. So we've had growth. We expect growth to continue for YUPELRI in the overall setting in the United States. Next slide, highlighting the hospital business. The U.S. hospital business has been a significant contributor to overall performance, as I mentioned. If you look at growth inside the hospital, we've been able to drive growth up 40% Q3 2024 over Q3 2023. And we expect continued growth, and we'll highlight that again at our end of year call on February 26th, 2024, this year. So the hospital business is driving, helping drive the overall YUPELRI business and working with our partner Viatris to achieve both use in the hospital as well as use in the community. Next slide.
And I mentioned in passing at the beginning the China opportunity. Viatris is responsible for YUPELRI in China. As I said, they filed for approval in China in the middle of 2024. And we look forward to that approval. Viatris is guided about a two-year approval review time. And then about fifth overall, the average review time in China is about 15 months. So the big market, big opportunity, and we look forward to updating you in the future on the progress in China. We get a $7.5 million milestone upon approval, and then a 14%-20% tiered royalties going forward. So next slide, please. Trelegy, the first and only triple therapy, single inhaler. I'll move through this pretty quickly. Next slide. This just highlights the thresholds for Theravance and earning milestones from 2024 - 2026.
As you can see, in 2024, again, the results that GSK released about a week ago strongly suggest that we'll earn the $50 million milestone for 2024 sales, and in fact, growth of the brand in 2024 through to 2025 and 2025 - 2026, consensus estimates really have us earning the upper end of the milestones in both of those years, so some very encouraging economic news, I think, for the company, enabling us to earn milestones over the next couple of years of quite significant value. Next slide, and then the other component is value from Trelegy or royalties that will return to Theravance beginning in 2029. ex-US royalties will revert to us in July of 2029, and US royalties will return to us on January the 1st of 2031. Now, Trelegy has just done terrifically in terms of global sales, both in the United States and beyond.
And we look forward to these royalties actually making a meaningful contribution to Theravance value in the future. So that's the Trelegy story. And now I'll move on to ampreloxetine. Very excited about Ampreloxetine. This is the first once-daily selective norepinephrine reuptake inhibitor in development to treat symptomatic NOH or neurogenic orthostatic hypotension in MSA. Next slide. MSA is a progressive neurological disorder that leads to autonomic failure and hence neurogenic orthostatic hypotension or the inability of the patient with MSA to regulate blood pressure. MSA causes alpha-synuclein deposits to localize in a couple of different areas in the brain and causes progressive neurodegeneration. This neurodegeneration leads to autonomic failure that's characterized by NOH and significantly reduces the quality of life in these patients.
However, with MSA, as differentiated from other synucleinopathies like Parkinson's disease, the peripheral nerves in MSA are intact, providing a norepinephrine reuptake inhibitor the opportunity to potentially enhance autonomic function and alleviate the symptoms of NOH. Next slide, please. What is NOH or neurogenic orthostatic hypotension? This is a devastating consequence of MSA. Patients experience a rapid blood pressure reduction upon standing that causes hypoperfusion or a lack of blood getting into various tissues. Weakness causes weakness, shoulder pain, trouble concentrating, significant dizziness, blurred vision, and again, significant shoulder, head, and neck pain. These symptoms are unremitting in patients. We measure these symptoms through something called an Orthostatic Hypotension Symptom Assessment or OHSA. This is how we measure symptoms, really judging how intense they are. In fact, a composite OHSA score is the primary endpoint in our ongoing phase III study.
If we move the OHSA symptom score by one point, that is a change that's considered clinically meaningful for the patient. Next slide, please. Ampreloxetine increases norepinephrine in the synapse in order to enable the treatment of neurogenic orthostatic hypotension. And this works in MSA patients because the postganglionic sympathetic nerves are intact, therefore allowing the norepinephrine to, in fact, cause constriction of the blood vessels and cause an increase in blood pressure. Now, importantly, these patients are hypotensive, so we're moving their blood pressure back into the normal range through the administration of Ampreloxetine. Next slide, please.
This is data from MSA phase III, an earlier phase III study that we did showing that, in fact, when Ampreloxetine is administered, it causes an increase in norepinephrine in the plasma and a decrease in, in fact, the metabolic byproduct of norepinephrine, DHPG, showing that Ampreloxetine is, in fact, causing the norepinephrine that's in the synapse to not be degraded when compared to placebo. We see, looking at the center figure, that we do change the blood pressure, about 16-18 millimeters of mercury, increasing levels of perfusion into the tissue, which, in fact, causes an improvement in the OHSA composite score. This data reflects a randomized withdrawal study that shows a worsening of over one point or a clinically significant worsening when Ampreloxetine is withdrawn to patients with MSA and NOH.
