Good morning, and welcome to the Agios' Second Quarter 2018 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 being recorded at Agios' request. I will now like to turn the call over to Renee Leck, Senior Manager, Investor Relations.

Thanks, Shannon. Good morning everyone, and welcome to Agios’ Second Quarter 2018 Conference Call. You can access slides for today's call by going to the Investors section of our website, agios.com. With me on the call is today are Dr. David Schenkein, our Chief Executive Officer, who will review key business updates and milestones for 2018; Dr. Chris Bowden, our Chief Medical Officer, who will provide an update on our clinical development activities; Steve Hoerter, our Chief Commercial Officer, who will discuss our recent commercial activities; and Andrew Hirsch, our Chief Financial Officer, who will summarize the second quarter 2018 financial results. Dr. Scott Biller, our Chief Scientific Officer, will also be available for Q&A. Before we get started, I’d like to remind everyone that statements we make on this call will include forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our most recent Form 10-Q filed with the SEC and any other filings that we may make with the SEC. In addition, any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements. And with that, I'll turn the call over to David.

Thanks, Renee, and good morning everybody. And welcome to our second quarter earnings call. 2018 has been a year of execution across the Agios and we're thrilled that our progress is culminated in the recent FDA approval of TIBSOVO. When our labs opened nine years ago, we set out to build a science-driven organization capable of creating important medicines against novel metabolic targets and making them available to patients whose lives we can impact. From where we stand today, we have a two approved precision medicines that met that bar, expansive clinical development programs across oncology in rare genetic disease and a rich research pipeline to support our next phase of growth. Earlier this year, we laid out an aggressive plan to initiate multiple clinical trials with the goal of bringing additional medicines to patients in need of new treatment options. During the first two quarters of the year, we’ve achieved several of these notable milestones. In pyruvate kinase deficiency, two pivotal trials for mitapivat, our pyruvate kinase activator, also known as AG-348, are now enrolling patients at U.S. and ex-U.S. sites. The initiation of the ACTIVATE and ACTIVATE-T trials marks an important step in our commitment to deliver the first targeted therapy for this chronic anemia. In our oncology portfolio, AG-270, our first-in-class MAT2A inhibitor and the latest program to emerge from research entered a Phase 1 dose escalation trial earlier this year in patients with MTAP deletions. With MTAP comprising the most frequently deleted metabolic gene in cancer, we're excited to kick-off the clinical effort to evaluate this investigational new therapy in a large genetically defined patient population. There is important work ahead in the second half of the year for our IDH inhibitors in the frontline AML and solid tumor settings that Chris will cover in more detail, including a set of ivosidenib abstracts we have submitted to ASH. Turning to research. At Investor Day, we disclosed active discovery programs in phenylketonuria, erythroid porphyria and Friedreich’s ataxia. These programs underscore our investment and commitment to build our rare disease portfolio and applying our research tools to develop novel approaches to treating these diseases. Our team, has began IND-enabling activities for AG-636, our DHODH inhibitor. The submission is on-track for the fourth quarter and represents the seventh investigational new drug application to emerge from our research engine. 2018 is shaping up to be a transformational year for our Agios with the approval and commercialization of our first wholly owned product, execution on an ambitious set of goals to advance our clinical and preclinical portfolios and the continued growth of our organization to support this important work. I'll, now turn it over to Chris to discuss our clinical development activities.

Thanks, David. The second quarter was an active one, marked by numerous clinical accomplishments expanding trial initiations, data presentations and journal publications. Starting with AML, the compelling Phase 1 data that supported TIBSOVO's approval, in IDH1 mutant relapse or refractory AML was presented at both ASCO and EHA in June, in addition to being published in the New England Journal of Medicine. Patients in this study were typically older and had their disease return after multiple prior rounds of therapy. Significant portion also had secondary AML, a challenging difficult to treat condition that usually evolves out of myelodysplastic syndrome MDS, or after treatments with cytotoxic chemotherapy. TIBSOVO's ability to produce durable responses in this patient population underscores its compelling efficacy as a single agent. The Phase 1 trial generated an important single agent data for ivosidenib in two other key patient populations, untreated AML and MDS. A significant number of patients with untreated AML are not offered any therapies for their disease due to their poor performance status and/or comorbidities and are therefore an important underserved population. We enrolled 34 of these patients in the Phase 1 trial, and ivosidenib demonstrated robust response rates, including a complete response rate of 21% and an overall response rate of 56% as of the most recent data presented at ASH last year. We have submitted an abstract with updated data focusing on longer follow-up to this year's ASH Conference. Out of the 12 patients with high-risk MDS we enrolled in the Phase 1 trial, 11 patients responded to ivosidenib with five having a complete response, which is an impressive outcome for this population. This data has also been submitted for presentation at ASH and will focus on longer follow-up. With U.S. approval established in the relapse or refractory AML setting, our goal is…

