Todd James - Vice President, Investor Relations and Corporate Communications Habib Dable - President and Chief Executive Officer Kevin McLaughlin - Chief Financial Officer Matthew Sherman - Chief Medical Officer.

Carter Gould - UBS Bradley Canino - Leerink Greg Harrison - Citigroup Eric Joseph - JP Morgan Christopher Marai - Nomura Instinet Paul Choi - Barclays Michael King, Jr. - JMP Securities.

Good afternoon, ladies and gentlemen, and welcome to the Acceleron fourth-quarter and full-year 2017 earnings conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be given at that time. 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..

Thanks, Chelsea. And welcome, everyone, to our fourth-quarter and full-year 2017 earnings call. The press release reporting our financial results, in addition to the presentation for today's webcast, are available on Investors & Media page of the corporate website at www.acceleronpharma.com.

Joining me for the call today are Habib Dable, our Chief Executive Officer; Matthew Sherman, our Chief Medical Officer; Kevin McLaughlin, our Chief Financial Officer; John Quisel, our Head of Corporate Development; and Chris Rovaldi, our Head of Operations and Program Management.

Our goal this afternoon is to provide an overview of our recent operational progress, review updated financial results for the full-year 2017 and outline our upcoming priorities. After that, we look forward to answering your questions.

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 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..

Thank you, Todd. Good afternoon, everyone, and thank you for joining us today. 2017 was an important year for Acceleron and I'm extremely proud of the progress we made across our entire pipeline and business. We spent a lot of time during the first half of the year thinking about and planning for our future.

We leveraged our R&D day in September to outline our corporate strategy and vision to build therapeutic area leadership within three disease areas – hematology, neuromuscular and pulmonary.

And to quickly recap a few 2017 events, one, we completed full enrollment of the MEDALIST and BELIEVE Phase III trials of luspatercept in myelodysplastic syndromes and beta-thalassemia with our partner Celgene. Two, we continue to advance our lead neuromuscular candidate, ACE-083, which is currently in Phase II trials in two neuromuscular diseases.

Three, we retained the rights to sotatercept in pulmonary arterial hypertension or PAH from Celgene, allowing us to begin a new Phase II program in the first half of 2018. And finally, we maintain a strong balance sheet.

With the completion of a follow-on offering in the fall, successfully raising $215.8 million in net proceeds, extending our cash runway into 2021.

With these important events and our strategic focus clearly defined last year, looking forward to 2018 and beyond, we are focused on clinical and operational execution to drive the strategy and vision for long-term growth and value creation.

I'd now like to review the most recent highlights for each therapeutic area, beginning with hematology and our lead product candidate luspatercept. With full enrollment completed and treatment ongoing in both Phase III trials, we are on track to report topline results from the MEDALIST and BELIEVE trials with our partner Celgene in mid-2018.

As you know, luspatercept is an erythroid maturation agent designed to inhibit multiple TGF-beta proteins that regulate late-stage red blood cell differentiation and maturation.

Based on our Phase II results that I will discuss in a few minutes, we believe it could be an important medicine for thousands of patients who are dependent on frequent red blood cell transfusions due to chronic anemia across multiple rare blood disorders.

In anticipation of luspatercept's potential commercial launch in late 2019, we recently hired a chief commercial officer, Sujay Kango, who joins us from AbbVie.

We are thrilled to have Sujay join our team as we accelerate the work we've been doing to prepare for the regulatory filings and commercial readiness of our lead product candidate luspatercept and his experience across multiple companies and product launches positions us to fully support the luspatercept franchise alongside our partner Celgene.

We're also preparing for a new Phase III trial with luspatercept called the COMMANDS trial in first-line lower risk ESA-naïve MDS. And we expect this trial to initiate in the first half of 2018. We continue to build upon the depth of the luspatercept opportunity with several new Phase II luspatercept trials ongoing.

The BEYOND trial is planned to enroll 150 non-transfusion dependent beta-thalassemia patients and the Phase II trial in myelofibrosis is planned to enroll 70 monotherapy and combination therapy patients. Regular updates from our ongoing Phase II base and long-term extension trials drive our confidence in luspatercept's clinical benefit to patients.

