Lora Pike - Head of Investor Relations David Schenkein - CEO Glenn Goddard - SVP, Finance Scott Biller - Chief Scientific Officer Duncan Higgons - Chief Operating Officer.

Anupam Rama - JPMorgan Nicholas Bishop - Cowen & Co. Howard Liang - Leerink Partners.

Good morning, and welcome to Agios Pharmaceuticals First Quarter 2014 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 David Schenkein, CEO of Agios.

Sir, you may begin..

Good morning. Before we get started, I’d like to introduce Lora Pike, our recently hired Head of Investor Relations. We’re thrilled to have Lora join the team. Let me turn the call over to Lora to get us started..

Thank you, David. Good morning, everyone, and welcome to Agios’ first quarter 2014 conference call. You can listen to our live webcast with slides or a replay of today’s call by going to the Investors and Media section of our website agios.com.

With me on the call today with prepared remarks are David Schenkein, our Chief Executive Officer who will review progress to-date in all three of our programs and provide an outlook for the remainder of the year; and Glenn Goddard, our Senior Vice President of Finance who will summarize Agios’ first quarter 2014 financial results.

Duncan Higgons, our Chief Operating Officer and Scott Biller, our Chief Scientific Officer are 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 provision 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 in 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. Thanks for joining us today. At Agios, our vision is to develop medicines that have the ability to dramatically change the lives of patients and to build a great biopharmaceutical company.

We’re uniquely focused on building our product engine and maintaining our competitive first-mover advantage in the field of dysregulated cancer metabolism and in our novel approach to rare genetic diseases. We’re making rapid progress towards realizing that vision.

We’ve had a strong start to 2014 highlighted by important clinical progress for all three of our lead programs, AG-221, AG-120 and AG-348 in both of our therapeutic areas.

We were pleased to present the first clinical data for AG-221, the IDH2 mutant inhibitor at the recent AACR Meeting, demonstrating both proof of mechanism and promising clinical activity in patients with advanced IDH2 mutant positive acute myelogenous leukemia.

We believe these preliminary data provide corroboration of IDH2 as an important cancer target and support our hypothesis that precision medicine has the potential to shift the treatment paradigm for these patients.

Today, we are announcing that we will be providing an update on these clinical data at the upcoming European Hematology Association Meeting in June as we have been informed that our late-breaker abstract has been accepted for an oral presentation.

We also initiated three clinical trials so far this year, two trials to evaluate our IDH1 inhibitor, AG-120, one in patients with IDH1 mutant positive advanced hematologic malignancies and one in solid tumors, and a third trial to evaluate AG-348, the pyruvate kinase activator in healthy volunteers.

In addition, our research organization continues to make great progress in generating the next wave of novel medicines. And on the business side, we recently strengthened our financial position through a public offering of our common stock.

We’re excited about the prospects for our three lead programs in 2014, which we believe will be highlighted by continued clinical progress. Let me provide more detail on our recent progress with each of these programs, starting with our IDH programs, which, as you know, are in collaboration with Celgene.

We believe these metabolic enzymes are two of the most promising targets in cancer biology today. The IDH programs are based on two normal metabolic enzymes, IDH1 in the cytoplasm and IDH2 in the mitochondria that are mutated in a wide range of cancers.

The scientists at Agios first discovered that these mutations confer a new and previously unknown ability of the mutant form of the enzyme to produce high levels of a novel oncometabolite known as 2-HG, 2-Hydroxyglutarate.

Research conducted by Agios and our collaborators have now determined that high levels of 2H-G lead to a block in the normal maturation of primitive cells, which we believe, both initiate and drive the cancers.

Our therapeutic hypothesis has been to engineer small-molecule inhibitors of the mutant IDH enzymes to suppress the level of 2-HG and allow the cancer cell to mature into a normal cell and then die off, a potentially paradigm shift in our conventional approach to treating cancer.

