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Agios Pharmaceuticals Inc  (NASDAQ:AGIO)
Q4 2018 Earnings Conference Call
Feb. 14, 2019, 8:00 a.m. ET

Contents:

Prepared Remarks:

Operator

Good morning, and welcome to Agios' Fourth Quarter 2018 Conference Call. At this time, all participants are in 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' requests.

I would now like to turn the call over to Kendra Adams, Senior Director, Investor and Public Relations.

Kendra Adams -- Senior Director, Investor & Public Relations

Thank you, Shannon. Good morning, everyone, and welcome to Agios Fourth 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 today are Dr. Jackie Fouse, our Chief Executive Officer, who will review key business updates and milestones for 2019; 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 provide an update on the launch of TIBSOVO; and Andrew Hirsch, our Chief Financial Officer, who will summarize our fourth quarter and full year 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 risk factors, 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 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 as 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 Jackie.

Jackie Fouse -- Chief Executive Officer

Thanks, Kendra. Good morning, everyone and welcome to our fourth quarter earnings call. I'm excited to join the call today in my new role as CEO of Agios. The company's accomplishments in 10 short years including seven INDs, two product approvals and the successful first wholly owned commercial launch are impressive.

And I'm proud to be a member of the incredible Agios team. This success comes from keeping patients and science at the core of what we do. I'm highly appreciative of what this team has accomplished and I look forward to continue building on this strong foundation. I would like to take this opportunity to thank David Schenkein for his invaluable contribution to making Agios what it is today. And also wish him well in his future endeavors.

My initial priority is to listen and learn from a new perspective as CEO. I'll be diving deeper into our discovery, clinical and commercial activities to determine how each can be further leveraged to continue creating value for patients and our shareholders.

Execution across the business in 2018 has put us in a strong position to create long-term growth and value, particularly on the heels of the notable achievements in the fourth quarter, which Chris and Steve will describe in more detail.

Our 2019 priorities are structured to broaden the opportunities within our oncology and rare genetic disease portfolios. First, we are working to expand the IDH opportunity in the frontline AML and solid tumor settings. The TIBSOVO, sNDA for newly diagnosed patients with AML who are not eligible for standard treatment is currently under review and we expect approval this year.

We plan to submit an sNDA for TIBSOVO in second line or later cholangiocarcinoma by the end of the year, assuming the ClarIDHy Trial data are supportive. And we are advancing vorasidenib into a Phase III study in low-grade glioma which is expected to initiate by year-end.

Next, for our PKR activator program. We continue to enroll patients in two pivotal trials for mitapivat mitapivat in adult PK deficiency with the goal of bringing to market the first disease-altering therapy for this chronic anemia. By year-end, we expect to complete enrollment in both the ACTIVATE and ACTIVATE-T trials, as well as achieve proof of concept in the ongoing Phase II trial of mitapivat in thalassemia.

With respect to our earlier clinical programs, during the first half of 2019, we expect to advance our MAT2A inhibitor, AG-270 into the expansion phase of the ongoing Phase I trial. In addition, our DHODH inhibitor, AG-636 is on track to enter a Phase I clinical trial in lymphoma in the first half of the year.

Finally, as always, we will continue to move compounds through our robust drug discovery engine and stay true to the pursuit of great science.

Before turning the call over to Chris, I would like to provide an update on our commercial strategy for Europe. Following the submission of our marketing authorization application for TIBSOVO in relapsed or refractory AML, we have made the decision to commercialize on our own in the EU-5 and certain adjacent countries. We believe this will allow us to maximize the full value potential of TIBSOVO for patients and our business and position us well for future planned launches across our oncology and rare genetic disease programs.

The necessary European infrastructure build will be aligned against and gated with milestones associated with the EMA review of the TIBSOVO application. We will share more details with you on this important initiative as our plans solidify.

I'll now turn it over to Chris to discuss our clinical activities.

