Agios Pharmaceuticals Inc (AGIO) 2017 Q1 法說會逐字稿

Good morning, and welcome to the Agios First Quarter 2017 Conference Call. (Operator Instructions) Please be advised that this call is being recorded at Agios's request.

I would now like to turn the call over to Kendra Adams, Senior Director, Investor and Public Relations of Agios, you may begin.

Thank you, Kevin. Good morning, everyone, and welcome Agios first quarter 2017, 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 today with prepared remarks are Dr. David Schenkein, our Chief Executive Officer, who will review business updates and key milestones for 2017; Dr. Chris Bowden, our Chief Medical Officer, who will provide an update on our clinical development activities; and Andrew Hirsch, our Chief Financial Officer who will summarize Agios first quarter and 2017, financial results. Dr. Scott Biller, our Chief Scientific Officer, will also be joining for Q&A. Before we begin, I would like to remind you that today's discussion will include statements about the company's future expectations, plans and prospects that constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our annual report on Form 10-K, which is on file with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. With that, I'll turn the call over to David.

Thanks, Kendra. Good morning, everyone, and thanks for joining us today. I'd like to begin by highlighting the tremendous progress we've made in advancing our portfolio of novel investigational medicines and executing against our 2017, priorities. Notably, in February, the NDA for enasidenib whose brand name is IDHIFA was accepted for priority review. We expect IDHIFA to be the first oncology product from our internal discovery engine to launch later this year, which is an important company milestone, and start of the next phase of our partnership with Celgene. This will be followed by the planned NDA submission of our wholly owned IDH1 inhibitor, ivosidenib by year-end 2017. We have a seat at the table for all regulatory interactions for IDHIFA which is helping inform the process for the ivosidenib NDA submission. We're also working closely with Celgene on launch preparation and co-commercialization activities. The Agios sales force has been hired and training is underway to ensure launch readiness later this quarter. Our medical science liaisons are also hired, trained, and are active in the field having scientific discussions. We will expand these efforts in 2018, to prepare for the potential launch of ivosidenib. As a physician, it's an exciting time in the treatment land of escape for AML with several new agents in development, including our IDH inhibitor, which have the potential to change the treatment paradigm for this disease.

Turning to our work in creating novel therapies for rare genetic diseases, we're focused on developing AG-348 as the first disease-modifying treatment for pyruvate kinase deficiency. Our key program milestones are on track. As you saw in our press release, updated data from the DRIVE PK study, has been accepted for an oral presentation at EHA. Last week, the FDA granted AG-348 Fast Track designation for PK deficiency. This is important, as we work with the FDA on the pivotal program design and we remain on track to share our plans with you in the third quarter. Our EU regulatory discussions on the AG-348 pivotal design are complete. Once we conclude our FDA interactions, we will integrate the feedback and finalize the program design for a worldwide registration in pyruvate kinase deficiency, which we expect to initiate in the first half of 2018. Even as we add important commercial capabilities this year, Agios remains an organization that is fueled and driven by our first-in-class research and a team of dedicated scientists. We continue to invest in research, knowing that our scientific expertise in the field of cellular metabolism will be instrumental for future growth as a long-term independent biopharmaceutical company. We had several exciting developments in research in the past few months. Data on our approach to the treatment of MTAP-deleted tumors were presented at the Keystone tumor metabolism meeting in March. MTAP is a metabolic gene deleted in 15% of all cancer, which is upwards of 98,000 new patients per year in the U.S. We're very excited to see this program moving closer to clinical development. The presentation at Keystone showed the first data, demonstrating that we can potentially treat MTAP-deleted tumors with smaller molecules.

Also in March, Celgene designated AG-270, our lead molecule in the MTAP pathway program as a development candidate under our 2016 research agreement. We are on track to submit an IND for AG-270 by the end of this year. This will represent the sixth IND that come from Agios research labs since inception in 2009. This month, we also signed a global license agreement with Aurigene for an advanced discovery program in cancer metabolism. This is the program rooted in novel Agios biology and the chemical matter we've licensed from Aurigene, will enable us to accelerate our preclinical program. We continue to focus on discovering and developing novel programs in-house, as we've always done. And we'll evaluate strategic licensing opportunities to create a complementary avenue to continue to grow our pipeline. To close, our recent financing provides important funding as we explore new R&D programs, advance multiple programs into pivotal development, and prepare for expected commercial launches. This is an exciting time for the company as we work to develop truly important medicines for patients. I'll now turn it over to Chris, to discuss our clinical activities.

