Good morning, and welcome to Agios' Fourth Quarter 2016 Conference Call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session at the end. Please be advised that this call is being recorded at Agios' request. I would now like to turn the call over to Renee Leck, Senior Management, Investor and Public Relations of Agios. Please go ahead.

Thanks, Ben. Good morning everyone and welcome to Agios' fourth quarter 2016 conference call. You can listen to a live webcast with slides or a replay of today's call by going to the Investors section of our website, agios.com. With me on the call today with prepared remarks are Dr. David Schenkein, our Chief Executive Officer, who will review our key milestone for 2017, Dr. Chris Bowden, our Chief Medical Officer, who will provide an update on our clinical development activities and Andrew Hirsch, our Chief Financial Officer, who will summarize Agio's fourth quarter and full 2016 financial results. 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'll turn the call over to David.

Thanks, Renee. Good morning everybody, and thanks for joining us today. 2017 is set up to be an extraordinary year for Agios with two precision cancer medicines leading our transition to a commercial company. Multiple pivotal trials in cancer and rare genetic diseases ongoing or in the planning phase and a rich resource pipeline which is poised to deliver our next investigational medicine. Before I dive into the 2017 milestones, I’d like to remind you of how far we’ve come since 2009 when we opened our labs with a blank piece of paper and a great team of scientists. We focused on culture, and interrogating a new and disruptive area of cancer biology, that of cancer metabolism. In just eight years, our breakthrough discoveries in IDH have brought us on the verge of becoming a commercial organization with the discovery engine capable of continued excellence in discovering novel first-in-class targets. Now let me share with you some of our key priorities for 2017. I’ll start with the IDH portfolio. In December, Celgene, together with our support submitted the NDA for enasidenib, relapse for factory AML with an IDH2 mutation. Both companies are preparing for a commercial launch later this year. We plan to follow a similar path and submit an NDA for our wholly-owned IDH one inhibitor, AG-120 now known as ivosidenib in relapse refractory AML this year. This submission will be based on data from our ongoing phase I clinical trial. To make sure that every patient with relapse and refractory IDH mutant positive AML has access to medicines, we’ve been building world-class capabilities to prepare for the expected launches of our IDH inhibitors. In 2016, we hired our medical affairs and commercial leaders who are now actively recruiting our field organization. In 2017, we’ll be ready to fulfil…

Thanks, David. This morning we are pleased to announce a number of data presentations we expect to make this year across the IDH and PKR portfolios. In AML, our plan 2017 presentations will deliver data supporting our speed and breadth clinical development strategy that is designed to demonstrate the clinical activity of our inhibitors across multiple lines of treatment. For AG-120 now ivosidenib, we plan to present the first Phase 1 expansion data in relapse refractory AML patients in the second half of 2017. This update will provide new efficacy and safety data in the group of patients that is the focus of our NDA activities ivosidenib. Also in the second half, we plan to present data from our Phase 1B frontline combination trial with standard-of-care intensive chemotherapy commonly known as “7+3”. This is one of two early-stage trials underway to newly diagnosed AML patient’s, one combining enasidenib or ivosidenib with VIDAZA for patients ineligible for intensive chemotherapy and the other combining both targeted agents with 7+3 chemotherapy. Both have cleared a safety hurdle in the dose escalation component, demonstrating the ability to combine full dose enasidenib or ivosidenib with full dose standard-of-care therapy. As we announced in January, we are on track to initiate a Phase 3 frontline AGILE study in the first half of 2017. Moving our drugs to the front line setting is an important component of our development strategy and will enable us to help more patients earlier in their diagnosis. AGILE will be a global, randomized, double-blind placebo controlled trial in newly diagnosed IDH-1 Mutant positive ALM patients who are not eligible for intensive chemotherapy. Participants will receive either the combination of ivosidenib at 500 milligram once daily, plus VIDAZA or placebo plus VIDAZA. The primary endpoint of the trial is overall survival with multiple…