Chris Bowden -- Chief Medical Officer

Thanks, Jackie. I will start with our broad AML clinical development strategy for TIBSOVO, where our next steps include expanding the relapsed refractory AML opportunity outside of the US and moving to the frontline setting.

As Jackie mentioned, we submitted the MAA application for TIBSOVO, an IDH1 relapsed or refractory AML at the end of 2018. Our application has now been validated by the European Medicines Agency and a review procedure is under way. With this validation, we have clarity on timelines for the review process and expect the Day 120 list of questions from the agency during the second quarter.

In addition to relapsed/refractory AML, our goal is to ensure all AML patients with an IDH1 mutation have access to TIBSOVO. So we are pursuing an ambitious clinical development strategy in the frontline setting that I will outline.

Today based on age, comorbidities and other factors, newly diagnosed AML patients are segmented into one of three categories, intensive therapy, non-intensive therapy and not eligible for any standard treatments. Our goal is to achieve TIBSOVO labeled indications in both the intensive and non-intensive therapy setting, and to be the first treatment approved for patients who today do not receive active therapy.

Let's begin with intensive therapy, where standard of care is a combination of chemotherapy known as 7+3. At ASH last year, we reported encouraging data from our Phase I study of both TIBSOVO and IDHIFA in combination with 7+3, where we've demonstrated a 91% CR plus CRi/CRp rate in the TIBSOVO arm. Additionally, in a subset of patients who achieved a CR or CRi/CRp, elimination of minimal residual disease was also observed, suggesting deep and durable responses with TIBSOVO. This sets the stage for the randomized Phase III study run by the cooperative groups HOVON and AMLSG which we expect to initiate this quarter.

In the non-intensive therapy setting, patients are not able to tolerate aggressive chemotherapy and often receive hypomethylating agents such as azacitidine. Our preclinical exploration of TIBSOVO's mechanism revealed a rational combination with azacitidine and now in the Phase I study, we've demonstrated a CR, CRi/CRp rate of 65% with a significant portion of these patients achieving a deep molecular response where we could no longer detect the mutant IDH clone.

In addition, the duration is impressive as all patients with the CR, CRi or CRp remained on treatment as of the data cut-off with patients on study up to 19 months. The safety profile of the IDH and azacitidine combination is consistent and as expected with the known profiles of each agent. We look forward to sharing the longer follow-up of these Phase I data at the 17th International Symposium on Acute Leukemias taking place later this month in Munich.

Our Phase III AGILE trial combining TIBSOVO and azacitidine continues to enroll patients with complete enrollment expected in 2020. In both the intensive and non-intensive settings, we believe the future of AML treatment will focus on targeting actionable mutations with a targeted therapy and adding on non-targeted agents as appropriate. This nears (ph) what we've seen in other cancers that experienced a multitude of new therapies entering the market, such as multiple myeloma. As such we are supporting a broad IST strategy that combines TIBSOVO with other recently approved medicines such as Venclexta and Xospata.

Finally, for the newly diagnosed AML patients who are not eligible for any standard treatment, the FDA is in the process of reviewing the TIBSOVO sNDA based on our Phase I data and we expect to have more clarity on approval timelines later this month. As a reminder, this submission is part of the FDA's new real-time oncology review pilot program, it would be the first targeted therapy to be approved in this important frontline patient population.

Within our IDH portfolio, we've also made significant progress in the solid tumor setting. Our Phase III CLARITY trial evaluating TIBSOVO in previously treated IDH1 mutant cholangiocarcinoma is now fully enrolled. We expect to report topline data from this study in the first half of the year and we'll plan to present 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.

Turning to low-grade glioma, we announced in January that we selected vorasidenib, also known as AG-881 as a go-forward molecule in this indication. Where approximately 80% of patients have an IDH1 mutation. Data from the perioperative window study study of TIBSOVO and vorasidenib have been submitted for presentation at the ASCO Annual Meeting taking place in Chicago in June, which will include data on the relative uptake of drug and reduction of 2HG levels in brain tumor tissue. As a reminder, our goal is to utilize vorasidenib treatment to delay the need for chemotherapy and radiation and grade-two glioma patients who are suitable for a watch and wait approach.

