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Acceleron Pharma Inc (XLRN) Q1 2021 Earnings Call Transcript

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XLRN earnings call for the period ending March 31, 2021.

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Acceleron Pharma Inc (XLRN)
Q1 2021 Earnings Call
May 6, 2021, 5:00 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Good afternoon, ladies and gentlemen, and welcome to the Acceleron First Quarter 2021 Earnings Conference Call. [Operator Instructions]

I would now like to hand the call over to Ms. Jamie Bernard, Associate Director of Investor Relations at Acceleron. Please go ahead.

Jamie A. Bernard -- Associate Director of Investor Relations

Thanks, and welcome, everyone, to our first quarter 2021 earnings call. The press release reporting our financial results in addition to the presentation for today's webcast are available on the Investors & Media page of our corporate website at www.acceleronpharma.com. Joining me on the call this afternoon are Habib Dable, our Chief Executive Officer; Kevin McLaughlin, our Chief Financial Officer; Dr. Jay Backstrom, our Head of Research and Development; Sujay Kango, our Chief Commercial Officer; and Todd James, our Senior Vice President of Corporate Affairs and Investor Relations. As a reminder, we will be making forward-looking statements regarding our financial outlook in addition to regulatory, product development and commercialization plans and research activities. These statements are subject to risks and uncertainties that may cause actual results to materially differ from those forecasted. A description of these risks can be found in our most recent Form 10-K on file with the SEC. In addition, today's discussion will include references to several non-GAAP financial measures, which are adjusted to exclude certain items. Reconciliations of these non-GAAP financial measures to the most comparable GAAP measures are available in today's press release on our website and at the Appendix of today's presentation. With that, I would now like to turn the call over to Habib Dable, our CEO.

Habib J. Dable -- Chief Executive Officer, President and Director

Thank you, Jamie, and good afternoon, and thank you all for joining us today. I am pleased to say that we are off to a great start in 2021, achieving meaningful progress in multiple ongoing and planned clinical trials within our pulmonary program, along with continued commercial and clinical expansion for REBLOZYL. Despite the many challenges brought on by the pandemic, our team continues to execute at a high level, positioning us well for future growth. Since reporting positive results last year from the PULSAR Phase II trial of sotatercept in patients with pulmonary arterial hypertension, or PAH, we initiated the registrational STELLAR Phase III trial and solidified plans for the other trials in our Phase III sotatercept program, which I'll elaborate on shortly. Our commitment to rare pulmonary disease extends beyond sotatercept. We are developing ACE-1334 in systemic sclerosis-associated interstitial lung disease, or SSc-ILD, a rare connective tissue disorder and the leading cause of death among patients with systemic scleroderma. You can expect to hear more about ACE-1334 in the upcoming months as we are currently planning a Phase Ib/Phase II study expected to initiate later this year in this patient population. Moving to our hematology program, REBLOZYL, also known as luspatercept, is the first and only erythroid maturation agent approved in the United States, Europe and most recently in Canada, for the treatment of anemia in certain blood disorders.

The Acceleron and Bristol-Myers Squibb joint commercial team has done a tremendous job in driving early sales success, and I'll be providing more detail on our growing footprint in a few moments. But first, I want to reflect on some of our most recent progress in our lead pulmonary program. Just last month, the New England Journal of Medicine published results from our PULSAR Phase II trial of sotatercept in patients with PAH. Having these results appear in such a prestigious journal highlights the significance of the PULSAR data, while raising awareness of sotatercept as we are advancing our Phase III program. This milestone also marks the 3rd time in the past 16 months that clinical trial results for an Acceleron discovered therapy have been published in the New England Journal of Medicine. We are excited to be returning to the American Thoracic Society International Conference this year to share new sotatercept data. And we recently announced that we'll be presenting interim results from the open-label expansion of the PULSAR Phase II trial through week 48. The presentation will highlight changes from baseline in a range of endpoints, including six minute walk distance, World Health Organization functional class and NT-proBNP. We will also review interim data from the SPECTRA Phase II trial assessing the effect of sotatercept on peak oxygen uptake and exercise hemodynamics as measured by invasive cardiopulmonary exercise testing.