Thanks, David. I'll start by reviewing our IDH heme programs. First, as David mentioned, the NDA for IDHIFA was granted priority review with a PDUFA date of August 30th, 2017. At this time, there is no ODAC expected. Updated IDHIFA for Phase I/II expansion data, and relapsed/refractory AML, has been accepted for an oral presentation at ASCO. Data from this trial supports the NDA currently under review by the FDA. Turning to our IDH1 program. The ivosidenib NDA submission is on track for year-end 2017. We recently completed enrollment of ivosidenib 125 patient expansion cohort. We plan to present the first data from the expansion phase of the ongoing Phase I trial and relapsed/refractory AML in the second half of this year. For both IDH programs, we expect to EU regulatory strategy will take shape throughout 2017. In addition to our near-term focus on relapsed/refractory AML, we continue to pursue a speed and breadth strategy to secure a set of labels that would enable physicians to use IDH inhibitors across multiple lines of treatment and AML. We have a wide range of trials planned or already underway to support our move to frontline. For the Phase I, 7+3 combination trial with ivosidenib, or IDHIFA, we plan to present early data, primarily safety and tolerability, with a preliminary look at efficacy in the second half of the year. As we announced last quarter, both the 7+3, and VIDAZA Phase I, combination trials have cleared the safety hurdle and the dose escalation components demonstrating the ability to combine full dose IDHIFA or ivosidenib with the full dose standard-of-care therapies. This sets the stage for AGILE, our Phase III trial with ivosidenib and VIDAZA, which is on track to begin this quarter. We are also actively planning for a Phase III in the frontline fit pollution, both ivosidenib and 7+3, which will be an important combination for those frontline patients eligible for standard-of-care chemotherapy with IDH1 mutant positive AML. To round out our speed and breadth strategy, we're also exploring ivosidenib with other novel agents in AML, and plan to support several investigate responsive trials. We continue to learn more about the potential for our IDH inhibitors with solid tumors. Recall our IDH inhibitors work in the AML by releasing the block on cellular differentiation. We're working to elucidate the mechanism of the clinical activity of IDH inhibitors in solid tumors, including understanding the role that differentiation might play. Thus far, we are encouraged by the level of disease control that we have seen in the Phase I study. Cholangiocarcinoma is a devastating disease where we believe we can have a meaningful impact delaying tumor growth with a targeted well-tolerated oral medicine. There are few effective and no approved therapies in cholangiocarcinoma and the median progression free survival in the second line setting is short. The first data from the ivosidenib Phase I cholangiocarcinoma expansion cohort will be presented in a poster at ASCO next month. This trial has enrolled approximately 70 heavily pretreated patients. We continue to add new sites for the Phase III ClarIDHy study in cholangiocarcinoma, and more are slated to open in the U.S., Europe and Asia over the course of 2017. We designed this trial to be randomized and placebo-controlled to confirm the early efficacy signal seen in Phase I study. We will share additional information on the ClarIDHy study design with the trials in progress poster at ASCO. The goal for ClarIDHy is to lead to global registration, and last week the FDA granted ivosidenib orphan drug designation in this indication.

Turning now to glioma, this is an indication where we have the potential to help a large number of patients who currently rely on surgery, radiation and chemotherapy as treatment options. We are working in collaboration with the neuro-oncology community to better characterize the clinical outcomes in subsets of IDH mutant positive patients and assess how to develop novel endpoints to better determine impact of either ivosidenib or AG-881 and tumor growth and patient outcomes. For ivosidenib, we plan to present an update on the dose escalation phase, including updated safety, tolerability and imaging data in the second half of the year. Understanding the safety and tolerability profile are essential in this disease setting and the potential for patients to be on therapy for many years. For AG-881, as we reported on our Q4 call, we are currently exploring additional doses to confirm a recommended Phase II dose.