We are in the process of working with regulators on the pivotal trial design, which will include event driven endpoint such as progression-free survival and effects on tumor growth using volumetric imaging. Assuming we get alignment, we plan to initiate this trial by the end of the year.

I'll now move to mitapivat, our PKR activator that is our most advanced rare genetic disease program and has the potential to be our first approved medicine in this field. Our goal in 2019 is to expand the opportunity of our PKR activator mitapivat broadly to patients who have the potential to benefit. Our initial focus has been in adults with pyruvate kinase deficiency, which is characterized by lifelong anemia and a significant disease burden with no currently approved treatment options. The pivotal studies of mitapivat ACTIVATE in patients who do not receive regular transfusions and ACTIVATE-T in regularly transfuse patients are on track to complete enrollment by the end of the year.

We initiated the study of mitapivat in thalassemia in December, and we hope to achieve proof of concept in this indication in the second half of this year. We also plan to pursue development of mitapivat in pediatric PK deficiency and we'll be working with regulators to design an appropriate clinical development strategy in this important patient population.

In January, we also unveiled a next generation PKR activator, which is currently advancing through preclinical development with the goal of addressing a wider range of PKR mutations. We anticipate submitting an IND for this molecule in the next 12 to 18 months.

In addition to our later stage clinical programs, we're advancing development of two early stage oncology programs AG-270, our MAT2A inhibitor for MTAP-deleted tumors and AG-636, our DHODH inhibitor. For AG-270 we initiated a Phase I dose escalation trial last year and we expect to select the go forward dose and begin the expansion phase of the trial by the end of the second quarter. One arm of the expansion phase will studies single agent AG-270 at the selected dose in the basket study across multiple tumor types.

The other expansion arm will assess AG-270 in combination with standard of care for a solid tumor. Preclinical data from the AG-270 program has been accepted for an oral presentation at the American Association of Cancer Research Annual Meeting taking place March 29 through April 3, 2019 in Atlanta. This presentation will focus on our translational findings, which suggest clinically actionable combination strategies that may further enhance the efficacy of AG-270 in some solid tumors with the MTAP deletion. In the second half of 2019, we expect to present the first clinical data from the dose escalation portion of the ongoing Phase I study.

Turning to AG-636, our DHODH inhibitor, we submitted the IND to the FDA at the end of 2018 and are on track to enter Phase I development in lymphoma during the first half of the year.

With that, I'll turn the call over to Steve.

Steve Hoerter -- Chief Commercial Officer

Thanks, Chris. I'd like to start with an update on the strong launch of TIBSOVO in the US. In the fourth quarter, we recorded $9.4 million in revenue, bringing total 2018 revenue to $14 million for the first five months of launch. Since the launch in July, our team of senior hematology sales consultants has been raising awareness of TIBSOVO and IDHIFA which we co-commercialize with Celgene. Their focus is on educating physicians on how these novel first-in-class precision medicines can be used to benefit their patients with relapsed or refractory AML with an IDH mutation.

As a result of our team's hard work on the launch of TIBSOVO, the number of unique prescribers doubled from the third quarter to more than 200 prescribers as of the end of 2018. As a comparison, there were approximately 600 unique IDHIFA prescribers as of year end, 1.5 years post launch. As the number of unique prescribers has expanded, we are seeing steady growth in the adoption of TIBSOVO in both the academic and community settings.

As we previously noted, testing for IDH mutations is high and has not been a barrier to use with approximately 80% of physicians testing their patients for these actionable mutations. While academic centers are screening the vast majority of their patients for mutations such as IDH, we have an opportunity to further drive IDH testing rates in the community setting. We are very pleased with the foundation that both products have established in the relapsed or refractory AML setting and now looking forward to the potential launch and the newly diagnosed population reflected in our TIBSOVO sNDA this year.