We presented at the American Society of Hematology, or ASH, in December, making the fourth straight annual ASH update where we reported updated preliminary results of the ongoing Phase II trials in patients with lower risk MDS.

The results presented demonstrated luspatercept achieving clinically-meaningful erythroid response in over 50% of patients and red blood cell transfusion independence in over 40% of the patients. As a reminder, these results are looking at all MDS patients treated at therapeutic dose levels with luspatercept.

We have also presented specific subpopulation response rates based on baseline EPO levels, ESA treatment experience and RS status. Duration of response was also significant as luspatercept continues to provide long-term benefit to multiple patients, now nearing three years on treatment.

With these data, we have now collected more than 1,200 patient months or 100 patient years of Phase II experience in lower-risk MDS. These results further support luspatercept's potential to be a transformative treatment option for patients with lower-risk MDS. Also at ASH, the investigator at M.D.

Anderson provided an update on the Phase II trial in myelofibrosis with sotatercept. Over 30% of both monotherapy and combination therapy patients have achieved an anemia response. The results inform the decision to initiate a company-sponsored Phase II trial with luspatercept that I mentioned on the previous slide.

Turning out to our neuromuscular franchise, we continue to advance ACE-083, our locally-acting muscle agent where we recently reported initial data from the dose escalation cohorts one and two of part one of the Phase II trial in patients with FSHD.

The preliminary results demonstrated safety and tolerability of ACE-083 treatment and achieved total mean muscle volume increases of over 12% in the tibialis anterior and biceps brachii muscle cohorts. Both cohorts also demonstrated reductions in fat fraction.

As a reminder, the key objective of part one is to evaluate safety and changes in muscle volume and to identify a dose level to take forward into part two. For part two, the key objectives are changes in muscle volume as well as muscle strength and function.

We're encouraged by the data reported to date and are on track to initiate part two of the trial in the second quarter of 2018.

We also continue to advance ACE-083 in our Phase II trial in Charcot-Marie-Tooth disease or CMT and plan to report preliminary results from part one of the Phase II trial in the second half of 2018 and to initiate part two of the Phase II CMT trial by the end of 2018.

For our systemic neuromuscular agent, we recently initiated a Phase I healthy volunteer trial with ACE-2494. The trial will enroll three single and three multiple ascending dose cohorts to evaluate safety, tolerability and pharmacodynamics. We expect to enroll a total of 60 healthy volunteers for this trial.

Additionally, with our focus in pulmonary, our collaborator, Paul Yu from the Brigham and Women's Hospital highlighted positive preclinical results with sotatercept in pulmonary arterial hypertension at the American Heart Association scientific sessions in November.

Data showed remarkable biological activity on the pulmonary vasculature across two well-established animal models of PAH, further supporting our mechanistic approach for sotatercept and its potential to be a first-in-class disease modifying therapy for patients with PAH.

Based on encouraging preclinical data, we plan to initiate a Phase II trial with sotatercept in PAH during the first half of 2018 and we plan to host an educational webinar beforehand to discuss trial design. So, please be on the lookout for a save-the-date coming out soon.

With that, I will now turn the call over to Kevin McLaughlin, our Chief Financial Officer, to run through our financials for the quarter..

Thanks, Habib. Good afternoon, everyone. Our cash, cash equivalents and investments as of December 31, 2017 were $372.9 million compared to $234.4 million as of December 31, 2016. This includes the net proceeds from our successful follow-on offering in 2017.

We believe that our existing cash, cash equivalents and investments will be sufficient to fund our projected operating requirements into 2021. Collaboration revenue for the year was $13.5 million.

The revenue is entirely from our Celgene partnership and is primarily due to cost-sharing revenue of $12.9 million related to expenses incurred by the company in support of our partnered programs. Total costs and expenses for the year were $123.5 million. This includes R&D expenses of $89.7 million and G&A expenses of $33.7 million.

The company posted a net loss for the year ended December 31, 2017 of $108.5 million. I will now turn the presentation back over to Habib for final remarks..

Thanks, Kevin. As you have heard, we have a busy and productive year ahead of us. I will briefly touch on our priorities for the remainder of the year and beyond. In hematology, we expect to provide topline results from our MEDALIST and BELIEVE Phase III trials by midyear and plan to initiate the COMMANDS Phase III trial in the first half of 2018.

