Agios Pharmaceuticals, Inc. (AGIO) Q4 2014 Earnings Report, Transcript and Summary

Good day, ladies and gentlemen and welcome to the Agios Pharmaceuticals’ Fourth Quarter and Full Year 2014 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 is being recorded. I would now like to introduce your host for today’s conference, Ms. Lora Pike, Senior Director, Investor Relations. Ma’am, you may begin.

Thank you, operator. Good morning, everyone and welcome to Agios’ fourth quarter and full year 2014 conference call. You can listen to a live webcast with slides by going to the Investors and Media section of our website at agios.com. Joining me today with prepared remarks are Dr. David Schenkein, our CEO; Dr. Chris Bowden, our Chief Medical Officer; and Glenn Goddard, our Senior Vice President of Finance. Scott Biller, our Chief Scientific Officer is also here today and will join 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 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 risk 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. 2014 was an outstanding year for Agios. It was a defining year backed by many significant events that occurred across our business. We presented the first clinical data from three distinct molecules from our own research platform, had strong business and clinical operation execution, and great success in hiring superb people into the company. Our culture continues to thrive and evolve and is an area of special focus for us now and into the future. And we are pleased to have closed out 2014 with a cash position of more than $467 million, thanks to the support of shareholders who participated in our December public offering, which added approximately $238 million in net proceeds. On the call today, we want to focus on our efforts towards building a long-term research driven multi-product biopharmaceutical company. In my remarks, I will review our strategy and upcoming milestones, Chris will provide a bit more detail on our clinical development programs, and Glenn will provide information on our fourth quarter and full year 2014 financials as well as our 2015 guidance. As patients, the community, investors and many others evaluate Agios, we want to focus everyone on our vision, which is a commitment to the fundamental transformation of patients’ lives through scientific leadership in the fields of cancer metabolism and the rare genetic disorders of metabolism or RGDs. I have been at Agios now for 5.5 years and I have never been more excited about our prospects for the future. You are most likely familiar with our story, but it’s worth repeating that just 6 years ago, we started with a blank piece of paper and today are advancing three distinct investigational medicines into the next stage of clinical development. You can see the progress we are making by looking at our portfolio of novel medicines. For our lead investigational medicine, AG-221, we started the first clinical trial in September 2013 in hematologic malignancies. In 2014, we showed proof-of-concept and we are now preparing to enter a global registration program in hematologic malignancies in the second half of this year. All of this on a timeline of approximately 2 years from IND. In addition, we have proof-of-concept for our second investigational medicine AG-120 and plan to start a global registration program in hematologic malignancies by early 2016, which would also be approximately 2 years from when we filed the IND. And our wholly owned investigational medicine AG-348 which targets pyruvate kinase are for the treatment of pyruvate kinase deficiency is advancing to Phase 2 in patients. Our rapid progress is driven by our precision medicine approach. The use of genetic or metabolism based biomarkers to guide patient selection. This progress is also a validation of our drug discovery platform in cancer and RGDs by targeting cellular metabolism. Dysregulated metabolism is at the core of our research. All of our investigational medicines will be initially tested in patients who are biomarker selected to more likely respond to treatment. This allows us to test proof of concept early, either positive or negative and if positive to move more quickly and efficiently through clinical development to potential approval. Last year we saw this approach play out in both of our Phase 1 trials for AG-221 and AG-120 where we selected patients for these trials on the basis of having an IDH mutation. And we were able to assess whether the drugs were hitting the target early in development by measuring 2HG. Our early results as Chris will review shortly offer a potential paradigm shift in our approach to treating AML, a deadly disease. We are pleased to see that precision medicine is being brought to the forefront of the industry. President Obama is putting a spotlight on it and recently endorsed the value of this approach in helping patients diagnose today with cancer. For us at Agios, this approach can benefit all of our relevant stakeholders and most importantly make a huge impact for patients. We are really excited for the potential this approach can offer to patients in the way we conduct our research and to help maintain our leadership position in cancer metabolism. We believe we have the most robust experience in cancer metabolism and we are the first and only company to conduct clinical trials with an IDH inhibitor for patients with an IDH mutation. We also believe that we are just at the beginning of mining the exciting new field of cancer metabolism. And in doing so, we can approach cancer treatments from a distinctly different angle than has been previously done in the