Additionally, we will have two preclinical poster presentations reviewing the effects of the murine version of sotatercept in animal models of PAH and pulmonary hypertension. Following the presentations on May 19th, we will be hosting a webcast and conference call for investors and analysts to discuss highlights from both clinical trials. We hope you'll be able to join us, so please stay tuned for more information as the conference nears. We believe the results to be shared this year further strengthen our confidence in sotatercept's potential to reshape the treatment of patients with PAH. To that end, we continue to invest heavily in our pulmonary program. With several late-stage trials planned or ongoing, our clinical trial's team is laser-focused on flawless execution. Our registrational Phase III trial, known as STELLAR, is open and enrolling patients. As a reminder, STELLAR is a randomized, double-blind, placebo-controlled study comparing the efficacy and safety of sotatercept versus placebo in approximately 284 patients with WHO Functional Class II or III PAH. The primary endpoint is change from baseline in six minute walk distance at 24 weeks. We are also preparing for two additional Phase III trials of sotatercept in expanded patient populations with PAH, HYPERION in patients who are newly diagnosed with intermediate or high-risk disease, and ZENITH in patients with WHO functional class IV disease.

Results from our Phase III studies will add to our understanding of sotatercept's unique mechanism, and we believe will validate its potential to become a backbone therapy for patients across all stages of PAH and with that, I'd like to turn to our hematology program. As we reported in our year-end earnings call, REBLOZYL had a strong first year of commercial sales, and we remain pleased with the launch and the uptake in new patient starts during the beginning of 2021. For the first quarter, BMS reported approximately $112 million in net sales of REBLOZYL, resulting in approximately $22.4 million in royalties for Acceleron. By comparison, net sales were approximately $115 million in the fourth quarter with royalties of approximately $23 million. We continue to transition from the initial bolus patient group from earlier in the launch to underlying new patient demand, which was the largest contributing factor to the slight decline in quarter-over-quarter sales in the United States. Additionally, there has been an overall decrease in new patient volume in hematology as compared to pre-COVID level. Outside of the United States, the launch is going well with Austria and Germany, where our partner, Bristol-Myer Squibb, launched REBLOZYL in the third quarter of last year. BMS expects launches in multiple new countries across the globe this year following reimbursement coverage.

We believe there is significant opportunity to grow the brand within existing indications through further penetration into the long-term underlying demand of patients earlier in their MDS treatment journey in the United States. Additional launches in regions outside of the U.S. and an increase in reopening activities, including overall physician visits following continued progress in COVID-19 vaccination rates, we expect that this will lead to a return to growth for REBLOZYL following the summer months in the second half of this year. Alongside BMS, the approval and launch of REBLOZYL in multiple diseases and global markets has been our biggest achievement to date, and we continue the important development work to bring this medicine to additional patient populations, who may benefit from REBLOZYL's novel mechanism of action. We look forward to presenting results from the BEYOND Phase II trial in adult patients with anemia associated with non-transfusion-dependent beta-thalassemia by the end of June, and two Phase III trials are under way to evaluate luspatercept in patients with first-line lower-risk MDS in myelofibrosis.

BMS recently initiated the independent Phase III trial in patients with myelofibrosis, who are on a JAK2 inhibitor and require red blood cell transfusion and we expect top line results from the COMMANDS Phase III trial in MDS by the end of 2022 or later. Assuming success in current and future potential indications associated with anemia, we continue to estimate annual peak sales of REBLOZYL of more than $4 billion. Finally, I am very much looking forward to providing updates on our numerous ongoing and planned trials across our rare pulmonary disease pipeline at our upcoming Research & Development Day, which will take place virtually on June 22. We have a robust program plan with contributions from several leading pulmonary physicians and members of the Acceleron's senior management team. We wish you that it could be in person, but are nevertheless looking forward to connecting with many of you in a virtual setting. Please look for more detailed information on the events soon and with that, I would like to hand over the call to Kevin McLaughlin, our CFO, to review the financials, and then we'll be available to take your questions. Kevin?

Kevin F. McLaughlin -- Senior Vice President, Chief Financial Officer and Treasurer

Thanks, Habib. Good afternoon, everyone. I'd like to refer you to our press release issued earlier today for a summary of our financial results for the first quarter 2021 and take this opportunity to briefly review a few items. We ended the first quarter with approximately $795.4 million in cash, cash equivalents and investments. Revenue for the first quarter of 2021 was $24.8 million, which includes $2.4 million of cost share revenue and $22.4 million of royalty revenue from net sales of REBLOZYL. All revenue was derived from the company's partnership with Bristol-Myers Squibb. On a GAAP basis, total costs and expenses for the first quarter of 2021 were $88.4 million. Non-GAAP total costs and expenses were $71.7 million. On a GAAP basis, the company's net loss for the first quarter of 2021 was $63.5 million. Non-GAAP adjusted net loss for the first quarter was $46.8 million. With that, I'd like to open the call to questions. Operator?

Questions and Answers:

Operator

[Operator Instructions] Your first question comes from the line of Yaron Werber with Cowen. Your line is open.