Thanks Chris. I'm excited to join the call this morning to provide an update on our ongoing launch of TIBSOVO. We've been in full commercialization mode across the organization since the FDA approval less than two weeks ago. And we are successfully executing on our launch plan. Thanks to an incredible cross-functional effort here at Agios, we shifted the first bottles of TIBSOVO into the distribution channel just hours after receiving FDA approval. And we received order that same-day that the first TIBSOVO prescriptions had already been written. Our team of 32 senior hematology consultants are engaging with the physicians across the country, providing information about TIBSOVO and how this novel, first-in-class precision medicine can be incorporated into the treatment approach for relapsed or refractory AML. We have been very pleased with the feedback the team has received from their customers. Our national account director team has been working with payers to understand their coverage policies for TIBSOVO. And to-date, we are not aware of any payer-related coverage issues. In addition, just yesterday, the NCCN published their updated treatment guidelines to include TIBSOVO for IDH1-mutated AML, recognizing the importance of this new targeted treatment. TIBSOVO received a category 2A recommendation as a single agent for the treatment of relapsed or refractory disease in patients with IDH1-mutated AML. And in newly diagnosed patients age 60 or older with IDH1-mutated AML, who are not candidates or decline intensive remission induction therapy. As the launch progresses, the commercial team is focused on three strategic competitors. First, increasing IDH testing rates, especially in the community setting; second, to educating physicians on the TIBSOVO label; and finally, ensuring appropriate relapsed or refractory AML patients have access to TIBSOVO. Turning to IDHIFA. Celgene reported second quarter net sales of $16 million in the U.S., representing 11% growth from the first quarter. Now that we are nearly one-year post-launch for IDHIFA, this moderation of quarter-over-quarter growth is consistent with our expectations. Before I close, I want to thank the entire team here at Agios for their hard work and ensuring a very successful launch of our first wholly-owned medicine. At Agios, we challenge ourselves to achieve the other side of possible. And with the launch of TIBSOVO, the team has done just that. I'll now turn the call over to Andrew.

Thanks, Steve. Before I review our financial results for the quarter, I'd also like to acknowledge my Agios colleagues for securing the recent full approval for TIBSOVO and ensuring commercial launch on the same day. This is just the beginning as we continue to translate our research discoveries into precision medicines in areas of high unmet needs. Our second quarter financial results can be found in the press release we issued this morning, which I will summarize. More detail will be included in our 10-Q filing later today. We recognized $40 million of revenue for the second quarter, compared to $11 million for the comparable period in 2017, all of which was collaboration revenue from Celgene. The significant year-over-year increase in revenue was driven by three factors: first, we recognized a $15 million milestone related to Celgene's second quarter MAA filing to the European Medicines Agency for IDHIFA. Second, in June, we entered into an exclusive license agreement with CStone Pharmaceuticals for the development and commercialization of TIBSOVO in Greater China. We recognized $12 million related to the license delivery under this agreement during the quarter. And finally, Celgene recorded IDHIFA revenue of $16 million for the second quarter, resulting in royalty revenue to Agios of $1.6 million. Given the one-time nature of the IDHIFA MAA milestone in CStone upfront payment, we expect collaboration revenue to return to its historical run rate going forward. Now turning to our operating expenses. We recorded $87 million of research and development expense for the second quarter of 2018, compared to $80 million for the same period in 2017. This increase was largely driven by increased investments in the mitapivat PK deficiency pivotal program, IND-enabling activities for AG-636, our DHODH inhibitor and ongoing research efforts across our discovery platform. Second quarter general and administrative expenses were $27 million, an increase of $11 million from 2017, driven by increased investment in our infrastructure and commercial capabilities for the launch of TIBSOVO. We ended the second quarter with cash, cash equivalents and marketable securities of $937 million. We expect that this cash balance in addition to expected TIBSOVO revenue will fund our current operating plans for at least the end of 2020. It's been an exciting first half of the year for us here at Agios. With the start of the AG-270 Phase 1 dose escalation trial, the initiation of registrational trials for mitapivat, and of course, the FDA approval of TIBSOVO for relapsed or refractory AML. We are in a strong financial position to execute on the ambitious plans we shared with you at our Investor Day in May. And I would like to take this opportunity to thank our shareholders for their continued support. With that operator, please open the line for questions.

