Acceleron Pharma Inc.
Q1 2015 Earnings Call Transcript

Published: 7 May 2015

[Operator:]

Good morning and welcome to Acceleron First Quarter 2015 Earnings Conference Call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session at the end. Please be advised that this call is recorded at Acceleron’s request. I would now like to turn the call over to Acceleron. Please proceed.

[Stephanie Ascher:]

Hey, and welcome, everyone, to Acceleron’s first quarter earnings conference call. The press release reporting our financial results in addition to the presentation for today’s webcast can be accessed by going to the Investors Section of the corporate website at www.acceleronpharma.com. On the call today with prepared remarks are John Knopf, Chief Executive Officer; Steven Ertel, Chief Operating Officer; Matthew Sherman, Chief Medical Officer; and Kevin McLaughlin, Chief Financial Officer. As a reminder, during today’s call we will be making forward statements regarding our financial outlook in addition to regulatory and product development plans. These statements are subject to risk 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-Q on file with the SEC. I would now like to turn the call over to Steve.

[Steven Ertel:]

Thank you, Stephanie. Good morning, everyone, and thanks for joining us today. During the first quarter, we presented exciting new data, highlighting the clinical and commercial potential of our lead hematology and oncology programs, luspatercept and dalantercept. We have also delivered great operational progress by advancing our entire pipeline of four innovative therapeutic candidates. We are building significant momentum that will generate even more strength as we advance our lead program luspatercept into phase 3 programs in myelodysplastic syndrome or MDS and beta-thalassemia. We and our collaboration partner, Celgene, remain committed to initiating these phase 3 programs by the end of this year. Beginning the company’s first phase 3 trial represents a transformational event for Acceleron. We discovered, designed, manufactured and developed all of our therapeutic candidates. And seeing the most advanced of the luspatercept generate encouraging phase 2 data is exciting for the company and the patients we aim to serve. We have a highly productive drug discovery platform that we are using to build a significant multi-product company. Acceleron is a leader in the field of developing therapeutic candidates that regulate cellular growth and repair. Our platform leverages the powerful biology and therapeutically rich field of cellular growth and differentiation factors. We believe we are scientific leaders in this field and have unique knowledge on how to optimally design therapeutic candidates to regulate different cell types. Using our platform, we have already discovered and advanced several therapeutic candidates which target red blood cells, bone, blood vessels and muscle. Our understanding of how to target the factors that regulate these and other cell types have enabled us to design increasingly tailored molecules that selectively affect different combinations of factors. These next generation molecules are highly differentiated with distinct therapeutic profiles. In the future, you will hear more from us as we describe some truly innovative and exciting new approaches to design new molecules targeting bone, muscle and adipose tissue as well as products that regulate fibrosis. We believe our productive discovery platform is about to reach a new level of productivity that may generate several new product candidates in the next few years fulfilling our vision to become a fully integrated multi-product company. As shown on this pipeline chart, Acceleron is building one of the industry’s most robust pipelines. We have a substantial number of ongoing clinical trials with luspatercept and sotatercept, both of which are partnered with Celgene. The most advanced our luspatercept clinical trials in MDS and beta-thalassemia, and there are several other ongoing phase 2 trial with luspatercept in hematologic diseases such as multiple myeloma and myelofibrosis, as well as in the renal space in chronic kidney disease. Our wholly-owned oncology program, dalantercept, is progressing very nicely to reach phase 2 studies. And we have a large number of earlier stage programs that we look forward to discussing in more detail in the future. I would now like to highlight some recent events that strongly position the company for future growth. Last week, we and Celgene announced that we have selected luspatercept as the chosen molecule to advance to phase 3 clinical trials in both MDS and beta-thalassemia by the end of this year. This past weekend, we presented new data from the luspatercept phase 2 clinical trial in MDS, that solidifies and strengthens our momentum towards our planned phase 3 study. The presentation showed that luspatercept increased hemoglobin levels enabled many transfused patients to become transfusion independent. During the quarter, we also presented encouraging data from the dalantercept Phase 2 renal cell carcinoma or RCC study showing that the combination of dalantercept and axitinib produced objective response and progression free survival rate that exceeded the historical axitinib monotherapy results. We view this demonstration of improved results of the combination of VEGF inhibition with our ALK1 inhibitor dalantercept as an indication of the significant potential of this program to access and leverage the enormous $10 billion VEGF inhibitor market and our initial opportunity in RCC is highlighting the excitement of this opportunity. I would now like to turn the call over to our Chief Medical Officer, Matt Sherman to give you more details on these data that we’ve recently presented.