AG-221 is an oral selective and potent inhibitor of the mutated IDH2 protein. We began a Phase 1 study of AG-221 in September 2013 in a genetically-defined population with hematologic malignancies carrying an IDH2 mutation.

We believe the development program was designed to generate all the information needed to establish clinical activity and to advance the program into late-stage development should the data support. The current AG-221 clinical trial continues to enroll patients in the dose escalation phase.

In this first stage of the study, patients are receiving ascending doses of AG-221 in 28 day continuous cycles using a three-plus-three dose escalation schema. We initially started with twice daily oral dosing, but due to favorable pharmacokinetics, we have started once-daily dosing in parallel.

We plan to continue dose escalation until maximal tolerated dose is reached. Once we’ve selected the best dose and schedule to move forward, we plan to initiate several expansion cohorts to further evaluate the safety, tolerability and clinical activity. We expect these cohorts to begin enrolling in late 2014.

They will give us more definitive safety and efficacy information in homogeneous subsets of patients. We also plan to initiate studies in a broad range of IDH2 mutant positive cancers, including solid tumors and combination trials as part of our comprehensive development plans.

On today’s call, I will only be discussing the clinical data that we presented at AACR, which used a March 20 data cutoff. At that time, patients were enrolled into four cohorts, 30 milligrams, 50 milligrams and 75 milligrams twice a day and 100 milligrams once a day.

The patients enrolled had relapsed and/or refractory AML had received multiple prior chemotherapy regimens, including some who had never achieved the remission to chemotherapy. As you know, this is a very sick patient population with extremely limited options and a very poor prognosis. The median age was 62 years with a range of 53 to 74.

The primary endpoint of this first study is safety but also evaluate PK/PD and evidence for clinical activity. Based on data from the 22 patients in the first four cohorts as of March 20, AG-221 demonstrated an excellent early safety profile. No dose limiting toxicities were observed and no safety signal has been observed to date.

Four patients died from infections unrelated to AG-221 during the first few weeks of treatment, consistent with other clinical trials done in this very ill population of relapsed and refractory AML patients.

AG-221 also demonstrated a favorable PK profile with excellent drug exposures and a longer half life than predicted from preclinical experiments, which have allowed testing of a once-daily dosing regimen.

Importantly, we demonstrated successful lowering of the oncometabolite 2-HG as early as a first cohort with greater than 95% reduction during continuous dosing in patients with the R140Q mutation. This pharmacodynamic effect established a definitive proof of mechanism. Clear signs of activity were evident as early as the first cohort of patients.

Of the ten patients enrolled in the 30-milligram and 50-milligram BID cohorts, there were seven patients who were on drug for at least 28 days, and thus, fully evaluable for efficacy.

Of these seven patients, six had investigator-assessed objective responses, including three patients who achieved complete remission, two who achieved complete remission with incomplete platelet recovery and one patient with a partial response.

A complete remission required no leukemic cells in the blood or bone marrow and normalization of all the blood counts. While it’s early to early assess the durability of these responses at this time point, all responding patients, but one, remained on AG-221.

One patient in cohort one achieved his first complete remission ever despite multiple rounds of aggressive standard of care chemotherapy. This patient was transplant eligible and therefore left the study to receive an allogeneic bone marrow transplant from a matched sibling donor.

The mechanism of response to AG-221 was entirely different from that seen with standard chemotherapy and could represent a paradigm shift in our approach to the treatment of acute leukemia.

Consistent with our preclinical modeling, we saw a dramatic reduction in the levels of the oncometabolite biomarker 2-HG, which causes the differentiation of leukemic blast cells leading to recovery in normal blood cell counts.

In our study, responding patients experienced an early normalization of their infection-fighting white blood cells known as neutrophils, which hopefully will translate into an improved ability to defend the body against the life-threatening infections which are so common (technical difficulty).