Beyond that, we believe there is tremendous potential for expansion into the broader frontline AML segments that Chris spoke about, as well as in cholangiocarcinoma. Each of these indications are important opportunities for us to provide TIBSOVO to patients who have the potential to benefit from this targeted therapy. I look forward to updating you on our ongoing progress in future quarters.

I'll now turn the call over to Andrew.

Andrew Hirsch -- Chief Financial Officer and Head of Corporate Development

Thanks, Steve. Our fourth quarter and full-year financial results can be found in the press release we issued this morning, which I'll summarize. More detail will be included in our 10-K filing later today. Total revenue for the fourth quarter was $30 million, which consisted of $9.4 million of net US sales of TIBSOVO, $18.4 million of collaboration revenue and $2.2 million of IDHIFA royalty revenue.

Total revenue for the full year 2018 was $94 million, an increase of $51 million compared to 2017. The year-over-year increase in revenue was driven by a $17 million increase in collaboration revenue, primarily related to our CStone collaboration, which we signed in June of 2018. A $15 million milestone payment from Celgene related to the IDHIFA MAA filings with the EMA. $40 million of net US sales of TIBSOVO and a $5 million increase in the IDHIFA royalty.

Cost of sales for the fourth quarter was $700,000 and $1.4 million for the full year 2018. Turning to operating expenses, R&D for the fourth quarter was $94 million and $341 million for the full year 2018, an increase of $48 million compared to the full year 2017. The year-over-year increase in R&D was largely driven by clinical trial activity for mitapivat and PK deficiency and sort of activities for our thalassemia study. IND enabling activities for AG-636, our DHODH inhibitor and ongoing research efforts across our discovery platform programs.

Selling, general and administrative expenses were $32 million for the fourth quarter and $114 million for the full year of 2018. This represents a $43 million increase over full year 2017, driven by increased investment in our infrastructure and commercial capabilities for the launch of TIBSOVO. We ended the quarter with cash, cash equivalents and marketable securities of $805 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 lines for questions.

Questions and Answers:

Operator

Thank you. (Operator Instructions) Our first question comes from Kennen MacKay with RBC Capital Markets. Your line is open.

Kennen MacKay -- RBC Capital Markets -- Analyst

Hey. Thank you for taking the question. First off, congrats to Jackie on taking the helm here and for first earnings call. How are you? And maybe one for Steve on the commercialization. I was wondering if you've seen any impact at all from FDA warning on differentiation syndrome that came out late last year. And maybe a second one for Chris on cholangio. I was just wondering if you could help us understand the sort of powering and assumptions for TIBSOVO in the control arm on PFS in the cholangio trial? Thank you.

Steve Hoerter -- Chief Commercial Officer

Yeah. Thanks, Kennen, it's Steve. So first, with respect to the ASH presentation on differentiation syndrome. As you may know, the data that FDA presented is exactly what the data are in our label for TIBSOVO, so there weren't any great surprises or really new information with respect to what was presented. And accordingly, we just haven't seen any impact since ASH with respect to DS. This is an important adverse events associated with TIBSOVO and so our teams, whether it's our sales teams or the MSL (ph) teams, since launch we've continued to educate physicians on how best to detect and then manage differentiation syndrome, should it occur.

Chris Bowden -- Chief Medical Officer

Okay. Kennen, it's Chris here. So the CLARITY study has 96% power to detect a hazard ratio 0.5. Our assumption for the control arm, progression-free survival is in the order of -- couple of months, two to three months.

Kennen MacKay -- RBC Capital Markets -- Analyst

That's it. Thanks so much.

Operator

Thank you. Our next question comes from Peter Lawson with SunTrust. Your line is open.