past. Let me now focus my comments on what excites us about our company today and our key priorities for 2015. As I noted earlier we are building a long-term research driven multiproduct biopharmaceutical company with a clear focus first and foremost on patients. As we grow in size, we will maintain a culture that provides the environment for the discovery and development of novel therapies and higher individuals who share the drive, energy and passion that are the essence of all Agios employees today. Now turning to our key priorities for 2015, first, execute on our planned global registration programs and maintain our leadership position in cancer metabolism, in particular within the IDH field. Starting the registration program is the key 2015 milestone for us. We have strong support from our partner Celgene in advancing our cancer metabolism program and our partnership is well aligned to shape the global development and registration strategies for both AG-221 and AG-120. Chris will provide a bit more detail on these programs during his prepared remarks. Second, build out our capabilities. We have an incredibly strong research group and a growing terrific development group. We need to continue to build up the clinical development function including regulatory, clinical operations and biostatistics. We are also excited to begin to build up commercial capabilities. In addition, as you may have read in our press release today I am pleased to welcome Megan Pace and Melissa McLaughlin who have joined our leadership team and will provide valuable expertise as we build out the company. Megan, whose first day at Agios is today, has joined us as the Senior Vice President of Strategic Operations and Communications. She joins us most recently from Vertex Pharmaceuticals where she was a member of the senior management team. Prior to Vertex, I have seen firsthand her passion and commitment to patients in the community while we worked together at Genentech. Her leadership and drive will be a tremendous asset to Agios. I am equally excited to have Melissa join us as our new Vice President of Human Resources. Melissa spent some time at J&J, but what really stood out for us was her most recent experience as Global Head of HR for some of Expedia’s fastest growing business units, including hotels.com. There she led the charge to develop bigger and better organizational muscle and was a key driver in creating Expedia’s HR operating model. Her expertise in shaping high-performance cultures is crucial to maintaining our culture during the time of significant growth. Also, demonstrating our commitment to people and culture is the addition of Kaye Foster-Cheek to our Board of Directors. Kaye joined our Board in December and she has more than 25 years of experience in human resources in the pharmaceutical industry and is a recognized biotech leader. She brings tremendous guidance in corporate strategy and a passion for patients. Our third key priority is to continue to invest in research. We are really excited by the excellent progress we are making in areas of biology. All of our novel molecules are being generated from our strong internal research platform that has quite a track record led by our three investigational medicines now in the clinic. We ensure that each potential clinical program has appropriate research support in a bench to bedside back to bench approach, which includes a strong investment in next-generation molecules. Our research efforts continue to be aimed at improving the lives of patients with cancer and rare genetic disorders. These efforts are concentrated on additional advancements in cellular metabolism that are distinct from our lead investigational medicines. We expect to advance several new molecules into the clinic over the next several years from both our cancer metabolism and the RGD portfolios. We will give more details on these programs as they approach the clinic. Celgene remains an important partner with us in cancer metabolism. Since the time we signed the collaboration with Celgene in April 2010, we have advanced two molecules in the clinic. And just last month, Celgene agreed to exercise its exclusive option to license development and commercialization rights to AG-120 outside the United States. In addition, over the course of the collaboration, Celgene elected to extend the research portion three times with the final option to extend the agreement elected back in December. This gives Celgene certain rights through April 2016 to cancer metabolism drug candidates to emerge from our research. Overall, 2014 was a very exciting year in which we achieved many milestones. I would like to thank all of our employees for their dedication and hard work. As we look ahead, 2015 will also be a busy year with numerous upcoming milestones that will enable you and us to measure our progress. We first announced these milestones to you during our investor event at the ASH Conference in December. Today, we are providing more clarity on the timing of these potential milestones. Let me highlight a few that will further shape and define the product profile of our investigational medicines. The start of the registration program for AG-221 in the second half of 2015, the first solid tumor data presentation for AG-120 also in the second half, and the start of the Phase 2 study in patients for AG-348 in the first half of 2015. In summary, we entered 2015 as a more mature and advanced company. We are executing on our key priorities and look forward to keeping you informed of our progress throughout the year. 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. Chris?