Standard chemotherapy works by destroying all cells in the bone marrow both normal and abnormal, which leads patients in a prolonged period of bone marrow depletion, and thus, they become vulnerable to infections. Our preliminary results with AG-221 were in sharp contrast to chemotherapy.

As seen in bone marrow images, when patients were dosed with AG-221, their leukemic cells matured into normal cells while the cellular content of the bone marrow was preserved. This approach has the potential to be safer and a more effective means of treatment for acute leukemia, and to reduce the potential of patients to succumb to infection.

Despite the fact that Phase 1 studies are designed to primarily evaluate safety, not efficacy, this degree of clinical activity is very encouraging albeit early. We look forward to providing more information on the patients and progress of this ongoing study at the EHA Annual Congress. I’d like to spend a few minutes discussing acute leukemia.

AML is the most common acute leukemia affecting adults and the incidence of this disease sharply rises with age. AML prevalence is estimated to be approximately 115,000 to 160,000 patients worldwide with approximately 20% of patients carrying an IDH mutation. The five-year survival rate for AML is dismal and estimated at 20% to 25%.

Today, patients diagnosed with AML have limited treatment options and the standard of care has not substantially changed in decades. In younger patients, the initial treatment goal is to utilize aggressive chemotherapy to achieve a complete remission and to proceed to allogeneic bone marrow transplant if a donor is available.

Unfortunately, based on age and donor availability, less than 10% of U.S. patients are eligible for transplantation. The vast majority of patients, especially those over the age of 60, do not respond to chemotherapy and progress to relapsed refractory AML and die of their disease or life-threatening infections.

The opportunity to help patients whose tumors carry an IDH mutation is much broader than acute leukemia with a total of greater than 40,000 patients diagnosed each year with either an IDH1 or IDH2 mutation, a wide array of both hematologic and solid tumors carry these mutations and we plan to test both our IDH1 and IDH2 inhibitors in all these diseases.

It is important to note that our estimates of patient numbers are likely to change over time as more patients are prospectively tested for common mutations. Let me now move to our other IDH1 mutant inhibitor program, AG-120. AG-120 is an orally available, selective and potent inhibitor of the mutated IDH1 protein.

(technical difficulty) We now have two Phase 1 clinical trials underway with an early development plan that is similar in scope and scale to that of AG-221. These trials were initiated in March.

The Phase 1 clinical trials for AG-120, one in advanced solid tumors and one in hematologic malignancies, will only enroll patients whose cancers carry an IDH1 mutation and we will begin with the dose escalation phase followed by multiple disease-specific expansion cohorts once the appropriate Phase 2 dose has been established.

We’re on track with enrollment. We look forward to providing the first data from this study at a medical conference next year. Now, let me switch gears to our pyruvate kinase deficiency program. This program, like all our IEM programs, are wholly owned by Agios.

Pyruvate kinase deficiency is an autosomal recessive disorder characterized by chronic hemolytic anemia, a severe rare genetic disease of metabolism. This disease results from mutations in pyruvate kinase R, also known as PK-R, an enzyme in glycolysis, the pathway to provide the dominant source of energy for the red blood cell.

These patients currently have no disease-altering treatment available and only have supportive care with transfusions and splenectomy as options. We estimate that there are approximately 1,000 to 3,000 patients with PK deficiency in the United States and similar numbers ex-U.S.

Our product candidate, AG-348, is a potent oral activator of pyruvate kinase-R for the treatment of patients with this debilitating disease. We initiated a single ascending dose Phase 1 clinical trial in healthy volunteers in April. This is a randomized placebo-controlled trial, the primary endpoint is safety, pharmacokinetics and pharmacodynamics.

The results from this study and from the subsequent multiple ascending dose trial that we plan to initiate in healthy volunteers later this year will allow us to move rapidly into a proof of concept study in patients with pyruvate kinase deficiency. Our IDH and IDM programs emanate from our clear vision, novel science and focused execution.