Peter Lawson -- SunTrust -- Analyst

Hi. Thanks for taking my questions. Just maybe a macro question for Jackie, just the thoughts around, I guess, buy versus build for additional products with the sales force and thoughts around that decision to go alone in EU-5?

Jackie Fouse -- Chief Executive Officer

Yeah. Hi, Peter. Thanks for the question and thanks for the welcome Kennen as well. So, we are in a terrific position of strength today, the portfolio that we have is a broader and deeper than it's ever been. When you look at the products that we've got in clinical development and the number of indications that they potentially can play and there's a lot of optionality in the pipeline and we've already got two approved products, one of which is wholly owned. So, I might turn it over to Andrew in just a minute for a little more color on the European decision, but when we look at what we have today in the near-term opportunity, as well as the opportunity for evolution of the portfolio over time we came to the conclusion that going on our own in the selected number of EU countries is the way to go.

In terms of priorities and the build or buy decision. I mean, as I've just said, we've a got a lot going on. The priorities for the team are to continue to support our early research team to bring those candidates through the discovery pipeline. We filed the IND for 636 late last year and now are moving that product into humans, it's been a very productive engine. So we want to continue to resource that. So we have this long-term organic growth. We've got stellar execution across our clinical programs with our clinical teams, we want to keep that up, move those along as fast as we can, and we're driving commercial performance and building those capabilities now.

So we have a lot going on, a lot of potential with what we have. Those are the kinds of moments from a physician and strength that you want to take to them. Also see whether there are other things that in the future could be complementary or adjacent, we'll do that over time as appropriate. But we're in a great position today, well just where we are. Andrew, I don't know if you want to say something just about the EU decision quickly?

Andrew Hirsch -- Chief Financial Officer and Head of Corporate Development

Yeah. So over the course of last year we went through a pretty deliberate process of evaluating multiple options for the commercialization of TIBSOVO, but also as we thought about the rest of our portfolio. We did see -- and that process included both partnering as well as building ourselves. And we did see broad strong interest in our assets in a variety of proposals and deal structures. But at the end of the day, as we sort of step back, we thought that commercializing ourselves really made the most sense to maximize the value, both TIBSOVO as well as the potential future launches in our platform. And so that's really where we came down as we went through that process.

Peter Lawson -- SunTrust -- Analyst

Thank you. And maybe a question for Steve or Chris, just on duration for IDHIFA, how that's trending? I know it's early days for TIBSOVO, but any comments you can make there around duration of treatment? Thank you.

Steve Hoerter -- Chief Commercial Officer

Yes. Thanks, Peter. Thanks for the question. So with respect to duration on TIBSOVO, still a little early for us to comment on duration. I mean, we fully expect that it's going to be pretty consistent with what we see on IDHIFA and what we saw on the clinical trial setting. As we spoke about at JP Morgan in January, we now see duration on IDHIFA of approximately four months, just over four months, which is consistent again with what we've seen in the trial setting. I think we'll continue to see that nudge a bit higher, but particularly in the relapse and refractory setting, we're in the range of what we would expect to see based on the clinical trial experience.

Peter Lawson -- SunTrust -- Analyst

Great. Thanks so much. Thanks for taking the questions.

Steve Hoerter -- Chief Commercial Officer

You bet.

Operator

Thank you. Our next question comes from Anupam Rama with JP Morgan. Your line is open.

Anupam Rama -- JP Morgan -- Analyst

Hey, guys. Thanks so much for taking the question. Can you talk a little bit about the next steps for Europe and timelines for TIBSOVO here. I think you said the 120 day questions are coming soon. And concurrently, what are some of the pre-commercial activities now that are ongoing for TIBSOVO in the region? And then a quick question about the cash position, being sufficient through at least 2020, can you confirm that this now includes sort of EU commercialization activities? Because this guidance appears to be unchanged from the conference just a couple of weeks ago. Thanks so much.