Thanks, David. First, I would like to spend a few minutes reviewing the emerging profiles of our two IDH mutant inhibitors, AG-221 and AG-120 and the potential of these to treat a wide range of hematologic and solid tumor cancers. Second, I will review on a high level the rationale and approach we are planning for the design of our registration programs for these two medicines in development. And finally, I would like to give you a brief update on the progress of AG-348. In the context of each of these programs, I will review the milestones we have planned in 2015. I am proud of our efforts in meeting our clinical milestones in 2014 for AG-221, AG-120 and AG-348. Achieving these milestones was the result a tremendous effort on the part of the entire company, particularly the clinical, operational and regulatory change and our manufacturing groups. Today, for our IDH programs, they are now focused on setting up additional U.S. and international sites to enroll more patients in our ongoing Phase 1 clinical trials for AG-221 and AG-120 and preparing for a registration program. For our PKR program, we are finalizing our discussion with regulators and making progress towards initiating a Phase 2 study of AG-348 in patients with pyruvate kinase deficiency in the first half of this year. Turning first to our two cancer metabolism investigational medicines, AG-221, an IDH2 mutant inhibitor and AG-120, an IDH1 mutant inhibitor. We believe these are two of the most promising targets in cancer biology today. The data presented in 2014 at four major medical conferences showed the potential of these two investigational medicines to provide significant clinical activity in genetically identified patient with advanced hematologic malignancies that have an IDH mutation. These are cancers that have limited treatment options and the prognosis for patients is poor. In particular, most of our data in 2014 were from patients with acute myeloid leukemia where IDH mutations are found in about 15% to 22% of AML patients. AML is a devastating form of blood cancer and there have been few improvements in therapy in decades. The 5-year survival rate is dismal and estimated at 20% to 25%. Overall, these two mutations are found in a wide range of cancer that in total are estimated to affect more than 40,000 new patients in the U.S. and EU5 each year. Now to the emerging profile and plan next steps for AG-221, we are very encouraged by the Phase 1 data we presented in December at ASH for AG-221 from 73 patients with IDH2 positive advanced myelogenous leukemia, myelodysplastic syndrome or other hematologic malignancies. The data which were from the last data cut on October 1, 2014 showed a favorable safety profile and durable responses with patients on study for up to 8 months. We also saw that AG-221 as a single agent resulted in overall response rate of 56% including durable complete remissions. AG-221 worked by differentiating the cancer cells or in essence repairing them as predicted from preclinical experiments. While these data are early, we believe they validate our approach to cancer metabolism and targeting dysregulated metabolic enzymes. So where are we today with the AG-221 program, we are entering 2015 with a strong understanding of the profile of this investigational medicine. We continue to dose escalate in the Phase 1 study to explore the maximum tolerated dose. We initiated four Phase 1 expansion cohorts in October 2014 and patient accrual continues to go well. In these cohorts we are evaluating a single daily 100 milligram dose primarily in a more homogeneous patient population of relapse and/or refractory hematologic malignancies including AML. One cohort of 25 patients is the basket cohort and is enrolling patients with other IDH2 mutant positive advanced hematologic malignancies, for example, myelodysplastic syndrome. The overall safety and efficacy information that we can gather from these cohorts will be important for the design of our registration program. Starting in the middle of 2015, we expect to present new data from the AG-221 Phase 1 study in hematologic malignancies at medical conferences throughout the year. These data could include early data from the expansion cohorts as well as new data from the dose escalation phase. We also plan to share the first molecular data obtained from patients enrolled in the Phase 1 dose escalation trial. As we think about the global registration program for AG-221 in heme malignancies. We are focused on designing studies that address speed and breadth. Our goal will be to obtain a broad set of global product labels and as many patient populations as possible and our quest to make AG-221 the foundation of care for all patients with an IDH2 mutant positive hematologic cancer. As David noted if you know the right patients to treat and we believe we do, we can move quickly and with the data we have gathered for AG-221, we believe we have enough information to start a global registration program. Our milestones for AG-221 in 2015 are to initiate the global registration program in the second half of the year. We will give you more details including patient populations and appropriate endpoints as we get closer to beginning the program. We are also on track to secure commercial diagnostic partner with the expectation that a companion diagnostics will be necessary for approval. We also plan to initiate combination trials in newly diagnosed untreated AML patients in the second half of the year. So, a very busy and important time for us. At the same time, we are conducting 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. We recently initiated this study in October of last year. Similar to heme malignancies, all of these tumors have limited effective standard of care therapies. In 2015, we expect to continue the dose escalation phase for patients in this Phase 1 study. Now, to AG-120, our orally available first-in-class selective potent inhibitor of the IDH1 protein, we retained U.S. development and commercialization rights for AG-120 under our agreement with Celgene. Similar to AG-221, we are well underway in two ongoing Phase 1 clinical trials in patients with an IDH1 mutation, one in advanced hematologic malignancies and one in advanced solid tumors. We announced the first clinical data for AG-120 in 17 patients with relapsed refractory AML at the EORTC-NCI-AACR Conference in November. AG-120 is from a different chemical scaffold than AG-221. We were pleased to see similarly strong data for AG-120 in patients with hematologic malignancies with an IDH1 mutation. Specifically, initial data showed objective responses in 7 out of 14 evaluable patients, including four complete remissions with early evidence of durability with a duration of study as long as 5.5 months. AG-120 also appears to induce remission by differentiating the cancer cells. We are on track to initiate several expansion cohorts