Thanks, Chris. Today we are in a strong financial position to support the anticipated product launches for IDH inhibitors and AML, advance our clinical programs into multiple Phase 3 trials and maintain our investments in our discovery research engine which has delivered six development candidates in the past eight years. As we disclosed in early January, we ended 2016 with cash, cash equivalents and marketable securities for approximately $574 million. This compares to approximately $376 million at the end of 2015. This increase in cash was driven by cash received from Celgene totalling $258 million. Net proceeds of $162 million from our September follow-on offering and $8 million from other sources including exercises of stock options. These cash inflows were offset by expenditures to fund our operating activities in capital purchases, approximately $231 million for the full year. Based on our current operating plans, we expect that the year-end 2016 cash balance together with anticipated payments from Celgene under our collaboration agreements will enable us to fund our operating expenses and capital purchases through at least the end of 2018. Turning to the full year P&L. We recognize $70 million of collaboration revenue in 2016 compared to $59 million for 2015. This increase in collaboration revenue was primarily driven by the early completion of our discovery efforts for the MTAP program and new research efforts under the 2016 Celgene agreement. During 2016, we incurred $220 million in research and development expenses compared to $142 million for 2015. The year-over-year growth in R&D expense was primarily driven by increased clinical trial enrolment as well as increased manufacturing activities for all of her ongoing clinical stage programs. In addition, as of August 2016 we are responsible 100% of the R&D cost for ivosidenib. General and administrative expenses were $51 million for the full year 2016 compared to $36 million for the prior year. The year-over-year increase was largely due to increased headcount and other professional expenses to support our growing operations. I will now turn it back to David to wrap up.

Thanks, Andrew. As we finish the call, I’d like to leave you with a vision we have for Agios that we articulated in early January. We are excited to become a commercial company in 2017, with the ability to impact patient lives. I’d like to thank all of the tremendous employees at Agios for their dedication and their passion to make a difference for patients. I also want to thank all of the patients, the caregivers and physicians who participate in our clinical trials and to thank our partners Celgene and with that operator, we’ll now open the line for questions.

Thank you. [Operator Instructions] Our first question is from Eric Schmidt of Cowen and Company. Your line is now open.

Thanks for the opportunity to ask question and for all the updates. Maybe for David or Chris on 881, I think Chris commented that you are sort of seeking out of Phase 2 dose. Does that mean you have made a go-decision on Phase 2 for glioma or is that still in the works and when will we see the Phase 1 data?

Thanks Eric, good morning. Let me turn it over to Chris to give you that.

So what we want to do Eric is identify a recommended Phase 2 dose. As you know we also have data with 120. So we’ve got two viable candidates to think about developing in glioma. 120 is farther ahead in terms of glioma experience and it’s also going to be helpful in terms of us thinking about what the next steps would be with 881 as well based on some of the data we got from that expansion cohort we published. So whether I wouldn’t say that identifying a recommended Phase 2 is a go, a clear go for 881, I mean we’ll have to look at both molecules and we’ll certainly need to work with Celgene on 881 as well in terms of thinking what the next steps would be. Right now, we are really focussed on understanding the safety and pharmacokinetics and honing in on what dose or doses we might want to think about as a recommended Phase 2 dose to go forward with 881. As far as publishing the data once we’ve got the requisite information around that dose escalation, and recommended dose piece then we’ll be bringing that data forward, we don’t have guidance on that yet.

Okay and then second question just on 348 in the DRIVE PK study, have you made any decision to expand or reopen enrolment with the potential second cohort?

Eric, do you mean the third optional ARM that we have in there.

Sorry, the third cohort, yes.

At this time Eric, we don’t have any plans to open that third, that third ARM. We feel like the data that we have from DRIVE PK at 50 milligram and 300 milligrams as always the duration of data that we have now was that we last published at ASH in December is providing us with ample information in terms of our forward plan.

Okay. Thank you.

Thanks, Eric.

Thank you. Our next question is from Anupam Rama of JPMorgan. Your line is open.

Hey guys, thanks so much for taking the questions. On AG-348 and the 3Q update on trial design, wondering what additional steps need to be taken between that point and say trial initiation in the first half of 2018. And then just a quick one, can you remind us for AG-221 or enasidenib if that was filed for breakthrough designation. Thanks so much.

Anupam, thanks for your questions. Let me take your second one first, and then I’ll turn it over to Chris to talk about 348. So, we don’t – we have never shared any information around our regulatory interactions at that level of detail that whether we applied or didn’t apply for breakthrough. As you know or may remember that both enasidenib and ivosidenib so 221 and 120 both have fast track and both have orphan designation. Turning back to 348, as you know, as we designed the pivotal trial its goal is to seek global regulatory approval and maybe I’ll have Chris walk you through what we expect to guide you in term of in the third quarter and what it will take open the trial.