In neuromuscular, we plan to present ACE-083 part one results from all dose cohorts in FSHD and CMT in the second half of 2018 and plan to begin FSHD part two in the second quarter of 2018 and CMT part two by year-end. For ACE-2494, we plan to present Phase I results during the first half of 2019.

And finally, in pulmonary, we're looking forward to initiating a Phase II trial in PAH with sotatercept in the first half of 2018 and we look forward to discussing the trial design during the first half of 2018.

In closing, we remain committed to moving our clinical programs into late stage development and our goal is to have three programs in Phase III within three years or by year-end 2020. Our long-term vision begins with luspatercept in hematology as our number one priority.

We remain confident in our ability to leverage this multibillion-dollar opportunity with luspatercept, which in turn will drive our ability to build therapeutic area leadership in neuromuscular and pulmonary disease. I will now open the call to questions.

Operator?.

[Operator Instructions]. And our first question comes from the line of Carter Gould with UBS. Your line is open..

Hey, guys. Good afternoon. Thanks for taking the question. There's been a lot of activity in the MS space since the start of the year, the recent business development activity.

Has that in anyway changed how you guys are looking at the commercial opportunity here or potential development plans? Do you still intend to share data on the Phase II MDS study at EHA and ASH as in years past given the Phase III readout coming up? Thank you. .

Hey, Carter. This is Habib. Thanks for your question. So, with respect to the activity in myelofibrosis, you're right. And more specifically, the recent acquisition of Impact by Celgene in that particular space speaks volume in terms of their commitment to the space.

But it also is very encouraging for us because, as you know, we are studying myelofibrosis with luspatercept. And, specifically, we're looking at the patients in myelofibrosis who are suffering from moderate to severe anemia.

And in many cases, patients are not only suffering from disease-induced anemia, but in many cases they are also suffering from drug-induced anemia.

And these JAK inhibitors – as you know, for those patients with an enlarged spleen, they're on a JAK inhibitor, are also having the opportunity – or finding themselves needing something to deal with that anemia.

And given the fact that there is a lack of pharmacology solutions in the space, we really are looking forward to studying luspatercept and having hopefully an available agent to treat patients with this unmet need. And, quite frankly, Celgene's recent move in that space is comforting on a number of fronts.

One, as one of their partners, it's very encouraging to see them so committed to the space, given the work with luspatercept. But it also gives an opportunity for more patients to have a potential alternative to rociletinib. which will in turn open the opportunity for more patients available for potentially on luspatercept.

With respect to data, I'll pass it over to Todd to give you an idea of what we can potentially expect at EHA..

Hey, Carter. So, just to first talk about the MF development plan, it continues to remain the same. We initiated the Phase II trial with Celgene about midyear last year, and so that trial continues to progress. And based off of clinicaltrials.gov, you could expect to see data mid-to-late 2019 in myelofibrosis.

As far as our upcoming plans at the medical congresses, we've been presenting this Phase II data quite frequently, every six-month updates. And so, we will continue to submit abstracts for the upcoming congresses as far as whether the Phase IIs will continue to be accepted or not. Hard for us to say.

And so, we'll be able to provide color when the abstracts go live. But we would anticipate that the Phase IIs would at least be presented one time this year, whether it be at EHA or at ASH..

Thank you. And our next question comes from the line of Geoffrey Porges with Leerink. Your line is open..

Hey, this is Brad coming on for Geoff. Thanks for taking our questions. Had a couple of clinical ones on my end. First for luspatercept, in the COMMAND study, based on your knowledge right now of the front-line population, what proportion of patients do you think are likely to be RS-positive versus RS-negative..

Sure. Hey, Brad. It's Todd. So, as you know, we've been talking a lot about the prevent population given the MEDALIST indication is in the second line, ESA refractory patient population. And so, we most recently have been talking about the incidence population.

And in the prevalent pool, we believe there's about two-thirds to 70% RS-positive due to their slower progression in disease. These patients live more, five to eight years, versus the RS-negative patients are on the lower of the five-year median. So, they'll progress more like three to five.