Yaron Werber -- Cowen -- Analyst

Yeah, hi. Thank you so much for taking my question. Maybe Habib, a couple of questions for you. In Europe specifically, now that the Austria and Germany launched, how fast do you expect some of the other countries to come online? And do you have any visibility into the cadence of which ones are going to come online faster than others? And then secondly, just curious, it sounds that you're expecting more of a rebound in the U.S. in the second half. Is that -- are you just thinking that's when COVID resolves and the summer is over? Or what drives the second half? Thank you.

Habib J. Dable -- Chief Executive Officer, President and Director

Great. Thanks for your question, Yaron. So with respect to the first question, in terms of Europe and the visibility, as you heard from our partners just last week on the conference call, the ex U.S. launch has been pretty much driven by two countries, Austria and Germany and we've been very, very pleased with the initial uptake in those two markets. I think what you can expect is that in the second half of this year, you're going to start seeing reimbursements on a staggered basis starting to kick in. Typically, in Europe, 12 to 18 months post-approval is when you start seeing full reimbursement in some of the main markets. Countries that you can expect to start coming onboard, Yaron, in the second half of the year, in addition to Austria and Germany, are countries like Belgium, Netherlands, France, Italy and some of the Nordic countries and that's really consistent with the guidance that our partners at BMS have been providing as well and so from that point of view, we're very much looking forward to those countries really starting to contribute to the overall success of the launch and that obviously segues nicely into the second part of your question in terms of what is it that we believe is going to be driving this inflection point in the second half of the year?

And again, a lot of that has to do with what's happening with the ex U.S. launch, of course and as new countries come on, that obviously is going to start contributing to the global success of the brand. But in the U.S., specifically, there's a couple of things that I believe will be contributing significantly and quite frankly, we're starting to see some of these elements starting to play in and really, a lot of that's being driven by the continued increase in the vaccination rates and as different markets start opening up, sales representatives are having more face-to-face access and then secondly, patients are having more of an ability to come in to see their physicians on a more frequent basis. You may have heard last week, Yaron, our partners at BMS have actually noted that in the MDS population specifically that they've seen about a 10% to 20% decrease in new patient visits in the MDS space from pre-COVID levels to where they are now and so we're really hoping that as vaccination rates continue and hopefully, as this virus and transmission subside that we're going to see a return to growth, but also a return to normal metrics when it comes to new patient visit in the MDS space and then finally, most importantly, Yaron, what is going to be a significant driver of this growth in the second half is really in the patient mix. Now in Q4, we had approximately 40% of our patients that were being treated in the MDS patient population were really these heavily transfused patients, the bolus of patients that were just waiting for something, heavily treated, high transfusion burden and quite frankly, even in the MEDALIST study, these were the patients that did not do so well and dropped out.

So the persistency levels were definitely nothing close to what we would expect for the on-target population. In Q1, we saw that number drop almost in half to about 20% to 25%. And so we believe over the next quarter or so, that we'll be pretty much at the tail end of that bolus. And that the majority, if not all, of the population within the MDS group on REBLOZYL are going to be on target, and that will really be a surrogate driving the basis for long-term growth. So at the end of the day, when you put all that together, we're very, very confident and as I said, we're starting to see signs now of this progress and that we believe the second half is going to have some -- contribute to some very significant growth and then obviously, we still remain very bullish on our long-term prospects of this drug being a $4 billion-plus drug with, again, yes, indeed, the life cycle management opportunities seem to be successful.

Yaron Werber -- Cowen -- Analyst

Thank you

Habib J. Dable -- Chief Executive Officer, President and Director

Thank you Yaron.

Operator

All right. Your next question comes from the line of Akash Tewari with Wolfe Research. Your line is open.

Akash Tewari -- Wolfe Research -- Analyst

Hey, guys. Thanks so much. So congrats on the updated PULSAR data. It was interesting to see kind of an additional improvement to week 48. That said, one concern we had, I think looking at the placebo crossover, why do you think there was a marked reduction in the average six minute walk distance improved versus the initial treatment phase? Is this a sign that maybe the true improvement ex background treatment versus sotatercept is really more in the kind of 30 to 40-meter range and not in the 50 to 60-meter range? Additionally, was there any imbalance of patients starting on background treatment within three to six months between treatment and the placebo arm in PULSAR? Thank you.

Habib J. Dable -- Chief Executive Officer, President and Director

Thanks for your question, Akash. I'm going to hand that over to our Head of Research and Development, Dr. Jay Backstrom.

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. Thank you for the question. So with respect to the change in medications, no, that didn't occur in the trial per protocol, so they would have been on the same medicines that they came in on. With respect to what to expect with the total change in 6-minute walk distance, again, if you take a look across from -- change from baseline for just about everybody, it's 50 meters. If you look at some of the updated data that we're going to present later for SPECTRA in that cohort, it's in the 50 to 60-meter range and I think we talked about before, I do think that we have the opportunity to add on top of in the 30-meter plus range and if you look across the programs that have been conducted, frankly, even in the very upfront setting where patients are on no therapy, change from baselines in the 50-meter range. So I think overall, our six minute walk distance data are really very strong against the background of double/triple therapy and really things sets us up nicely for the STELLAR study.

