Lora Pike - Senior Director, IR and Public Relations David Schenkein - CEO Chris Bowden - CMO Glenn Goddard - SVP, Finance Scott Biller - CSO.

Eric Schmidt - Cowen and Company Lilly Maisel - Goldman Sachs Tim Tynan - Citigroup Eric Joseph - JPMorgan Howard Liang - Leerink Partners John Newman - Cannacord Genuity Arlinda Lee - MLV & Company Debjit Chattopadhyay - ROTH Capital Partners.

Good morning, ladies and gentlemen and welcome to the Agios Pharmaceuticals Incorporated First Quarter 2015 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time.

[Operator Instructions] As a reminder, this conference call is being recorded. I would now like to turn the call over to your host, Ms. Lora Pike, Senior Director, Investor Relations, Public Relations. Miss Pike, you may begin..

Thank you, Operator. Good morning, everyone and welcome to Agios’ first quarter 2015 conference call. You can listen to a live webcast with slides or a reply of today's call by going to the Investors & Media section of our Web site agios.com. With me on the call today with prepared remarks are, Dr.

David Schenkein, our Chief Executive Officer who will review progress to-date in all of our programs and provide an outlook for the reminder of the year. Dr.

Chris Bowden, our Chief Medical Officer, who will review our recent clinical development update and Glenn Goddard, our Senior Vice President of Finance will summarize Agios' first quarter 2015 results. Dr. Scott Biller, our Chief Scientific Officer is also here today and will join us 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 the 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 will turn the call over to David..

Thanks, Lora and good morning everybody and thanks for joining us today. 2015 is an important year for Agios as we execute on a number of important clinical events and so far this year we're off to a great start. On the call today, we will highlight the efforts we're making on our 2015 key priorities.

As a reminder, they are to execute on our planned global registration programs, build out our capabilities and continue to invest in research to maintain our leadership position in cancer metabolism and the rare genetic disorders of metabolism.

Over the past four months, we have made great progress both meeting and exceeding important clinical regulatory and business milestones.

This progress is highlighted by the selection of our fourth development candidate AG-881 for the clinic and a new joint worldwide collaboration with Celgene for this molecule, as well as the rapid advancement of AG-221 and AG-120 into large scale Phase 1 expansion cohorts in AML in the existing trials which we're announcing today.

AG-348 is also advancing on schedule and we remain on track to initiate the Phase 2 study in patients with pyruvate kinase deficiency in the second quarter.

Through the natural history study conducted by Boston Children's Hospital we continue to refine our understanding of the severity of the disease, disease manifestations, identify patients and help to provide measures of clinical outcomes.

Our culture at Agios continues to thrive and evolve and is an area of special focus for us now and into the future. And we're pleased, we've ended the quarter with a strong cash position of approximately $440 million, these efforts are the result of hard work, prioritization and disciplined decision making.

We are uniquely focused on maintaining our competitive leadership advantage in the field of dysregulated cancer metabolism and in our novel approach to the rare genetic diseases.

We're proud that our productivity has created four novel medicines in clinical development in the six years since Agios’ inception and with the rapid advancement of our investigational medicines we're now positioned to become a late stage clinical company with a broad pipeline of first in class medicines.

These advancements are bringing us one step closer to realizing our vision of becoming a long-term science-driven multiproduct biopharmaceutical company.

Today, we also announced that we expect to provide an update on clinical data for our three lead programs at the upcoming European Hematology Association meeting in June, as we've been informed that six Agios-authored abstracts have been accepted for presentation with another two abstracts excepted from Boston Children's Hospital.

We're looking forward to a strong presence at EHA, while attending this important hematology meeting will be interacting with and engaging with many of the global thought leaders in the field of cancer and rare genetic disorders. We expect to present data that will further characterize the product profiles of our investigational medicines.

We are very pleased to already be working with leading investigators at high profile institutions in both the U.S. and France. This reflects our efforts to build a strong network of scientific and medical experts.

It is equally important to us to see the understanding and enthusiasm that is building in the physician community for AG-221, AG-120 and AG-348 as their broad potential while attending this medical conference.

Before I ask Chris to review our clinical programs, I want to comment on how excited we are as we prepare to initiate clinical development of our fourth internally developed investigational medicine AG-881, a brain penetrant pan IDH mutant inhibitor.