And so, due to that difference in the progression time for the patients, the incidence pool was actually more weighted towards the RS-negative patient population. So, within the incidence or first-line setting, we believe that the RS-negative is probably more like two-thirds in that setting.

And then, you see that conversion due to the progression rate when you think about the refractory or prevalent pool..

Okay, thank you.

And then, moving on to muscle for ACE-083, have you yet disclosed the dose you're taking forward into part two for FSHD and can you tell us how many injections that dose would be required to give?.

Hi. This is Matt, Brad. So, as we updated the folks at J.P. Morgan in terms of the data from part one of the FSHD study, showing increases in muscle volume in the muscles that were treated, the biceps and the tibialis anterior muscle, and decreases in fat fraction, also a very important measure of muscle quality and function.

We have not yet disclosed the dose levels that we'll be taking forward into part two of trial. We have indicated that will be initiated in part two in the second quarter of this year. So, stay tuned and we'll be able to give you further information about that..

And then, I just wanted to clarify a timeline. You had previously stated –.

I'm sorry. You did ask about injections. We do administer the drugs and for injections. So, we take the total dose and divided into four injections across the length of the muscle.

This is what we piloted in the Phase I healthy volunteer trial where we also showed very significant increases in muscle volume at that time both in the rectus femoris muscle as well as in the TA muscle..

Okay, that's clear. Thank you. And then, you previously committed to a full dose escalation data release for the CMT trial by year-end 2018.

Are you changing your guidance with stating preliminary part one results now in your press release or will that still be preliminary, but from all cohorts?.

Hey, Brad. It's Todd. So, yeah, in the second half, we will be able – it will still be preliminary results from part one of the dose cohorts because we have some follow-up period, about – past three weeks after the last dose. And so, until we get through that further follow-up, we won't be able to say final.

But for both FSHD and CMT, we'll be through three weeks after the last dose of all cohorts in the second half of the year and we'll be able to provide that update. So, really, no change in guidance still before year-end, but we've been a little bit more specific with the second half. .

Okay, got it.

And then, on 2494, the systemic therapy, what muscle will you be measuring and how will this differ from what you've looked at in healthy volunteers for 083? And, I guess, could you compare your expectations for the size of increase between the two molecules?.

Hi, Brad. So, again, Matt here. So, ACE-2494 is a systemically administered Myostatin+ agent. So, as we did [indiscernible] trial, we'll be looking at muscle increases by MRI scan and we generally have focused on MRI scans in the lower extremity for changes in those patients.

I'm sorry, the second part of your question?.

I guess, wanted to know more on your expectations of muscle size increase from a systemic agent versus what you saw in healthy volunteers for your local acting agent..

So, again, based on the mechanism, we expect to see substantial increases in muscle volume. We haven't really given information in terms of the head to head comparison of the systemically administered agent versus a locally acting agent, but they do target the same range of ligands. So, we expect to see significant increases in muscle volume..

But as far as our expectations for success, Brad, similar to how we're guiding with ACE-083, we really feel like 5% for either a systemic or a locally acting agent is what you need to hopefully then – subsequently be able to see strength and function increase in patients.

So, that's something we're hoping to see both initially in Phase I in healthy volunteers and then, hopefully, subsequently in diseased patients when we go into Phase II.

And to just give a little bit more color on the MRI in Phase I, everyone – the myostatin selective agents that have also looked at Phase I in our earlier trial with ACE-31 in healthy volunteers, everyone really images the thigh muscle to look at the change relative to baseline in patients..

And in terms of timing, we initiated that trial and, as we've indicated, we will have data from the trial in the first half of 2019. .

Okay, that's all from me. Thank you. .

Thanks, Brad..

Thank you. .

Thank you. And our next question comes from the line of Robyn Karnauskas with Citi. Your line is open..

Hi. This is Greg Harrison on for Robyn. Thanks for taking the question. Another one on 2494.

Since the mechanism of action is different from typical anti-myostatin, how does that help you guys decide which indications you would want to target with it?.

Thanks, Greg. We went over this in some detail at the R&D presentation back in September. And there, we were really talking about the novel mechanism for ACE-2494. And the indication that we went into some detail, although we've not selected an indication yet for Phase II development, include FSHD, DMD, ALS and spinal muscular atrophy.

