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Agios Pharmaceuticals Inc (AGIO -4.40%)
Q1 2019 Earnings Call
May. 02, 2019, 8:00 a.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Good morning, and welcome to Agios' First Quarter 2019 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 this call is being recorded Agios' request. I would now like to turn the call over to Kendra Adams, Vice President, External Communications and Investor Relations.
Kendra Adams -- Vice President, External Communications and Investor Relations
Thank you, operator. Good morning, everyone, and welcome to Agios First Quarter 2019 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 are Dr. Jackie Fouse, Chief Executive Officer who will review key business updates including TIBSOVO commercial performance. Dr. Chris Bowden, our Chief Medical Officer, who will highlight our clinical development progress; and Andrew Hirsch, our Chief Financial Officer, who will summarize our first quarter 2019 financial results. Dr. Scott Biller, our Chief Scientific Officer, who will also be available for Q&A.
Before we get started, I would like to remind everyone that statements we make on that 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-K filed with the SEC and any other filings that we 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 as of any subsequent date. We specifically disclaim any obligation to update or revise any forward looking statements.
With that, I'll turn the call over to Jackie.
Jacqualyn Fouse -- Chief Executive Officer
Thanks, Kendra. Good morning, everyone, and thanks for joining us on our Q1 2019 earnings call. I am now three months into my role as CEO here at Agios, and I've been meeting with employees across the organization, learning more about our research platform and discovery portfolio, and digging into our commercial strategy to maximize the value of our clinical assets.
I believe that for our size we have one of the best pipelines in the industry with significant optionality across multiple compounds and indications in oncology and rare genetic diseases. In the first quarter, our teams produced achievements that move us closer to realizing those opportunities. We've made progress across our IDH development programs where we continue to drive frontline AML and solid tumor label expansions and broaden access for patients worldwide.
For our most advanced rare genetic disease program made a pivot. In addition to enrolling patients in the Phase 3 Pyruvate Kinase Deficiency program, we have expanded clinical development to other diseases where PKR activation may play a critical role in treating the underlying disease.
We've started dosing patients in the Phase 2 Thalassemia Study, and later this year a new study in sickle cell anemia is on track to initiate. For our earlier stage programs at AACR we presented compelling preclinical data demonstrating the rationale for synergistic activity of our MAT2A inhibitor AG-270 with standard of care therapies for the treatment of certain solid tumors. In addition, trial sites are now open in screening for the Phase 1 lymphoma study of our DHODH inhibitor AG-636.
Within our research organization our teams remain dedicated to the pursuit of terrific science and are focused on making smart decisions to advance compounds through our robust drug discovery engine.
Before I hand the call over to Chris to provide more detailed updates on all of our clinical and regulatory activities, I will provide the commercial update this quarter. In April, we announced the new commercial organizational structure that will allow our commerical teams to focus on the ongoing market success of TIBSOVO in the US. While we also build a lean effective organization in Europe where our MAA for TIBSOVO in relapsed or refractory AML remains under active review with EMA.
Darrin Miles has assumed the new role of SVP and Head of Commercial for the US as well as Global Marketing. Darrin is transitioning from his prior role as IDH Program Lead and you'll hear from him on future calls. With respect to US sales of TIBSOVO, net revenue for the first quarter of 2019 was $9.1 million. Underlying commercial unit growth continued, but the rate of that growth was a little slower than we expected. This was mainly due to an increase in patients receiving free drug as part of our patient assistance program, likely related to the typical Q1 seasonality seen in oncology that results from rollovers of benefit coverages and pressure on patient out-of-pocket costs.
Though we were short on revenues for the quarter compared to our internal forecasts, we saw several positive trends during Q1 and moving into Q2 including continued growth in the number of unique TIBSOVO prescribers especially in the community setting and increase in testing with close to 90% of academic and community physicians now testing their patients for the IDH mutation at diagnosis, and positive volume trends starting in late March and continuing through April.
Despite the slight revenue softness in Q1, we believe we're on track to deliver on our full-year internal forecast and drive solid performance for our first full-year of TIBSOVO on the market. In addition, I was in the field in April and heard enthusiastic feedback from the AML physician community regarding the potential approval in the newly diagnosed patient population reflected in our TIBSOVO sNDA and for which our commercial team is launch ready. Many thanks to our commercial team and our teams across all functions and our hard work on behalf of our patients.
With that, I'll turn the call over to Chris to update you on our clinical and regulatory progress.
Chris Bowden -- Chief Medical Officer
Thanks, Jackie. I'll begin with updates across our broad clinical development program for TIBSOVO and frontline AML, where we've made significant progress since the beginning of the year and each of the three treatment categories: intensive therapy, non-intensive therapy and those patients not eligible for any standard treatments.
