Acceleron Pharma (NASDAQ: XLRN) Q4 2018 Earnings Conference CallFeb. 27, 2019 5:00 p.m. ET
Contents:
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- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Good afternoon, ladies and gentlemen, and welcome to the Acceleron fourth quarter and full-year 2018 earnings conference call. [Operator instructions] As a reminder, this conference call is being recorded. I would now like to hand the call over to Mr. Todd James, vice president, investor relations and corporate communications at Acceleron.
Please go ahead.
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Todd James — Vice President, Investor Relations and Corporate Communications
Thanks, and welcome, everyone, to our fourth quarter and full-year 2018 earnings call. The press release reporting our financial results in addition to the presentation for today’s webcast are available on the investors and media page of the corporate website at www.acceleronpharma.com. Joining me for the call today are Habib Dable, our chief executive officer, Robert Zeldin, our chief medical officer, Kevin McLaughlin, our chief financial officer, John Quisel, our chief business officer, and Sujay Kango, our chief commercial officer. As a reminder, we will be making forward-looking statements regarding our financial outlook in addition to regulatory and product development 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. I’d now like to turn the call over to Habib Dable, our chief executive officer.
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Habib Dable — Chief Executive Officer
Thank you, Todd. Good afternoon, everyone, and thank you for joining us today. 2018 was an important year for Acceleron, and I’m extremely proud of the progress we’ve continued to make across our entire pipeline. 15 years after our founding, we have one of the most advanced TGF-beta superfamily based pipelines in the industry focused on three disease areas, hematology, neuromuscular and pulmonary.
Looking ahead, 2019 and 2020 include several key milestones for all of our programs including the potential approval and commercial launch of our lead product candidate, Luspatercept, in both the United States and Europe. We also expect important Phase 2 results from each of our ongoing trials in neuromuscular and pulmonary disease. Turning to our pipeline in hematology. Alongside our collaboration partner Celgene, we currently have multiple ongoing Luspatercept trials in patients with anemia associated with myelodysplastic syndrome or MDS, beta-thalassemia and myelofibrosis.
In neuromuscular, we have two Phase 2 trials of ACE-83 under way in two diseases associated with focal muscle weakness, FSHD and CMT. Lastly, in pulmonary, both our PULSAR and SPECTRA trials are active and will be evaluating sotatercept in patients with PAH. Focusing first on Luspatercept. In the middle of last year, we were excited to announce positive results from our pivotal Phase 3 trials, MEDALIST and BELIEVE, in lower risk MDS and beta-thalassemia respectively.
This set the stage for a very strong showing at ASH 2018 with Luspatercept front and center. The Acceleron and Celgene teams did a phenomenal planning and executing at this key hematology congress attended by more than 25,000 people. Among the key highlights at ASH, the topline results from both MEDALIST and BELIEVE trials were reviewed and discussed at the meeting’s opening press conference along with only two other clinical trials. The BELIEVE trial presented by Dr.
Nica Capellini from the University of Milan to a full room along with multiple ancillary rooms of attendee overflow. The MEDALIST trial, the first of six plenary presentations presented by Dr. Alan List from Moffitt Cancer Center to a main conference center room packed with over 10,000 meeting attendees. Both trials were selected from among thousands of scientific presentations at the meeting for Best of ASH Honors, distinguishing them as some of the biggest breakthroughs in hematology.
Finally, with these important results in both MDS and beta-thalassemia, we and Celgene remain on track to submit regulatory marketing applications in the US and EU in the first half of 2019, starting with the submission of the BLA to the FDA expected in April. In addition to the patient populations studied in the MEDALIST and BELIEVE trials, we have continued to expand Luspatercept’s overall development plan with three additional trials already under way. This includes the COMMANDS stage 3 trial in first line lower risk MDS, the BEYOND Stage 2 trial in non-transfusion dependent beta-thalassemia, and the Phase 2 trial in myelofibrosis which recently reached its target enrollment of 70 patients. Patients with anemia associated with lower risk MDS, beta-thalassemia and myelofibrosis are in dire need of new therapies with current treatment options largely related to red blood cell transfusions and unapproved agents.
Because of this significant unmet medical need, we and Celgene estimate annual global peak sales of Luspatercept to exceed $2 billion for the MDS and beta-thalassemia indications alone. We also estimate as much as another $1 billion of global peak sales potential for the opportunity in myelofibrosis-associated anemia. With our low to mid-20%-tiered royalty rate and Celgene covering approximately 100% of the program costs, these peak sales estimates have the potential to translate to significant royalty revenue for Acceleron. As you could expect with an opportunity in an unmet need of this magnitude, the teams at Celgene and Acceleron remain highly focused on all upcoming regulatory and launch readiness activities along with continued clinical trial execution and expansion.