Operator

Thank you. Your next question comes from the line of Carter Gould with Barclays. Your line is open.

Carter Gould -- Barclays -- Analyst

Great. Good afternoon guys andHabib, thanks for all the color on the market dynamics. I guess two questions for me. Maybe just following on the prior question. I guess, what additional metrics can we expect in the ATS presentation of PULSAR? Are we going to get the results also broken out by background therapy? And I guess, changes also in multicomponent improvements? Any additional color on that front would be appreciated. And then just, Habib, I guess a clarifying question. In terms of the time line for COMMANDS, we noticed that the primary completion got updated, I think, believe, June 2022. You're talking still about for the year-end readout in 2022? Just wanted some clarity there. Appreciate it. Thank you.

Habib J. Dable -- Chief Executive Officer, President and Director

Thanks for the question, Carter. I'll tackle the COMMANDS one right now, and then I'll hand the rest of it for Jay to continue. So with respect to COMMANDS, what I can tell you is that the guidance has remained the same, end of '22 or later. So definitely our goal is to be able to get it in the late '22, first half of '23, but that -- none that -- our guidance has changed there on that, Carter. So with respect to the rest of the question, I'll hand it over to you, Jay again, please.

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. So carter, so the update here is up to week 48, the trial is still going. And so effectively, you can see just more granularity around of the six minute walk, NT-proBNP and WHO Functional Class improvement. That will be the focus at the presentation as well as -- because we have additional safety data, update on the safety data, you'll see that broken out by dose. So that will be the focus here. Again, it's still an ongoing trial, and we have an opportunity to then present complete results, but that will be a future event, not at this ATS.

Operator

Thank you. Our next question comes from the line of Danielle Brill with Raymond James.Your line is open.

Danielle Brill -- Raymond James -- Analyst

Hi guys. Thanks-Thank you so much for the question. Habib, I've had some conversations recently with investors talking about your primary endpoint and selecting six minute walk at six months, primarily in context of seeing the 48-week data and how the magnitude of benefit seems to improve over time. Can you just maybe comment on why you're confident in the trial design and the primary endpoint selection at six months? And then as a follow-up, do you have any updated thoughts on maybe extending the primary endpoint assessment in either HYPERION or ZENITH out to 12 months? Thank you.

Habib J. Dable -- Chief Executive Officer, President and Director

Yes. Thanks for your question, Danielle, and maybe I'll start off by outlining how pleased we are that at week 48, we continue to see improvement not only with six minute walk, by the way, but also in NT-proBNP as well as in WHO Functional Class. Just to kind of remind everyone, when we were looking at the primary endpoint at six months, we had approximately 25% of patients, who had a functional class improvement versus at 48 weeks, where that number is now at 41% and so, you're right, in a progressive disease to continue to see improvement across a concordance of endpoints, we are very, very pleased and so I'll hand it over to Jay in terms of some of the thinking behind our confidence on why we chose those endpoints and the timing of them. But as you rightfully note, in a progressive disease to continue to see improvement, this is something that we're going to continue to watch, and we're obviously very, very excited about.

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. Maybe I'll just start there. I mean, I think as we were -- we talked about before, what would we expect to see in the open-label extension, what would we be looking for and as Habib said, and the disease defined by progression, stable, maintain or improve and frankly, if you look at the abstract and you come and listen to the ATS presentation, that's what you'll see. Now with respect to your question about the confidence and the endpoint, we ran a randomized Phase II study with a 24-week endpoint. And when you look at both doses combined and we're going into -- we're not doing a three arm trial, we're doing a titration approach to treating. Both doses combined in a very small 106-patient study, we had significance on six minute walk distance. As a 24-week endpoint to try to get our program with a very efficient, and you've heard me say that word before, a way to get a registration program with efficient endpoint 24 weeks is, frankly, quicker, obviously, than a 48-week and I think with the size of the study, the confidence that we're seeing, the consistency and improvement of 6-minute walk over what I expect is clearly significant. I think the endpoint is solid. We've socialized the protocols, both with FDA and in Europe. So we've got biased with the regulatory authorities on this approach. And so I think for STELLAR, we're in a very good place. But again, recognize, it's one study of three programs and if you look at the secondary endpoints included in STELLAR, we also have a multicomponent endpoint.