Jackie Fouse -- Chief Executive Officer

Yes. It's Jackie. I'm just going to jump in and then neither Andrew or Steve will take over after me. But as we said in the remarks, we are going to gate the plans in Europe very carefully in terms of when we start to invest and what we start to invest in, in line with the milestones that we see as we make our way through the regulatory process.

And we can let Chris comment on that. If we want -- I mean, the MAA is in, but we don't have a lot probably to say about the process other than that we make our way through that with the regulator. So I don't -- we're not going to go into the details of the specifics about that commercial plan just yet, but we will share more details with you as we start to make our way through that in line with what we see, with respect to expectations for the potential timing of the approval of the product.

Andrew Hirsch -- Chief Financial Officer and Head of Corporate Development

And Anupam, this is Andrew for your question around runway. Yeah, so the guidance does include the runway -- the European build over kind of the runway time period.

Anupam Rama -- JP Morgan -- Analyst

Great. Thanks for taking my questions.

Operator

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

Mohit Bansal -- Citigroup -- Analyst

Great. Thanks for taking my question and congratulations from my end to Jackie as well. Maybe if you could delve little bit on the cholangiocarcinoma opportunity in terms of the size of the opportunity and the commercial infrastructure that may be needed for launch there? And how would you think about that opportunity versus the trend that may be needed there? Thank you.

Chris Bowden -- Chief Medical Officer

Yeah. Thanks Mohit, it's (Technical Difficulty). I'll take the first two parts of your question there. So with respect to the size of the opportunity, as we previously disclosed and talked about, we believe there are about 21,000 patients in the US and in Europe that are diagnosed each year with the disease. We estimate that between 2,000 and 3,000 of those patients have the IDH1 mutation. So that's the size of opportunity. We believe that's pretty evenly split between the US and Europe.

And now when it comes to kind of commercial infrastructure in the US to support a launch and whether we would need to significantly expand. Now what we've previously guided to is, we would need to have a modest expansion of our sales organization, we think that's in the range of 10 to 12 FTEs. But we'll be doing some more work on that during the course of this year to further refine that assumption and we'll share that with you as we get closer to a potential launch.

Mohit Bansal -- Citigroup -- Analyst

Got it. Helpful. Thank you.

Chris Bowden -- Chief Medical Officer

You're welcome.

Operator

Thank you. Our next question comes from Chris Shibutani with Cowen. Your line is open.

Chris Shibutani -- Cowen -- Analyst

Thank you very much. Perhaps, a question for Chris. In later this month in Munich you let us know that we are going to be seeing some additional data. Could you just clarify for everyone exactly what the incremental data that we will see and what you feel would be the appropriate way to think about comparing this with perhaps other competitive regimens that became a bit of a source of consternation or debate when we came out of ASH? Thanks.

Chris Bowden -- Chief Medical Officer

Yeah. So we published the data from this ongoing Phase I/II study for the TIBSOVO plus azacitidine combination at ASCO last year. So you're going to see a dataset with 23 patients who are treated with that combination with longer follow up. So what that will allow one to do is to make further conclusions and dry insights in terms of CR rates, overall response rate, importantly duration, how durable responses are, as well as some molecular data to understand what's happening with regards to the IDH clone.

So I think that will be very important -- and then the last piece of course is safety. So this will be very helpful, I think in terms of placing this in the context of the number of emerging new drug, which makes this a really exciting time for patients with AML, and we think it will underscore and reinforce what we've been saying is that we have a very active and well tolerated combination. And so it looks like it's going to be a very good option for patients who are ICN (ph) eligible, who have an IDH1 mutation.

Chris Shibutani -- Cowen -- Analyst

Great, that's helpful. And Jackie, welcome. Have you had any opportunity to interact with the folks at Celgene and/or Bristol obviously since their announcement? And any thoughts about implications about that upcoming combination as far as your commercial outlook and how you're thinking about your business planning? Thanks.