to further evaluate the safety, tolerability and clinical activity of AG-120 in heme malignancies. We expect these cohorts to begin enrolling in the first half of 2015. We are also planning to initiate a global registration program for AG-120 in heme malignancies by early 2016 that will be similar in scale and scope to the AG-221 global registration program and utilized a combination of speed and breadth. Similar to AG-221, we also plan to initiate combination trials in untreated AML in the second half of 2015. We are also exploring development of AG-120 in other IDH1 relevant populations. In March 2014, we initiated a Phase 1 dose escalation study in advanced solid tumors. That 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, this study is evaluating varying doses of AG-120 in a wide range of solid tumor types that carry an IDH1 mutation. Let me remind you that we observed similar preclinical data in both heme and solid tumor cancer models and observe that the mutation leads to a block in differentiation, which could be reversed with our molecules. We are encouraged by this preclinical finding. However, it is too early to know how this will play out in the clinic. Now, to AG-348, the novel activator of pyruvate kinase-R for the treatment of pyruvate kinase deficiency, which is a rare inherited form of hemolytic anemia. This is a serious disease with no available treatment other than supportive care. A biology of pyruvate kinase deficiency is straightforward. A mutation in the red cell pyruvate kinase gene also called PKR leads to a decrease in ATP and an increase in 2, 3-DPG, which are key biomarkers of PKR activity and primary indicators of pyruvate kinase deficiency. We designed AG-348 as small molecule to target this underlying metabolic defect. The goal is to correct the metabolic imbalance created by the pyruvate kinase mutations that lead to the destruction of red cells and potentially improve outcomes by preventing hemolysis. We have worldwide rights to AG-348. In December of last year, we announced data from 64 people who participated in the Phase 1 single ascending and multiple ascending dose escalation trials in healthy volunteer studies. These data included final SAD results in data from the first two cohorts of the multiple ascending dose study. They provide an early proof of mechanism and we are consistent with our preclinical work. This show that AG-348 was well-tolerated and caused a dose-dependent activation of the PKR pathway as evidenced by a substantial increase in ATP and decrease in 2, 3-DPG levels. This is consistent with the biomarker activity that we saw in our preclinical animal models. We completed dosing in the MAD study and plan to present final data from this clinical trial in healthy volunteers at a medical conference in mid 2015. We are progressing AG-348 into the next phase of development with the plan to have our Phase 2 study in patients with pyruvate kinase deficiency, up and running in the first half of this year. This will be a global study that will include sites and patients located in key areas of the U.S. and Europe. While the program is preparing to enter Phase 2 development, we are also working with investigators at Boston Children’s Hospital for conducting a global natural history study of pyruvate kinase deficiency to identify patients and better understand the disease and how it progresses over time. The study has enrolled approximately 100 people at more than 20 treatment centers and continues to enroll. This is encouraging and is a reflection of our disease awareness efforts for pyruvate kinase deficiency. The study will also help us to better understand the disease as well as identify patients and treatment centers for our clinical development. We look forward to the potential presentation of the first data from this study in mid 2015. In summary we are really excited about the progress that teams have made over the past year, but we recognize the challenges and are prepared for and eager to embrace the opportunities ahead. With that I will 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 into late stage clinical development. As David mentioned, we are very pleased to end 2014 with an overall cash position of approximately $467 million. Moving on to the financial results for the year ended December 31, 2014, as I just referenced our cash, cash equivalents and marketable securities as of December 31, 2014 were $467 million compared to $194 million as of December 31, 2013. The increase was driven by the addition of $332.6 million of net proceeds received from our two public offerings during the second and fourth quarters of 2014. During 2014, we also received approximately $40 million from Celgene related to the reimbursement – reimbursable cost from AG-221 program and from Celgene’s decision to extend the discovery phase of our collaboration agreement through April of 2015. These enclosed in 2014 have been offset by cash used to fund operating activities of approximately $99.5 million. For the year ended December 31, 2014, we recognized $65.4 million of collaboration revenue compared to $25.5 million in the prior year. The increase was due to the application of new accounting guidance to our collaboration agreement with Celgene as a result of the July 2014 amendment of the collaboration agreement. As a result for the period of January 1, 2014 through the amendment date, the company recognized a total of $42.7 million under the previous accounting guidance and upon the modification of the agreement. The company recognized $22.7 million in revenue subsequent to the modification date. Research and development expenses were $100.4 million for the year ended December 31, 2014 compared to $54.5 million for the full year of 2013. The increase was largely due to increased spending on the ongoing development activities for 3b programs advancing in the clinic. As a reminder, Celgene is responsible for all development costs of AG-221 and reimburses Agios for all development costs we incur for AG-221. General and administration expenses were at $19.1 million for the year ended December 31, 2014 compared to $9.9 million for the full year of 2013. This increase was largely related to increased headcount and other professional services as we strengthen our team and support our growing company operations. Taking a look at our financial guidance for 2015, we expect to end 2015 with more than $320 million of cash, cash equivalents and marketable securities. This guidance includes a $20 million payment we expect to receive from Celgene in 2015 for extending the discovery phase of our collaboration agreement for the final year through April 2016. This does not include additional program-specific milestones that we are eligible to receive. In addition, we expect this cash position to give us runway through late 2017. And with that, I will now turn the call back over to David.