[Matthew Sherman:]

Thank you, Steve. In our discussion today, I will review the exciting progress of our luspatercept and dalantercept programs. We recently announced that Acceleron together with its collaboration partner, Celgene, have selected luspatercept for phase 3 development in patients with MDS and beta-thalassemia. We continue to generate encouraging data from our phase 2 studies and plan to present additional analyses at upcoming medical conferences this year including the European Hematology Association meeting in Vienna next month. We and Celgene are working to initiate phase 3 clinical trials in both the MDS and beta-thalassemia indications by the end of this year. I will now summarize the encouraging preliminary data presented last week from our ongoing phase 2 study in lower risk MDS patients. This study was designed to evaluate luspatercept in patients who were nonresponsive refractory or deemed ineligible to receive an ESA. These patients were early in the treatment algorithm. 61% of the patients previously received an ESA and only 20% had received prior treatment with lenalidomide. None of the patients received prior treatment with a DNA hypomethylating agent. The study enrolled 58 lower risk MDS patients with 44 patients who are valuable for response at the time of this presentation. 35 of the patients were treated with high dose levels of luspatercept. In the patients receiving higher doses, 54% achieved the International Working Group hematologic improvement erythroid threshold of efficacy, the standard measure of hematologic response. 36 of these patients who previously received transfusions became transfusion independent with 90% of these patients achieving the onset of transfusion independence within the first six weeks of treatment. Additionally, luspatercept is generally safe and well-tolerated. MDS is a very heterogeneous disease. One of the goals of the phase 2 study was to identify biomarkers that predict the patient’s responses to luspatercept. We have identified the presence of ring sideroblasts as a cellular morphological biomarker as associated with the greater likelihood of response. Ring sideroblasts are a type of abnormal precursor cell in the bone marrow associated with ineffective erythropoiesis and animea. When at least 15% of the cells in an MDS patient’s bone marrow are ring sideroblasts, this patient is considered to be RS positive. Approximately 30% of all MDS patients are RS positive, the proportion is likely even greater within the segment of lower risk MDS patients. Among the RS positive patients now at trial that were treated with high dose level, 63% of the patients achieved an IWG HI-E erythroid response, and 39% achieved transfusion independence. Based on these highly encouraging results, we and Celgene are developing luspatercept to treat lower risk MDS patient early in the treatment algorithm. We and Celgene plan to initiate the phase 3 program in MDS before the end of the year. Turning to our program in renal cell cancer, we recently presented very encouraging preliminary data from part one of the DART study, an ongoing phase 2 clinical trial with our ALK1 pathway inhibitor dalantercept, in combination with axitinib in patients with advanced renal cell carcinoma. These data, presented at ASCO-GU in February 2015, demonstrated increased progression-free survival in patients receiving the dalantercept combination compared to historical with axitinib as a single agent. The DART study is composed of two parts, part one was a dose ascending design, in which we study dose levels of 0.6, 0.9 and 1.2 mg/kg of dalantercept administered subcutaneously once every three weeks in combination with axitinib. The presentation at ASCO-GU builds in a data presented at ASCO last year, when our data indicated encouraging response rates compared to single agent axitinib alone from its phase 3 studies. Our data with combination has now matured to the point where we were able to present data at GU-ASCO showing that progression-free survival of patients receiving the combination of dalantercept plus axitinib was 8.3 months. To put this in context, this slide compares the PFS with part one of the DART study shown in orange, to previously reported data from phase 3 studies in advanced RCC of two approved tyrosine kinase inhibitors, shown in the first two blue bars. The first bar shows the 11 month PFS reported from the phase 3 study of sunitinib as first line therapy. The second bar shows the 4.8 month PFS data, reported from phase 3 AXIS trial of axitinib in second line patients. The third, fourth and fifth bars illustrate the expected pattern of declining PFS as patients moved through and failed further lines of therapy. So in part one of the DART study, we treated second through fourth line patients and across all of those patients second, third and fourth line patients together the combination of the dalantercept and axitinib generated the PFS of 8.31 months. We are very encouraged by this and believe that it does exceed the current standards of care in second line RCC patients receiving axitinib monotherapy. We are now enrolling patients in part two of the DART study, an ongoing randomized placebo-controlled study, in which we’re enrolling up to 130 patients randomized between the dalantercept and axitinib versus placebo and axitinib. Data from this study will be forthcoming in 2016. I’ll be happy to answer questions during our Q&A and next I’ll turn the presentation over to Kevin McLaughlin, to discuss our financials.