Jackie Fouse -- Chief Executive Officer

So, I mean, I have ongoing interactions with people across the industry all the time. And so it's not related to the deal specifically between those guys. So let's let them get their deal closed and see what happens after that. We continue to work with Celgene in the same way that we have in the past as a valued partner, and all of that is going extremely well and as we would have expected it to.

So let's say, better not the comment on these sorts of situations. I can't see anything negative for Agios in this situation at all, and so we wish them well and there you go.

Chris Shibutani -- Cowen -- Analyst

Great. Thanks very much.

Operator

Thank you. Our next question comes from John Newman with Canaccord. Your line is open.

John Newman -- Canaccord Genuity -- Analyst

Hi there, good morning. Thanks for taking my question, and welcome from me as well to Jackie. Question is, after doctors get a look at the Phase I, 7+3 combination data in AML, obviously, you would never promote this way, but do you think that there might be immeasurable off-label use of that combination? Thanks.

Steve Hoerter -- Chief Commercial Officer

Yeah. Hi, John. It's Steve. Thanks for the question. You're right, we only promote what is within the FDA approved label. I think as is the case with any disease where there is significant unmet need, physicians will take an interpret data from Phase I/II trials and may choose or not -- or choose not to experiment with that with their own patients. As you know, NCCN tends to be pretty quick to recognize emerging data as it comes out and accommodates that use in their compendium and in their treatment guidelines.

I think, I'd just say that, this is a very dynamic space in AML as Chris has said, this is great news for patients and it's an exciting time for the physicians who treat these patients given the number of new options. And we view part of our role is to ensure that we generate the right data with the right combinations to inform future treatment decisions and to evolve the standard of care. And that's exactly what our broad program is focused on doing.

John Newman -- Canaccord Genuity -- Analyst

Great. Thank you.

Operator

Thank you. Our next question comes from Alex Duncan with Piper Jaffray. Your line is open.

Alex Duncan -- Piper Jaffray -- Analyst

Hi. Thanks for the question. Two questions, first on TIBSOVO and cholangio and then followed by another question in MTAP. With TIBSOVO and cholangio, I'm wondering what are the current rates of genetic testing in cholangio and do you potentially need to do some promotion here? And in regards to the sNDA package later this year is the PFS in CLARITY, which will be reported in H1 and you eventually plan to file the sNDA package later this year. There is a certain benchmark at the end of the year needed to be met in the final analysis to allow this filing instead of just being filed on PFS. And with successful topline results in H1 this year allow you to move to frontline trials or is this final analysis later in the year needed to justify this?

And in MTAP, I'm wondering how common is genetic testing across all the tumor types that you're enrolling? And could these testing rates bias patient enrollment? And do you have data on outcomes for MTAP-deleted patients on current standard of care in these indications? And are these outcomes similar to the general population or are they worse? And I'm just wondering, that's because, I'm curious if this can be used to guide tumor specific paths forward? Thank you.

Chris Bowden -- Chief Medical Officer

Okay. It's Chris here. And with regards to your questions around CLARITY design and the aspect of progression-free survival and the important secondary endpoint of overall survival. So what we're going to do is, announce top line results of the data in the first half of the year and then we plan to submit the data from the trial to be presented at the meeting in the second half of the year. So it's in the second half of the year when one could expect to see a detailed results from the study.

I think that the trial being positive is predicated on a meeting, its primary endpoint of progression-free survival. Overall survival as well as other secondary endpoints can be important and supportive. I will remind you that trial has crossover. So, at the time of progression patients are offered a crossover, we thought that was an important component of the study because patients coming into the trial know there IDH status and there are no other therapies available for them.

So that doesn't mean that survival isn't something that we need to look at, but we would not consider in the setting of a persuasive positive study that one would need to have overall survival and wanted to garner approval, of course, that's something that needs to be debated and discussed with the various authorities throughout the world as they look at the totality of the data.