Looking ahead to the rest of 2014, we expect continued progress in each of our three lead programs. AG-221, we will continue dose escalation and we will present additional data on the Phase 1 study at EHA. We also expect to initiate expansion cohorts later in the year.

For AG-120, we will continue dose escalation in the two Phase 1 studies and we expect to provide updates on both trials at medical conferences in 2015. For AG-348, we will continue to enroll patients in the first healthy volunteer study and plan to initiate a second trial in volunteers later this year.

We also expect to provide clinical data from this program at a medical conference in 2015. Importantly, we continue to conduct research to advance and expand our pipeline in both cancer metabolism and the inborn errors of metabolism. So with that, I’ll now turn the call over to Glenn..

Thanks, David. Agios is in a strong financial position today. We’re very pleased with the strong support we received from investors and from our partner, Celgene, which allowed us to raise net proceeds of $94.7 million in a public offering.

This includes proceeds we expect to receive in connection with the closing of the underwriters option to purchase additional shares later today. With the closing of this equity offering, we expect to have the runway to drive all of our lead programs beyond proof of concept into later-stage clinical development.

We expect that our existing cash, as of March 31, 2014, the $94.7 million from our public offering and the Celgene discovery term extension payment of $20 million due later this month will enable us to fund operations until mid-2017.

Now, moving on to our financials, our cash, cash equivalents and investments, as of March 31, 2014, were $167 million, compared to $194 million as of December 31, 2013. The decrease was mainly driven by cash used to fund operating activities as our three lead programs advanced into clinical development.

Our total revenues were $8.4 million in the first quarter of 2014, compared to $6.3 million in the first quarter of 2013. Total revenue comprised of the amortization of deferred revenue payments received in previous periods from our collaboration agreement with Celgene.

The increase in the first quarter of 2014 related to revenue earned on Celgene’s December 2013 election to extend the discovery phase of the collaboration agreement through April of 2015. Research and development expenses were $17.4 million in the first quarter of 2014, compared to $11.5 million in the first quarter of 2013.

The increase was largely due to increased spending on development activities for our three lead programs now in the clinic. General and administration expenses were $3.3 million in the first quarter for 2014, compared to $1.9 million in the first quarter of 2013. The increase was largely related to the expense of supporting public company operations.

Today, we’re also providing guidance that we expect to end 2014 with more than $200 million of cash, cash equivalents and marketable securities. And with that, I’ll turn the call back over to David..

Thanks, Glenn. I want to thank everybody today for joining us and for your continued interest and support. The first part of this year has seen strong performance against key clinical objectives and we fully expect this trend to continue in the months ahead.

Our clinical programs have the potential to define transformational therapies to improve the lives of patients with cancer and those with rare genetic diseases.

We are focused on maintaining the momentum throughout 2014 and achieving important objectives that we hope will provide near-term and long-term value for our shareholders and benefit to patients and their families.

Our research programs continue to make excellent progress in new areas of biology and we continue to hire great people and focus on building a culture that provides the environment for the discovery and development of important therapies.

We’ll continue to push the frontiers of science and medicine, all in our efforts to realize our long-term vision of bringing medicines to patients while building a great multi-product biopharmaceutical company. With that, I’d like to ask the operator now to open the call for your questions..

This is Anupam in for Geoff. Thanks for taking our question. Just a quick question, as you’re sort of looking at the PK, the once-daily AG-221, David, in your opening comments you mentioned that you want to push the dose to the MTD.

So, as you move forward, are you going to -- or is the focus going to be on the once a day or the BID as you push the dose?.

We’re still dose escalating in parallel both for the BID and the once-daily dosing. And at this point, we’ll wait till we gather all the data as we go further up and define both safety and PK/PD and efficacy, and then make that decision as we move into the expansion cohorts.

So it’s too early to commit to it at this time as we’re still continuing to dose escalate in parallel. So, we’ll obviously look at all that data carefully before we make that decision..

And then, just a quick follow-up for AG-348, is there any site overlap between 348 and 120 and 221? I know that there is site overlap on the IDH programs?.