Thanks, Glenn and thank you all for your time today. In closing, we expect 2015 to be highlighted by important milestones from each of our three lead investigational medicines. For AG-221, we expect to present the first data from the Phase 1 expansion cohorts in mid-2015, initiate the global registration program in heme malignancies and combination trials for frontline AML in the second half of the year. For AG-120, we expect to start heme expansion cohorts in the first half, present the first data from the Phase 1 solid tumor study, and initiate combination trials in frontline AML in the second half and prepared to initiate global registration programs in heme malignancies by early 2016. For AG-348, we are on track to start the Phase 2 trial in patients with PK deficiency, expect to present the final MAD results and first data from the natural history study in mid 2015. We look forward to keeping you updated on these events on future calls and we want to thank all the patients, their caregivers, the nurses and doctors who have participated in our clinical trials and of course all our employees and shareholders for continued support. And with that operator, we are happy to open the line for questions.

Thank you. [Operator Instructions] Our first question comes from Yatin Suneja with Cowen & Company. Your line is open.

Hi, guys. Thank you for taking my question. First one is on the AG-221 registration program, do you guys knows that you would have to show OS benefit in the registration program and are you also planning to apply for an SBA?

So, thanks for your question. This is David. So, as Chris articulated, it’s a bit too early for us to give out all the details of primary endpoint, secondary endpoints. We will give all that out as Chris and his team rolled this out later in the year. So, it’s just a little bit too early to speculate as you know both overall survival and response rate have been used as endpoints for approval in AML in the past. And it’s – we are not going to comment on our regulatory strategy at this point other than we have a very strong relationship with both regulatory agencies at this time.

Just one more question if I may. Recently, there was a nature medicine paper I think it was published last month that highlighted potential synergies between IDH inhibitor and BCL2 inhibitors in AML. Could you give us your views on that? And then could ABT-199 be one of the drugs that you could use in combination trials going forward? Thank you.