With regards to MTAP, you had -- I captured three questions. One is around, what's the rate of testing and does do we have data around outcomes? We don't have any data in terms of understanding with regards to survival progression-free survival or response rates for that matter in a selected group of patients within an indication with an MTAP-deletion. Testing rates, I would say that, there's probably very little testing for the MTAP-deletion at this point. However, P-16, CDK2NA (sic.) [CDKN2A] is a part of some of the routine testing panels and MTAP tends to travel with that.

Certainly, if this drug continues to move along its development, that will be a very important part of what we do, which is not just education which you alluded to, but also we might end up in a physician like with TIBSOVO where we developed the companion diagnostic.

Alex Duncan -- Piper Jaffray -- Analyst

Great. Thanks so much.

Operator

Thank you. (Operator Instructions) Our next question comes from Mark Breidenbach with Oppenheimer. Your line is open.

Mark Breidenbach -- Oppenheimer -- Analyst

Hey, good morning and thanks for taking the question. Just a quick one from me on the PKD program with mitapivat. Basically, I'm wondering, given the diversity of mutations that can cause PKD in this population. I'm wondering how the trials stratifying or type of mutation and as you're expecting better efficacy, better hemoglobin response in some mutational backgrounds versus others? Thank you.

Chris Bowden -- Chief Medical Officer

So, it's Chris here. Thank you for your question on this fascinating component of developing a drug in this disease. There are over 300 mutations that have been described. And I think, hence the nature of your question, the way -- when we think about this based on the data that we've generated from dry PK, which is where we're trying to understand how genotype is predictive of response with mitapivat. We tend to look at genotype categories, missense-missense, non-missense-non-missense, or if -- and then there's is missense-non-missense. And 80% of patients have at least one missense mutation. They fall into that category, which makes them potentially eligible to be -- to have a response with mitapivat.

So we don't need to stratify when you look at it from that perspective. That's a good thing, because if we had to consider a 300 different genes, we would be in a pretty challenging position. So that's how we've designed the trial and based on some of the aspects that we learn from dry PK, patients with a non-missense-non-missense gene category don't come into the trial. So that really takes care of any stratification aspect that we would need to address in ACTIVATE, which is the randomized trial within our portfolio of pivotal studies in this indication.

Mark Breidenbach -- Oppenheimer -- Analyst

All right. That's perfect. Thanks for clarifying that for me.

Operator

Thank you. And I'm currently showing no further questions. At this time, I'd like to turn the call back over to Jackie Fouse for closing remarks.

Jackie Fouse -- Chief Executive Officer

Thank you, operator. Thanks everybody for joining us on the call today. 2019 is going to be a terrific year for us, it's an important year for us. We've got broader, deeper portfolio of programs than we've ever had before. We're going to continue to ensure stellar execution across those, we are going to see a nice flow of data over the course of the year. And we'll have our first full year revenues from TIBSOVO and we'll be starting our plans for commercialization outside the US.

So there's a lot going on, more to come. I just want to thank all of the tremendous employees and our team here at Agios for their dedication, passion for the patients that we serve. And I would also like to thank the patients, caregivers and physicians who participate in our clinical trials, because without them we could not do what we do. Thank you and we'll see you soon.

Operator

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

Duration: 42 minutes

Call participants:

Kendra Adams -- Senior Director, Investor & Public Relations

Jackie Fouse -- Chief Executive Officer

Chris Bowden -- Chief Medical Officer

Steve Hoerter -- Chief Commercial Officer

Andrew Hirsch -- Chief Financial Officer and Head of Corporate Development

Kennen MacKay -- RBC Capital Markets -- Analyst

Peter Lawson -- SunTrust -- Analyst

Anupam Rama -- JP Morgan -- Analyst

Mohit Bansal -- Citigroup -- Analyst

Chris Shibutani -- Cowen -- Analyst

John Newman -- Canaccord Genuity -- Analyst

Alex Duncan -- Piper Jaffray -- Analyst

Mark Breidenbach -- Oppenheimer -- Analyst

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