We have a strong partnership with Celgene and AG-881 is another example of our commitment to cancer metabolism, leadership in the IDH space and improving the treatment for many patients with IDH mutant positive tumors.

We also believe AG-881 underscores our research platform and focus on broad discovery and development of novel investigational medicines.

We remain excited about our continued growth and evolution as a company with a platform driven pipeline with multiple investigational medicines and multiple opportunities to help improve the lives of cancer patients and those living with rare genetic disorders.

Our research organization continues to make great progress in generating the next wave of novel medicines. I will now turn the call over to Chris so he can review with you our clinical progress and the specifics of our clinical development milestones..

Thanks, David. I’d like to start by saying that our expanding clinical development programs underscore our commitment to bringing important new medicines to patients. The most recent example is the addition of the newly selected AG-881, a brain-penetrant, pan-IDH inhibitor to our IDH portfolio.

With this addition we now have three IDH mutant inhibitors being developed in collaboration with Celgene. Our progress so far in 2015 is marked by the key clinical events we announced today, the initiation of large scale expansion cohorts as part of AG-221 and AG-120 ongoing Phase 1 studies in hematologic malignancies.

I will start with the Phase 1 trial of AG-221 and hematologic malignancies. As a reminder the ongoing Phase 1 dose escalation study of AG-221 has four expansion cohorts of approximately 25 patients and al our evaluating a single daily 100 milligram dose.

Three of these cohorts are in clinically defined AML population and one comprises a basket cohort enrolling patients with other IDH 2 mutant positive advanced non-AML hematologic malignancies, for example, myelodysplastic syndrome. I’d like to highlight our decision to add the fifth cohort to the Phase 1 study in hematologic malignancies for AG-221.

The early part of the expansion cohorts, four cohorts I just described are designed to generate additional information to continues to develop the clinical profile that is advancing the AG-221 program toward late stage development.

The amendment of this study we announced today broadens the trial by adding an additional cohort of 125 patients in a selected group of AML patients who are in second or later relapse our refractory second line induction or re-induction treatment or have relapsed after allogeneic transplantation.

AG-221 will be administered at the same dose of 100 milligrams once daily as in the other four cohorts.

Given the strength of the AG-221 clinical activity data presented at ASH last December in patients with AML and the ability to leverage an ongoing and actively enrolling study we thought that was logical top add this additional cohort and take advantage of the momentum of the ongoing study to further understand the clinical profile of AG-221.

Our objective is to build a compelling set of data that can demonstrate the potential for AG-221 to become a new foundation of care in treating AML.

Since the additional cohort is just initiating, it is too early to provide an accurate prediction of when we expect to complete this portion of the study and we'll keep you apprised of our expectations as we know more. The expansion cohorts will give us more robust safety and efficacy information in these clinically defined subsets of patients.

The safety and efficacy information that we can gather from all of the cohorts will be important for other clinical development. The clinical activity and safety profile of AG-221 we are observing in the ongoing Phase 1 study in hematologic malignancies will be discussed in greater detail at EHA next month.

Specifically we expect to present new data from the AG-221 dose escalation study. Early data from the expansion cohorts and early molecular data obtained from patients enrolled in this study.

In addition as part of AG-221’s comprehensive development plan in hematologic malignancies, a global registration enabling Phase 3 study is planned to start in the second half of 2015. We'll give you more details including patient populations and appropriate end points as this study to be led by Celgene gets underway.

Agios and Celgene plan to initiate combination trials to evaluate AG-221 as a potential frontline treatment for patients of AML and a broad range of hematologic malignancies in the second half of 2015. Now the clinical program for AG-221 in solid tumors.

In October 2014, we initiated a Phase 1-2 dose escalation study of AG-221 in patients with IDH2 mutant positive advanced solid tumors including gliomas as well as angioimmunoblastic T-cell lymphoma. Similar to hemo melagnancies all of these tumors have limited effective standard of care therapy.

In 2015, we expect to continue the dose escalation Phase for patient from this Phase 1 study. The second investigational medicine in our cancer metabolism program with Celgene is AG-120 an orally available selective potent inhibitor of the mutated IDH1 protein. We retain U.S.

development and commercialization rights for AG-120 under our agreement with Celgene. For this program we now have two Phase 1 clinical trials underway. One in advanced solid tumors and one in hematologic malignancies with the development plan that is similar in scope and scale with that of AG-221. Both of these studies were initiated in March 2014.