In February, the FDA accepted our supplemental new drug Application for TIBSOVO and newly diagnosed IDH1 mutant AML patients and eligible for standard therapies gave us a PDUFA date of June 21st. Our sNDA application which is part of the FDAs new real time oncology review pilot program and was granted priority review is based on results from the newly diagnosed arm from our Phase 1 study in IDH1 mutant hematologic malignancies.
Updated data from this arm have been accepted for presentation at the ASCO Annual Meeting in June. The presentation will include updated data since it was last shared at the ASH Annual Meeting in December 2018. In the intensive therapy setting with standard of care is a combination of chemotherapy known as 7+3 randomized Phase 3 study of TIBSOVO or IDHIFA in combination with 7+3 recently initiated sites. This trial run by the cooperative groups HOVON and AMLSG will enroll approximately 1,000 patients and compare event-free survival between our IDH inhibitors in combination with induction and consolidation therapy versus induction and consolidation therapy alone.
Importantly, this trial allows for IDH maintenance therapy for up to two years, which will -- enable us to evaluate longer duration in the intensive setting. In the non-intensive therapy setting, patients are not able to tolerate aggressive chemotherapy and often receive hypomethylating agent such as azacitidine.
In February, we presented compelling data from the Phase 1 study of Ivosidenib and Azacitidine at the leukemia meeting in Munich demonstrating an overall response rate 78% and increase CR rate of 57% since the prior data presentation at ASH 2018 and a 20 -- 12-month survival rate of 82%. In addition, the majority of CR patients achieved IDH1 mutation clearance. The median duration of CR and CR+CRh has not been reached with the lower bound range of 7.7 months. From a safety perspective, results from the combination were consistent with the safety profiles of each drug used alone cytopenias were in line with those seen for azacitidine alone and favorable compared with other emerging hypomethylating agent combinations.
We will present updated results with a longer follow up at ASCO. These data support FDA decision to grant us breakthrough therapy designation in March, which will allow us to interact with the agency on a broader level around this program moving forward.
Our Phase 3 AGILE trial with this combination is ongoing with enrollment expected to complete in 2020. Beyond AML, myelodysplastic syndrome is an important patient population for which we've actively explored development opportunities. As a reminder, the last presented data at the ASH Annual Meeting in December where we demonstrated the compelling overall response rate of 92% in the 12 patients enrolled in our Phase 1 study.
In order to further evaluate the utility of TIBSOVO in the approximately 3% of MDS patients with an IDH1 mutation. We decided to reopen the MDS on the Phase 1 study to enroll approximately 30 additional patients. This will allow us to further understand the role that TIBSOVO can play in this disease and determine a path forward with regulators. We expect the arm to reopen later this year and look forward to providing updates on subsequent calls.
Moving to solid tumors, we're on track to share top line data this quarter from our Phase 3 ClarIDHy Trial of TIBSOVO and previously treated IDH1 mutant cholangiocarcinoma with a more complete clinical update at a medical meeting in the second half of 2019. TIBSOVO has the potential to be the first targeted therapy approved in cholangiocarcinoma and we are prepared to file a supplemental NDA by the end of the year assuming a positive trial results.
In low-grade glioma, we announced in January that we selected Vorasidenib also known as AG-881 as the go forward molecule in this indication where approximately 80% of patients have an IDH1 mutation. Molecule selection was based partially on data from the Perioperative window study of of TIBSOVO and Vorasidenib. As a reminder, this study was designed with the following objectives to determine the amount of drug exposure in the brain to confirm the magnitude of IDH target engagement as measured by 2HG levels and brain tumor tissue. To assess the impact of IDH inhibition on exploratory biomarkers of response and to assess the safety of both molecules. Data from the first Cohort of the study has been accepted for presentation at ASCO.
I'll now move to Mitapivat. Our PKR activator that is our most advance rare genetic disease program and has the potential to be our first approved medicine in this field. We are currently enrolling two pivotal studies of Mitapivat in adults with pyruvate kinase deficiency. Activate in patients who do not receive regular transfusions and ACTIVATE-T and regularly transfused patients. But the ACTIVATE-T trial we are in the process of opening trial sites and there were more patients eligible and interested in participating than we initially anticipated. As a result we are increasing the trial size from 20 patients to up to 40. We expect to enroll the first 20 patients by the end of the third quarter.
For our Phase 2 study of Mitapivat in thalassemia, we have started dosing patients with multiple trial sites open and expect to achieve proof-of-concept in this indication by the end of the year. Finally, we've been working with the National Institutes of Health on a clinical trial of Mitapivat and sickle cell disease, where we believe there is potential for a PKR activator to provide benefit for these patients. The study is in the final stages of planning and is expected to initiate later this year.