Moving to our wholly owned rare disease program, we're committed to leading the science and driving disease awareness for pyruvate kinase deficiency, as we work to initiate a pivotal development program for AG-348. Data from our Phase II study of AG-348, DRIVE PK has been accepted for an oral presentation at EHA in June. We will present updated clinical data on all 52 pyruvate kinase deficiency patients. If you recall, enrollment to this trial was completed in November of 2016. Based on our last DRIVE PK update at ASH 2016, we and physicians remain encouraged by the robust hemoglobin responses seen in many of these patients who are in need of a disease-modifying therapy for this serious anemia. In addition, we in conjunction with Boston Children's Hospital, plan to present an update on the pyruvate kinase deficiency natural history study in the second half of 2017. The study is now closed for enrollment at 258 patients. Additional data from the DRIVE PK study will also be presented in the second half of the year, as patients continue to receive therapy in the extension phase. On the regulatory front, we were pleased that AG-348 has been granted FDA fast track designation for pyruvate kinase deficiency. Fast track is designed to facilitate the development and expedite the review of drugs that treat serious conditions and fill in unmet medical needs. We remain on track to provide a third quarter update on the planned registrational program for AG-348, once our regulatory discussions are complete. The key aspects of the clinical development plans under consideration are patient population, trial size, dose and endpoints. Our MSLs are actively engaged in educational efforts with physicians to support global patient recruitment, as we prepare to launch the registration program in the first half of 2018. I'm now going to turn the call over to Andrew, to review our financials.

Thanks, Chris. Today, we are in a strong financial position to support the significant activities that Dave and Chris just outlined. Let me start by walking you through the first quarter P&L. We recognized approximately $11 million of collaboration revenue in the first quarter compared to $31 million for the same period in 2016. If you recall during the first quarter of 2016, we recognized a $25 million milestone from Celgene for the initiation of the phase III IDHENTIFY trial with IDHIFA, so that accounts for the decrease when comparing the periods. Also, it's important to note that, while we earned an $8 million milestone in the first quarter due to Celgene's designation of AG-270 as a collaboration development candidate, we only recognized about $2 million of that amount in the first quarter of 2017. The remaining balance of this milestone payment will be added to the deferred revenue line of our balance sheet, and recognized in proportion to the achievement of our deliverables under the Celgene agreement as outlined in our 10-K. Research and development expense during the first quarter of 2017, was $63 million compared to $44 million for the same period in 2016. The year-over-year growth in R&D expense was primarily driven by increased costs related to the initiation of ivosidenib phase III ClarIDHy trial, the planned ivosidenib Phase III AGILE trial, and research related to AG-270 our program focused on MTAP deleted cancers. In addition, a significant portion of the increase in R&D expense was due to the fact that Celgene supported 50% of the R&D costs for ivosidenib in the first quarter of 2016. As of August 2016, Agios is responsible for 100% of the R&D costs for ivosidenib going forward. General and administrative expenses were $50 million for the first quarter of 2017 compared to $11 million for the same period in the prior year. The year-over-year increase was largely due to increased headcount and other professional expenses to support our growing commercial infrastructure.

Now, let me turn to our cash position and runway guidance. We ended the first quarter with cash, cash equivalent and marketable securities of approximately $503 million. This compares to approximately $574 million at the end of 2016. This decrease in cash was driven by expenditures to fund our operating activities, of $79 million during the first quarter. These expenditures were offset by an increase in cash of $5 million in program funding received from our partner Celgene, and $4 million received from the exercises of stock options. On April 28, we completed a follow-on offering, resulting in a net proceeds of approximately $270 million. Importantly, these proceeds allow us the financial flexibility to invest across the business through at least the end of 2019. This provides runway through and beyond a number of important milestones critical to reaching our vision for the company including, initiation of multiple Phase III trials by ivosidenib and AG-348; buildup of our commercial capabilities and infrastructure; support the anticipated product launches of our IDH inhibitors and AML; advancement of AG-270, our program in MTAP-deleted cancers in to Phase I clinical trial; and continued funding of our robust discovery research engine, which is on track to put 6 development candidates into clinical trials in just 8 years. I'll now turn the it back to David to wrap up.

Thanks, Andrew. As we finish the call, I would like to leave you with the vision we have for Agios that we articulated at the beginning of the year. We have proven our ability to discover novel biology and translate those discoveries into precision medicines in areas of high unmet needs. IDHIFA is just the start, as we expect to launch ivosidenib in 2018 and continue to fund R&D to build our capabilities to do this again and again. I'd like to thank all the tremendous employees at Agios for their dedication, and their passion to make the difference for patients. I also want to thank all of the patients, the caregivers, and the physicians who participate in our clinical trials, and to thank our partner Celgene. And with that, operator I'll turn it back to you for questions.

(Operator Instructions) Our first question comes from Anupam Rama with JPMorgan.