We have included time to clinical worsening, although in this cohort, we may not see the number of events that we would expect in some of the other studies and then I'll turn to HYPERION, which is now posted on clinicaltrials.gov, if you take a look at that, the primary endpoint there is a morbidity and mortality endpoint. It's not 6-minute walk distance. It's not measured exactly at week 24. It's an event-driven trial and so time will be a variable here as we anticipate the potential for sotatercept when added upfront to really reduce the probability of those patients having such events. It's a thoughtful design of an intermediate and high-risk cohort that are at risk for these events and so we think we'll be able to demonstrate that and then similarly, in the ZENITH study, which we haven't talked a lot about, we'll share more of that at the R&D Day. It will be looking, again, at a morbidity and mortality endpoint, but also with functional improvements, et cetera, like we built across the program. So when I put all that together, again, the best way to have a positive Phase III study is to have a solid positive Phase II program and do very little to vary from what you've done there, except potentially strengthen it and that's what we've done with STELLAR. We strengthened STELLAR, and I feel we have a very high probability of technical success given the Phase II data.

Danielle Brill -- Raymond James -- Analyst

Got it. Thank you so much.

Habib J. Dable -- Chief Executive Officer, President and Director

Thank you Danielle

Operator

Your next question comes from the line of Eric Joseph with JPMorgan. Your line is open.

Eric Joseph -- JPMorgan -- Analyst

Hi, good evening. Thanks for taking the question. Just a quick one from us on STELLAR, which is really, how should we frame expectations in terms of recruitment time lines with the pandemic representing a particular challenge. Is it fair to sort of graph from the PULSAR experience such that it is larger, if not... Thanks.

Habib J. Dable -- Chief Executive Officer, President and Director

Again, over to you, Jay?

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. So what I'll say, a couple of things. We're on track, as I would have hoped us to be, as we opened up the trial at the end of the year. So, so far, so good, Eric. There's clearly, clearly interest in the study and in the program, which is to the good. We've got investigators working hard to get the centers up and running. So I feel like we're at a place where things so far, so good. Of course, it's early in the recruitment phase and early in the beginning of the study. But again, I think we were very fortunate with PULSAR. I think I've said on previous calls that we had completed enrollment before we got into the middle of the pandemic and then as things got better, we were able to keep patients on and continue to follow, hence, the ability to get the open-label data out and presented. I feel like we're in a similar place. The centers are really interested. They want to get patients on trial. They're working hard with us to get the centers open. And as Habib commented on, hopefully, we're getting to open so that we won't even ask if the pandemic is going to influence our accrual, right? We'll just be back to the routine business. But so far, so good, and we'll see how we go, but we're on track.

Eric Joseph -- JPMorgan -- Analyst

Do you think the pandemic has effected prevalence?

Jay T. Backstrom -- Executive Vice President of Research and Development

Has it affected the prevalence?

Eric Joseph -- JPMorgan -- Analyst

Has there been increased mortality as -- I guess, susceptibility really to infection and mortality among PAH patients that might have had an impact on just the prevalence...

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. Obviously, it's a vulnerable group, that's for sure. What I can tell you from our own experience and without generalizing across, from our programs with patients on trial, we haven't seen -- our patients are fine and not succumbing to the pandemic, to COVID. We still have over 90-plus percent who came into open-label, on open-label, so they're able to both access our medicine and manage through it. So interesting question. I would trust that with vaccination strategies and pulmonary good management, hopefully, they can minimize that. But interesting question, but we're not seeing that effect in our studies.

Eric Joseph -- JPMorgan -- Analyst

Great. Thanks for taking the question.

Habib J. Dable -- Chief Executive Officer, President and Director

Thank you Eric.

Operator

Your next question comes from the line of Geoffrey Porges with SVB Leerink. Your line is open.

Geoffrey Porges -- SVB Leerink -- Analyst

Thank you very much. Appreciate taking the question Jay. So I'll keep banging on the theme of STELLAR. STELLAR is a relatively small study, 284 patients and I know you're very confident about the effect that you saw in the PULSAR study, but is it absolutely clear that you won't need any of the experience -- the patient observations or experience from HYPERION for regulatory approval in the U.S. or Europe? That's the first question and then I just wanted to follow-up on the frontline luspatercept study in MDS. Could you comment on how recruitment is going because you pointed out that MDS patients are not seeking medical care. So I'm wondering what's happening to that trial and then lastly, Jay, could you just talk about what proportion of the newly diagnosed MDS patients are going to be transfusion-free on EPO in the control arm? And then what you have to show in the active arm to achieve superiority? Thanks. Apologies for all the questions.

Jay T. Backstrom -- Executive Vice President of Research and Development

Okay. Well, let's start with six minute walk, shall I?

Habib J. Dable -- Chief Executive Officer, President and Director

Yes, please.