I'll now move to our early stage oncology programs. As you know, in March 2018, we initiated a Phase 1 dose-escalation trial of AG-270. Our MAT2A inhibitor in MTAP-deleted tumors with the goal of establishing a recommended dose based on safety, pharmacokinetics and pharmacodynamics markers of MAT2A inhibition.
As we have previously commented, we are pleased with what we have seen related to the effects on the pharmacodynamics markers of MAT2A inhibition which we continue to monitor. As we review the data from the once daily dose cohorts, we decided to explore b.i.d dosing as a way to potentially optimize monotherapy exposure for patients In the most recent b.i.d cohort, we saw dose limiting toxicities that we need to evaluate further in order to select the appropriate dose and schedule the expansion are since future studies.
With that, we now plan to finalize a dosing regimen and initiate both a monotherapy and combination expansion arms in the third quarter. As we've said before, getting dose rate early on in clinical development is one of the most important steps to ensure the best possible outcome for the program, shareholders and most importantly for patients.
In April, we presented compelling preclinical work at AACR demonstrating that the mechanism of action downstream of MAT2A creates a synergistic vulnerability to antimitotics including clinically applicable taxing. Based on these data we now plan to initiate two combination arms in areas of high unmet need. The first will test AG-270 in combination with Docetaxel in MTAP-deleted non-small cell lung cancer. And the second will test AG-270 in combination with nab-paclitaxel and gemcitabine and pancreatic ductal adenocarcinoma.
We will share additional details about these expansion items once they are initiated. And we look forward to sharing the first clinical data from the Phase 1 dose escalation study later this year. For AG-636, our DHODH inhibitor, we have initiated sites for the Phase 1 lymphoma study and are currently screening patients.
With that, I'll turn the call over to Andrew.
Andrew Hirsch -- Chief Financial Officer and Head of Corporate Development
Thanks, Chris. Our first quarter results can be found in the press release we issued this morning, which I'll summarize. More detail will be included in our 10-Q filing later today. Total revenue for the first quarter was $30.2 million, which consisted of $9.1 million of net US sales of TIBSOVO. $18.9 million of collaboration revenue and $2.2 million of IDHIFA royalty revenue. The year-over-year increase in revenue was primarily driven by an $11 million increase in collaboration revenue due to the satisfaction of a performance obligation under the Celgene collaboration. $9.1 million of net US sales of TIBSOVO and an $800,000 increase in the IDHIFA royalty.
Despite an increase in TIBSOVO demand. Quarterly, ex-factory sales were impacted by lower inventory build when compared to the fourth quarter, as inventory levels remained relatively flat over the quarter. As a result, we saw a small decrease in sequential TIBSOVO revenue.
Cost of Sales for the quarter was $300,000. During the first quarter, we started to capitalize a portion of the period expense related to manufacturing resupply, which is why there is a sequential decline in cost of sales from Q4 levels.
Turning to operating expenses, R&D for the first quarter was $95.6 million. An increase of $17.4 million compared to the first quarter of 2018. The year-over-year increase in R&D was largely driven by clinical trial activity for TIBSOVO. As we continued development in the frontline combination setting, including the initiation of the Phase 3 combination trial with 7+3. Clinical trial activity from Mitapivat in PK deficiency and thalassemia, as well as tech transfer for the production of registration batches. And stat-up activities for AG-636 our DHODH inhibitor.
Selling, General and Administrative expenses were $31.8 million for the first quarter representing a $7.2 million increase over first quarter 2018 driven by increased investment in our infrastructure and commercial capabilities. We ended the quarter with cash, cash equivalents and marketable securities of $708 million. We expect that this cash balance in addition to expected product revenue and royalties, but excluding anticipated program specific milestone payments, will fund our current operating plan through at least the end of 2020.
With that operator, please open the line for questions.
Questions and Answers:
Operator
(Operator Instruction) Our first question comes from Anupam Rama with JP Morgan. One moment.
Anupam Rama -- JP Morgan -- Analyst
(technical difficulty) by the impact of TIBSOVO seasonality here in 1Q and maybe the timeframe in which patients kind of work through the donut hole and plan changes and other seasonal headwinds. And then the second question on clarity with top line results here on the horizon. Maybe you can help us understand what you are hearing from the physician community about a minimal threshold for like a clinically meaningful effect and what's kind of that win scenario for you guys. Thanks so much.
Jacqualyn Fouse -- Chief Executive Officer
Hi, Aunpam. Thanks for the question. This is Jackie. I have to say that you were cutting out during the first part of your first question, so I'm going to answer what I think you wanted to ask, because I heard the last half of it. So as we said in the prepared remarks we saw a good strong commercial growth on the demand side for TIBSOVO. And as we moved through Q1, we saw a fair increase in the number of patients that moved from having been on commercial brought back in Q4 to going on to free drug in Q1, and that had an impact there on the net revenues as we talked about. As we made our way through the quarter we saw we were very happy with the volume growth that we saw and we have had good strong volume growth in the month of April as well. So I think that gives us a lot of confidence in how we're going to round out the year here.