Just wondering on the updated glioma, effective second half of the year. What will you be looking for in the data set to help you decide next steps for that program? And related, are the next steps with AG-881 tied to these data?

I will have Chris, talk to you a little bit more about glioma next steps.

Chris here. We're doing a couple things, and low grade glioma, there's really been very few new therapies for patients. And so one of the things we want to understand with 120, is further -- obtain further safety and efficacy data that builds on what we presented at SNO last year. One of the things that I pointed out in my remarks is that given these natural history of this disease, we anticipate the patients would be on treatment for potentially long periods of time. So getting an understanding of how their disease behaves and how they tolerate the drug is really important. And from the perspective 881, we're still in dose escalation and dose finding, and we'll look forward to presenting that information when we have a story to tell. So from my perspective, we have 2 shots on goal if you will, 2 molecules to think about in this disease which really is in need of some new treatment option, so it's something we are really looking forward to.

Our next question comes from John Newman with Canaccord.

I just wondered if you could talk a little bit about what we might see in cholangiocarcinoma at ASCO, if that [substance would] lose a little bit of efficacy or if it was mainly focus on safety side?

Yes, thanks, John. Again, I'll have Chris give you an answer on that one.

So, at the Triple meeting in 2015, we had data on 25 patients that were presented by Skip Burris, and as I said in my remarks, we're getting -- we've got approximately 70 patients now. So with the passage of time, additional patients, we'll have additional data from both an efficacy and a safety perspective. So you should expect to see both, and again, in an area where there is a really high unmet need, the patients are in need of new therapies. And 1 other aspect that we're also working hard on is around translational biology understanding how an IDH inhibitor in an IDH mutant patient and its mechanism of action will translate into patient outcomes.

Our next question comes from Eric Schmidt with Cowen & Company.

Maybe first for David, I see you got the Fast Track approval for -- sorry, Fast Track status for 348, is that in lieu of breakthrough designation or is breakthrough still possible?

Look, we're really pleased with the Fast Track. It's independent of a potential breakthrough. And it's very encouraging and we're very pleased about getting the Fast Track, it's very important for us. We've had no issues with communication with the agency and so, this will even help speed that up even more and give us future advantages as we move the programs forward. So it's all good.

And maybe for Chris on a upcoming ASCO presentation on enasidenib. You're saying Phase I/II data, is that still just a update of the dose escalation phase of the trial or will we see all the cohort expansions?

Well I think, the title is helpful in terms of giving you a sense of the -- what patient population will be presented there, so the fact that there is dose escalation and expansion in that title means you should expect to see efficacy and safety surrounding both. That's a particular opportune time for that data to be presented given that 221 is currently under review, for relapsed/refractory AML with a PDUFA date of August 30.

And then maybe just one more also for you Chris, on the European approval outlook, I think you said it would shape in 2017 for the IDH1 inhibitors. Can you clarify what that means? Are you're committed to giving some guidance this year on filing strategy?

Well, we haven't committed to providing new guidance in 2017, Eric, and what we mean by that -- or what I meant by that my in my remarks is that, we're pursuing various avenues that you have to interact with the agency both at the EMA level and we're considering -- there are options where you can consult at the country level as well. So those are the types of things we are pulling together, our first priority is in the U.S. obviously, given how we've talked in the regulatory environment here. So, we want to get going on this and wanted to let you know we're starting to move forward on it, but that's about as much detail as we want to provide now.

Of the next question come from Alethia Young from Crédit Suisse.

This is on for Slanix Alex on for Alethia. Just had a quick question on PKD program, I was wondering if you could maybe comment on some of the similarities and differences between your discussions with the EMA versus the FDA in terms of points of focus et cetera?

As you know, we conduct regulatory meetings on both sides of the of pond and they're critically important, As we said in our prepared remarks, we've concluded the discussions we've had with the European regulators, and I really can't provide any details from there, but our -- and this is pretty common with regulatory packages. You get feedback from both sides and they're usually pretty aligned, but not always exactly aligned and our job will then be, after we get our FDA interactions, to integrate the 2 and come up with the pivotal program that we're confident will support global registration. And while so I can't share with you any details, we're very confident that we'll be able to integrate both those feedbacks and create the program that's in the best interest of both regulators and patients.

Okay. Great. And another quick question on the MTAP program. I was wondering if you could help us -- help frame for us in which specific tumor types the biggest opportunity would be?