I will now hand the call over to our chief medical officer, Robert Zeldin, to review our neuromuscular and pulmonary disease programs.
Robert Zeldin — Chief Medical Officer
Thanks, Habib. I’d like to begin with ACE-83 in neuromuscular disease. We continue to advance ACE-83, our locally acting muscle agent in Stage 2 trials in patients with facioscapulohumeral muscular dystrophy, or FSHD, and Charcot-Marie-Tooth disease or CMT. FSHD is a myelopathy caused by the expression of a typically dormant protein that is toxic to muscle tissue, while CMT is a neuropathy in which diseased nerve leads to muscle atrophy.
At the World Muscle Society annual meeting in October, we presented positive results from part I of the trials, the open label part which evaluated safety and tolerability along with changes in muscle mass to enable dose selection for part two. Patients with FSHD and CMT treated with ACE-83 experienced mean total muscle volume increases from baseline of greater than 14%, reduction in absolute fat fraction, and a favorable safety profile over the 12-week treatment period. Based on these positive results, we moved into part two of the trials designed to assess the efficacy and safety of ACE-83 versus placebo over a six-month treatment period followed by a six-month open label period. The primary endpoint is the percent change in total muscle volume via magnetic resonance imaging with secondary endpoints including motor function tests such as timed walking tests in both FSHD and CMT, as well as upper limb tests in FSHD.
We will also be evaluating disease specific patient-reported outcomes in both trials. I am happy to announce that the FSHD trial recently completed full enrollment of 55 patients and we remain on track to present the topline results in the second half of the year. Patient recruitment in the CMT trial is ongoing. With that, I’d like to turn to our pulmonary disease program.
As we described at our Pulmonary Arterial Hypertension or PAH deep dive event in November, we are very excited to be developing sotatercept in PAH, a rare, progressive disorder characterized by high blood pressure or hypertension in the arteries of the lungs. There is an urgent need for new therapies in PAH. Despite 14 drug approvals over the last 20 years, the median survival for these patients is still only five to seven years post diagnosis. Also in November, we and our collaborators at the Brigham & Women’s Hospital presented preclinical research on sotatercept at the American Heart Association Annual Scientific Sessions which demonstrated sotatercept’s ability to reverse pulmonary vascular remodeling and improve pulmonary hemodynamics and right ventricular structure and function in an animal model of PAH.
Our Phase 2 PULSAR trial to evaluate sotatercept’s activity in patients with PAH is ongoing. This is a randomized, double-blind, placebo-controlled trial that will enroll 100 patients with World Health Organization Group 1 Functional Class 2/3PAH. The primary treatment period is six months. The primary endpoint is change in pulmonary vascular resistance with multiple secondary endpoints.
We also recently initiated an exploratory study called SPECTRA. This trial will look at innovative endpoints of invasive cardiopulmonary exercise tests or ICPET and cardiac MRI in addition to the more traditional PAH trial endpoints being assessed in the PULSAR trial. With that, I will turn the call over to Kevin McLaughlin, our CFO, to review the financials.
Kevin McLaughlin — Chief Financial Officer
Thanks, Robert. Our cash, cash equivalents and investments as of December 31, 2018 were $291.3 million, compared to $372.9 million as of December 31, 2017. Additionally, we were recently able to successfully execute a follow-on offering of common stock including the full exercise of the underwriter’s overallotment option for net proceeds to Acceleron of approximately $248.2 million from new and existing institutional shareholders. Based on our current operating plan and projections, we believe that our cash, cash equivalents and investments, together with the net proceeds from the offering, will be sufficient to fund our projected operating requirements until such time as we expect to receive significant royalty revenue from Luspatercept sales.
Collaboration revenue for the year was $14 million. The revenue is all from the company’s Celgene partnership and is primarily related to expenses incurred by the company in support of Luspatercept. Total costs and expenses for the year were $138.4 million. This includes R&D expenses of $103.9 million and G&A expenses of $34.5 million.
The company posted a net loss for the year ended December 31, 2018 of $118.9 million. I will now turn the presentation back over to Habib for final remarks.
Habib Dable — Chief Executive Officer
Great. Thank you, Kevin. And with that, I’ll briefly summarize our priorities for the remainder of this year and beyond. Beginning with Luspatercept in hematology, we and Celgene plan to submit regulatory marketing applications to the US and EU health authorities in both lower risk MDS and beta-thalassemia in the first half of 2019 starting with the submission of the BLA to the FDA expected in April.