I would remind everybody this, but it's the first time that we go through a Q1 for TIBSOVO, And because we launched last July. So we're learning a little bit about some of the patterns here and we're talking about relatively small numbers in the grand scheme of things compared to some other drugs. So you can have some kind of small changes make a little bit more of an impact and you might think about. We feel like this is going to all settle out the base of the demand keeps building. We've seen an increase in the number of unique prescribers that continue to increases in testing right, so is that a base gives strong growth over the course of the year. Then we think that the impact of these seasonal things will be a little bit relatively maybe less in the future, but we're learning something about these trends. But the underlying trends are quite good, we're very happy with where we are.
Chris Bowden -- Chief Medical Officer
Hi, Anupam. Chris here. I'll take the clarity question. So we design clarity with a group of investigators who specialize in the treatment of cholangiocarcinoma. So that the statistical assumptions around that, that PFS in the second line setting based on literature and discussions with them is around two to three months. And the study we assume that PFS will be about three months in the sample size. Overall, the study has a 96% power to detect a hazard ratio 0.5, so that's an essentially a doubling of PFS.
I remind you though that the trial can be positive based on the shape of the curve and being statistically superior to the control arm. So when to get to your question of what do clinicians think a meaningful clinical benefit would be is that a statistically positive study, they think has the potential to be clinically beneficial. And you can see, if you think about Kaplan-Meier curves which is the way we look at these things from a statistical perspective. You can see curves that are steadily in front. You can see curves that have a tail at the back and are statistically positive. And in this case, TIBSOVO which is a drug that's taken orally once daily in a setting where there's really very little treatment options that are high on that need. We think any number of scenarios and with a positive study would be clinically beneficial for these patients.
Anupam Rama -- JP Morgan -- Analyst
Great. Thanks so much for taking our questions.
Operator
Our next question comes from Kennen MacKay with RBC Capital Markets.
Vikram -- RBC Capital Markets -- Analyst
Hi this is Vikram on for Kennen. He's on the flight right now, so I'll fill in for him. So quick two questions for us on AML, with frontline AML expansion in June. Can you help us understand the size of the patient population you're looking at versus the current label. And what will be the anticipated treatment duration there, was it is the currently labeled our last line IDH mutation patients?
Jacqualyn Fouse -- Chief Executive Officer
Thanks for the question. So I'm -- it's Jackie, I'm going to start, and I think until we have the exact wording for the label we would hesitate to give you too much of a range yet on the number of patients that would potentially be there. We've shown you some information in the past about the percentage of patients that we think are in the different buckets between untreated and treated. And so we need to just get that final label name will be able to give you a little bit better idea of what the range of the number of patients associated with that particular label indication would be. We're really looking forward to it, it's going to be a great moment for us to get into that frontline setting in any patient population.
Vikram -- RBC Capital Markets -- Analyst
Thank you. If I can squeeze in one more in terms of AML landscape, how is it evolving with relief to influx there? I think, there are number of clinical trials which are academic centres that are pursuing is not something you are thinking about to pursue in combination with itself or any potential synergies there (technical difficulty) and if you can comment on?
Chris Bowden -- Chief Medical Officer
Yes. It's Chris here. And in the time when we took our IDH inhibitors into the clinic, till now and especially in the last 18 to 24 months there are now 11 drugs that have been approved in this space. So that's after decades of really not having much in the way of Clinical Investigation to improve outcomes for patients.
So it creates challenges but opportunities into your -- to your point we've talked about an investigator sponsored study that Dr. DiNardo -- Courtney DiNardo at MD Anderson is running with TIBSOVO plus Venclexta. And in fact, that's getting ready to expand to look at a triplet which is adding Agios side of being to that combination. And she is in fact, getting ready to expand that with additional centers. So we're looking forward to that being initiated, because we think that's going to be important data for us and for patients. And of course, we're looking at and talking about with investigators about other combinations whether it's with flt3 inhibitors, Vyxeos and whole number of drugs. So there's going to be a lot of activity here, not just newly diagnosed patients but in patients who relapsed, looking at how do you sequence these drugs, given that there are -- they are oral agents it can be given in combination, it can be given in sequence and they're rather sensitive tools that we have around looking at changes at the molecular level whether it's through MRD or variant real frequency which we talk a lot about with IDH1.
So lots of opportunity and we're really happy with Dr. Dinardo's progress on our trial, she's in control of that whether it is going to be published and looking forward to getting that data out there and as well as with the expansion that I just talked to.
Vikram -- RBC Capital Markets -- Analyst
Thank you so much.
Operator
Our next question comes from Michael Schmidt with Guggenheim.