Yes, thanks for your question. As we have talked about before, we do think that as we move into combination trials, clearly, the initial combination trials need to be with standard of care chemotherapy if we are going to move into the frontline AML setting. We do think ABT-199 is an interesting agent. We saw some of the data at ASH. And certainly as our team goes through the preclinical data that was recently published in the clinical data, we will keep open mind about whether that’s a combination partner we want to explore as we think about doing novel-novel combinations.

Thank you very much.

Our next question comes from Yaron Werber with Citi. Your line is open.

Great. Thanks for taking my question. I have a couple of questions. One is just financial and I am trying to understand a little bit, the $20 million milestone in Q2, how – would you amortize that over time and I am trying to – as we sort of trying to model the revenue line, I am trying to get a sense under collaboration revenue since it’s so lumpy and we don’t have great visibility, if you can give us a little help there? And then I have a follow-up.

Hey, Yaron, this is Glenn Goddard. So – yes, so when you think about $20 million payment that will come in the middle of next year that is something that even though we are under a different kind of revenue recognition model and different elements are treated differently, that particular piece would very likely be kind of done on a proportional performance methodology, which is almost ratably as we do work under the research term through the remainder of that term, which ends in April of 2016.

Okay. So, you will – so, it’s almost to think about it over four quarters and it’s almost $5 million a quarter so?

Correct.

I think that it’s a fair way to model it.

Okay. And then do you have any sense on what data we may be able to expect at ACR and ASCO, it sounds like there was really not much on the solid tumor front?

Yes, so Yaron, this is David. So as you know from the – what we refined the guidance a little bit and as you can see that for we are not going to – as always we never commit to exactly which media we are going to present to until we are it’s upon us. But as you can see some of the data that we projected will be in the second half or mid-2015. And in particular some of the heme data for 221 and 120 will be in mid and the solid tumor data for 120 will be in the second half.

Okay, great. Thank you.

Our next question comes from Terence Flynn with Goldman Sachs. Your line is open.

Hi this is Irene in for Terence. Thanks for taking the questions. For AG-120 the Phase 1 solid tumor trial what are you looking for to make the decision to take this for into Phase 2 trial?

Yes. So it’s a good question. We are always obviously you know – as you know the primary endpoint for these first-in-human studies is safety pharmacokinetics and pharmacodynamics. And for us that’s the most important findings to help us decide how to move forward. And with each of our molecules, we have done that for 221 and we will do that for 120 is as we analyze that data we will also give you a sense of how we plan to proceed with them. So we don’t have a pre-specified certain degree of clinical activity that’s required. It really is totality of the data will help us make those decisions.

Thanks very much.

Our next question comes from Anupam Rama with JPMorgan. Your line is open.

Hey guys. Thanks for taking the question. Just a quick question on AG-348 in the ongoing natural history study in PK deficiency what have you learned or what you are hoping to learn that has helped to inform the Phase 2 trial design. And then I guess within the 100 or so patients that you have in the natural history study, is there enough of a breakdown of mild, moderate and severe patients that would help you understand what spectrum of disease to assess in Phase 2? Thanks.

Hi this is Chris Bowden here answering your question. The natural history study is a really important component of the clinical development program for this molecule because there is not as much known about the diseases we would like to. So over the course of the study and we are just starting to get some of that data in now we can understand what happens from the time patients were diagnosed and then going forward from the time when they come into the study. So aspects around transfusions, changes in hemoglobin over time what stressors might cause the disease to flare, these are all important components that we can think about as we are designing, not just designing the study but thinking about how we are going to analyze the 348 study. Once we start to get patient data who were actually using the drug. From the perspective of the spectrum as you described mild, moderate and severe, we are going to design a stage that allows us to really understand what effect the drug is having on some of those pharmacodynamic endpoints as well as there important clinical endpoints. And when we get rate to finalize and start the study we will be able to disclose that information.

Great. Thanks for taking my question.

Our next question comes from Howard Liang with Leerink. Your line is now open.

Thanks very much. First question is on the AG-120 solid tumor trial, has the – how has the enrollment for the solid tumor trial progressed compared to the liquid tumor trial?

Yes. Howard this is David. Enrollment has been fine. We never give out real specific guidance on that, but enrollment has not been an issue. We have fantastic sites that we are working with both in the U.S. and one in Europe and it’s not been an issue.