We look forward to present the new data from the Phase 1 dose escalation study in hematologic malignancies at EHA and the first data from the ongoing Phase 1 study in advanced solid tumors at a medical conference in the second half of this year.

First to the ongoing Phase 1 hematologic cancer trial for AG-120, we announced today the start of three extension cohorts where AG-120 will be administered at a 500 milligram once daily oral dose in 28 days cycles. We selected the 500 milligram dose based on a careful assessment of safety, pharmacokinetic, pharmacodynamic and efficacy data.

These cohorts will evaluate AG-120 in a total of 175 patients with advanced hematologic malignancies.

The first cohort, similar to the fifth cohort as announced for AG-221 will evaluate 125 relapse refractory AML patients who are in second or later relapse or refractory to second line induction or re-induction treatment or relapsed after bone marrow transplantation.

The second cohort will evaluate 25 untreated AML patients and the third cohort will evaluate 25 patients with IDH 1 mutated advanced hematologic malignancies not eligible for cohorts 1 or 2. The primary objectives for this study are to confirm the safety, tolerability and clinical activity of AG-120.

As for the next steps we also plan to initiate a global registration enabling Phase 3 study for AG-120 in AML in the first half of 2016. We expect to conduct this trial in collaboration with Celgene. Similar to AG-221, we also plan to initiate combination trials for untreated AML in the second half of 2015.

Now to the AG-120 clinical development program in solid tumors. Given the potential for this molecule to have broad application across a number of tumors, we are evaluating AG-120 in a Phase 1 dose escalation study in advanced solid tumors.

The study remains on track and we expect to report the first data at a medical conference in the second half of 2015. As we have previously mentioned, the study is evaluating varying doses of AG-120 in a wide range of solid tumor types that carry an IDH 1 mutation.

Pre-clinical data in solid tumor cancer models has demonstrated that the IDH mutation leads to a block in differentiation which could be reversed with our molecules. We are encouraged by this pre-clinical finding; however it is too early to know how this will play out in the clinic.

AG-221 and AG-120 remain our lead IDH programs and we are pleased with the profiles that are shaping up for both.

The data presented in 2014 at four major medical conferences show the potential of these two investigational medicines to provide significant clinical activity in genetically identified patients with advanced hematologic malignancies with an IDH mutation.

As you know from our announcement last week we now have a third IDH inhibitor, AG-881 a pan inhibitor of both IDH 1 and IDH 2 mutant proteins. Based on our proof of concept data in hematologic malignancies for both AG-221 and AG-120 we have shown that mutant IDH is a key target for cancer therapy.

The primary pre-clinical difference is the improved predicted brain penetration for 881 with the attendant potential to support our ongoing development efforts to provide treatment options to patients with glioma, especially in newly diagnosed patients where the blood brain barrier is expected to be intact.

We're excited to evaluate AG-881 for the first time in patients with the start of Phase 1 clinical development expected in the second quarter of 2015. Data from this study will inform our future development plans.

With the advancement of AG-881 from research toward the clinic we entered into a new joint worldwide collaboration with Celgene for this molecule. Glenn will review the terms in his prepared remarks. Now switching gears to our pyruvate kinase deficiency program, this program is wholly-owned by Agios.

Pyruvate kinase deficiency is an autosomal receptive disorder characterized by chronic hemolytic anemia, a severe rare genetic disease of metabolism. AG-348 is a potent oral activator of pyruvate kinase R for the treatment of patients with this debilitating disease.

Data presented at ASH in December from the single ascending dose and first two cohorts of the multiple ascending dose study provided early proof of mechanism and were consistent with our pre-clinical work, they showed that AG-348 was well tolerated and caused a dose dependant activation of the PKR pathway as evidenced by a substantial increase in ATP and a decrease 2, 3 DPG levels.

The MAD study is complete and our abstracts have been accepted by EHA to present the final data from this clinical trial. In the coming weeks we expect to have our Phase 2 study in patients with pyruvate kinase deficiency opened for enrolment.