So, in that range, we showed a fair amount of preclinical data showing very meaningful increases in muscle in several of those preclinical indications. So, that would be – updates, we would be able to provide to you as we move along with the program. .

Great, thank you. .

Thank you. And our next question comes from the line of Eric Joseph with JP Morgan. Your line is open..

Hey, guys. Thanks for taking the questions. Just one for me related to the COMMANDS trial. I know we will get some additional color on that on the trial design as it gets underway in the coming months.

But I just want to get a sense of what docs would view as sort of meaningful differentiation from ESAs, considering [indiscernible] that you're going up against here.

Is superiority on erythroid response a reasonable expectation based on the prior Phase II and historical data that we've seen to date or would the focus more be on sort of longer-term measures, sustained erythroid response or duration of therapy, transfusion avoidance, that sort of thing? Thanks..

Hey, Eric. This is Habib. Thanks for your question. So, with respect to what doctors have seen so far, I'd probably guide you to the two company-sponsored trials that were presented at ASH 2016. And there you can see where the unmet need that was really amplified, if you want.

When you took a look at some of the data with respect to a specific response, HI-E or hematologic improvement erythroid, where in those two trials where you had subsets of less than 100 and less than 200 endogenous EPO levels, you had HI-E response rates of 15% to 30%.

And in those cases, that compares to the HI-E rates within our Phase II trials where we were looking at HI-E response rates above 50%. And with respect to the quality of the response, that also becomes extremely important.

So, you touched on a very important point here because when you think of quality, one of the ways to look at quality of response is the duration.

And as you know, one of the biggest benefits of continuing to follow-up patients in our Phase II studies, not only do we continue to gain encouragement from the overall response rates as well as the safety and tolerability profiles of patients of luspatercept, we're also gaining very beneficial information on the quality of response.

And to take you back to the April data [indiscernible] when we presented at EHA last year, the duration of therapy for patients who were TI responders was 14.7 months. We updated that again at ASH of 2017. And there, we were able to update that with the September data cut where that response rate moved to 19 months.

So, again, when you think of the quality of the responders, it's going to be really important for us to continue to follow these patients. And again, as a reminder, the patients that very much informed us within the Phase II study or the MEDALIST study were seeing response rates in terms of transfusion independence of 39%.

So, when you think of all of those markers, we go into the COMMANDS study with a certain degree of confidence that going head-to-head against ESAs in a superior design fashion is absolutely the right thing to do based on a number of data points, not only from our study, but also from company-sponsored studies from Amgen and J&J..

Got it. And maybe just kind of following up with reference to those Amgen and J&J studies, how useful are those as sort of guides in terms of the size and scope of trials and what we might see in terms of baseline patient characteristics, baseline EPO levels that you're targeting in COMMANDS? Thanks..

Yeah. Hi, Eric. This is Matt. Just to go into those two studies, so they were actually two of the only randomized studies that were done with ESAs. There were a lot of open-label studies that were done that, I think, falsely – so, they elevated expectations in terms of ESA response rates.

So, these two randomized double-blind studies, they were well controlled studies. The Amgen study was 146 patients. The J&J Jameson [ph] study was 145 patients. So, again, fairly robust data sets. Again, showed the 15% response rate in the Amgen study, only 31% in the Jameson study.

And the responding population for the IWG HI-E response population was only in patients with ESA levels less than 100 in the Amgen study and less than 200 in the J&J study.

So, a population that, in fact, is the prevalent population for lower risk, first-line MDS patients and one that we feel that we'll be able to compete and show superiority with –as Habib reported the data that we've had shows a high degree – excess of 50% of responses in the similar patient population..

Eric, it's Todd.

As far as expectations for what you can think about as far as the size of the trial, given that we're going to go head-to-head and want to show some superiority, be more in line with our MEDALIST and BELIEVE trials versus these Phase III trials from J&J and Amgen and then as far as how you should be thinking about baseline EPO levels and potential endpoints, that's something that we'll get into closer to the initiation of the trial in just a few months here..

Got it, got it. Very helpful. Thanks, guys. .

Thanks, Eric..

Thank you. And our next question comes from the line of Christopher Marai with Nomura Instinet. Your line is open..