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. So let's start with the six minute walk distance. As I mentioned, Geoff, we took full advantage of being granted breakthrough therapy designation in PRIME and so we have discussed not only STELLAR, but the entire program with the health authorities and we've aligned with them that the primary endpoint, which is a measure of functional benefit, six minute walk distance, is an acceptable regulatory endpoint. So we've got that alignment. In addition, we discussed all the other secondary endpoints included in that. So that, I think, is to the good. I think also to recognize you put the totality of the information together that we have, when you look at PULSAR now with the additional crossover patients, we have SPECTRA. So we're adding a body of evidence within the clinical parameters in addition to STELLAR and then when you bring on the other programs, of course, over time, we'll have all of that. So straight answer, yes, acceptable regulatory endpoint, and we certainly socialized. With COMMANDS, I think it's like anything, our BMS partner running those programs, they're working to get the completion of the study so far. It did have some effect on the pandemic back in the March. BMS took a decision to close the program for a period of time, but they've since reopened. They're adding additional centers. So they're pushing a lot to actually get patients in. It's a fairly narrow patient population, and so that has been principally the challenge of accrual.

Nonetheless, there is clear interest in getting patients on the trial and then with respect to your last question about what to expect. Recall, that these are patients that still require transfusions. We are stratifying by EPO levels and if you look at the publications that were out in the last two years or so from Platzbecker and Fenaux, for the ESAs in settings where patients start to begin to get transfusions, and for -- particularly, once they start to get EPO levels above 200, it does not work well. At best, you begin to see, even in the best of circumstances, something in the 15% to 20% range. But quite honestly, once you get over EPO levels of 200, they don't get transfusion independence on an ESA. It just not -- doesn't work well. So the trial is really looking at that population and then if you take a look at the data that we have with luspatercept, even if you take a look at the data that we have in the MEDALIST study, where patients were in that two unit range at the beginning. We had over 80% of those patients achieving transfusion independence, which is really quite durable. So without going into more detail on the stats, Geoff, I think those two kind of bookends should give you some sense of what to expect for the probability of success on that study.

Geoffrey Porges -- SVB Leerink -- Analyst

Great. Thank you Jay.

Habib J. Dable -- Chief Executive Officer, President and Director

Thanks Geoff.

Operator

Your next question comes from the line of Yigal Nochomovitz with Citigroup. Your line is open.

Yigal Nochomovitz -- Citigroup -- Analyst

Hi. Thanks very much for taking the questions. I just had one on ACE-1334. Could you describe what you're hoping to see in the Phase Ib/II data in patients with SSc-ILD that you believe will meet the objectives for the target product profile for this program? Thanks.

Habib J. Dable -- Chief Executive Officer, President and Director

Thanks for your question Yigal, I'm going to hand that over to Jay as well.

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. So we designed it as a Ib, and we haven't really gone into a lot of the details. So that's going to be my teaser to come to R&D Day as we get into it further, but just to kind of frame it, I think what's really going to be important for us in that opening setting is to be able to identify a go-forward dose, that's the Ib portion and to try to define that in a quick manner as possible, and so there's a number of ways to do that. It will be rich in clinical pharmacology, PK/PD parameters, biomarker to look for target engagement and I think we do have clinical endpoints in there that will give us some guidance as to what we anticipate as we go into the Phase II. But really, it is trying to get to that place where we feel good about a dose. If I extrapolate back to what the clin pharm team did with sotatercept, and we need to give them the same opportunity with some data to generate it, and this preceded me coming into the company. I was very impressed. They -- with their understanding of what they saw in their PK/PD model, and they predicted that 0.3 mg and 0.7 mg would be good doses, and they were spot on both active doses. So we're going to look for that in the Ib and then based on that Ib, I always say that the most critical step moving forward into any development program is getting the dose and schedule right and once we've established that, then we have some latitude as to where to go and how to run and so that will position us nicely for the Phase II. So we we're getting the centers opened, and Ib will be absolutely critical. It's a cohort-type study, and it affords us the opportunity as we see things that we can share it prior to that. But right now, we're in the study starting phase. So no data to share yet. We're getting the study ready.

Yigal Nochomovitz -- Citigroup -- Analyst

Got it. Thank you very much Jay.

Jay T. Backstrom -- Executive Vice President of Research and Development

Thank you Yigal.

Operator

Your next question comes from the line of Corinne Jenkins with Goldman Sachs. Your line is open.

Corinne Jenkins -- Goldman Sachs -- Analyst

Hi. I was wondering with regard to HYPERION and the endpoint of time to clinical worsening, what's the natural history for the population of patients that you're going to be enrolling into that study?