In addition, we plan to submit the Phase 3 MEDALIST and BELIEVE results for publication in 2019. For the Phase 2 trial in myelofibrosis, we anticipate reporting topline results in the second half of 2019 and expect to provide preliminary topline results for the BEYOND Phase 2 trial in 2020. The recently initiated Phase 3 COMMANDS trial continues to enroll patients. We also expect to discuss our initial clinical trial expansion plan for Luspatercept in 2019.
Looking at our neuromuscular programs, we plan to present preliminary results form Part 2 of the Phase 2 trials with ACE-83 in the second half of 2019 for FSHD and by yearend 2019 for CMT. We expect to provide ACE-2494 preliminary results for the Phase 1 Healthy Volunteer trial in the first half of this year. And lastly, for PAH, we expect to provide preliminary results for the PULSAR and SPECTRA trials in 2020. In closing, Luspatercept has created significant value to the company to date and we believe it will continue to do so through its commercial launch and further indication expansion over time.
We are also approaching important value inflection points with both ACE-83 and sotatercept expected to produce Phase 2 proof of concept data in neuromuscular and pulmonary disease over the next 12 to 18 months. We have a busy year ahead and remain confident in our ability to continue advancing these potentially transformative therapies for patients while focusing on long term value creation for both our business and shareholders. I will now open the call to questions. Operator?
Questions and Answers:
Operator
Thank you. [Operator instructions] Our first question comes from Carter Gould of UBS. Your line is now open.
Carter Gould — UBS — Analyst
Great. Good afternoon, guys. Thanks for taking the question. I guess first on ACE-83, you’ve been clear on the need to show a benefit in terms of function and strength, but I just kind of wanted to get a little more detail on how you’re thinking about the clinical hurdle in terms of then potentially moving that forward into potentially a Phase 3 study.
Any color on how you expect the placebo arm to perform or kind of what’s a clinically meaningful separation there? And then since the study is enrolled, any color on the demographics for that Part B enrollment and maybe how that compares to Part 1? Thank you.
Habib Dable — Chief Executive Officer
Hey, Carter, this is Habib. Thanks for your question. Maybe I’ll just kind of kick it off and then hand it over to Robert to add any additional color. So you’re right, with respect to ACE-83 in both Charcot-Marie-Tooth which we plan to — in Charcot-Marie Tooth as well as FSHD where we plan to disclose topline results for Part 2 of the studies in the second half of this year, the important part of this study as you know is all about function as you alluded to.
We have to date been able to demonstrate double digit growth in both indications in terms of total muscle volume in a generally safe and tolerable way. Now what we want to be able to do is to replicate that muscle growth and to be able to translate that into a functional benefit. Now when you’re looking at FSHD where we’re dosing the biceps as well as the TA muscles, in the biceps we’re looking at functional improvements by measuring using a measurement called the PUL or the performance upper limb test where patients are asked to engage in various exercises like putting pegs in holes, stacking cans, etc., and timing them. When you are looking at the TA muscle, for both Charcot-Marie-Tooth as well as FSHD, we’re looking at endpoints such as for stair climbs, timed 10-meter walk/run, 6-minute walk distance, etc.
So at the end of the day, Carter, we again as I said, we are powering the studies to be able to demonstrate total muscle volume increases and we are looking across a spectrum of functional endpoints including quality of life assessments through a validated PRO where we’re working with collaborators at the University of Rochester. And we will be looking at all of that data in totality and again, we’ve powered the studies to be able to show us a functional improvement. We’re looking for double digit increases in function, but again, looking at the totality of the data at the end of Part 2 of these studies, we hope to be able to be very well informed in terms of what a Phase 3 would look like in terms of a go/no-go. Robert, I don’t know if there’s anything on top of that you’d like to add?
Todd James — Vice President, Investor Relations and Corporate Communications
Hey, Carter, it’s Todd. I would just add about the baseline demographics, we targeted patients based off the muscle scores for the trial, that they’d be mild to moderate patients so the patients wouldn’t be too far gone that we couldn’t provide an improvement with a therapy like ACE-83. And so that’s in line with the patients that were enrolled in the trial.
Operator
Thank you. Our next question comes from Danielle Brill of Piper Jaffray. Your line is now open.
Danielle Brill — Piper Jaffray — Analyst
Hey, everyone, this is Naresh on for Danielle Brill. I just had a couple of quick questions that I wanted to hit on. First was the myelofibrosis trial. Would you be able to give us some color on what we should be looking out for in the preliminary data that’s going to coming out in the second half?