Hi. Thanks for taking the questions and congrats on all the progress.

I was wondering if you can further comment perhaps on some of the data that we might see second half on 083 with respect to FSHD, what should we be really looking for here in terms of functional outcome measures that you might be able to re-examine in, what I would assume, would be a registrational trial that would kickoff maybe later this year, early 2019, maybe remind us of your plans there.

Thank you..

Hey, Chris. It's Todd. Thanks for the question. So, just want to be clear on – we're in a Phase II. That's a part one and part two and we don't believe that either parts are registrational, that we believe that we'll need to then take the part two data and then move into registrational Phase III after we get health authority feedback.

And as far as what you could expect from the – we updated part one dose cohorts one and two earlier in the year. And then, we'll be able to provide cohort three in the second half of the year. As far as strength and function expectations, the ends continue to be small, six patients per patient group and there's no placebo.

So, as far as expectations for strength and function, I'd really point you to part two of the trial, which will kick off in the second quarter of this year and then you could expect results from part two in the latter half of 2019.

And that will be a larger randomized, placebo-controlled trial where we'll be able to get a really nice read on strength and function endpoints..

Right. And so, when should we expect an update on the kind of design that you're looking to execute on there? Thank you..

Sure. So, we gave a preliminary look at the design when we kicked off the study in late 2016 and we've since updated that trial design which you can look out for an update on clinicaltrials.gov shortly. And so, we were initially going to looking at 40 patients, randomized, placebo-controlled, three to two across the two cohorts.

We've updated that, extending – expanding the size of the patients up to 56, 28 in each dose cohort randomized one-to-one. We'll be looking at six months of treatment on ACE-083 and we'll be focused on things like six-minute walk test, 10-meter walk run and other functional endpoints for walking.

And on the upper limb, we will be looking at the performance upper limb score in patients and also there's an FSHD health inventory PRO that we're also interested in that – the six-month time point of treatment..

Okay. And then, just lastly, with respect to the FSHD patient population, is there potentially any group of patients you could target that would be, I suppose, similarly affected by some functional outcome that you might be able to move on an endpoint with respect to basically intramuscular injection.

That is a modification of one or a series of specific muscle groups. Would you be able to resolve, in the clinical outcome, benefits that could form a registrational worthy endpoint? Thank you..

So, sorry, Chris, just want to understand your question.

You're asking if we could potentially, outside of the tibialis anterior or bicep, look at a different affected muscle in the patient to try to move quicker?.

Yes.

So, with respect to even those two muscle groups, whether you could identify a sub-patient population with FSHD that would be most meaningfully impacted by lack of function in those particular muscle groups to design a registration trial?.

Hi, Chris. It's Matt. I think the study as it's designed right now, it's designed in the subpopulation of the FSHD patients who have mild to moderate weakness. We're not taking patients who have normal muscle function nor are we enrolling patients who have severe muscle weakness.

But it's folks that have mild to moderate muscle weakness that are eligible for the study. So, it's in this a population.

And then, of course, whether or not they have a weakness in the upper extremity in the biceps or in their walking and foot drop function in the tibialis anterior muscle puts them into one of the two subsets or cohorts of those patients. So, this, right now, we feel is the fastest way to Phase III.

As we indicated, we will be kicking off the [indiscernible] part two of the study in the second quarter of this year. And as Todd just indicated, that data from the part two of the study in the latter half of 2019..

Okay, thank you..

Thank you. And the next question comes from the line of Paul Choi with Barclays. Your line is open..

Hi. Good afternoon. And thanks for taking our questions. If I could maybe go back to 083 for a moment here. And I'm just thinking about the competitive landscape with regard to a myostatin-positive approach versus some of the competing active NA [ph] approaches.

Can you maybe – just in your mind, think about how the market might evolve recognizing that the studies are still all at early stage. And your thinking about, is there any more evidence supporting 083 versus some of the competing assets here in your mind..

Hey, Paul. It's Todd. Thanks for your question. Yeah. So, I think there's an important point to make here is that ACE-083 is a locally acting agent.

And all of the myostatin selective or even Regeneron's most recent combination of myostatin selective plus active NA [ph] selective antibodies is these are very different molecules for very different disease.