This will be a global study that will include sites and patients located in key areas of the U.S., Canada, and Europe.

Rounding out our milestones for AG-348 are the presentation of the first data from the global natural history study for pyruvate kinase deficiency which is designed to identify patients and better understand the disease and how it progresses overtime.

Abstracts of data from this study conducted by Boston Children's Hospital have been accepted for presentation at EHA. Our cancer metabolism and rare genetic disease programs emanate from our clear vision, novel science and focused execution. We've always thought about patients first and where we think we can go.

In summary, we expect continued progress across our pipeline in 2015 and look forward to keeping you updated on our progress. So with that I'll now turn the call over to Glenn..

Thanks Chris. Agios is in a very strong financial position today; it is well capitalized as we advance multiple programs in the late stage clinical development. As David has mentioned we are very pleased to be advancing our fourth internally developed investigational medicine AG-881, a brain-penetrant pan IDH mutant inhibitor.

AG-881 will be jointly developed with Celgene under a new world wide profit share collaboration agreement. Under the terms of the new collaboration agreement, we'll receive an initial payment of $10 million and are eligible to receive regulatory milestone payments of up to $70 million.

Agios and Celgene will jointly share 50-50 in both worldwide development costs and worldwide profits. Now moving on to our financial results for the first quarter. Our cash, cash equivalents and marketable securities as of March 31, 2015 were 440 million compared to 467 million as of December 31, 2014.

The decrease was driven by cash used to fund operating activities of approximately 32.2 million which was offset by AG-221 cost reimbursements of approximately 6.6 million made by Celgene during the first quarter of 2015. Our total revenue was 34.2 million in the first quarter of 2015 compared to 8.4 million in the first quarter of 2014.

Approximately 15.8 million of the increase related to the delivery of the ex-U.S. license for AG-120 at Celgene. In addition the first quarter of 2015 included revenue for reimbursable cost related to development services for ongoing Phase 1 studies.

Research and development expenses were 32.4 million in the first quarter of 2015 compared to 17.4 million in the first quarter of 2014. The increase was largely due to increased investments in our three lead investigational medicines as they advance into later stage development activities.

General and administration expenses were 7 million for the first quarter of 2014 compared to 3.3 million in the first quarter of 2014. The increase was largely related to increased headcount in other professional expenses to support growing company operations.

Today we are also reorienting our previous guidance that we expect to end 2015 with more than 320 million of cash, cash equivalents and marketable securities. In addition, we expect this cash position to give us runway through late 2017. And with that I'll turn the call back over to David..

Thanks all for your time today. We're excited by the progress we have made so far in 2015 and look forward to executing on our remaining milestones and updating you on our clinical progress at EHA and on future calls.

And we want to thank all the patients, their caregivers, the members of the medical community who have participated in our clinical trials and of course all our employees and shareholders for their continued support. And with that operator we can open it up for Q&A..

Thank you. [Operator Instructions] And our first question is from Eric Schmidt with Cowen and Company. Your line is open..

I guess the question on the new 125 patient expansion cohorts for both 221 and 120 it looks like they are very specific patient sub-populations so I guess I am just asking how those would have been chosen, why those might have been chosen?.

Thanks Eric this is David. I'll kick it over to Chris in a second. So, I appreciate your comments and your support. As you know and as have we articulated in the past our goal is to get 221 and 120 as quickly as possible to the patients out there with IDH1 mutant positive disease in particular AML who need desperately a new treatment.

And we've always said that we would combine both speed and breadth as we move these molecules forward in development and I think this is the first component of that and so with that let me turn it over to Chris who can articulate a little bit more about the patient selection..

That's a group of patients in that 125 patient cohort that has very limited if any treatment options. If you really look at that what I outlined there in my remarks they have are on second or later relapse the refractory to the second line induction and four have relapsed after allogeneic transplant, bone marrow transplantation.

So those patients don’t have a lot of options whereas to clearly seeing activity in that group of patients and we think that's an important group of patients for us to build a really robust efficacy and safety data set and as we plan further steps in our clinical development..

And does your commercial team have a sense of what percent of the AML community might fit in one of those three buckets?.

So I don’t think we've gone through that yet in any extensive detail but as you know with current standard of care, the majority of AML patients are elderly over the age of 65 and very few of them will be cured of their disease.