Habib Dable — Chief Executive Officer
Thanks for your question. So for myelofibrosis, just to remind everyone, this is a Phase 2 study that we’re running where we have recruited 70 patients and we have also guided that in the second half of this year that we would be presenting data on these patients. Again, the way we looked at these 70 patients was looking at 40 patients who are being treated with our asset, Luspatercept, without the combination of ruxolitinib because of the fact that they don’t have an enlarged spleen. And then 30 patients out of that 70 are looking at Luspatercept in combination with ruxolitinib.
And again, we’re looking at transfusion-dependent patients as well as non-transfusion-dependent patients. So at the end of the day, I think it’s important to highlight the unmet need with these patients because of the fact that they are suffering from anemia in many cases just due to the fibrotic bone marrow. And so therefore, the disease induced anemia is something we’re looking at in the mono patients. But also, please remember when you think about ruxolitinib and JAK inhibition in general, they also suffer because of the mechanism of action.
In many cases it is transient, but it is an impact on these patients where they’re suffering from the fibrotic bone marrow as well as drug induced anemia because of the JAK inhibition. This also led us to announce together with our collaborators recently of a Phase 1-2 study with fedratinib which is Celgene’s JAK inhibitor where we will be looking at combination use of Luspatercept as well as part of our myelofibrosis study.
Todd James — Vice President, Investor Relations and Corporate Communications
Hey, it’s Todd. As far as the primary endpoints for the Phase 2, depending on which cohort the patient is in, whether it’s the anemia only cohort, there we’re looking for consecutive 12-weeks hemoglobin increase of a gram and a half or greater within the first 24 weeks or the six-month primary treatment period. And for the patients that have the two to four-unit transfusion burden over a 4-week period of time, there we’re looking for transfusion independence or no transfusions over a 12 consecutive week period within that 24-week primary treatment period. So that’s the main endpoints that you’d expect to see when we do present results in the second half of the year.
Danielle Brill — Piper Jaffray — Analyst
Got it. Thank you so much, that was really helpful. I guess the second question I had was, you mentioned you’re getting ready with launch readiness activities right now for Luspatercept. Could you expand on that a little bit? What are you guys doing and how is it coming about?
Habib Dable — Chief Executive Officer
Yeah, so thanks for your question. Obviously now with the announcement that we made recently with the BLA expected to be filed in April, and under a standard review process, we could anticipate that a year later from April we could be in launch mode. Now that said, we also are doing a number of activities together with our collaboration partner Celgene in preparation for that as well as the fact that if indeed we were surprised with a priority review and we were able to launch earlier, that we would be prepared. So a number of activities in terms of launch readiness, whether it’s in preparations from our positioning strategy, in terms of our pricing research, in terms of manufacturing and supply, I can tell you that that’s a tremendous amount of work that’s going on.
Now with respect to specifics in terms of commercial launch, perhaps, Sujay, you maybe want to add a little bit of color in terms of some of the things that we’re working on right now with our partners.
Sujay Kango — Chief Commercial Officer — Analyst
Sure, thanks, Habib. So a couple of thing. As Habib mentioned, we do have joint commercialization teams already in place. And as far as that, we are clearly understanding what the patient needs are on the forefront in putting programs together that would be necessary for launch as and when we get approval.
So in that instance, what we have is preparing all the materials that are necessary, trying to think from a payor engagement, early payor engagement perspective, planning around that component to ensure that access is appropriate. Understanding where those patients are within the US so we are able to deploy the right team members appropriately at the right timepoint. So all this planning in a prelaunch phase is what we are doing to prepare with ensuring that at launch we’ll be ready to go day one and have the patient needs on the forefront of our minds. So that’s what we are working on.
Operator
Thank you. Our next question comes from Yaron Werber of Cowen & Company. Your line is now open.
Yaron Werber — Cowen and Company — Analyst
Great. Thank you so much. I have a couple of questions and maybe just the first one, to clarify. The endpoint, Todd, you mentioned the consecutive 12-week endpoint.
Is that any consecutive 12-week and you sort of record the best data within the 24 weeks? Or is it, it needs to be consecutive 12-weeks within a specific timepoint?
Todd James — Vice President, Investor Relations and Corporate Communications
Yeah, Yaron, it’s the first. So if it’s weeks zero to 12 or 2 to 14 or 12 to 24 within that 24-week period, all those instances would be considered a responder within that 24-week period.
Yaron Werber — Cowen and Company — Analyst
And can you just remind us, with the sotatercept study that was done, obviously in that single center, how was the endpoint defined? Was it defined the same way, that 30% to 39% response rate?
Habib Dable — Chief Executive Officer
That’s right. Whether it was the sotatercept IST or our MDS trial, there we’re looking for a consecutive eight weeks. That’s how we have done the endpoints over the treatment periods.