I’m sorry, Anupam, I couldn’t -- what kind of overlap?.

Clinical trial site overlaps. .

So, there definitely is overlap in sites between the IDH inhibitors 221 and 120. We don’t anticipate any overlap for 348 at this time. And remember the 348 study right now is done in healthy volunteers..

Our next question comes from the line of Terence Flynn of Goldman Sachs. Your line is open. Please go ahead..

This is (indiscernible) for Terence. Just first, can you provide any color on what kind of data we should expect at EHA? And then, secondly I noticed recently AbbVie has generated some preclinical data for ABT-199 in mouse leukemia model looking at IDH mutations, do you have any thoughts on that and the possible mechanism and what it means? Thanks..

I’ll take the first one around the EHA data, so we really can’t give out any additional color right now. All this is under embargo, as you know, but clearly there will be an update from the dose escalation component of the ongoing study. And I think your question, second question, I’ll have Scott address around ABT-199..

So ABT-119 is a proapoptotic molecule. We think the best way to treat IDH tumors is to go directly at the actual lesion. It’s a precision medicine approach. And, as what’s unique about these tumors is they make 2-HG, which drives the tumor and blocks, the differentiation. We feel that IDH inhibitors are the best way forward.

That doesn’t mean there won’t be other therapies that are less specific to these tumors that could be used in combination with our molecules..

Operator, next question..

Our next question comes from the line of Nicholas Bishop of Cowen & Co. Your line is open. Please go ahead..

David, I noticed that you said in your prepared remarks you emphasized that durability of 221 was not really assessable at the time point, those presented at AACR.

Do you think that, that will be something we can understand after we see the EHA data?.

It’s an ongoing process so obviously there will be more follow-up on those patients, and so we’ll have our first look at that. But it’s -- as you know, with these trials particularly in Phase 1, at each time point we’ll update both existing patients on the trial, as well as new patients.

And so, as time goes on we’ll get more and more information in this patient population..

And then, a follow-up on future plans for 22 1.

One is that you mentioned you want it to get to the MTD before going to the expansion cohorts, but I mean the therapeutic window is so wide on this molecule, it’s possible that you won’t reach an MTD in a reasonable time frame, is there a point in which you’re going to kind of call it and move on to the expansion cohorts? And then in addition to that, on the expansion cohorts, we’ve only seen data on AML patients so far, I’m curious as to what types of homogenous patients you’re going to be enrolling in the monotherapy parts of the expansion? And if you can stand a bit on what you said about potential for combination trials as well.

That would be helpful..

I’ll address those. So the first is around the selection of dosing schedule for the expansion cohorts versus the MTD, and I’ll be clear and I think I’ve said in the past that where we may and I think it’s likely that we may pick a dose for the expansion cohorts that is below what ultimately will be the MTD for the reasons that you’ve stated.

And so, when you believe that we’ve achieved the appropriate dose based on all the normal factors of PK/PD and activity, then we’ll initiate the expansion cohorts, and we’ll obviously articulate that at that time.

We may still keep additional cohorts dose escalating because we do believe this is the only opportunity we’re likely ever to have to define the upward safety profile of the molecule.

And so, I don’t want to give the impression that the expansion cohort dose will necessarily be the MTD dose, it may not and those expansion cohorts may start before the MTD is achieved.

With respect to the expansion cohorts themselves, we’ll give out a fair amount of granularity, but when I mean homogeneous, you can imagine, right now, all the patients have relapsed refractory AML but they’re at different stages of their disease, they are different age groups, eligibility for alternate therapies and so there are ways to really refine that take so that the groups are much more homogeneous.

And then it’s certainly likely we’ve always said we’ll explore other hematologic malignancies whether it’s a myelodysplastic syndrome, as you know, that carry the mutation, whether it is a angioimmunoblastic T-cell lymphoma et cetera and there may be an extension cohort that deals with those patients.