And so, ACE-083 sweet spot is really in patients that have local muscle weakness, so diseases like FSHD, CMT and other diseases where there's local muscle weakness and the systemic approaches from these other molecules and even with our ACE-2494 is for patients that are afflicted with systemic muscle weakness.

And so, we wouldn't view ACE-083 as being competitive with any systemic agent. But in our portfolio, makes a lot of sense with our franchise to have both a locally acting and systemic agent. And there might even be a synergistic approach with the two compounds in certain diseases..

Yeah. Paul, this is Habib. Just to add to the comments from Todd, of course, we are, obviously, delighted with the fact that we've got the opportunity to be studying both a local and a systemic agent in treating very important neuromuscular diseases.

But in terms of the trends that you're seeing right now, I have to admit that we're actually quite confident by the fact that you're seeing more activity now in terms of agents being beyond just GDF-8 or myostatin.

But as you know, Paul, we've been positioning ourselves with both ACE-083 and 2494 as Myostatin+ agents and the fact that we do believe, for various reasons, that inhibiting GDF-8 as well as other selected act events [ph] will play a – potentially a very significant role in treating some of these serious neuromuscular diseases..

Great.

And just with regard to the initial – the Phase I result that might be coming out in the second half of year, is that something you would just do a top line with or would that be something that we would see at a medical meeting?.

Hey, Paul. It's Todd again. So, yes, just to be clear, the Phase I results will be the first half of 2019 and that would be something that we would probably update at a medical congress in the first half of the year. .

Okay..

That will also include a release in conjunction with the conference..

Great..

And then, just one quick one on PAH with regard to the Phase II.

With regard to the endpoints and some of the learnings from the initial data that you presented, is there anything that stands out in your mind as being either incrementally more likely with regard to sort of the classic PAH endpoints that you would want investors to focus on or anything else that you think would be probably less significant going forward?.

Hey, Paul. It's Habib again. So, I think with respect to the endpoints, we are, obviously, collaborating with a number of our key stakeholders as we think through this. We are, obviously, benefiting from regulatory input. And we do plan to host the webinar with both our internal colleagues as well as some external experts.

And during this call, we'll actually shed a lot more light on the trial design, the specific endpoints that we would guide you to be focusing on, where we'll be initiating the studies as well time, duration, number of patients, et cetera. So, more to come..

Great, okay. We will stay tuned. Thanks for the questions..

Yeah. Thank..

Thank you. [Operator Instructions]. And our next question comes from the line of Mike King with JMP Securities. Your line is open..

Hey, good, guys. Thanks for squeezing me in. I just wonder – I'm just sort of following up on a couple of other questions that have risen on 2494.

And just wonder if some of the recent FDA decisions about guidance on therapies for DMD has caused you to rethink your development timelines and/or strategy for 2494 in DMD and what suitable surrogates you might think about that could satisfy some of the recent agency directives?.

Hi, Mike. This is Matt. That's actually a great question because, obviously, we are aware of the new FDA guidance that came out, that spoke to some of these diseases, particularly some of the opportunities for companies to move more quickly with their agents in this area. So, we're fully aware of them. We want to be aggressive and move quickly.

And I think being on the cutting edge of development with these agents gives us the opportunity to really blaze a new trail and come up with potentially novel endpoints or composites of endpoints.

I think right now it's a little too early to be specific about what the specific target endpoints that could be considered and what the timeline might be to [indiscernible] in the specific diseases..

And, Mike, it's Todd. Just to be clear, we haven't picked a lead indication for ACE-2494. We have discussed DMD as one of four disease areas that we're interested in. So, we continue to evaluate that disease area along with FSHD systemic therapy, SMA and ALS. So, stay tuned over the next 12 to 18 months as the Phase I comes in.

In early 2019, we'll be able to discuss more the disease area that we think is the lead indication..

Thanks, guys..

Thanks, Mike..

Thank you. And I'm showing no further questions at this time. I would now like to turn the call back to Mr. Habib Dable, Acceleron's CEO, for his closing remarks..

Yeah. So, I just want to thank everybody for their question, for your continued interest in our company. Wish you all a great evening. And look forward to seeing you at upcoming congresses..

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone, have a great day..