Yaron Werber — Cowen and Company — Analyst
Great. Then it sounds like you’re going to, the way I’m hearing you correctly, it sounds like you’re going to be asking for priority review. Can you just remind us, I don’t know if you’re comfortable sharing this, whether — which division of FDA is actually reviewing the application? Is it the same division reviewing both filings for both indications?
Habib Dable — Chief Executive Officer
Robert, would you like to answer that?
Robert Zeldin — Chief Medical Officer
Division of Hematology. So it’s hematology. Our expectation is that that division will review both applications.
Yaron Werber — Cowen and Company — Analyst
OK. So it will be single priority review and they’ll review them at the same time?
Habib Dable — Chief Executive Officer
Yes, so that’s not necessarily the case that it would be single. So obviously, Yaron, that’s standard practice. We would be looking and asking for that. But just to remind you again, just so I’m clear, our base case assumption is that it’s a standard review process.
Operator
Thank you. Our next question comes from Robyn Karnauskas of Citi. Your line is now open.
Unknown Speaker
Hi, this is Nicole on for Robyn, thanks for taking my questions. Just going back to the regulatory process, could you — do you expect the regulatory process to be the same or similar between the US and EU? And did you get a sense from your communications with the regulatory authorities that there would be any potential hurdles or concerns about acceptance of the application?
Robert Zeldin — Chief Medical Officer
I mean I think that the pre-BLA meeting was a very positive, open discussion. I think the agency was excited about receiving the application. And I could not identify any specific areas of concern. As folks are now clearly aware, we intend to file with the FDA in April and subsequently submit the marketing authorizing application in the first half.
Unknown Speaker
OK, great. Then just a quick follow-up, given the evolving and competitive landscape in beta-thal with multiple different modalities being investigated, where do you see greater potential for Luspatercept in beta-thal? And do you expect there to be any difference in uptake between the transfusion-dependent and non-transfusion-dependent patients?
Habib Dable — Chief Executive Officer
With respect to beta-thalassemia, so let me answer the second part of your question first. The BELIEVE study, just to remind everyone, was studied in transfusion-dependent patients. So the initial approval that we will be looking for is exactly that. Now I think it’s important to also note though is that there is a significant population, probably equivalent to the transfusion-dependent population, that we’re exploring through the BEYOND study.
And so we’re recruiting 150 patients there and so obviously this is a population, and again this is just to kind of repeat what was cited by Dr. Capellini on stage, is that this is a population with a very high unmet need because of the fact that they are not actually being transfused, but they are, in many, many cases, very symptomatic. So we’re very much looking forward to the results of that study. Now in terms of the first part of your question in terms of competition and how, what the potential is for beta-thalassemia and Luspatercept would be, is one of the things that we’re extremely proud of is that Luspatercept has been able to demonstrate the ability to restore healthy red blood cell formations in 2 very distinct diseases, lower risk MDS as well as beta-thalassemia to date, which has given us the confidence to want to proceed with other lifecycle management activities such as myelofibrosis and potentially other disease of chronic anemia.
With respect to beta-thalassemia, if we are approved, we feel that there will be a tremendous unmet need that we will be catering to. Now obviously I know there’s a lot of attention right now on gene therapy and if gene therapies are proven to be safe and efficacious, I am thrilled that the community is going to have that as an option. Do I feel that that option is going to cater to the many, many patients with unmet need? No, I don’t. And I feel that if indeed it is another option for patients, I feel there will be a tremendous opportunity for Luspatercept to find a space and a very significant space for this patient population who may not feel or be qualified for such a therapy.
Operator
Thank you. Our next question comes from Geoff Meacham of Barclays. Your line is now open.
Greg Harrison — Barclays — Analyst
Hi, this is Greg Harrison on for Jeff. Thanks for taking the question. So now that potential Luspatercept launch is on the horizon, do you think the expanded indications in development could end up garnering the same penetration as with MEDALIST and BELIEVE populations? And if so, what factors could possibly enable that outcome?
Habib Dable — Chief Executive Officer
So I just want to make sure I understood your question. You are asking for the follow-on indications beyond MEDALIST and BELIEVE as to whether or not we feel that they will be equally robust in terms of the opportunity, in terms of the unmet need, is that correct?
Greg Harrison — Barclays — Analyst
Yes, exactly.
Habib Dable — Chief Executive Officer
OK, great. So again, let’s start with MEDALIST and BELIEVE and make sure that we’re on the same page. When we look at MEDALIST and BELIEVE, we feel that we are going to be catering to a very significant population. So for example, when we look at the datasets that we’ve got that we feel we have the most robust information around and we look at US and Europe, for the MEDALIST population we feel that there is approximately about 40,000 patients between the US and Europe that we’ll be able to have an opportunity to serve.