And so again we’ll give out that granularity later. And then finally your last question on combinations, I think Scott’s already mentioned that it’s likely that as we begin combination trials, we’ll think about two broad approaches with AG-221.

One is obviously we need to combine with standard of care chemotherapy because our hope is that AG-221 becomes sort of the foundation for all future therapies for IDH2 positive disease. So we need to understand that.

But also novel combinations with drugs that attack acute leukemia from alternate mechanisms is certainly attractive and we’re continuing to do those preclinical experiments now..

And if I could sneak in one last one on 120. On the solid tumor trial, just curious what types of patients you're enrolling there. I think -- is there some possibility that some of the more smaller indications, such as chondrus carcinoma and cholangioma could be rapid pass to market.

I'm wondering if there are going to be many of those patients enrolled in that Phase 1?.

I can’t give you any details at this time, but I can tell you that the study is designed to allow all patients who carry an IDH1 solid tumor into the study.

And if you just look at the -- and so I think it’s fair to suspect that over time patients with cholangiocarcinoma and chondrosarcoma, which really have no good standard of care treatment options now. We’ll certainly enroll into this study, but we expect gliomas as well as a variety of other solid tumors.

So in the first part of the trial until we get to the expansion cohorts we’re allowing -- it’s essentially a basket enrolment for anybody with an IDH1 tumor enrolled..

(Operator Instructions) Our next question comes from the line of Howard Liang of Leerink Partners. Your line is open. Please go ahead..

I have a couple of questions on 120, but before I get to them, a question on 221.

Is it fair for us to expect that the cutoff for EHA data would be at least two months after your ACR data cutoff, which I think is -- would it be like late May cutoff for EHA data?.

I can’t give you the detail on that. I can tell you it’s certainly going to be later than March 20, which was the cutoff. But you’ll see that when the presentation comes out. I can’t give you that kind of detail at this time..

On AG-120 you said that in this trial and all of your trials you're enrolling only patients with IDH1 mutations.

This is assessed in the tumor, I'd assume? And if so, is it difficult to get glioma patients with a biopsy?.

So you are right that everybody is assessed through their -- biopsy of their tumor. It’s not going to challenge for us. We’ve been working with these sites for a long time in preparation for the clinical trial, and so they’ve been making sure their local test is functioning well and they have access to samples.

As you know, every glioma patient, particularly the low-grade glioma patients, get multiple biopsies over time to see if they’ve had any transformation, and so there usually is adequate tissue to be able to do the molecular testing for the mutation.

So, we don’t expect it to be a major hurdle or a challenge and we worked very hard with these sites prior to enrollment. .

In terms of assessing whether there is activity in the brain, whether the drug crosses the brain blood barrier, are you doing, I think it’s like a MRI study to look at 2-HG levels? Are you able to determine the activity in the brain by looking at biomarkers?.

So, as you know in many of the solid tumors, we’re able to detect that 2-Hydroxyglutarate in their plasma, and so we’ll obviously use that. For the glioma patients, that’s been more challenging historically, and that’s why in the study we do have MRI with MRS capabilities at the sites that are enrolling patients.

So they will be able to track using the MRS fraction of the MRI to determine if 2-HG has been affected..

And the last question, two studies for 120, solid tumor and liquid tumors, I know it’s a little bit early but would you say that -- which one of them is progressing more rapidly?.

There are actually both on track. Everything is going really well, and there is really -- they were initiated within a week of each other and sites are doing great, and so there is really no distinction at this time..

Thank you. And ladies and gentlemen, this does conclude our question-and-answer session. I would like to turn the conference back over to Dr. Schenkein for any closing remarks..

I just like to end with thanking everybody for participating today and for your ongoing support as we try and achieve our long-term vision of building a great company and helping a lot of patients. So, thanks very much and have a great day..

Ladies and gentlemen thank you for your participation in today’s conference. This does conclude the program and you may all disconnect..