Anupam, Chris here, Chris Bowden. The way I think about your question is that there is the kind of the qualitative phases of development, and you're in the conceptualization phase and then you have to present your plans to regulators and in this case, FEMA [ph], FDA and potentially others. That feedback that you get on your designs is rarely 100% consistent. And so, then you get into some judgments in terms of which directions you're going to take. You also are interacting with investigators and so support putting all that information is what drives you to what your final plans are around your clinical development plan which translates in the protocols. And those are the things that we need to pull together and that gets us into the third quarter of this year, and at that point we’d be talking about issues around patient population, sample sizes and some of the other factors that I alluded to in my prepared remarks when I was showing the slide. And then the other part of your question was then what happens? And that's when you get into the operation phase and that's getting your sites on board, getting through IRB's and then ultimately starting accrual. And that really account for that that the time it takes to do what David emphasized which is a global trial which will capture those patient populations that we talked about.

Great. Thanks so much for taking up questions.

Thanks, Anupam.

Thank you. Our next question is from Kennen MacKay of Credit Suisse. Your line is open.

Thanks for taking questions. Maybe David, one for you first, I was wondering if you could give some sort of sense of when we could see data from the submission package of AG-221 especially given that the endpoints of the confirmatory Phase 3 for about 221 and 120 are survival and hoping maybe we can get a sense of how long this patients living here?

Yes. Thanks. Good morning, Kennen. Thanks for your question. So as you know together with Celgene, the enasidenib submission went in December. And obviously this quarter we’ll hear from the FDA around their acceptance or not of the package and the PDUFA date and obviously Celgene and Agios will give you an update on that. We haven't articulated today what the disclosure or presentation plans are for enasidenib 221, obviously Celgene will take the lead on that with AGILE support. I think we still assume that you will see data during the year, but I can't give you that right at the moment. Celgene will articulate that and then will follow up with that. And so during the year both 221, enasidenib and as Chris articulated in his prepared remarks you’ll see data from ivosidenib.

Got you. Thanks David. And as far as I understand FDA had 60 days to let you know about acceptance. So that should be coming up based on the December NDA filing. Am I thinking about that right?

You are. The FDA does have 60 days to accept the NDA and therefore we expect to see that this quarter. We haven't articulated exactly when that submission went in December, though it could go in the near the end of the year, so we’re obviously waiting to hear that together with Celgene.

Okay. Thanks, David. And then, Chris, maybe just one for you, you’d mentioned AG-881 is now going to be sort of a backup molecule in hematologic malignancies. I just wanted to get a sense of sort of where that evolved from, whether it based on conversations with Celgene or what, and obviously this seem sort of like a best case scenario for Agios and sort of outlook for 120 given your full ownership there and split economics of 881? Thank you.

Hey, Kennen, it’s David. Let me start there and then if I need be, Chris can follow-up. Remember that 881 was never expected to be a lead molecule in the hem [ph] side. It was developed as you remember as a backup molecule for AG-120 or ivosidenib, because with better brain penetration. Our expectation was that given how far ahead both enasidenib and ivosidenib were in the hem malignancies space that the only utility on the hem side for 881 would be if one of those molecules had something that caused it to be delayed or stumble et cetera, which we have not seen. And so, really the Phase 1 study in the hem space was really a safety study to give us the information we need if we needed to move that molecule forward. So it's always been viewed as a backup on the hem side and its still in that same pole position.

Got you. Okay. Thanks for the clarification there. And then maybe just one 348 if I can work it in. Just wanted to get a sense of whether the timeline you outline for sort of registration design in Q3 was based on guidance for meetings you’d already had with the FDA or whether this was based on sort of expectations following future meetings? Thank you.

Yes. Kennen, I can't share any of the details about whether when we schedule meetings and things like that. We do believe that it’s fair to say that, we expect to have conducted all the regulatory interactions and other internal work and work with investigators we need to be able to articulate for you and the rest of the outside world what the pivotal plans look like in the third quarter.

Okay. Thank you so much and looking forward to the update on 221 filing. Thank you.

Thanks Kennen.

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

Hi, guys. Thanks for taking my question. Question is in terms of AG-120, can you talk about maybe the endpoint that you think the FDA is going to focus on when you submit that dataset. Do you think they’re simply going to be looking at the response rate, do you think they’re going to be looking at PFS. Do you think they're going to want to kind of follow patient for survival, obviously this is the narrow indication given that you have to have mutation, but just curious of how you’re thinking about that?

Thanks John. This is David here. I’m going to turn it over to Chris.