Michael Schmidt -- Guggenheim Partners -- Analyst
Hey, thanks for taking my question and congrats on all the progress. I had a few follow up questions on -- on your comments around AG-270. Can you maybe help us walk through the implications of the recent pre-clinical data presentations from AACR on the potential development in monotherapy and combination. What was the basis for specifically selection of lung cancer and pancreatic for the initial expansion cohorts for example. And then, you did talk about some DOTs and then need to optimize dosing of AG-270 particularly around monotherapy. Can you just help us understand that a little bit better. Thanks.
Chris Bowden -- Chief Medical Officer
Okay, great. It's Chris here. Let me do the dose piece first now. I'll finish with the -- some of the things we're thinking around combination therapy, and because that's predicated on some of the interesting data that our teams are working on and was presented today AACR. So we -- when we wrote to study, we specified upfront that we were going to investigate both daily and b.i.d dosing.
In Phase 1 as you're increasing your dose and investigating your dose, with an oral agent especially one -- that's one of the schedule manipulations that you can do given that the work that we've done with biomarkers and pharmacodynamics markers that is looking at same levels in the finding. It's really important for us to understand how that will change it all with our daily dosing we've seen nice impacts on the pharmacodynamic outputs.
So we have pre-specified that we could look at b.i.d which is what we did and that's when we've encountered these dose limiting toxicities. So the important thing for us now is to look at all the data that's come out from those cohorts that we've recently does. And take a look at that exposure data and that PD data reference that back to what we've seen so far with our once daily dosing data. In order to really been make sure we've looked at everything as we make our decision to go forward. And that's why there's a slight delay to the program.
With regards to the combinations is that, what our research team presented at AACR demonstrated that when you inhibit MAT2A of downstream effects that can affect placing and DNA repairing cell cycle defects that can be addressed by combining a MAT2A inhibitor AG-270 with taxanes. And taxanes are ubiquitous in the treatment of patients predominantly with solid tumors. And two areas if you think about the frequency of MAT of MTAP-deletion with high unmet need, non-small cell lung cancer and pancreatic cancer come to the floor, it's two important indications, because taxanes can be cornerstone therapy depending on the setting et cetera. So that's why we've selected them as our first two combination indications that we want to look at.
Michael Schmidt -- Guggenheim Partners -- Analyst
Okay. Thank you. Maybe one follow up. I mean, do you feel you are getting to the high enough exposure levels based on your dosing schemes and the PD data that you have in hand.
Chris Bowden -- Chief Medical Officer
Overall, we're very satisfied with the progress of the trial in terms of information we've gotten in terms of exposure, exposure related to pharmacodynamic effects understanding the toxicity profile. And now as we want to -- we've got some more data coming in we want to look at this in b.i.d. setting, so yes.
Michael Schmidt -- Guggenheim Partners -- Analyst
Okay. Great. Thank you.
Operator
Our next question comes from Chris Shibutani with Cowen.
Chris Shibutani -- Cowen -- Analyst
Thanks very much. If I could ask you a commercial question in the past you've talked a little bit about some of the underlying patterns of use the types of patients in terms of severity initially and the duration of use as the launch continues to progress. Can you comment about how those patterns are continuing to shape. And then secondly, with the decision that you've made, I realize it's still early to go it alone so to speak in Europe, can you comment about what you're learning there, how that's progressing maybe the cadence of new, so that we can expect there. Thank you.
Jacqualyn Fouse -- Chief Executive Officer
So with respect to the first question. Thanks for that Chris, it's Jackie. I think that, I mean, what we're seeing is -- our Chris here on this side just was talking about we've had quite a number of drugs come into the AML market in the last 12 to 18 months. We had three loan approved in Q4 of last year. Some of those are targeted agents so some of them are less targeted agents and what we're starting to see. I think it's still a very early days is that all of these drugs that are going to settle in to the marketplace and find their respective roles in treatment paradigms for patients which is a great thing as compared to the past when there were fewer choices. Some of you have heard me use the analogy of how we saw the multiple myeloma play out over the past four or five years when there are a bunch of new therapies that came to market there as well.
So I think for drugs in particular when you think about patients with the IDH mutation. There is no reason why patients shouldn't see one of our drugs over the course of their treatment -- treatment paradigm. And I believe that and as we have our ongoing label expansions and we'll be able to play across all the different patient segments in AML. And as Chris also spoke about, we will now and face -- physicians will have the choice of using more combination therapies than they ever have in the past and they'll find the best ways to sequence those therapies.
With respect to the EU build. We again, as you said we're in the early days of that we all have a lot of new news to report. We're working on starting to recruit the most senior members of that team. We're seeing some very talented people with a lot of experience building in that geography and hopefully we'll be able to announce something in that regard soon. But things are going quite well. The regulatory process continues to move along as we would have expected to it. So you'll hear more to come from us on that in the future. Thanks.
