Thank you, Candis. Good morning.

This is Manisha Pai with Epizyme Corporate Communications, and welcome to our third quarter 2014 conference call. This morning we issued a press release with our third quarter financial results and company updates.

We also issued a news release summarizing preliminary data from the Phase 1 adult study of EPZ-5676, our DOT1L inhibitor. These preliminary data will be published in abstract forms on the website of the American Society of Hematology or ASH at 9:00 AM today.

A more complete updated data will be presented at the ASH annual meeting on December 8. As always, those press releases can also be found on our website at epizyme.com.

With me on the call today with prepared remarks are Dr. Robert Gould, our President and Chief Executive Officer, who will review our third quarter accomplishments and Dr.

Peter Ho, our Chief Development Officer, who will review progress to date on our clinical programs and expected milestones. Dr.

Gould will then summarize Epizyme’s third quarter 2014 financial results and make closing remarks. Dr.

Bob Copeland, our Chief Scientific Officer, is also here today and will join us for Q&A. Before we begin, I would like to remind you that today's discussion will include statements about the company's future expectations, plans and prospects that constitute forward-looking statements for 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 Form 10-Q filed with the SEC on August 13, 2014. 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. Now, I will turn the call over to Robert.

Thanks Manisha. Welcome everybody and thank you for joining us this morning.

2014 continues to be a productive year for Epizyme and we are making very important progress on both of our clinical programs, as well as our pipeline. I would like to begin by highlighting our two clinical development programs and the upcoming Phase 1 data readout.

We are particularly excited about the upcoming data presentation for our EZH2 inhibitor, EPZ-6438, also referred to as E7438 by our partners at Eisai. We have just completed the Phase 1 dose escalation portion of a Phase I/II trial of EPZ-6438 in patients with advanced solid tumors or B-cell lymphomas.

We plan to present these data at the late breaking abstract at the EORTC NCI AACR Meeting, also known as the Triple Meeting, on November 20. In past August, at the ASH Meeting on Lymphoma Biology, Epizyme presented early clinical observations from the first three completed dosing cohorts of [Indiscernible] in the Phase 1 portion of the EPZ-6438 study.

The four non-Hodgkin lymphoma or NHL patients enrolled in these cohorts had four entirely distinct types of NHL with respect to histology. Among these patients, we saw two confirmed partial responses, one instance of stable disease and one of progressive disease.

What was notable even in the early cohorts of this phase 1 experience is that responses were observed in a patient with refractory transformed lymphoma, which is a germinal center origin lymphoma, and also in a patient with refractory primary mediastinal B-cell lymphoma PMBCL, a subtype of diffused large B-cell lymphoma, DLBCL, that is not of germinal center origin. Further both responding patients were found to have wild-type EZH2 upon sequencing.

The early clinical observations combined with our cumulative pre-clinical experience suggest a clinical opportunity for EPZ-6438 that includes both wild-type and the EZH2 mutant B-cell lymphomas. We believe that this could significantly expand our potential patient population by as much as six-fold.

We look forward to sharing more complete updated Phase I dose escalation data in the late breaking oral presentation at the Triple Meeting in Barcelona on December 20. This will include an update on the first three cohorts as well as new data from patients in the 800 mg and 1600 mg dose cohorts.

As a reminder, we are jointly developing EPZ-6438 with Eisai who’s funding 100% of the development cost. Along with our partners at Eisai we expect to initiate the first of our Phase II study in the EPZ-6438 program during the first quarter of 2015.

This will be a multi-cohort Phase II study evaluating single agent EPZ-6438 in NHL patients both with and without EZH2 mutation. In addition to the planned NHL Phase II study, we expect to initiate two studies in INI1-deficient tumors, such as malignant rhabdoid tumor and synovial sarcoma.

The first will be a Phase I pediatric study that we anticipate initiating in the first half of 2015. The second will be a Phase II adult study which is also expected to open in 2015.

Turning to our second clinical program, this morning we reported preliminary findings from the Phase I study of our DOT1L inhibitor EPZ-5676, the first HMT inhibitor ever to be studied in a clinic. As a reminder, EPZ-5676 is a potent and selective inhibitor of the DOT1L HMT and is being developed for the treatment of acute leukemia with alterations in the MLL gene, MLL-r or partial tandem duplications within MLL-PTD.

These preliminary findings will be published online at 9:00 o'clock this morning in an abstract for the ASH annual meeting and reflect data as of the abstract cut-off on July 15, 2014. Updated data will be presented at the annual meeting in San Francisco on December 8.