John, they’re going to be interested in all of the endpoints that you talked about and then some. We’re in a patient population relapse refractory AML that has limited to no treatment options. And we’ve talked about a number of facets, the R-IDH [ph] inhibitors that offer clinical benefit to patients and that's the overall response rate, the CR rate, the duration of response and they'll also as they always are even in single agent studies interested in overall survival. So those are all -- those are a number of the aspects that we need to bring forward from an efficacy standpoint. And then of course the other perspective is what does the safety profile of a molecule look like? And there they are there going to be looking at this, a number of the same aspects that is what does the safety profile look like in the early phase of dosing. What does it look like over time? There's a lot of questions around disposition. How many patients came on? How many discontinued for progressive disease, drug-related side-effects, side-effects overall. So, all kinds of pieces of information come into play in terms of their overall assessment. We tend to get a lot of questions and an appropriate focus on what the primary endpoint is and that's important. I certainly acknowledge that, but it’s really the totality of data that really sways them in terms of making a decision yes or no.

Great. And I have one additional question on 348s actually kind of follow-up to the first question from Eric, which is I think in the past, at ASH last year, when you give the update I can remember correctly you alluded to potentially being able to modify the dose for 348 going forward. And I’m just wondering if we should assume that this is a program where there’s still active discussions with the agency and its still a possibility that if you chose to you could potentially think about a different dose for 348 or should we just assume that at this point in time you're going forward with just one dose? Thanks.

I think if you look at the data that was presented at ASH, that’s where and in December 2016, that was where that we were talking about the fact that we were seeing durable responses, and responses that were maintained at doses below 50 milligrams. And over the course of since we published the date of first at EHA and in ASH. We've also talked about patients who had very robust increases in their hemoglobin and then started to have the dose titrated down. So, we don't have guidance right now on what a dose would be and there certainly some discussion as we look at the data and talk to investigators who are using the drug, that there might be a range of doses whether there could be an upper limit that where they won’t go any higher, but at this point what one of the things were gratified by is the fact that we’re able to explore range of doses and that we’re seeing robust and sustained increases in hemoglobin in those who do respond at a range of doses. So, I could see us, I’m not going to commits to 50 milligrams at this point for sure, since we’re seeing durable responses of 25 in milligrams and even lower. So it will be an active area of continued investigation and certainly our interactions with the regulators and IRBs is going to be an important part of the program.

Great. Thank you.

Thanks, John.

Thank you. Our next question is from Yatin Suneja of SunTrust. Your line is open.

Hi, guys. Thank you for taking my question. Just following up on John's question, I think earlier this year in January you said, you might use a dose titration up to optimize hemoglobin response for 348, but have you done that in the DRIVE PK? Do you think that trial is enough or do you have to do another like small trial to figure out an idea of those titrations strategy for 348? And then I have one more.

Yatin, it’s Chris here. We have not done a -- I would say of a formal dose titration up. We are -- investigators are exploring some opportunities to dose between 50 and 300. They are allowed to do that. At the same time what the data is telling us from the patient experience as we showed it at ASH, is that we tend to see pretty robust hemoglobin responses and then most of the moves when investigators have titrated going down is because the hemoglobin response is so robust, they’re into the normal range and so they start to titrated down to keep there. And the second part of your question is do we think we need to do additional work that is a separate trial to study this further? At this point I do not think so. And one of the reasons why that is because the safety profile between that 50 and 300 milligram range and below gives us a sense at this point that we can probably start to -- that that we can ask this question and answer this type of question when we get into a pivotal trial design, but more details to come there.

Got it. Thanks. And then just one more. You are planning to include transfusion dependent patient in the pivotal program, could you maybe tell us what gives you confidence in that patient population given that you have not evaluated that subset yet. What sort of data you have? And then what needs to be done to evaluate this drug in kids in the future? Thank you.

Yes. So, Yatin, it’s David here. So we have not yet articulated the patient population that you should expect to see in the pivotal -- global pivotal study. That’s part of the information that you'll see in the third quarter. Obviously, we’re having that discussion with regulators and investigators as Chris articulate earlier. So, I shouldn’t make any assumption yet about what the patient population is that some of the work we’re doing now. As you may remember from our natural history study the incidence of adults who are transfusion dependent is very small. We’re exploring that. We’re trying to understand that and so you’ll need to stay tuned on that piece. And second part of your question, it was about pediatrics. As we’ve talked about before our commitment is to develop a disease altering therapy for all patient population including pediatrics. Obviously, we need to capture more adult safety data before we can move down to children. And as we've articulated before with the known mild to moderate aromatase activity we’re seeing with 348, the real questions going to be as Chris articulated as we go down in the dose, can you we get to a dose where it makes sense for us to move into pediatrics. It just too early to commit to that at this point other than our overall plan is to at some point get to children once we've established safety and efficacy in adults.