So keeping them on therapy, in fact, alleviates these symptoms in a clinically significant way. Next slide, please. Cypress, the study that's ongoing, is designed to reproduce an earlier study that we did in MSA patients, Study 170. Cypress has a 12-week open label period and an 8-week double-blind randomized withdrawal period. As I said earlier, our objective here this year is we plan to finish our enrollment in the open label period in mid-2025, and then we will have data about six months later from the study from the randomized withdrawal period. Very exciting. There's really no treatments in the market that reliably treat neurogenic orthostatic hypotension in MSA patients, and a positive outcome in Cypress will be sufficient for a regulatory filing in this rare neurological condition. Next slide.
As I mentioned, there are no therapies that are approved and no therapies that have been shown to be valuable beyond two weeks. MSA patients need the therapy because NOH is really the debilitating condition that prevents patients from really being able to participate in life. There are medicines that are used to treat NOH, but these medicines are insufficient. So we're very excited about the opportunity of Ampreloxetine to be the first medicine approved to treat NOH and MSA patients. Next slide. There's a significant opportunity. About 40,000 patients in the United States with MSA and NOH are rare disease. We have received orphan drug designation by the FDA, and about the same number of patients in Europe and about the same percentage of the population, regardless of where you go in the world, has MSA and NOH.
So it is a significant opportunity to go in and meet this unmet medical need, and we look forward to doing that. Next slide, and so that, Frank, will wrap up my comments and look forward to any questions that the audience might have.
Excellent, well, thank you very much. That's a great review of the company. There's a lot going on here. Maybe on the YUPELRI side, I was just wondering, in terms of headwinds, tailwinds for growth going forward. It's obviously tricky because you guys are disclosing numbers soon. But what has been the biggest challenges and what makes you feel confident about the future of YUPELRI?
Well, I think the challenge has simply been getting out and commercializing, getting the hard work that's necessary to commercialize the product for us in the hospital and getting on formulary.
And then for us, not only do we get on formulary, but many times, in fact, most of the time now, we're designated for therapeutic interchange such that any time that a medicine of this class is used or prescribed in the hospital, that it's substituted for YUPELRI. It's a Medicare Part B drug, so everyone in Medicare is covered. There's a difference sometimes depending on the copay with regard to whatever plan that the patient may be on. But in many instances, the copay for YUPELRI is zero. So I would say the greatest barrier is really educating physicians and giving them the understanding that this product, YUPELRI, is a once-daily product. As I said, many of the products that are used by patients are used four to six times a day.
YUPELRI can be used once a day in a very small handheld nebulizer for optimal patient convenience and, in fact, provides a very medically meaningful level of bronchodilation or the ability to breathe for these patients based on once-a-day administration.
Okay, great. And then in terms of ampreloxetine, can you help us understand a little bit more of the history here? And is there something that's kind of misunderstood in terms of its commercial opportunity?
Yeah, that's a great question, Frank. We did an earlier phase III study where we looked across synucleinopathies and Parkinson's disease, primary autonomic failure, and MSA. Going into that study, we over-enrolled sort of relative to what you'd find in the community MSA patients, and we pre-specified an analysis by disease type. And what we found is we didn't show a difference in Parkinson's disease, and we did show a difference in multiple system atrophy.
I think what's maybe misunderstood is the prevalence of the disease and the significance really that ampreloxetine can make in the treatment of this disease based on the data that we have from 170, an earlier study, and then what we hope to deliver with Cypress. The ability to treat these patients with NOH can really enable them to enjoy more of their life, get up off of their couch or chair, and participate in life because of the alleviating the symptoms of NOH. That's what we're very excited about being able to do. As I said, we'll finish the open label portion of the study in the middle of this year and can expect that phase III data about six months later.
Okay, that's super helpful.
Then it's tough to share with the quarter coming, but you mentioned on the Trelegy side, it seems like based on GSK suggesting growth continues in 2025, which would seem like you're on track for that $50 million milestone next year as well, is what that amounts to.
Yeah, that's a great point. I think based on consensus estimates today of Trelegy, it really does put both the 2025 milestone and the 2026 milestone, $50 million and $100 million respectively, into the frame. Trelegy has been a terrific product, very strong grower globally. Consensus estimates are that it will continue to grow and will enable us to earn those milestones in 2025 and 2026.
And again, based on the disclosures that GSK made about a week ago, it does strongly suggest that we've reached the threshold to earn the $50 million milestone in 2024, and we'll address that on February 26th in our quarterly call.
Okay, well, Rick, I think we're up on time. Thank you very much for attending, and hopefully this was helpful to listeners.
Thanks, Frank. Really appreciate you and the invitation from Oppenheimer to participate. Have a great day.
Thank you.