Yes, so it's a little bit too early to give you that guidance yet, as you know, we're looking forward to submitting -- Scott and his team will be submitting the IND later this year and as we get ready to begin into the clinic, you'll see the clinical trial design. So it's, obviously, a very exciting time for us, given how broad this metabolic gene deletion occurs across a wide range of both blood cancers and solid tumors. I think you can expect that our clinical trials will be restricted to patients with the appropriate genetic marker, meaning a deletion of that metabolic gene. But how we'll focus later, after we've achieved proof of concept, on which individual disease, it's just a little too early to comment.

Sure. And let me just ask a final question on the ID -- commercialization for IDH inhibitors. I was wondering if you could maybe help us -- help frame for us what that expansion might look like in terms of going from the commercial, organizational requirements for 221 and then expanding to 120's launch in 2018. I'm sorry, for...

This in Andrew, I'll take that question. So as you know for IDHIFA we're responsible for 1/3 of the commercialization effort -- or the field effort and we've sort of defined that with Celgene as sales and MSL. So if you think about what a total effort would be. We would do 33% of that. So as we would move to the potential launch of ivosidenib, we would rightsize that for a complete launch, wholly-owned company launch. We've not really giving any guidance and we're not prepared to do that yet at this stage in terms of specific numbers. But as we get closer, we will have further discussions around that.

Our next question comes from Terence Flynn from Goldman Sachs.

This is Samir on for Terence. One more on the cholangio data at ASCO. Can you remind us what stage of patient you enrolled in that trial? What's currently typically used to treat these patients? And what efficacy that generates?

Yes. So, our patients that we have enrollment as Phase I are generally progressed after prior chemotherapy and cytotoxic therapy is the standard. In general, globally the majority of patients get platinum-based chemotherapy, usually platinum and gemcitabine of course 5FU, fluorouracil, plays a role here. Response rates tend to be in the 20% range or so and survival is generally less than a year. So, that's in the frontline setting. After patients progress, there is really no standard at that point. And so you're looking at single agent chemotherapy and clinical trials. So overall, the situation is pretty grim. So the patients that we've enrolled in our Phase I trials have all had prior chemotherapy, prior treatment, and then depending on how they initially presented, they may have had surgery. Radiation therapy is not used too often in this disease.

Our next question comes from Yatin Suneja with SunTrust.

Just a couple of questions on the IDH program. Could you maybe help us understand how refractory are these patient populations that you have enrolled in both 221 and 120 expansion cohort? I mean is that very well understood patient population? And then confidence that you have in approval comes from the fact that these are very sick patient population and you have very limited options. And then I have one more.

Sure Yatin. I'll start, this is David, and then I'll pass it over to Chris, for more detail. So obviously, we're -- have a high degree of confidence in the data that we've generated both with what now known as IDHIFA AG-221 and also ivosidenib in that. These are patients, as you've seen from the prior presentations you'll see more at ASCO for IDHIFA and you'll see more in the second half of the year for ivo, these are patients who have had multiple rounds of conventional chemotherapy if they're younger, and probably, HMAs if they're older and really have very few conventional options left. And -- well we obviously think the data has been -- is very compelling and we're very pleased, obviously, with the regulatory interactions we have had to date. Obviously getting the priority review and no [ODAC] scheduled gives us the high degree of confidence and we'll use that information as we build the ivosidenib as well. Maybe I'll have Chris talk a little bit more about the refractory. Remember this is -- our trials have been for relapsed and refractory.

Yes. So the definition for the 120 expansion cohort Yatin, is relapsed/refractory AML in second or greater relapse. Patients who have relapsed after stem cell therapy. Those patients who were refractory to induction or re-induction and/or relapsed within one-year. So from clinical perspective and a patient need perspective, it's a very bad patient population. And then when you think about this from what other options do these patients have. They have very few so they really fulfill that definition of unmet needs. So when we would define that patient population we did it very carefully for that expansion cohort, to isolate if you will a group of patients who really have no approved therapies and that's really important. And to David's point, we've been very gratified with the data that we've seen both in terms of response, duration of response, as well as the overall safety profile and we think we're going to be able to meet an unmet need there. The other thing I would point out that gets missed sometimes, as bad shape as these patients are, we've seen around 10% of the overall patient population go to transplant. So they achieve CR after -- despite the fact that they're in this really bad -- have a very bad prognosis with, in 120's case 500 milligrams daily. So that gives you a sense of how refractory these patients are and why we think we have good a new treatment option with both drugs.