Thank you. [Operator Instructions] Our first question comes from Anupam Rama with J.P. Morgan. Your line is open.

Hey, guys. Thanks for taking the question and congrats on all the progress. For the AGILE study, you guys have talked about evaluating a move to event-free survival from OS on the primary endpoint. Just wondering if there's any regulatory update? Or when we could get an update? Thanks so much.

Yes, good morning, Anupam. It’s Chris Bowden here. So we're still working through that and engaging with the regulators. So we don't have any updates – I don't have any updates at this time, it's certainly something we are continuing to focus on.

Great, thanks so much for taking my question.

Thanks Anupam.

Thank you. Our next question comes from Yatin Suneja with SunTrust Bank. Your line is open.

Hey, guys. Congrats on all the progress and thanks for taking my question. Just a couple of questions, maybe I’ll start with AG-348. It will still take some time for me to remember the new name. So have you disclosed the powering assumptions for the ACTIVATE trial. I was looking at the DRIVE PK study, and I think 60% of the DRIVE PK study should meet the eligibility criteria for ACTIVATE. And I think in those patients, about 47% achieved the threshold of 1.5 gram per deciliter increase in hemoglobin. So could you help us understand how these data point helped you with the powering assumption? And any sort of update on the enrollment time frame for these two trials, ACTIVATE and ACTIVATE-T? Thanks. And I have another question as well.

So Yatin, we are in the operational phase of getting all the sites up globally. So we're not ready to provide any projections around accrual. As far as the setting up the design for the study, certainly the efficacy results we saw from DRIVE PK were able to be analyzed according to the population that we are looking at in the ACTIVATE study. So we can take some of the eligibility criteria that we put in the ACTIVATE study that you touched on and come up with some projections of how we can develop the study that we think will be positive. I think the other aspect to also keep in mind is that in the placebo arm, we don't expect – there's some general fluctuations in hemoglobin. But we have a pretty good idea of how the placebo arm will perform. So that allows us to power the study adequately and we think with the study we design will certainly be demonstrate that mitapivat has important clinical benefit in this patient population.

Got it. And then on IDHIFA, can you give us a little bit more color on the quarter in terms of maybe unit growth that you see, I think, in Q1 there are some seasonal impact from Donnatal and close to that anything particular in Q2? And then the second question on IDHIFA is, our academic consultant suggest that they are already using the drug in high-risk front-line patient and reimbursement does not seem to be an issue at least for the academic. Can you perhaps give us a little bit more color in terms of what you are seeing in the marketplace there?

Sure, Yatin. It’s Steve. Thanks for the question. So first with respect to IDHIFA and color on the quarter – the second quarter performance, we continue to be really pleased with how the drug is performing, now that we are approaching one year post-launch. I don't have updated metrics for you similar to the metrics that I disclosed at the Investor Day earlier this year. We'll have those on a subsequent call. But we are pleased with how growth is continuing. I would add that in terms of unit growth, it's consistent with the revenue growth that we've seen quarter-over-quarter. So we remain pleased with progress. I mean, as we would expect, uptake in academic centers is likely exceeding that what we're seeing in the community. And that's really just a function of time, awareness, increase in testing rate. So this is very much an active work in progress for the combined Celgene and the Agios commercial teams. With respect to your second question, which I think Yatin related to what you're hearing from academic consultants about their use of the drug outside of label in the front-line setting. Of course, that's a use that neither Celgene or Agios promotes to. It's unsurprising to me in a sense that those physicians are not seeing reimbursement challenges there. As you know, as we disclosed earlier, IDHIFA does have Category 2A listing in the front-line setting as monotherapy in patients who are not eligible for intensive chemotherapy. And it doesn't surprise me that physicians then would also be seeking to combine the drug potentially with HMA or with chemotherapy in that population of patients.

Got it. Thank you very much. And then for TIBSOVO, are we able to track the prescription using third-party service? And then one final question for Andrew. Andrew, could you help us with the P&L, I mean a little bit, especially with regard to R&D going forward, seems like a little bit of an uptick in Q2, is that a good proxy for rest of the year? Thank you very much, guys.