With the BELIEVE patient population, we feel that there’s approximately 20,000. Now admittedly, the opportunity for that to expand is going to be driven by success in our subsequent studies. So if indeed the BEYOND study is successful, we feel that that patient population for Beta-thal alone could double. If indeed the COMMANDS study, which is our first line treatment naive study in lower risk MDS is successful, we believe that that population of patients has an incidence rate of approximately 15,000 a year.
Is that right, Todd?
Todd James — Vice President, Investor Relations and Corporate Communications
Yes, 15,000 to 25,000.
Habib Dable — Chief Executive Officer
15,000 to 25,000 a year. And the nice thing about that is it allows us to get into this space and to be able to provide Luspatercept much earlier in the disease setting as well. When you look at myelofibrosis, myelofibrosis patient population between the US and Europe is approximately 30,000, 35,000 patients. And if you look at that patient group, probably 50% to 60% of them suffer from moderate to severe anemia.
So now you’re again looking at another 15,000 to 20,000 patients and independent as to whether or not they are on ruxolitinib or not, as I said before, these patients are suffering from chronic anemia due to this fibrotic bone marrow as well as the drug induced anemia. So the opportunity for Luspatercept to play a role here as an erythroid maturation agent can be pretty profound in this group. So all of these groups that we’re looking at have a potential to have a very high unmet need and an underserved population. And then beyond that, we obviously have talked about looking at expanding the lifecycle management strategy.
We’re working very closely with our partners at Celgene. They are very motivated to continue to moving forward beyond the already identified disease indications. I think you’ve heard us talk a little bit about chronic induced anemia as one that we’re exploring, but it is one of many. Sorry, chemo induced anemia.
And that’s just one of many areas that we’re exploring and prioritizing and hopefully more to come as that analysis continues to finalize. And by the way, just to kind of close off on that, we — just recently this year, we’ve given a little bit more granularity in terms of the commercial opportunity of these indications where we have traditionally always said that if you look at the lower risk MDS and beta-thalassemia, that represented a $2 billion plus opportunity. And now as we move forward with our next indication, the myelofibrosis, if indeed the myelofibrosis study is successful and the drug is approved in that indication, we and our partners at Celgene believe that it’s an incremental $1 billion opportunity, $1 billion opportunity in that indication alone.
Operator
Thank you. Our next question comes from Eric Joseph of JP Morgan. Your line is now open.
Eric Joseph — J.P. Morgan — Analyst
Hey, guys, thanks for taking the questions. A couple from us. I guess the first on Luspatercept in myelofibrosis. Assuming that Phase 2 data are good, maybe can you talk a little bit about just the registration path forward? Whether you would need to pursue the individualized trials in the non-transfusion-dependents versus transfusion-dependent populations? And whether there’s sort of a wholesale way of pursuing the indication? And how should we be thinking about where the fedratinib combination study factors into later stage development?
Habib Dable — Chief Executive Officer
Yeah. So Eric, I think the first question is pretty easy to answer in that it’s too early right now. Let’s wait and see how the Phase 2 reads out. Let’s see what data comes out of that and based on that we’ll obviously have the appropriate interactions with the regulatory agencies and then we’ll be guided by that feedback and then we’ll share with you the development path forward for Phase 3.
With respect to fedratinib, I think all I can tell you at this point is what’s already been disclosed in terms of the Phase 1-2 study that Celgene disclosed just last month. And then on top of that, I think it’s important to note that that also sends a very strong signal in terms of their commitment to myelofibrosis with Luspatercept as their anchor.
Eric Joseph — J.P. Morgan — Analyst
Maybe just a quick clarification question on ACE-83. You made a point earlier that — is it the expectation that you’ll be able to detect a stat sig benefit in functional improvement based on trial sizing and which measures specifically are you expecting to see that benefit be shown?
Robert Zeldin — Chief Medical Officer
I think Habib’s point was that we’re going to look at the totality of the data. So we know the primary efficacy endpoint is clear, that’s overall muscle growth. And now we have a number of assessments of functional benefit and we’re going to look at them in the totality. So I’d say in general, we’re guiding to say that we’d like to see a 10% improvement on those individual measures, that would give us the confidence to advance the program.
But I don’t think we would pick one of our children above the other.
Eric Joseph — J.P. Morgan — Analyst
Got it. And just can you comment around sort of how frequently subjects are assessed, the number of intervals that we’ll see in the Part 2 readout?
Habib Dable — Chief Executive Officer
Yes, so we haven’t gotten to the granularity of the assessment timelines, but again, just so you know, these patients are coming in every three weeks for their injections, their intramuscular injections that are done in the office.