[Kevin McLaughlin:]

Thanks, Matt. On the first quarter ended March 31, 2015 Acceleron’s cash, cash equivalents and investments were $165 million. As of December 31, 2014, the company had cash and cash equivalents of $176.5 million. Acceleron expects that its balance of cash, cash equivalents and investments will be sufficient to fund the company’s operations into the second-half of 2017. For the three months ended March 31, 2015, collaboration revenue was $4.4 million compared to $3.3 million in the same period of 2014. All of the revenue in both periods was derived from the Celgene agreement. Total cost and expenses was $19.5 million for the three months ended March 31, 2015 compared to $15.5 million in the same period of 2014. This change is primarily due to an increase in clinical trial and personnel-related expenses. The company’s net loss for the quarter ended March 31, 2015 was $14.6 million. I’ll now turn the presentation over to John Knopf, our CEO.

[John Knopf:]

Okay. Thanks, Kevin. I would like to start by describing the operational progress we’ve made and how pleased I am that our data continues to improve as we accumulate more patient experience. I’ll start by highlighting our rapid progress in MDS. At ASH, just about six months ago, we reported on data from 17 patients in the higher dose group. And this past weekend at the MDS symposium, we were able to present data from twice as many patients in this higher dose group. Importantly, the data continue to demonstrate clinically meaningful responses in patients that are nonresponsive, refractory or ineligible for ESA treatment. 54% of these patients that received higher doses of luspatercept showed a positive response and 36% of these patients achieved transfusion independence. Furthermore, we have also confirmed our original observation, first reported at ASH in December that a subset of patients that are ring sideroblast positive demonstrated an enhanced likelihood to respond to luspatercept with 63% of these patients now achieving an IWG HI-E response. Following the analysis of this robust dataset along with the sotatercept data presented at the MDS Symposium, Celgene and Acceleron have selected luspatercept to move forward into a phase 3 program this year. In summary, luspatercept continues to emerge as the very promising therapeutic candidate for the treatment of low and intermediate risk MDS patients early in the treatment algorithm. This brings us to upcoming key events and value drivers. Certainly, two key value drivers for Acceleron will be the start of the phase 3 studies in 2015 for both beta thalassemia and MDS. During the upcoming months, we expect to hold meetings with multiple health authorities to finalize our phase 3 programs. Starting two phase 3 programs in this timeframe is the substantial and exciting undertaking for Acceleron. Fortunately, we’re collaborating with Celgene, the world’s best hematology company to collectively realize these important opportunities. We also continue to make good progress in part two of the DART study, our placebo-controlled blinded study of dalantercept in combination with axitinib in RCC patients. We are on track to complete the accrual early in 2016. The next several quarters will continue to be rich with data presentations. We expect to provide updated data on beta thalassemia and MDS at EHA just next month and then again at the end of the year at ASH. For the sotatercept program, we will present data from the phase 2 study in patients with chronic kidney disease at the ERA-EDTA meeting at the end of this month. Additionally, we will provide an update at ASCO in June on dalantercept. We also expect to present data from our expanding muscle portfolio at the World Muscle Society Conference in September. From what both Steve and Matt have presented today, you can see how our deep expertise targeting the TGF-beta superfamily has enabled us to produce therapeutic candidates that have profound biological and clinically meaningful effects for patients. We have continued to leverage this discovery platform to generate novel differentiated product candidates targeting significant unmet needs. Steve has provided an overview of these new agents, and the tissues and diseases we are initially targeting. Throughout this year, we will update you on our progress with these new therapeutic candidates at medical and scientific conferences, something we very much look forward to. I’ll close today by looking ahead to 2020. These next five years will continue to be productive and very exciting. Our goal is to have approvals and five indications, and have eight distinct protein therapeutics in clinical trials. Importantly by 2020, we aim to be cash flow positive and have the U.S. sales and marketing organization. We believe we are on track to build one of the world’s great biotechnology companies. Thank you very much for your attention. And I now like to open the call to questions.