Yes, Yatin, it’s Steve. I'll take your question on TIBSOVO tracking. And so as you know, as we have spoken about previously, we have a relatively limited distribution channel for the drug, given the special nature of the product and the population that we're serving. So we distribute the drug through both specialty distributors as well as through specialty pharmacies. And given the nature of the distribution channel, we wouldn't have expected that IMS would have very complete prescription data, as a result of that. And so we've taken the decision to have our channel partners not share any script level data with other parties as a result of that. So we'll be providing the usual updates on our quarterly call and that's how we'll be communicating our progress with the TIBSOVO launch.

Hey, Yatin, this is Andrew. So just in your question on R&D spend. Yes, we did see an uptick this quarter that was really driven by several of our ongoing clinical trials, including startup ACTIVATE and ACTIVATE-T now up and running and starting to enroll, continued enrollment in AGILE clarity, the perioperative study, the Phase 1 AG-270 trial as well as some of the research activities, IND-enabling activities for AG-636. So I think you could probably expect that level kind of to continue at that run rate going forward given all the activities we have across the R&D portfolio.

Thank you. Our next question comes from Kennen MacKay with RBC Capital Markets. Your line is open.

Hi, thank you for taking the questions and congrats on the recent and very expedited approval of TIBSOVO.

Thank you.

Two quick questions. First on the IDH side of the business, just wondering how we should be thinking about potential for the venetoclax to change the AML treatment paradigm if or once it's approved in combo with HMAs or lower dose ara-C, and then secondly, I was just wondering if there was any kind of color you could help us with on the enrollment into the AG-270 MTAP initial dose escalation? And maybe when we could think about initial data from that dose escalation even if it’s just potentially biomarker data? Or what internally you would like to see before presenting some of that data?

Thanks Kennen. Maybe I'll answer your second question first on 270 and then Steve can talk a little bit about venetoclax. So with 270, what we've said historically with all of our first in-human study that it is really hard – in fact impossible to predict, when we're going to have enough data that it makes sense to bring to a major medical meeting. As you know, we began enrollment in the dose escalation phase just in March. So we're still early on in dose escalation. Things are going well. But it's too early to really commit when we're likely to see data. So for us the trigger is having enough data, both safety, PK, PD that it makes sense to us and the investigators to bring this to a meeting. And so stay tuned. Things are going well, but it's just too early to put out any commitments of when we're going to see it. And maybe I'll have Steve talk a little bit about venetoclax, and then Chris can also add if we need to.

David, just a quick follow-up on MTAP, should we sort to be thinking that that would be following the accrual of those initial 50 patients? Or could it potentially be in front of that or again, just too early to say?

Again, it's too early. If you look back historically at our Phase 1 studies, there's been a mixture of ones where we presented data before dose escalation ended and those where we presented after dose escalation ended. It's really having enough data that really hangs together that it warrants bringing to a medical meeting and is not too premature. So it's just impossible to really say at this point, it's early on.

Hi, Kennen, it’s Steve. I’ll answer your other question and with respect to the landscape in AML. As you know, over the last 18 to 24 months, we've seen a number of new medicines approved for the treatment of this disease, whether you look at RYDAPT, Vyxeos, Mylotarg, IDHIFA and then, of course, you referenced venetoclax coming. So this is – in our estimation, this is all great news for patients. This is a patient population that has been underserved for many, many years. And so the fact that we now have many new therapies getting approved by the FDA is great news for patients and for the physicians who treat them. Specifically, with respect to venetoclax, what we've heard from physicians that we've spoken with is that when there is an actionable mutation that's identified in this disease like an IDH1 or an IDH2 mutation that physicians by and large prefer to select a medicine that targets that mutation. And so we expect that to continue to be the case with other drugs that might get approved in this disease.

Kennen, Chris here. I just want to add a couple of things. We have a Phase 1 trial ongoing at MD Anderson of combining ivosidenib with venetoclax and that's part of our overall strategy given the plethora of new drugs coming in to test a lot of different combinations because in terms of Steve talking about how the horizon and the treatment landscape is changing and that's a positive thing for patients. We anticipate a lot of activity as we try to further move the needle in terms of better patient outcomes by new targeted therapies as well as other molecules that have come on the landscape like Mylotarg, Vyxeos et cetera. So lot of work to do and overall, our take is, as Steve stated, it's good for patients.