Operator
Thank you. Our next question comes from Gerard Smith of SVB Leerink. Your line is now open.
Gerard Smith — SVB Leerink — Analyst
Thanks for taking the question. This is Gerard on for Jeff. A couple on muscle. Could you remind us how you expect to disclose the 2494 Phase 1 data, what type of disclosure, what will you say exactly in terms of safety and volume, etc.? And then could you also talk about the different ligand specificities for the two different muscle agents? And how we should be thinking about making inferences on 2494 based on the ACE-083 function data that we’ll get later in the year.
Can we sort of try to make inferences about the two or is that not appropriate? Thank you.
Todd James — Vice President, Investor Relations and Corporate Communications
Hey, Gerard, it’s Todd. As far as the communication plan for those results, hard to say if it will fall exactly at a congress or not, but at the very least there would be a press release that discloses the results. As far as what you could expect, it’s a single ascending dose trial across I think five, six different doses. And safety as you can imagine, anything that is serious would absolutely be outlined.
Typically, if things are just great in 1-2, we categorize them. If they are injection site reactions for example like we saw in Part 1, we would comment about that. And as far as the PD that you could expect to see, we’re looking at potential increases in muscle volume of the quad which is very regular to do in this style of a trial. As far as if you can read anything in from the ACE-83 results to the 2494 results, I think it would be fairly difficult to do that.
Very distinct molecules. 83 is a locally acting agent that we can take very high therapeutic dose levels, inject it right into the target muscle and there we’ve seen in Part 1 increases of 14% plus at the high doses. Whereas a systemic agent like 2494, you’re most likely to see mid to high single digit increases, at least agents whether it be regeneron, bimagrumab that have come before us, have seen increases of that nature. And so yeah, don’t think there’s much reading through from one to the other.
As far as the binding affinity, I think I’d let John Quisel get into those details.
John Quisel — Executive Vice President and Chief Business Officer
Hey, the important thing to remember to know about the ligand binding is that both ACE-83 and ACE-2494 are what we call Myostatin+ so they conform with our view how best to stimulate muscle growth and improve function by inhibiting as many of the relevant ligands that are negative regulators of the muscle as you can safely. The two molecules, so apart from being Myostatin+ in their approaches, as Todd mentioned data are very different, ACE-83 being locally administered, being able to reach local concentrations that you probably can’t get to with the 2492 like systemic agents. So where we’ve shown the muscle mass increases in the teens, it would be surprising probably to see that kind of effects from a systemic agent like 2492 even though the two agents are engaging similar spectrum of ligands. Just speaking briefly to the protein scaffolds that are built off of ACE-83, it’s based generally around a fallen statin structure while the other one, 2494, is a ligand trap based on the cell surface receptors that are involved in binding the key ligands.
So they are very different proteins with similar ligand binding spectra, and due to their different modalities, we have very different, we expect very different effects on the muscle mass.
Operator
Thank you. Our next question comes from Jeff Hung of Morgan Stanley. Your line is now open.
Jeff Hung — Morgan Stanley — Analyst
Thanks for taking the questions. Can you talk about conversations you’ve had with payors in making a surprise view or any discussion on value-based pricing?
Habib Dable — Chief Executive Officer
I don’t think there’s much we can say about that discussion, but do you want to comment, Sujay, in terms of anything we can share with respect to payor research that’s ongoing?
Sujay Kango — Chief Commercial Officer — Analyst
Sure. As you know, we are conducting PR research. We’re getting insights there and Celgene has a very methodological approach to value-based pricing, so at this juncture, we are getting that insight. That’s what I can comment and we’re sort of taking into account that we want to ensure that we have the broadest access possible for the patient population.
So with that in mind, I think they are in a good position at this juncture to get all that insight. We can also, based on FDA guidance, we can do early payor engagement and through that we are collecting that insight. And then very close to launch we’ll be able to disclose a price related to the value proposition. But we feel that at this stage it is strong.
Jeff Hung — Morgan Stanley — Analyst
Great. Maybe to the neuromuscular and pulmonary franchises, can you talk your strategy in terms of your thoughts on partnering versus going it alone?
Habib Dable — Chief Executive Officer
It’s a good question, Jeff. I think at the end of the day we are fully committed to both therapeutic areas as we disclosed during R&D day in 2017. We just successfully were able to execute on our secondary which gives us obviously the appropriate fire power to drive these studies to conclusion. At the end of Phase 2 and based on that data, we will take a good look in terms of what would drive the most value strategically for the programs and for Acceleron and we’ll make a decision at that point.