So, if one looks eventually most of the patients with AML over the age as 65 which is the majority are going to end up heading towards that category overtime with the current standard of care but we don’t have any detailed market numbers yet..

Thank you and your next question is from Terence Flynn with Goldman Sachs. Your line is open..

Hi. This is Lilly actually in for Terence, thanks for taking our question.

Just a few on the AG-881, are you planning to start like a heme and a solid tumor trials in parallel as you did with the 120? And then also on the solid tumor side kind of related I know it all depends on the data, but will you wait to move 124 in solid tumor until you get the 881 data?.

As you know as we've articulated from the beginning when we broke open the IDH story, our commitment has been to lead the space and with that it was to not only bring the first two lead molecules as quickly as possible to patients and eventually to the market but have that flexibility with additional next generation molecules of which 881 is an important component of that.

We've not yet articulated what the development plan will be for 881, we'll do that as we enter into the clinic shortly and we will do that and it’s just too early to speculate on how 881 will fit into that paradigm.

There's no question 221 and 120 are moving as quickly as we can to the patients who need it towards approval and then as we generate data with 881 we'll decide how to dovetail that into the development programs..

All right, and our next question's from Yaron Werber with Citi Group, your line is open..

Hi guys this is Tynan on for Yaron here.

A question on the, your new 881 IDH inhibitor, can you address how much better the brain penetration is here versus 221 and 120? And maybe also address the IC50 since this is a pain inhibitor can we assume that it's less specific for each mutation or is that not the case?.

Yes, I'll let Scott Biller our CSO take that one..

Yes, so I'll start with your second question first. All of the molecules we brought forward into the clinic are potent inhibitors of the respect of enzymes, so 881 is potent against all of the mutated isoforms of IDH1 and IDH2, so no real differentiation on potency.

They all effectively lower 2HG and the tumortation and your first question, remind me your first question again..

Degree of brain penetration..

Yes, certainly, sorry about that, certainly AG-881 is a very highly brain penetrant molecule, AG-221 does also get in the brain and AG-120 less so, so clearly 881 is an advanced in being able to get penetration with a potent IDH inhibitor..

And then maybe just a follow-up on the data at EHA, you mentioned on the call that there would be some molecular identification data there.

Is this going to potentially address sort of when IDH mutations arise in tumor genesis sort of whether they're ancestral or as subsequent sort of clonal mutation?.

Yes, it's probably a little bit too early to commit to exactly what it'll be in those presentations. As we get closer to the meeting we'll be putting out a statement on the titles and things.

As you know we've been partnered closely with Foundation Medicine on the development pathway for all three of our molecules which allows you to look not only at the IDH mutation but across a broad range of mutations. But as we got closer to the presentation Chris and his team will articulate what we expect to see in those data sets..

Thank you and our next question is from Anupam Rama with JPMorgan, your line is open..

Hi, morning guys this is Eric in for Anupam. Just a follow-up question on the whole refractory AML population you would be looking at, the expansion cohorts you would be looking at.

And just wondering, given the size there -- would there be potential for maybe an accelerated approval filing based on an overall response in things assuming positive data? And also maybe just a quick question on 348 and PKD. You talked previously about hemoglobin changes being a key potential end point.

What kind of delta do you think would be clinically meaningful across a spectrum of PKD? Thanks..

Sure, Chris will handle both of those..

To your first question around the potential for regulatory filing with that expansion cohort, that's part of a -- that cohort as well as all the expansion cohorts are really around getting more information and more robust feel around our efficacy and safety data in AML patients.

The possibilities as a filing data set really is dependent on a number of factors, it really depends on what the data looks like and our discussions and interpretations of that internally. We of course work with experts in the field, our partner Celgene and then finally and perhaps most importantly with the regulatory authorities say.

So we're anxious to get these expansion cohorts up and running we’ll be looking at the data carefully and that will really drive those types of decisions.

For 348 the question around dose exposure and what we would expect to see in terms of impact from hemoglobin we have a clearly very important measure of whether this drug is going to be effective or not.

We don't know yet at this point, that would be speculation and that's one of the reasons why we're getting ready to launch our first trial in patients which, the details which we hope to be able to disclose relatively soon. And so that's really going to help us understand what types of dose and what the safety and efficacy profile looks like in 348..