Habib J. Dable -- Chief Executive Officer, President and Director

Yes, good question. We take a look at that. There's been some recent -- there are several studies that have looked at this upfront population. We've selected out an intermediate and high-risk cohort and the way this is defined is it from newly diagnosed patients if, in fact, you can achieve goal, which is really getting them under control and to like functional Class I, if possible, they're at high risk for such events in between 20%, maybe 30% a year. It really depends on the population. The higher risk patients come through so well. If you look at the data out there, principally, the time to clinical worsening is kind of a composite endpoint. So that does include all-cause mortality. Fortunately, with the number of therapies out, early lines of treatment, deaths are not the most common event, that's fortunate. But hospitalization because of worsening and some of the other criteria, typically would be the ones that tend to drive it. We've deliberately selected this population because it's enriched for patients that should have such events and quite honestly, there's just recent publications out where the field is hungry to get these patients under control. There's a strong desire to do it. I believe that the PULSAR data showing that we can add on top of and bring advantage to patients, particularly if you look at that PVR reduction, that is a really good goal for patients upfront to be controlled. So like the trial, we're working hard to get it open, but that's what to expect, so they need rescue.

Corinne Jenkins -- Goldman Sachs -- Analyst

Yes. That's helpful. Maybe just one more point of clarification. You mentioned earlier that you were -- about 40% of patients in Q4 were prevalent population, they're 20%, 25% now. Is that with respect to a total patient on REBLOZYL? Or is that new patients coming on therapy?

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. No, that's with respect to the total population on REBLOZYL with MDS because don't forget, we still have a portion of the population that's on beta-thalassemia in the United States as well.

Corinne Jenkins -- Goldman Sachs -- Analyst

Great. Okay, thanks. Thank you.

Operator

Your next question comes from the line of Leland Gershell with Oppenheimer. Your line is open.

Leland Gershell -- Oppenheimer -- Analyst

Hi, good afternoon and thanks for taking my questions and thanks for the color. We appreciate the publication on the PULSAR data in the New England Journal. I wanted to ask in terms of the safety profile, we did see hemoglobin increases in the patients. Want to ask maybe a question for Jay, just in the context of the PAH patient population, how we should think about potential for license in hemoglobin? Any concerns about the inconsistency of that predictability and any possibility for monitoring requirements that might come in for patients who go on sotatercept with PAH? Thank you.

Jay T. Backstrom -- Executive Vice President of Research and Development

Yes. So let me just start. I think PULSAR was quite instructive to us. As you know, sotatercept was -- I worked actually on it in 2008 when I was at Celgene for MDS. So that it has an effect on hemoglobin is expected as part of its profile. When we take a look at the data that we presented, it's in the range of 1.2 to 1.5 grams per deciliter. So the magnitude of that change is not dramatic and in fact, actually, a number of the therapies, the ERAs have anemia associated with it. So I don't think it will be something that most patients will be concerned with and frankly, probably not going to be anything looked at is anything but a potential benefit. The patients where we potentially have to think about it is those that are really at the upper end of normal that are running already with high hemoglobin. Touching that up and getting that up a little bit higher would certainly require some potential monitoring in those patients. What we do know is that this isn't something that continues to rise steadily dose after dose. Actually, with our strategy of 0.3 mg to 0.7 mg, we attenuate the effect, and then usually by the second or third dose, you don't see any further increases. So this is just -- it's present, easy to take to look at. Patients are already considered -- being managed for anemia potentially because of some of the other therapies. So I think it's going -- kind of can be woven neatly into routine care for patients, which is kind of what we're replicating in our study.

Leland Gershell -- Oppenheimer -- Analyst

Thanks and then just a question in terms of further indication potential with your pipeline and, obviously, a lot you could do with this mechanism and pathway in fibrotic indications and so forth. Just wondering if maybe Habib, you could allude to any further development plans that you may have? And maybe we'll have to wait until the R&D to hear other than pulmonary or outside about what you may be looking at to do as you go forward in the R&D side? Thanks.

Habib J. Dable -- Chief Executive Officer, President and Director

Yes, it's a great question, Leland. So I guess the first thing I would say is I think you need to remind everyone that the licensing agreement for sotatercept with BMS allows us to develop and commercialize across all areas of pulmonary hypertension. So we've talked quite a bit today about different functional classes within group one pulmonary hypertension, or PAH. But we obviously have a tremendous amount of work that we're going to share at R&D day in terms of our findings preclinically, in group two pulmonary hypertension, basically PAH with associated left heart disease and you're going to hear about our clinical development plan and where that confidence is coming from in terms of that path forward. These are -- are there opportunities within pulmonary hypertension, including group three and beyond? We're not there yet in terms of the robustness of our preclinical work to be able to share and make any commitment. But we're obviously exploring that heavily and so yes, please try and make it to the R&D day where you're going to hear a lot more, not only about group 1, but also specifically about group two pulmonary hypertension and sotatercept.