[Operator:]

Thank you. [Operator Instructions] And our first question comes from Yaron Werber from Citigroup. Your line is now open. Please go ahead. Hi, Mr. Werber, please check your mute button.

[Unidentified Analyst:]

Sorry, this is actually Jimmy dialing in for Yaron, and thanks for taking my question, and congrats on all the success. My first question is there was a grade 3 blast count increase in one of the patients. How concerning is this given that transformation to AML is a concern for MDS patients? And is it directly related to the function of the drug?

[John Knopf:]

Good morning, Jim. This is John Knopf. Matt, why don’t you take that question?

[Matthew Sherman:]

Yes, thanks. Good morning. So no, we’re not concerned at all by the increase in blasts. This is a patient who actually had boiler-line [ph] blast counts for entry into the study and there was some variability even in the reading of that patient’s bone marrow at the time of entry. So this change was felt from the - by the investigator who look closely at it to be well within the normal range of what was seen in these patients and no evidence of progression into AML.

[Unidentified Analyst:]

Got you. And just one more question, sorry, if I missed this. But would you be using something like a RS positive or SF3B1 mutation status as some kind of inclusion criteria for the phase 3?

[Matthew Sherman:]

Yes, well, as we showed at the MDS Symposium meeting, we certainly had in the rich response rate in patients who are RS positive. We’re still having our discussions with the regulatory authorities and the details of the phase 3 design, now certainly may include in the rich population, but final details of that would be forthcoming. We’re about to initiate the phase 3 study.

[Unidentified Analyst:]

Thank you.

[Operator:]

Thank you. And your next question comes from Howard Liang from Leerink. Your line is now open. Please go ahead.

[Howard Liang:]

Great, thanks very much for taking the question. I have a question on the ongoing expansion cohort. Is that all enrolled in Germany and are there more RS negative patients enrolled?

[John Knopf:]

Good morning, Howard. This is John. Steve, do you want to take that?

[Steven Ertel:]

Sure. Hi, Howard, thanks for your question. So the entire luspatercept MDS study is being conducted in Germany. We have now fully enrolled the expansion cohorts, so this study is now fully enrolled. Patients in the expansion cohort though continue to be treated in this study. And, I’m sorry now, I think there was a second part of your question that I haven’t yet addressed.

[Howard Liang:]

Yes, so I think we’ve seen the makeup of the 44 patients that we reported over the weekend, I think there’s additional - the total is something like 58 patients. So just wondering if we’re going to see more data in RS negative patients to know that it is indeed have a lower response rate?

[John Knopf:]

Sure. Okay, great. Thanks. So we have shown as Matt summarized encouraging results in the RS positive patient population and we are interested in seeing the activity in RS negative patients, and we and Celgene are discussing opportunities to be able to access a number of RS negative patients and that’s something that we can talk to you about in the future.

[Howard Liang:]

Okay. Regarding the ERA-EDTA update coming up, can you talk about the nature of the additional data, how many official data or how much in your data will have on the vascular classification?

[Matthew Sherman:]

Yes. Hi, Howard, this is Matt. So just regarding ERA-EDTA meeting in London, we will be giving an update of the data that we presented last year at the ASM meeting in November. And it’s similar it’s the ongoing phase 2 trial, in which there are just escalating cohorts of sotatercept, and we’ll be able to evaluate both the hemoglobin response as well as the effect in vascular calcifications, where previously we did show with this pertinent improvement in vascular calcifications, as well as an improvement in bone density in those patients. So that will comprise the update that you will see at ERA.

[Howard Liang:]

Okay, if I can save me one more question maybe for Kevin, are there financial milestones that you will receive from Celgene on starting phase 3 or for luspatercept in the two indications?

[Kevin McLaughlin:]

Hi, Howard. Yes, that is correct. At the start of the phase 3 with luspatercept we would receive $15 million milestone. On the start of phase 3 with sotatercept it will be $10 million milestone.