Thank you and our next question is from Howard Liang with Leerink, your line is open..

Great thanks very much.

Regarding the phase 3 for AG-120 since it's a phase 3 should we assume that these will be randomized studies?.

Hi, Chris here. We haven't disclosed the design of those trials yet and where the end points of the patient populations. We're still working through that internally and again with looking at experts as well as with Celgene and we're still in the discussion phase with the regulatory authorities.

So a lot of that information is really in the works so we’re working very hard on it but we haven't finalized a lot of that components of the design yet, but to the extent that we're ready to talk about it..

AG-120 you talk about the selection of 500-milligram q.d. as a dose. Did you go up above 800-milligram q.d.

in the -- in the dose escalation and can you talk about whether you run into DLT?.

So, we're going to provide new data for AG-120 at EHA and early June that was point will update the experience to-date with that trial. As you know, what we published last year at Triple meeting in Barcelona was we went up to 800 milligrams and that's what we've stopped put in the public domain to-date..

AG-120 in solid tumors, other than lack of a brain penetration with AG-120 in -- which will be more specific for glioma patients are there other reasons why an IDH inhibitor would not work as well in solid tumor patients as compared to liquid tumors? I think you mentioned that pre-clinically you also see induction of differentiation..

Yes, Howard, David here. I mean as you know, we've talked about this in the past our goal is to be obviously develop these medicines as broadly as the science allows us and if you take a step back and you look at the mutation and the ability of 2HG to block differentiation it is pretty similar across all the different diseases.

And now that's why we've designed the experiments, so we've done both on the heme side and on the solid tumor side to look at a wide range of solid tumors in the ongoing trials of both 120 and 221 to give us an understanding not only the safety but also the potential for efficacy and changing the biology in these patients with diverse set of tumors.

And that's why we're looking forward to completing this data set and brining that out to you in the second half of this year..

Thank you and our next question is from John Newman with Canaccord Genuity. Your line is open..

First one I had is should we view the characteristics of the expansion cohorts for 120 and 221 as informing the specific types of patients that may be looked at in phase 3 or have those patient groups already been accepted? And my second question was on 348, just wondered if you could give us a sense on terms of timing when we might see data in humans I know that study is just getting going but just curious? Thanks..

So on your first question about the expansion cohorts, I think again I'll bring you back to where Chris had mentioned that at several different events we've done about our quest to make these molecules foundation of care for certainly the disease we've already shown data such as AML and the other heme malignancies.

The whole spectrum as a disease from newly diagnose patient through the refractory patient.

And so obviously the cohorts that we're expanding are highly refractory but that's we're also going to combine that we multiple other trials, which will articulate as the year goes along including the combination trails that will likely be in the front line patients that will allow us to give us that breadth across that whole patient population.

So I don't think you should read in from the design of the expansion cohort anything more than that's a very high unmet medical need population that we're moving quickly on. With respect to 348, just correct you little bit, we have been in humans already remember we've done two normal volunteer studies.

The patient study will be starting shortly and until we start that study we won't yet give out any guidance, it's a bit premature on when to expect to see data from that phase 2 study. Thanks for your question..

If I could ask one additional question, what is your thinking in terms of the mechanism, or the potential mechanism for 120 in solid tumors such as gliomas versus what is known about the mechanism in hematological malignancies? I know that in the hematological malignancies it seems very logical as to how and why the drug works in terms of the differentiation of the blasts but I'm just curious as to how you think about it in solid tumors.

Thanks. .

Yes, this is Scott. We know, we've seen that 2HG and the mutation induces a block of differentiation and all the tumors and which we've looked there which is included the major tumors we have seen the mutations, glioma, chondrosarcoma, and cholangiocarcinoma.

As you know, in liquid tumor setting there is precedent for therapeutic affects with ATRA of the relief in the block in differentiation. You can actually see complete remissions and durable remissions with ATRA and combined with arsenic.

So we have more precedent in therapeutic sense, we've liquid tumors but certainly in solid tumors we're seeing the very similar biology of course tissues specific but very similar biology. So we're looking forward to the results of the trials to tell us whether this continues to work in a therapeutic mode..

[Operator Instructions] And our next question is from Arlinda Lee with MLV, your line is open..