And maybe just one final question. Going back to your – one of your three strategies on sort of increasing the rate of IDH testing, obviously, this was pretty limited when we only had IDHIFA approved and we can only be looking for IDH2, maybe sort of increased this from sort of 12-ish percent of the population to 20% with the recent approval of TIBSOVO, looking for either IDH1 or IDH2. I guess, any perspective as to sort of the current level of IDH testing using companion diagnostics? And sort of what the aims are there? And then additionally, wondering if diagnostics other than the current companion diagnostics such as in-house sequencing were sufficient for approval and reimbursement of IDHIFA historically or moving forward.

Yes, thanks Kennen, it’s Steve. So I'll answer your questions there for you. With respect to testing rates, as you will recall, and we had Investor Day earlier this year, we talked about the data that we had at that time with respect to IDH2 testing rates, which were about 70%. And we disclosed then that we expected at that time that IDH1 testing rates were relatively close behind that. So I don't have updated data for you today, but we would expect that those testing rates have continued to grow over time and we'll have some updated data on a subsequent call. I will say that what we know to be happening at major academic centers and at other hospitals is that practices generally in that setting have moved to panel testing. So that's been the case, I would say for a number of months, if not years, including incorporating IDH1 and IDH2 testing into those panels. And so that, that sort of work – that sort of practice we expect, of course, to continue. And then similarly, when we think about the large commercial labs, they too offer myeloid panels that incorporated IDH1 and IDH2. So this whole marketplace of lab-developed tests continues to flourish and physicians and labs make their own determination as to what specific tests they're going to use. We, of course, with TIBSOVO and IDHIFA, are indicated for use with our companion diagnostics and that is how we promote both products. But in the community and in academic settings, these centers approaching testing in ways that they see fit.

Okay, thanks so much for the color and appreciate you taking the questions.

Thanks

Thank you. Our next question comes from Mohit Bansal with Citigroup. Your line is open.

Great, thanks for taking my question and congrats on the progress as well from my end. I have a quick question on MAT2A inhibition. Just wanted to understand that why – there is literature out there, but why direct inhibition of PRMT5 in the MTAP-deleted tumor did not result in growth inhibition in your mind? I mean, there are some reasons out there, I'm just trying to understand what do you think is a more plausible reason here? And do you think this was specific to the molecules used there or it is in general the direct inhibition of PRMT5 is not the right strategy?

Yeah, Mohit, this is Scott. And I will take that question. So, certainly we don't think it's an issue of PRMT5 inhibitors not being active. It's about selectivity. So, in MTAP neural cells, there's an elevated level of the metabolite methylthioadenosine. And this gives us special sensitivity to the inhibition of MAT2A relative to MTAP replete cells. So cells that have MTAP will be spared and those are all the other cells in your body as opposed to the cancer cells. The cancer cells have the MTAP deletion and they are particularly sensitive. We don't expect and it hasn't been demonstrated that PRMT5 inhibitors have that selectivity. So it's not about whether one is active or not, it's whether you get a therapeutic window with one relative to the other.

Got it, this is very helpful. And, then if I could change gear a little bit to thalassemia. In our discussions with the KOLs they mentioned that they do understand that this drug could be helpful, but more like in earlier setting. Given the price there will be in pyruvate kinase deficiency, I mean, so two things I want to understand is, what would be a good data for you to move forward? And is this the molecule you will go forward with? Or do you have a strategy in terms of more like life-cycle management strategy here rather than going with the same molecule? Thank you.

Hi, Mohit, it is Chris here. So, our view of this trial it’s a proof-of-concept study. And in pyruvate kinase deficiency, we're looking at activating mutant pyruvate kinase in an effort to restore, address anemia and hopefully ameliorate the signs and symptoms associated with the disease. Thalassemia, due to some very interesting preclinical work, had demonstrated that activating, wild type pyruvate kinase may in a sense provide more ATP through that pathway to stressed cell on the basis of the thalassemia genetic defect. Our preclinical data indicates we have a pretty good effects on anemia and that we're comparable to some drugs that are in testing in the clinic now. So, it's too early for me to talk about what type of data would trigger the next level of development, et cetera. Right now, we’ve got the study in operation mode, we're getting ready to launch it in fourth quarter. But certainly, we'll look at the data that we generate with our molecule. And of course, we have to take a look at the evolving landscape. And as you know, there are many new therapies coming along and there's not much approved at this point. So, we'll see where we are when we have our data and where new drugs are in terms of making decisions for the next wave of development. Because this is a rapidly evolving field and we first need to demonstrate proof-of-concept for our molecule and get some data in terms of safety and efficacy before we can decide on next steps.