Chris Shibutani -- Cowen -- Analyst
Great. And then just a quick clarifying what Chris said about AG-270, when you mentioned it's light delay to the program. Is that relative to the combination or monotherapy program, if you could just clarify what you meant there? Thank you.
Chris Bowden -- Chief Medical Officer
Well, we had, we were thinking and JP Morgan we would get everything those -- that the combinations as well as the expansion of the middle of the year by the end of the first half of the year. So it's really for everything, Chris.
Chris Shibutani -- Cowen -- Analyst
Okay. Great. Thanks very much
Chris Bowden -- Chief Medical Officer
The two combination cohorts and the monotherapy expansion.
Chris Shibutani -- Cowen -- Analyst
Got it. Thanks.
Operator
Our next question comes from Mohit Bansal with Citigroup.
Mohit Bansal -- Citigroup -- Analyst
Great. Thanks for taking my questions. I mean, just to follow up on the AG-270 program. When we see the data in the later half of the year. Should we be expecting any responses as though or we should be more focused on the biomarker time decline? And then I have a follow up in that. Thank you.
Chris Bowden -- Chief Medical Officer
Hi, it's Chris here. When I look at Phase 1 data from our drugs, other drugs I look at several things. The mechanism of action, are you able to demonstrate that you're hitting the target? Or how well is the data that you're looking at able to demonstrate that you're heading the target? How well is that target validated as important in that. The exposures is that which that is demonstrated and the variability, and then the safety that you see across the entire spectrum of dosing and efficacy.
So I think to focus in on one singular component that, that's not what we do and that's not our intent here. Our intent is really to understand the appropriate dose of take into Phase 2, for further development. If you think about this trial, it's a solid tumor study where we see it just a variety of patients with different diagnoses. They've had varying levels of varying prior therapy. And so to -- from your question around efficacy making conclusions on the basis same -- I have a small number of patients treated at a bunch of different doses with varying exposures. Is it a tenuous thing to do? So that's not how we're seeing the primary endpoint of this -- objective of this study.
Mohit Bansal -- Citigroup -- Analyst
That's very helpful. Thanks for clarifying. And if I can fit one more on beta thal and sickle cell disease? Can you just help us remind, because there is a lot of development going on in these diseases? Where do you see of Mitapivat fitting in and could you please help us understand what do you think is the internal bar for success which will make you move ahead in trials there.
Chris Bowden -- Chief Medical Officer
Yeah. So the bar for declaring an effective drug is not something I can answer right now. What the way we design the study is as a pilot study, designed to see what level of clinical activity we could see based on our hypothesis work within -- what we think is a pretty good pre-clinical model that activating wild-type PKR ameliorated some pretty significant disease associated vaccine in mice with thalassemia.
So you're right, there's lots of things happening and lots of good things happening in thalassemia with luspatercept (ph) or gene therapy. And what we want to understand first is, can we validate our hypothesis that activating wild-type PKR can improve in some meaningful way that we can detect outcomes for these patients. And then we can decide how to go forward there, whether this is a single agent or with some of these new drugs coming in combination. So there's just a lot of a possibility here. But the thing that we really wanted to do first was to see if we can demonstrate proof-of-concept in a relatively small number of patients.
Mohit Bansal -- Citigroup -- Analyst
Got it. Very helpful. Thank you, Chris.
Operator
Our next question comes from Terence Flynn of Goldman Sachs.
Terence Flynn -- Goldman Sachs -- Analyst
Hi. Good morning. Thanks for taking the questions. Maybe just two for me. First, on vorasidenib in low-grade glioma. Just wondering what getting to starting the Phase 3 trial there and anymore details you can share on the potential endpoint for that study. And then secondly, on AG-270, just wondering if you can give us any more details around the DLT. Was that on target or off target? And any potential venue in mind yet for the presentation of that data. Thanks.
Chris Bowden -- Chief Medical Officer
So Vorasidenib and moving forward with a pivotal trial now -- Terence, it's Chris here. We're interacting with regulators getting feedback, defining the patient population, understanding from them how they see this patient population in this watch and wait approach, what they think are outcomes that would be associated with clinical benefit whether it's from a primary endpoint to secondary endpoints. So all those things are coming together and we're working hard to get that study designed. We're also interacting with our investigators who've been extremely helpful in putting this trial together patient groups, et cetera.
As far as AG-270 (ph) goes, I can't share the individual details of dose limiting toxicities that we've seen. However, some of them would be predicted from our preclinical toxins, some not. That's pretty typical for a Phase 1 trial in oncology. And can't guide on the venue yet, but certainly as we head into the second half of the year will be able to provide that for you.
Terence Flynn -- Goldman Sachs -- Analyst
Okay. Thanks a lot.