Got it. And then maybe one for Andrew, Andrew, could you help us, figure out how should we model the revenues this year. Any milestone that we should be modeling this year or that you had anticipate to receive this year?

Sure. Thanks. So, the revenue model, I think as we’ve disclosed in the 10-K, probably several pages on that, its quite complex. So, what we’ve done is we have assigned value to each of the elements of deliverables under that collaboration agreement. And then we recognize revenue kind of as we progress along those deliverables. And so, it's hard to sort of give you guidance on how to do that because for example, this quarter one of the deliverables was development candidate around the MTAP program. We had a pickup in revenue because we completed that earlier than the planned timeline we assumed in the initial revenue models, so we had a pick up, it maybe worth us putting some time off line to go through that in some detail. And as the second part of your question around milestone, so we don't anticipate any milestones in the sense that we would recognize as of one time pickup in revenue. I think as we’ve disclosed what Celgene accepts the MTAP development candidate as a collaboration development candidate, there is an $8 million milestone, but that gets folded into this revenue recognition model, so you won't see a pick up, a one time pickup.

All right. Thank you very much guys.

Thanks, Yatin.

Thank you. Our next question is from Debjit Chattopadhyay of Janney. Your line is open.

Hey, good morning guys and thank you for sneaking in here. So, as you think about 881 and as you move both the 120 and 221 in the frontline settings, how do you see 881 play out in patients who have a disease progression on either one 120 or 221. What I’m trying to get at is in the completed Phase 1 safety study, do you have a feel for activity in patients who have had disease progression with the other IDH inhibitors?

Thanks, Debjit. I’ll have, Chris take that.

When we think about the use of the IDH inhibitors in AML, our main focus is really with ivosidenib and enasidenib. David talk to some of the aspects around 881 and how we thought about it and hematologic malignancies, and how we presented it as a backup molecule just to be have it there in case either one of the lead molecule stumble. I think the aspect of resistance and progression when you're on an IDH inhibitors is a very interesting one. We think this going to be important to suppress the IDH clone over the course of treatment. And one of the areas that we’re very interesting and studying and that was starting to get some data on is what other malignant clones might emerge that would need an additional therapy put on whether its [Indiscernible] or some of the other potentially durgable clone that come up. So at this point we don't see a role for 881 coming in with those patients, but rather we're thinking more from a combination perspective and really understanding what -- how the molecular signature changes over time with the intent that there's going to be – there’s a strong scientific hypothesis at least to consider continuing to suppress your IDH clone. There is some precedent for that and probably the one that we think about most is in the treatment of breast cancer, metastatic breast cancer with Herceptin we'll see that drug continued on over multiple different other therapies in an attempt to maintain disease control. So, we’ve a lot of work to do there, but we’re focused more on thinking about adding other therapies that dictate emerging patterns of resistance since we demonstrated that we continue to suppress 2HG in the presence of progressive disease in AML in our patients so far who are on at least AG-120.

Great. And just one follow-up on 348, given the preferential response that you’re seeing in certain genotypes, do you think the pivotal study is likely to be enriched for the very specific patient groups where you’re seeing activity and hence these are narrower label to go out with based on the data at hand or the interactions you may have had with the agency so far? Thank you so much.

Yes. Thanks, Debjit. It’s too early to speculate on that. For DRIVE PK we’ve not restricted enrolment by genotype, as you know even though we put the genotypes into these broad classes, each individual mutation is different and that's what we've not restricted enrolment. And it just too early for us to comment on what the pivotal design will look like with respect to that factor, so we’ll just need to stay tuned.

Thank you so much and good luck.

All right. Thanks for you questions.

Thank you. At this time, there is no other questions in queue. I’d like to turn it back to Mr. Schenkein for any closing remarks.

Yes, I would like to thank everybody who listened in and participated today. Thanks for your questions and look forward to speaking to you again in the future. Enjoy the rest of your day.

Ladies and gentlemen, thank you for your participation in today’s conference. This concludes the program. You may now disconnect. Everyone have a great day.