I think the most important nuance to all of that is we are positioning ourselves to be in a position of potentially partnering these programs to maximize value rather than the necessity to partner these programs because we would otherwise not be able to afford to run them. I think it’s a very important nuance.
Operator
Thank you. Our next question comes from Kennen MacKay of RBC Capital Markets. Your line is now open.
Kennen MacKay — RBC Capital Markets — Analyst
Hey, thanks for taking the question. Habib, that $2 billion to $3 billion in peak sales guidance is reminiscent of Babe Ruth pointing at center field bleachers. That’s quite the move. I like it.
A couple of quick questions. On Luspatercept, clearly in Medalist there’s a major impact on hemoglobin and transfusions, but it looked like there was also some impact on platelets. Could you maybe remind us how requirements for GCSF were impacted in MEDALIST and potentially how this could factor into a label or usage in the clinic? Then also, in MDS, correct me if I’m wrong, but Luspatercept will likely be sort of thought of as supportive therapy to patients. I guess how should we think about that impacting usage of either high or low intensity immunoblastic or immunosuppressant therapies in these patients? Obviously, there is no difference in leukemic transformation, but is there any combo data out there with some of these antileukemics? Thank you.
Habib Dable — Chief Executive Officer
So I’m going to ask Dr. Robert Zeldin to comment. I’m not sure how much depth you want to get into in all of that. And I think the first part of that question, I’m not sure if you caught all of that, but it cut out a little bit.
Robert Zeldin — Chief Medical Officer
Yeah, if you could repeat it.
Habib Dable — Chief Executive Officer
Just repeat the first part on the platelets.
Kennen MacKay — RBC Capital Markets — Analyst
On platelets, yeah. It looked like there was an effect on platelets in some of those Forrest plots that had been presented in the MEDALIST trial. Was wondering if there was any difference in requirements for GCSF in MEDALIST?
Robert Zeldin — Chief Medical Officer
No. I can’t speak to the specifics on an individual patient basis, but I can tell you having very comprehensively reviewed the safety data, that we have no concerns regarding thrombocytosis in the population of patients treated in the MEDALIST study.
Kennen MacKay — RBC Capital Markets — Analyst
Oh, no, I was thinking more that you could reduce the need for some of the platelet reducing therapies for [Inaudible].
Operator
Thank you. [Operator instructions]
Habib Dable — Chief Executive Officer
So Kennen, sorry, because I think we tripped over each other in here. I think the first part of the question was answered by Robert in terms of the comment that you got from him. The second part of your question though, I don’t believe was answered. So do you want to repeat that again, Kennen? OK, we lost him.
We weren’t catching it all. OK, we’ll have to go to the next question, Operator.
Operator
Our next question comes from Terence Flynn of Goldman Sachs. Your line is now open.
Unknown Speaker
Hi, guys, it’s Holly on for Terence. Just one for us is can you discuss the status of the COMMANDS trial enrollment and when we could potentially see data? Thanks.
Todd James — Vice President, Investor Relations and Corporate Communications
Sure. Hey, Holly, it’s Todd. Yes, we kicked off the COMMANDS trial with our partner Celgene late in the third quarter of last year. So as you can imagine, in the first six to 12 months of a trial, that’s all about getting sites up and running and obviously the initial patients into the trial.
But as you get more sites on, enrollment starts to pick up pretty quickly, so we’re still in the early days here. As far as when you could expect data, we haven’t guided to that today, but there are typically some initial forecasts listed on Clinicaltrials.gov for trials.
Operator
[Operator instructions] This does conclude our question and answer session. I will now turn the call back over to Habib Dable for any closing remarks.
Habib Dable — Chief Executive Officer
If there’s no other questions, thanks, everybody, for your participation. Thanks for your continued interest in the company and look forward to meeting you at future investor conferences or scientific symposiums. With that, everybody, have a good night.
Operator
[Operator signoff]
Duration: 48 minutes
Call Participants:
Todd James — Vice President, Investor Relations and Corporate Communications
Habib Dable — Chief Executive Officer
Robert Zeldin — Chief Medical Officer
Kevin McLaughlin — Chief Financial Officer
Carter Gould — UBS — Analyst
Danielle Brill — Piper Jaffray — Analyst
Sujay Kango — Chief Commercial Officer — Analyst
Yaron Werber — Cowen and Company — Analyst
Greg Harrison — Barclays — Analyst
Eric Joseph — J.P. Morgan — Analyst
Gerard Smith — SVB Leerink — Analyst
John Quisel — Executive Vice President and Chief Business Officer
Jeff Hung — Morgan Stanley — Analyst
Kennen MacKay — RBC Capital Markets — Analyst
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