Operator
The next question comes from Peter Lawson with SunTrust Robinson.
Waleed -- SunTrust Robinson Humphrey -- Analyst
Hi, guys. This is Waleed (ph) on for Peter. Thanks for taking the question. Just a quick question on the upcoming ASCO presentation. Can you help that some investor expectations on what we may be in that data?
Chris Bowden -- Chief Medical Officer
Mostly, what you're looking at on the heme side is a longer duration, understanding durability, understanding what aspects, how safety looks as we continue to go on in time. And then of course, the other presentation that we're focusing a lot on is our perioperative study. And I went through what the objectives are in my remarks and so we're going to present information around that in the first cohort. So you're gonna get some information in terms of how these two drugs TIBSOVO and Vorasidenib get into the brain and effects they have on 2HG. What the overall safety looks like. And now will then provide some further understanding in terms of our statement that we make around looking at the totality of data in terms of our molecule selection. Is the perioperative study has been really helpful for us in selecting vorasidenib go forward into a further considerations around pivotal development. It's not the only data set. And you've heard us reference there's no data for both TIBSOVO and Vorasidenib in this patients with low-grade glioma.
Waleed -- SunTrust Robinson Humphrey -- Analyst
Great. Thank you. That's really helpful. And just a follow up, if we're thinking about Mitapivat. Can you talk about how you're thinking about the market opportunity for PKR deficiency given that's widely under diagnosed. And do you expect that to be a hurdle for patient enrollment in your clinical studies.
Chris Bowden -- Chief Medical Officer
With the commercial opportunity.
Jacqualyn Fouse -- Chief Executive Officer
I can talk about that -- I think there is excellent enrollment in the studies based on.
Chris Bowden -- Chief Medical Officer
No our approval has been going well and we expect to complete by the end of the year for both studies and activate key. We actually we're able to find in more patients than we initially anticipated which is why we increased the sample size.
Jacqualyn Fouse -- Chief Executive Officer
So, and it's Jackie. I think we may be giving you a couple of different sources in the past to go and have a look at the ranges right now that you would find if you go out and try to identify patient population for this indication that are pretty broad. So over time we'll be refining what we think about that with our PEAK Registry and some other things that we've done we feel like we now how to identify these patients we're working with the physicians in that regard. And we'll again give you more information around those opportunities as we take them forward.
Andrew Hirsch -- Chief Financial Officer and Head of Corporate Development
This is Andrew. I think what we said previously is we think there's about 3,000 to 8,000 patients in the current US and EU, that are addressable. We know that that number is wrong and as we continue to do patient finding work that number will kind of get tighter a little bit, but we'll be perfect obviously as you know, since some other diagnosed disease you're never perfect until you're actually on the market.
Waleed -- SunTrust Robinson Humphrey -- Analyst
Great. Thank you.
Operator
Our next question comes from Mark Breidenbach with Oppenheimer.
Mark Breidenbach -- Oppenheimer & Co -- Analyst
Hey, guys, good morning, and thanks for taking my question. Just a quick one on the recent break through therapy designation in elderly patients are for TIBSOVO. I'm wondering if this can lead to an acceleration in your filing planned or label expansion plans in this population or is that the plan right now is to kind of let the adult trial run its course and pile after that completes. Thanks.
Chris Bowden -- Chief Medical Officer
I can't comment on specific interactions we have with FDA. But breakthrough does give us the opportunity in the indication the group of patients that you discuss -- to discuss TIBSOVO plus azacitidine and how we're going to develop it whether it's how we would look at the AGILE trial which is we've stated previously we're changing the primary endpoint to event free survival which shrinks the sample size and has us guiding to finishing accrual by the end of 2020.
We also have some other activities going on. We have beta AML where we're treating patients with TIBSOVO and Enasidenib as well as our five studies. We've got a number of different datasets that we'll want to discuss with them -- with in the setting of breakthrough discussions. And I think the previous questioner who brought up novel combinations as well and perhaps that triplet depending on what Dr. Dinardo's data says, shows might allow us to think about another way of building onto this combination in this group of patients. So a number of different ways we can go with it, but breakthrough designation does is FDA states give you the opportunity to have some increased access to them to get guidance that may turn into opportunities either to expand one's label or to get there faster.
Mark Breidenbach -- Oppenheimer & Co -- Analyst
Okay. Thanks.
Operator
Next question comes from Tyler Van Buren with Piper Jaffray.
Alexander Duncan -- Piper Jaffray -- Analyst
Hi, this is Alex Duncan on for Tyler. Thanks for the question. Great to see the HOVON trial kick off and congratulations on that. When do you expect full enrollment to be completed and assuming the primary datas are positive. Will you be able to file the sNDA prior to completion of the maintenance phase. Thanks.