[Howard Liang:]

$15 million for both two indications - both indications together?

[Kevin McLaughlin:]

No, on luspatercept the first indication that goes into phase 3 earns the milestone. It’s not on both.

[Howard Liang:]

Okay. And on your - the projection for cash runway, did that include the $15 million I would assume with that?

[Kevin McLaughlin:]

Yes, the guidance that we have that gets us into the second-half from a cash use standpoint does include the reimbursement from Celgene, of course, as well along with this milestone.

[Howard Liang:]

Okay, great. Thanks so much.

[Operator:]

Thank you. And your next question comes from Ted Tenthoff from Piper Jaffray. Your line is now open. Please go ahead.

[Ted Tenthoff:]

Great. Thank you very much and thanks for the update. Just with respect to the muscle program. What you would be expecting as an update for on that and when can we see phase 2 study start there?

[John Knopf:]

Steve, do you want to take that?

[Steven Ertel:]

Hey, Ted. How are you? Thanks very much.

[Ted Tenthoff:]

Good. Hey, Steve.

[Steven Ertel:]

So we are continuing to enroll patients in the ACE-083 phase 1 study and as we make more progress on that study we’ll be back in touch with timing and plans on phase 2. And as we get closer to the World Muscle Society meeting, we’ll be in a position as we approach that, when abstracts become available to describe what data we’ll be presenting at that conference as well.

[Ted Tenthoff:]

Okay, excellent. Thank you.

[Operator:]

Thank you. And your next question comes from Mike King from JMP Securities. Your line is now open. Please go ahead.

[Mike King:]

Hey, guys, good morning. Thanks for taking the question. I had a couple of follow-ups. I apologize if you had answered these. I dropped off for a couple of minutes in the middle of the call, but some of the questions that Howard was asking about the upcoming dataset, just curious with regard to EHA sort of rough order of magnitude on the luspatercept MDS data update in terms of number of patients.

[John Knopf:]

Yes, Matt. Do you want to address that?

[Matthew Sherman:]

Yes. Hi, Mike. It’s Matt again. So, yes, I’m not sure we can give you the exact numbers of patients yet, because we really haven’t at least the details of what will be included in the EHA presentation. Sufficed to say though, as we indicated, we didn’t complete enrollment of 31 patients in the expansion cohort. They were 17 initially who had data available by our February cutoff date that were present at MDS Symposium. So it would be additional number of patients that will be included at EHA expected to be meaningful and look forward to that presentation.

[Mike King:]

Okay. And I know you get a lot of questions on the patients with ring sideroblast. Can you describe any translational work that’s going on right now that may help us understand better why that patient population responds better to luspatercept versus patients without ring sideroblasts?

[Matthew Sherman:]

Sure. It’s actually a really exciting area of research going on right now. There has been a number of groups that have been looking at this as well. Some of the published work in fact was presented at ASH last year, where when the genetic mutation that accounts for the majority of patients with ring sideroblasts, the SF3B1 gene mutated, when it was knocked into a moss model, induced a phenotype that was reflective of ring sideroblasts and ineffective of erythropoiesis. And it’s this status or stage ineffective erythropoiesis, which we’ve been able to show, we are able to overcome with luspatercept treatment. And exact - the molecular target for that is still under investigation. But we believe it’s the rest of red blood cells in a certain stage of erythroid differentiation that we’re targeting by inhibiting negative ligands in TGF-beta family.

[Mike King:]

Okay. And is the SF3B1 gene produced or is it response in that pathway for producing those negative ligands?

[Matthew Sherman:]

Yes, not known yet. Just folks are uncovering a few of the target genes that are regulated by that glycine factor. So there is still an ongoing list of genes that are being been discovered that might be downstream target at SF3B1.

[Mike King:]

Okay. And then just to turn to more advanced studies, I’m just wondering, so it seems in general the target patient population for phase 3 trials will be this, previously untreated low to intermediate risk MDS population. Is there anything else you can say about what you’re thinking in terms of other patient characteristics, duration of treatment, and I’d ask same questions about luspatercept in beta cell. Have you determined what the most suitable patient population would be for luspatercept and beta cell? Thanks.