Okay. Is there any synergy so to speak in running AG-221 and AG-120 pivotal trials at the same time and in the same centers?

In the context of AML or any other indications for that matter there could be and I think it could play to the aspect of having both an IDH1 and an IDH2 inhibitor would allow a site that’s participating in a study anytime they see a patient with acute myelogenous leukemia to understand what their IDH status is and then be able to enroll them into one trial or the other. Now, that there is a number of assumptions that go with that, that is you have two trials up and running at the same time, which at least at this point in time for several of the studies on the Phase 1 side we do, but that’s one thing that has to be in place, but certainly it offers the option for a hematologist in this setting to be able to – if you can offer the option to a hematologist to be able to enroll a patient into either a trial that allows for either an IDH1 or an IDH2 mutation positive leukemia to come in. That’s a good thing.

Thanks. For the – I think you are also presenting 348 data, additional data this year, what’s the nature of the data that we haven’t seen before at ASH?

So, if you remember, Howard, this is David, at ASH, we presented the data from the single ascending dose trial and just the first two cohorts those were the only two cohorts in the MAD study that were un-blinded. So that when we present data in mid-2015, we will have un-blinded and analyzed all of the data from that MAD trial.

Okay, thank you very much.

So, that will – we have clinical data and laboratory data, pharmacodynamic data, PK data etcetera.

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

Hi, guys. Thanks for taking my question. I am just curious in terms of the AG-120 solid tumor study it looks like you are planning on enrolling about 145 patients. Is there specific number of patients that you are looking to have data on in terms of when you would present the data? I am just curious as to whether or not that is tied to the timing in terms of when we are going to see that this year?

Yes, great question. Thanks. So, first of all, let’s take a step back to the design of that study. The way that study was designed and that’s reflected in clinicaltrials.gov was always to do just like we have done with 221 and 120 on the heme side is to do a dose escalation phase to explore all the different doses and schedules. Obviously, we are looking – we have looked at both twice a day and once a day and then go into disease-specific expansion cohorts. And that from the beginning has been the plan for both the heme studies and the solid tumor studies. One of the distinctions between the solid tumor study and it does affect the timing is that unlike heme patients, solid tumors patients are evaluated in much more distinct periods of time rather than continuously with a blood draw. And importantly, I have characterized this trial a bit like Noah’s Ark, in that we are enrolling multiple tumor types that all carry an IDH mutation. And so for us we need to have enough data within the dose escalation phase within a group of tumors that it makes sense to bring to a medical conference. And that’s why we are at least at this point targeting the second half of 2015, if that changes and we have done that in the past, then we will revise our guidance and we will let you know.

Right. And are you looking for data in gliomas specifically or are you just looking to see that one specific tumor type has enough data that you can feel comfortable presenting that?

Yes. I mean, again, our bias is always to make sure we have enough data within a trial that it makes sense to bring to a medical conference. And so I think it’s fair to assume we are looking across all the tumor types and we have not articulated what are the dominant – who has been enrolled into that trial, but it’s fair to assume that there are numerous tumor types that carry this mutation. They will be dominated most likely by the tumors that carry the highest frequency, which are glioma, chondrosarcoma and cholangiocarcinoma, but you should expect the wide range of tumors that carry the mutation.

Great, thank you.

Our next question comes from Debjit Chattopadhyay with ROTH Capital Partners. Your line is now open.

Hey, good morning and thanks for taking the questions. Quickly on the IDH1 and 2 programs, given the 56% response rates that you have seen so far, is the response rate a factor of the baseline status that is the high versus low risk AML patients or prior lines of therapy or the duration of prior remission? I am just trying to understand what happens to the other 44% of the patients who don’t respond or why they don’t respond?

Yes, it’s a good question. I think it’s just too early. And as Chris articulated during the year as we present more data, you will get follow up on some of the patients in the dose escalation phase. Remember, they were at a variety of doses some of them had stable disease. We will have to see if some of those went on to respond or not and we will better understand how some of the molecular information that Chris will articulate later in the year as we present. So, it’s just a little bit too early to know. What I can tell you is that the patients who have been enrolled into these studies have seen multiple prior treatments and these are very sick AML patients across both the studies.