Chris Bowden -- Chief Medical Officer
So the trial, Alex, is a big multi country international cooperative group effort. So it's in its early phases of initiation now. And in the beginning if you think about accrual curves it's relatively flat. And then we look for it to really get going. So it's too early to be able to guide to accrual and timelines.
Your question around filing on the basis of the prior to all patients had completed maintenance is a really interesting one. It's an event driven trial. So once you see the requisite number of events that are prespecified then you can unbind the study. So and that really is a very interesting question you raise. I just can't answer now, but it is really going to be dependent on when patients progress, meet that that primary endpoint of events resurvival is one it would be on blinded. So I guess, yes it could be, but I can't, we can't really predict at this point when that will happen or whether that will happen.
Alexander Duncan -- Piper Jaffray -- Analyst
Makes sense. Thank you.
Operator
Our next question comes from Michael Schmidt with Guggenheim.
Michael Schmidt -- Guggenheim Partners -- Analyst
Hey, guys, thanks for taking the follow up. I just had a couple more regarding ACTIVATE-T, so the addition of these 20 additional patients. I guess, can you help us understand sort of timelines to potential data, data releases, I guess, does that impact potential data disclosure or the end point itself. And then I had a second question after that.
Chris Bowden -- Chief Medical Officer
So we got -- we're guiding to getting the first 20 patients in by the end of the third quarter. And we hope to get that additional up to 40 patients in. Now then you have to follow them too, because that this is a group of patients that are regularly transfused. So they have to be followed for a period of time up to a year in order to ascertain the primary endpoint. So we can't guide to when we have a data read out. We're thinking about activating in the setting of activate as well. But we're very encouraged by this development and it sort of ties into all these questions about how many patients are there, how many patients who are regularly transfused versus not.
Michael Schmidt -- Guggenheim Partners -- Analyst
Right.
Chris Bowden -- Chief Medical Officer
The timeline that we've given you before. Yeah. Same time on.
Michael Schmidt -- Guggenheim Partners -- Analyst
Well the endpoint now be based on the 40 patients or it will be assessed based on the initial 20 as before?
Chris Bowden -- Chief Medical Officer
Can't say that. I think that the way we wrote the study is that -- was really dependent on a number of patients we would have -- we could accrue and so then we'll take a look at how we would do that and how many patients we need it's an open label study and that will really depend on help things to go.
Michael Schmidt -- Guggenheim Partners -- Analyst
Understood. And then the second question I had is just whether you could update us on the status of the European filing for TIBSOVO. I think you should have the day 120 questions in hand. Now I was just wondering are there any updates on that.
Chris Bowden -- Chief Medical Officer
We were validated in January, so we expect to see the day 120 questions before that -- within the first half of the year and it's May. So sometime within the next eight weeks or so. But yes we're right in the period. We're expecting to receive them. And then the next steps whether there's a clock stop and sort of what we're thinking in terms of potential approvals will depend on that. We have been talking about 2020. But when in 2020 really depends on some of those factors that -- just got touched on. The nature of the questions is how long the clock stop we take whether there's an oral explanation and other factors.
Michael Schmidt -- Guggenheim Partners -- Analyst
Understood. Great. Thanks for clarifying that and taking the follow up questions.
Chris Bowden -- Chief Medical Officer
You're welcome.
Operator
I'm not showing any further questions at this time. I would like to turn the conference back to Jackie.
Jacqualyn Fouse -- Chief Executive Officer
Thank you, operator. 2019 is an important year for Agios as we work to execute across our broad oncology and rare genetic disease portfolios. We will also complete our first full year of US launch of our first wholly owned commercial product TIBSOVO. And we will commence our plans for commercialization outside the US.
I would like to take this opportunity to thank all of the tremendous employees that Agios for their dedication and passion to making a difference for patients. I also want to thank all of the patients, caregivers and physicians who participate in our clinical trials. Without them, we cannot do what we do. Thank you all for joining us on the call today.
Operator
Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day.
Duration: 50 minutes
Call participants:
Kendra Adams -- Vice President, External Communications and Investor Relations
Jacqualyn Fouse -- Chief Executive Officer
Chris Bowden -- Chief Medical Officer
Andrew Hirsch -- Chief Financial Officer and Head of Corporate Development
Anupam Rama -- JP Morgan -- Analyst
Vikram -- RBC Capital Markets -- Analyst
Michael Schmidt -- Guggenheim Partners -- Analyst
Chris Shibutani -- Cowen -- Analyst
Mohit Bansal -- Citigroup -- Analyst
Terence Flynn -- Goldman Sachs -- Analyst
Waleed -- SunTrust Robinson Humphrey -- Analyst
Mark Breidenbach -- Oppenheimer & Co -- Analyst
Alexander Duncan -- Piper Jaffray -- Analyst
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