Got it. This is very helpful, thank you.

Thank you. Our next question comes from Terence Flynn with Goldman Sachs. Your line is open.

Hi, thanks so much for taking the question. This is Holly on for Terence. Just a quick one on AG-881 for glioma. Should we expect an update at the SNO Conference in November? And can you remind us, what you're looking for to take this program forward? Thanks.

Yes, so Holly thanks for your questions. So, as you know in the release today, we did put out some of the presentations that have been submitted for medical meetings, but I wouldn't assume that's comprehensive and there will be additional presentations during the year. We just haven't outlined them all yet because not all the abstract submission dates have come to fruition. So we'll update that. So it's certainly possible that 881 or other data will be presented at the SNO meeting, which we’ve attended pretty much every year. With respect to where 881 is relative to developing in glioma. As you know, we have an ongoing perioperative study looking at 881 and ivosidenib in a head-to-head comparison in patients who are scheduled for surgery and we're going to use that data to determine, which is the appropriate molecule to bring into the next stage of development. So stay tuned. And once the data is completed in the perioperative study, which is going very well, then we will be able to give an update on that. We hope to be able to do that as soon as possible.

Great, thanks so much.

Thank you. [Operator Instructions] Our next question comes from John Newman with Canaccord Genuity. Your line is open.

Hi, this is David on for John. Just a quick question for Phase 2 trial in PVD are you guys measuring hormone levels at the same frequency as in Phase 2 in terms of potentially detecting aromatase inhibition, et cetera? Thank you.

Hi, it is Chris here. We will be tracking steroid hormones in the ACTIVATE studies in a manner similar to what we're doing with ACTIVATE.

Great thank you.

Thank you. Our next question come from with Tyler Van Buren with Piper Jaffray, your line is open.

Hi, good morning, thanks for taking the questions. I had a question with respect to the 270 in the MTAP ongoing Phase 1 program. I guess, specifically based upon could you just remind us what you saw preclinically perhaps with respect to talks or just in general that allowed you to define the dosing range for that program? And therapeutically, relevant levels and where you decided to start the dosing at? And perhaps even some sort of qualitative or understanding of where we are in that range right now?

Look before I turn it over to Scott to give you more details, in general, we don't give out a lot of details in terms of the exact dose that we begin with after our discussions with the agency, we are very pleased. So let me have Scott give you a little bit more flavor there.

Yeah, hi, this is Scott. Yes, so clearly we tested AG-270 across a number of MTAP-deleted tumor models and saw robust antitumor activity against multiple models. And we use that data together with biomarker data to give an estimation at exposure required in new elements to get efficacy, that's pretty straightforward near preclinical work and the FDA provides guidance for oncology on safe starting doses and we just follow that guidance. So nothing really unusual.

I would say that we have been very pleased as we have with all of our molecules to date, very pleased with the safety package we had and the discussions we had with the agency and that's what allows us to bring our molecules into the clinic.

And maybe this is the second question. Could you discuss the MDS opportunity for ivo and how do you think about the magnitude of that distinct potential opportunity?

Well we generated some data that I talked about in my prepared remarks. The IDH1 mutation frequency in myelodysplastic syndrome is around 3% to 5%. It tends to be detected in more advanced phases of myelodysplastic syndrome. The magnitude of the opportunity, I think, is predicated on A, the data we have seen so far, where we were very encouraged by the efficacy data. And the fact that there are not a lot of treatment options for patients especially in the later stages of MDS that often progresses to AML. And this is, again, in a group of patients who are older and frequently have comorbidity, so our drug offers a lot of potential opportunity to improve clinical benefit in that patient population. So we're encouraged by our early data and we're thinking of how we're going to move this forward. There's certainly a lot of interest from the academics and the community out there in terms of another potential treatment option for their patients with IDH1 positive myelodysplastic syndrome. Same goes for IDHIFA as well.

Thanks again.

And I'm currently showing no further questions at this time. I'd like to turn the call back over to David Schenkein for closing remarks.

Thanks, operator. Our 2018 progress validates Agios as an organization built to bring medicines, all the way from lab to patients and I'm confident in our ability to do this again and again. I'd like to thank all the tremendous employees at Agios for their dedication and passion to make a difference for patients. And I especially want to thank all of the patients, the caregivers and the physicians who participated in our clinical trials. Thanks for joining us today and hope you have a good rest of the summer.

Ladies and gentlemen, this concludes today's conference. Thanks for your participation. Have a wonderful day.