Leland Gershell -- Oppenheimer -- Analyst

.[Indecipherable] Thanks Habib.

Operator

Your next question comes from the line of Kennen MacKay with RBC Capital Markets. Your line is open.

Michael Murray -- RBC Capital Markets -- Analyst

Hi. This is Michael Murray, on for Kennen. Thanks for taking my question. On the luspatercept launch, I know commercial is out of your hands. But what are you hearing from the boots on the ground, where is the remaining low-hanging fruit from a sales and marketing perspective? And then just another quick one. How do sales breakdown between current MDS and beta-thalassemia markets? And where do you think is the larger near-term growth opportunity? Thank you.

Habib J. Dable -- Chief Executive Officer, President and Director

Yes. Great. Well, let me start off, Michael, by saying commercial is not out of our hands. It's predominantly in BMS' hands worldwide. But in the United States, in North America, we do have the opportunity to co-promote and in the U.S. now with the first launch, we have 20 commercial people in the field that are funded by BMS under the leadership of Sujay Kango, our Chief Commercial Officer, and perhaps he can give you some live color in terms of answering some of the questions that you've asked. Sujay, over to you.

Sujay R. Kango -- Executive Vice President and Chief Commercial Officer

Yes, absolutely. So if I understood your question, you're trying to kind of get a sense as to the low-hanging fruit and the second question was a little bit with regard to the split. Now maybe I can take the second part first. We don't really kind of breakdown the sales as to how much of the revenue today is coming between the two indications that we have, which is transfusion-dependent beta-thalassemia as well as low-risk RF-positive MDS patients, right? However, what I can tell you is you can almost sort of imagine that largely speaking, the cohort of MDS patient population is significantly more to the tune of, say, the beta-thalassemia patients and you can assume somewhere to the tune of the low-risk MDS patient population in totality is about 20,000 in the U.S., combined close to 40,000 between U.S. and Europe, which is low-risk patient population. If you think about the beta-thalassemia patient population in the U.S., particularly that is transfusion-dependent, you have about 1,500 patients. You can almost assume that the majority of the revenue stream, at least in the United States, which right now is the bulk of the revenue stream, is going to come from MDS.

So hopefully, that gives you a generic, but a pretty reasonable framework of how to expect. Now, your primary first question was the low-hanging fruit on the commercial, where do we see growth is how I kind of assume that's the question. We do see a lot of growth still continuing in the MDS segment because we haven't yet capitalized on all the patients that are earlier in the patient journey, as Habib and our peers at BMS have quantified in the prior sort of conversations. So we do believe that we can still sort of get a larger segment of earlier lines of ESA-treated patient population similar to what we have treated in our Phase III registrational study, and that should drive further growth within the coming second half of the year and moving forward. So hopefully, that gives you a line of sight as well.

Michael Murray -- RBC Capital Markets -- Analyst

Yeah, it did. Thank you

Habib J. Dable -- Chief Executive Officer, President and Director

Thank you, Michael.

Operator

We have reached the end of the Q&A session. I would like to turn the call back to Acceleron's CEO, Habib Dable, for closing remarks.

Habib J. Dable -- Chief Executive Officer, President and Director

Great. Thank you, operator. Thanks, everyone, for joining us today. Very much looking forward to connecting with many of you around ATS in the next few weeks as well as during the virtual R&D Day in June and in the meantime, if you have any questions, please feel free to reach out to Todd or Jamie and in the meantime, I hope everyone continues to stay safe and healthy, and wishing you all a great evening.

Operator

[Operator Closing Remarks]

Duration: 47 minutes

Call participants:

Jamie A. Bernard -- Associate Director of Investor Relations

Habib J. Dable -- Chief Executive Officer, President and Director

Kevin F. McLaughlin -- Senior Vice President, Chief Financial Officer and Treasurer

Jay T. Backstrom -- Executive Vice President of Research and Development

Sujay R. Kango -- Executive Vice President and Chief Commercial Officer

Yaron Werber -- Cowen -- Analyst

Akash Tewari -- Wolfe Research -- Analyst

Carter Gould -- Barclays -- Analyst

Danielle Brill -- Raymond James -- Analyst

Eric Joseph -- JPMorgan -- Analyst

Geoffrey Porges -- SVB Leerink -- Analyst

Yigal Nochomovitz -- Citigroup -- Analyst

Corinne Jenkins -- Goldman Sachs -- Analyst

Leland Gershell -- Oppenheimer -- Analyst

Michael Murray -- RBC Capital Markets -- Analyst

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