On the expansion cohorts and the phase 3 that you guys are planning to start for 220 -- 221, sorry, I'm kind of curious, what is the difference in patient populations that you have? My understanding is the phase 3 is for second line AML with IDH2 mutations as well, so I am kind of curious what the difference is there..

The expansion cohorts for 221 and 120 that is the 125 patients where I describe the inclusion criteria, the selection criteria. I think you should look at them as comparable.

The language is slightly different but really at the end of the day from a clinical perspective the way clinicians are looking at them and in terms of thinking about the unmet medical need and the lack of treatment options for these patients, they're largely comparable.

On the phase 3 design is in the works and as per some of the previous questions we're working through what that design and patient population will look like and looking forward to discussing that when the time is right..

And then maybe another question on the solid tumors, are you seeing -- I know that David and I had talked about the IDH1 and 2 mutations in a single patient being very rare.

Are you seeing more of those in solid tumors versus hematologic malignancies? And I guess this comes back to the question of whether IDH in the instigator mutation in some of these molecules..

So Arlinda, David here, we haven't obviously yet disclosed any of that data and we're crunching through a lot of that data with Foundation Medicine both on the heme side and on the solid side, and certainly as Chris articulated in his comments on the heme side, we said that in one of EHA presentations we will have some molecular data, we haven't yet decided or articulated on the solid tumor side whether any of that data will be available.

Importantly we believe we've done the right experiment in patients with these diseases to be able to answer these questions and by partnering with Foundation Medicine and other collaborators we'll try and understand as much as we can of the molecular underpinnings of their disease.

As you know these patients have to have an IDH mutation to come into the study and then we're looking for other mutations as well using that technology, so just a little bit too early..

And then I guess lastly on 348 will some of the data at EHA help us figure out I guess the proportion of patients that require blood transfusions or help us better get a handle on the addressable population? Thanks..

The data that will be presented at EHA will be an update of the new data for the multi ascending dose study, that's in healthy volunteers, and that will be a follow up in new data from what we initially presented at ASH. Dr.

Grace from Boston Children's Hospital will be presenting some of the first data from the natural history study and that's looking at patients who are coming onto the trial and helps us understand a lot of aspects in terms of disease, disease progression and so on and so forth.

So there should be some information there that people will be able to start to understand more from the disease especially given that most of the data that's been presented to date has been from single institution experience..

Thank you and our next question is from Debjit Chattopadhyay with ROTH Capital Partners, your line is open..

Just first one on 348, do we know of the relationship between ATP increase 23DPT decrease, at what level these become clinically meaningful for patients? Is there any kind of natural history study at different levels which should help us translate the healthy volunteer data into patients?.

Yes, there is no natural history study that's looked at that kind of data but what I will remind you is that we do have some data based on the level of enzyme activity and ATP in the patients themselves and then along with that we have the data available in their parents because remember the parents are heterozygotes and they have one defective allele and have depressed ATP levels and enzyme activity but are clinically normal with no hemolysis.

So we know at least where the bar we need to achieve is approximately up to about 50%-60% of normal ATP levels.

And we know from the data that we’ve already previously presented that if we take samples from patients with the disease and ex vivo activate the enzyme with 348 we believe we can restore ATP levels into that range which we think hopefully will help patients.

Certainly the ATP increase we've seen in the healthy volunteers also we believe is into that range and now we just need to still occurs in patients with the disease and that's why we're so excited about moving ahead with the clinical trial..

Thanks. And then one more if I may on the -- the pan IDH [indiscernible] selection.

So I'm just wondering in terms of the other driver mutation is which patients very often have along with IDH I mean how would inhibition of both agonist 1 and 2 impact the other driver mutations?.

These molecules are highly selective for the IDH mutation and so for say, they shouldn't have any impact on other mutations and so this will all come down to as it is on the heme side and solid side and in individual patient in tumor which are the driver mutations and which are the cooperating mutations..

Thank you. I am not showing any further question at this time. I'll now turn the call back over to your CEO, David Schenkein for closing remark..

With that, I want to thank everybody for your support. We're obviously very excited by the results of our first quarter and look forward to keeping you updated on our progress and then our request to help as many patients as possible out there. So thank you very much and have a great rest of the day..

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