A question on the companion diagnostic, I believe you had been working with Foundation Medicine before, now given the strategic collaboration between Foundation and Roche, would they still be your partner or would you look for a different partner at this point?

Yes. So, two things, so first let me just disclose publicly that I am on the Board of Foundation Medicine just for full disclosure, but the relationship that they have recently crafted with Roche has no impact on our working relationship with Foundation Medicine. We have not disclosed who we will be selecting as our companion diagnostic partner. Suffice to say that we are well on track to selecting a partner well in time for the use of a companion diagnostic for approval and we will work together with Celgene and we will articulate that as we get closer.

And my last question on 348, once you have access to the natural history data, do you think there could be multiple trials in severe, moderate and mild patients and could severe patients be leveraged on the natural history study, so you basically run a single arm pivotal registration program?

It’s Chris Bowden here. The Phase 2 trial will be really important for us, because it will help us understand both the activity as well as the safety of the drug as well as the pharmacodynamic effects for the first time in patients who actually have the disease. So, depending on how that trial goes, if it went well, then a larger and more expansive clinical development program would go forward, of course with the assumption that there – we are able to accrue and we are pretty confident that we are going to be able to do that at this junction. So, yes, I think that we could see multiple trials come out, but that’s really dependent on having success in the first one and that’s why we are really looking forward to getting that up and running in the first half of this year and we eagerly await some of that initial data.

Thank you so much and good luck going forward.

That’s fine.

Our next question comes from Arlinda Lee with MLV & Company. Your line is now open.

Hi, it’s Ben Shim calling in for Arlinda. I just got a question about your partnership with Celgene, can you provide additional detail and mechanics on at what point do you or Celgene handover, takeover development responsibilities? And can you remind us what the financial milestones are associated with them? Thanks.

Yes, this is David. I will start with the first part. So, for AG-221, remember that Celgene will have primary commercial rights for 221 should it be successful and Agios will participate with both co-development and co-promotion in the United States. I think it’s fair to assume that going forward, so right now Agios is conducting all of the clinical trials with AG-221 and AG-120 which we will get to in a minute. I think going forward you will see some clinical trials set from an operations perspective will be managed by Agios and some that will be managed by Celgene. To the physician out there, it will likely be seamless. It will be a single voice of Agios and Celgene together working to develop 221. With 120, it will look a little bit differently, because for 120, Agios retains full U.S. development and commercialization rights. So, the clinical trials in the United States will all be managed by Agios and rest of world will be managed by Celgene. And then I will ask Glenn to give you a sense of the financial milestone structure.

Yes, hi. So, if you look at each program, each program is eligible to receive $120 million in milestone payments. And they break down into really three buckets. The first is a $25 million payment that can be paid as we transition into pivotal trials. The second bucket is a mixture of several payments related to regulatory and approval milestones, that bucket totals $70 million. And the last milestone is a commercial milestone of $25 million. So, again, each program is eligible to achieve $120 million of milestones. And then there are kind of specific unique milestones that we could receive over and above that stream of milestones. Does that cover that question?

Yes, that’s very helpful. Thank you very much Glenn. And just housekeeping question, can you minus what the basic share count was at to December 31?

Yes, so roughly about 37 million shares outstanding as of the end of the year.

Thank you very much.

Our next question comes from Yaron Werber with Citi. Your line is now open.

Hi, this is actually Kenon [ph] on for Yaron. I had another share count question. I was wondering if you could tell us what the share count was at the end of Q4 and just looking at this if share count went down quarter-over-quarter?

So I think part of maybe what you are looking at is if you are looking at the press release, I think what kind of gets included, so remember I think as part of the IPO process we had preferred stock prior to going public. So, the total outstanding shares were less if you are looking at just common. But then overall as of the end of the year like I just mentioned there was roughly 37 million outstanding shares of common stock.

Got it. Thank you so much

Thank you. I am showing no further questions at this time. I would like to turn the call back to David Schenkein, CEO for closing remarks.

Thank you everybody. And again I would like to thank everybody for your support for participating today and for following along with us. We expect 2015 to be as exciting as 2014 and we look forward to having you help us help as many patients as possible out there. So with that we will end the call. Thank you very much. Have a great day.

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