[John Knopf:]

Hi, Mike. This is John. I’ll let Steve take that question, but these will be previously treated patients, not untreated patients. So, Steve, perhaps you can clarify.

[Steven Ertel:]

Sure. So excuse me - thanks for your question, Mike. So why don’t we start in MDS and then we’ll move to the second part in beta cell. So I should preface this by saying we and Celgene are still finalizing our phase 3 plans and, of course, as mentioned, having the discussions with health authorities, we’ll be able to provide more specifics after those. But we do intend to have a patient population that in many ways resembles what we’ve shown in this phase 2, which are patients who have previously received ESAs and other were nonresponsive or refractory, or otherwise deemed ineligible to receive them. But before, they would have received agents such as revlimid or hypomethylating agent. So what we sometimes refer to as sort of an ESA experienced patient population. We mentioned earlier, still having discussions, whether or not they’ll be a selective patient population based on the ring sideroblast morphology. And the final piece is, yes, these are of course lower risk MDS patients. In thalassemia, again there is similar…

[Mike King:]

Sorry, Steve. Just in terms of duration of therapy, are you thinking about 12-weeks, 24-weeks a year, any thoughts on that.

[Steven Ertel:]

Yes, it will be similar to some other phase 3 studies that have been conducted, but again I want to hold off on answering the specific duration until we have those discussions with the health authority.

[Mike King:]

Fair enough.

[Steven Ertel:]

In terms of beta-thalassemia, we remain very excited about running studies in the two subsets of patients one being the transfusion dependent population the other the non-transfusion dependent patient population. We expect to run distinct studies in these distinct patient populations and, of course, having those discussions now with Celgene and over this summer with health authority to finalize the phase 3 plans in terms of endpoints, number of patient’s duration, and so forth. But we are excited about starting phase 3 studies in each of the non-transfusion independent and the transfusion independent beta-cell patients.

[Mike King:]

If I might just quickly follow up, where - coming back to MDS, heterogeneity of the condition, can you say whether you’re contemplating any studies, I mean, I understand that the principal trial for registration purposes, but in order to maximize commercial potential for luspatercept and MDS, I don’t know if you can speculate at this point whether what other types of trials in different patient population you might be contemplating, but anything you could speak to in that regard would be helpful? Thanks.

[John Knopf:]

Sure. Okay, Mike. So, yes, we are interested in getting going as quickly as possible with this study I described. But there are patient populations as you referred to that that remain of interest to us. One is a possibly a first-line study in advance of ESA use, something that we would consider over time, another is, as mentioned earlier trying to understand the activity in RS negative patients or other patient population. So there are, as Matt mentioned, this is heterogeneous patient population. We’re excited about the signal we have clearly in these RS patients - RS positive patients, and that’s where we’re starting. But there’s opportunities go beyond that, but our focus now remains on these previously treated with patients with ESAs and plus or minus the RS positive selection.

[Mike King:]

Thank you.

[Operator:]

Thank you. And your next question comes from David Lebowitz from Janney Capital. Your line is now open. Please go ahead.

[David Lebowitz:]

Thank you very much for taking my question. Given the length of the luspatercept MDS trial and the eight-week transfusion free requirement, could you give us perspective on what that means and what we can expect with that number - the transfusion independent number going forward?

[John Knopf:]

Yes. Hi, David. Matt, would you like to take that?

[Matthew Sherman:]

Sure. Hi, Dave. So, yes, as you pointed out, this initial trial was only three months in duration, it was actually a limited duration and yet the endpoint that was required was an eight-week transfusion free period. So we’re actually quite limited in seeing that throughout the duration of the trial, yes, you have a very substantial response rate. So as we move into an extension phase of this trial, we expect that, we have the opportunity to have even a higher greater response rate. So that would - that certainly maybe forthcoming in the future.

[David Lebowitz:]

That’s helpful now. And also just jumping over to sotatercept, given the biomarkers that have been seen with luspatercept in MDS, should we have any expectations that you are looking for certainly, biomarkers with respect to sotatercept potentially in DKD, but also in the more hematologic indications, as the drugs are somewhat similar?