Got it. That's helpful. And then on 120, so you've completed the enrollment in the expansion cohort, I mean, is there a particular median duration of follow-up that you are targeting or what should we anticipate in terms of median duration of follow-up that you will file on? And how does that compare to IDHIFA?

Yes. So Yatin, David here. We can't give you any of those details at this time, but what we can tell you is that we remain on track to submit our NDA by the end of this year at -- near the end of the year for ivosidenib and that's based on our conversations with the agency around the type of follow-up that we expect to have on the patients in our package. And I think we're pleased with the follow-up we've had, particularly in this setting for both ivosidenib and for IDHIFA. And so I think, that's based on our regulatory interactions and our understanding of what they would like to see.

Our next question comes from Michael Schmidt of Leerink.

I had a couple of questions regarding the frontline AML opportunity and my first question is your decision to move into a Phase III trial in combination with VIDAZA with ivosidenib, was that based purely on safety to date? Or have you seen already efficacy data from the frontline Phase I study to support this decision. And can you remind us of the benchmark in frontline AML for either 7+3 and VIDAZA? And where do you need to get to get to (inaudible) registration in terms of efficacy.

So our desire and long-term goals from the very beginning, given the novel of mechanism of action here and the compelling data, we've seen in the relapsed/refractory as you've heard us articulate in the past is the strategy of speed and breadth. And the breath part is really moving the drug into the frontline setting so that patients -- any patient with an IDH mutation, either IDH2 or IDH1, can have the opportunity to receive 1 of the drugs in the frontline setting and follow them through. And so, the decision to move ahead to the Phase III first beginning with VIDAZA and then after that will be with 7+3, is based on our preclinical scientific hypothesis that shows a unique mechanism of action, which is not overlapping with conventional therapy. The safety profile we've seen of the single agents, which has really been very favorable and, again, doesn't overlap with conventional therapies. And then some of the early data that we've seen from the ongoing Phase I studies, obviously help us shape all of that. So it's the combination of all of that.

In terms of what to expect with conventional therapy, remember with 7+3 and the newly diagnosed fit patient, a very high percentage of them have the complete remission, and it actually cured the potential in the small number of those patients. And so our goal would be obviously, to improve the long-term survival of those patients and even increase the cure rate for some of those patients. For the HMAs, particularly for VIDAZA, in single agent, newly diagnosed patients who aren't fit, you'd expect about 20% complete remission rate and overall survival of about 10 months and there really is a very little curative potential. So there is a big opportunity to make a big impact in patients' lives in that setting as well. And we plan to go after both.

Okay. And one question regarding the cholangiocarcinoma pivotal study that's planned. I guess, my question is there was some activity in this disease with FGFR inhibitors and I was wondering if the IDH patient population, if there is an overlap between those in the FGFR positive patients? And if you also could remind us of the percentage of patients with IDH1 mutations in cholangiocarcinoma.

So the frequencies is around 20% to 25% of patients with the diagnosis of cholangiocarcinoma have an IDH mutation. You're asking is there an overlap between FGFR receptor or amplified patients in IDH? And I don't have the exact numbers, but they tend not to -- what limited data there is, I haven't been impressed there's a lot of overlap there. From the perspective of the ClarIDHy study we're emphasizing, what you -- you must be have an IDH mutation documented. We certainly look at other co-occurring mutations and other aspects of their molecular components of their tumor.

And Michael, just to clarify the ClarIDHy study you mentioned planned, it actually began in December, and is ongoing open sites and enrolling as we speak today.

And then one last question on -- you already commented on your plans to build out the commercial infrastructure and my question is really around your activities going forward, and I guess, is it fair to assume that the plan is to commercialize ivosidenib in Europe in-house should it be approved in the future there?

Yes Michael, this is Andrew. So our plan is to make it available globally, I think these are plans for how we commercialize that ex U. S. are really going to kind of dove tail with the ex U.S. regulatory strategy. So as that comes into sharper focus that will really drive how and when and what form that takes.

And I'm not showing any further questions at this time. I would like to turn the call back over to our host.

Thank you, very much. I'd like to thank obviously, everybody, who has participated on the call today and always, a special thanks to all of the patients and physicians and caregivers who participate in our clinical trials, that makes all this exciting progress possible. So with that, we'll end the call and thanks for participating.

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have wonderful day.