[Matthew Sherman:]

Yes. So we’ll just step back, so we really wanted to indicate and clarify that luspatercept has been taken forward into phase 3 development for MDS and beta-thalassemia. And that really represents the hematologic indications that we’re moving forward at this point in time with sotatercept, as you know, is still in two phase 2 trials in chronic kidney disease. There are earlier investigator initiated studies with sotatercept that was started a while ago, not necessarily under our drug control, but initiated - investigator trials and other indications, including multiple myeloma and myelofibrosis. So those are signal seeking trials, we’ll see what they show and then we can make a position, which molecule could move forward in the future in those indications.

[David Lebowitz:]

Okay, thanks for that. And one more question is, when we expect to see some data from the HCC dalantercept trial?

[Matthew Sherman:]

Yes, so we’re continuing to enroll patients to its phase 1B study, so it has a dose escalation as well as an expansion cohort. So as we get closer to completing that trial, we’ll be able to provide an update as to which medical meeting we plan to present the data at.

[David Lebowitz:]

Thank you very much for taking my questions.

[Operator:]

Thank you. And your next question comes from [indiscernible]. Your line is now open. Please go ahead.

[Unidentified Analyst:]

Thanks very much for taking my questions. So just very quickly on sotatercept in end stage renal disease, could you perhaps comment on the differentiation of this product profile versus, for example, luspatercept. And if we look at, for example, the luspatercept phase 3 program and the outcome measures that are being assessed there versus what you would potentially be looking to assess with sotatercept in end stage renal disease, what are the differentiators, for example, with respect to improvement in vascular calcification that you would expect with sotatercept in end stage renal disease specifically? And secondly, wanted to ask about the prospect of utilizing dalantercept in combination with not just Nexavar, but also potentially Stivarga, whether you at this point are in a position to comment on the timing of any potential studies that might be studying that specific combination? And then finally, on the earlier stage programs 2531, 2491, 2791 and 3891, could you give us a bit more color on the timing of entry into the clinic with those programs, which one you expect to enter into the clinic first, and in what context? Thank you.

[John Knopf:]

Great. Yes, thanks for the question. This is the John. Why don’t I take the two of those the first and the last question? So with regard to sotatercept that we’re differentiating from, say, the 5th [ph] factors in a significant way, and then we don’t really feel as a very significant unmet need in dialysis patients for the treatment of the anemia. The really unique aspect of sotatercept is the effect on bone and the effect on vascular calcification that we’ve shown both pre-clinically and then validated that initially in some of our clinical studies. So, again, we feel the unmet need in these particular patients is, again, the vascular calcification, which we suspect to lead to drive much of the mortality that’s observed in these particular patients. So slowing that vascular calcification down, we would hope we would really address the unmet needs of some of the cardiovascular events that are posed here. So we don’t really view the agents to treat the anemia exclusively as competitive agents. And then in regard with your third question in terms of which molecules might be expected to take forward in the pipeline. And we expect to bring one of those molecules forward into 2016, and as we go through the year, we’ll update you on the nature of some of these molecules and their activities. And then by the end of the year, we would - I expect to give some guidance as to which of those molecules would go into the clinic in 2016. Now, for the second question you had, maybe I’ll turn that over to Matt.

[Matthew Sherman:]

Hi, Ram. [ph] So, this is Matt. So, yes, so your second question about other combinations with dalantercept, I think it’s very good one and we’ve been actually discussing this. As we described, we’re really building a new platform of combining dalantercept the ALK1 pathway inhibitor with VEGF pathway inhibitor, so initial approach here was using axitinib in RCC and sorafenib in HCC. But with the emerging class of other DKIs, certainly stivarga or ramucirumab and others in this space. We are actually actively looking at those potential combinations, so whether it’s in colon cancer, gastric cancer, even soft tissue sarcoma, where TIs have been approved, those all represents future opportunities for this dual angiogenic blockade of VEGF inhibitor plus the ALK1 inhibitor.

[Unidentified Analyst:]

Thank you.

[Operator:]

Thank you. [Operator Instructions] And I’m not showing any further questions at this time. I would now like to turn the call back to John Knopf for any further remarks.

[John Knopf:]

Well, I’d just like to thank everyone for tuning into our call this morning and we’re just very excited over - the progress we made over the past quarter, and look forward to updating you in the future.

[Operator:]

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