Peter will discuss the abstract data in more detail, but I would like to highlight the top line preliminary results. Data in the ASH abstract show that EPZ-5676 was safe and well tolerated in the 36 patients evaluable for safety.

Adverse events were predominantly grade one or grade two in severity. Of the 28 patients who were evaluable for efficacy we observed complete responses in two MLL-r patients.

These were the same two patients from the 54 mg/m2/day cohort whose objective responses we reported in January 2014 at the trigger for a proof of concept milestone payment from our partner, Celgene. The abstract data also show biological activity in several patients who experienced resolution of cutaneous leukemia or differentiation effects.

We are very pleased with the safety and tolerability results we saw in this study. We clearly saw single agent efficacy in two patients with complete responses in this extensively pre-treated patient population and as a result we are now expanding the number of patients treated at 54 mg/m2/day.

This summer the Epizyme team published pre-clinical data in The Journal of Pharmacology and Experimental Therapeutics demonstrating strong synergy between EPZ-5676 in standard of care chemotherapy. We are therefore considering several possibilities for further development, including combination with existing standards of care.

In addition, we initiated a pediatric study evaluating EPZ-5676 in children between the ages of three months and 18 years with acute leukemia. We will present pharmacokinetic modeling from this study at ASH on December 8 and we anticipate presenting clinical results from this study in the first half of 2015.

we have also continued to invest in our pipeline of inhibitors of additional HMT target. We were pleased to announce recently our upcoming oral presentation at ASH, where along with our GSK colleagues; we will be presenting preclinical data on our first in class PRMT5 inhibitor in models of Mantle Cell Lymphoma.

PRMT5 is the most advanced of our pipeline targets beyond DOT1L and EZH2, and we expect to provide further pipeline updates in the year ahead. We also continue to expand our intellectual property estate.

We now have patents and patent applications covering composition of matter, therapeutic and diagnostic methods, combination therapy methods and pharmaceutical compositions for 13 of the 20 prioritized targets that comprise our pioneering HMT platforms. We believe that this places us in a strong position to build our company for the long-term, and accelerate our development efforts.

It further demonstrates the breadth of our leadership in the field of HMT. Over the course of this year, US Patent and Trademark Office has granted us one patent and two notices of allowance covering diagnosis and treatment of cancer with EZH2 inhibitors, as well as two notices of allowance covering inhibitors of PRMT5 and methods of cancer treatment with PRMT5 inhibitors.

Finally, we recently announced the publication of 10 patent applications covering chemical matter targeting five additional HMTs that are implicated in a variety of solid tumors in hematologic malignancies. On the hiring front, I am very pleased with the recent addition to our management team over the past few months.

We appointed Michael Shih, J.D. as Vice President, Business Development to lead our partnership strategy and execution.

In September, we also welcomed Peter Ho, M.D., Ph.D., as Chief Development Officer to oversee all of our clinical development, regulatory and translational medicine function. A pediatric hematologist oncologist by training Peter brings with him extensive experience in drug development and translational medicine, including work at the Dana-Farber Cancer Institute, the NCI and the FDA, as well as oncology leadership roles at J&J and GSK.

We are very enthusiastic about moving our clinical programs forward under his leadership. Our search for a new chief financial officer is proceeding well and we will provide additional updates as this search progresses.

Before I turn it over to Peter to walk you through more specifics on the ongoing clinical program, I would like to pause and take a moment to thank all of the patients who participated in our three Phase I studies, as well as their families and doctors and nurses who care for them. Without them our progress would not be possible.

Peter.

Thanks Robert. I am pleased to join Epizyme at such an exciting time in the company’s evolution and to be part of the clinical progress to come.

I will start today by discussing the EPZ-5676 results from the ASH abstract. As a reminder, we will only be discussing data within the abstract or data we have previously disclosed publicly.

Full data will be presented at the ASH meeting this December. And by way of background on this study, a Phase I clinical trial of EPZ-5676 is a open-label, multi-centered trial that has two stages.

The first involves dose escalation in adult patients with advanced haematologic malignancies, including but not limited to MLL-r patients. The second is an expansion stage that is enrolling only MLL-r and MLL-PTD patients.

The dose escalation cohorts range from 12 mg/m2/day to 90 mg/m2/day and the dose expansion was at 90 mg/m2/day Study objectives included safety and tolerability, dose identification, pharmacokinetics, pharmacodynamics, and early evidence of anti-leukemic activity. As of the date of cut off for the ASH abstract, 36 patients were evaluable for safety having received at least one dose of EPZ-5676 by continuous intravenous infusion.

31 of these patients had acute myeloid leukemia, including 21 MLL-r and 5 MLL-PTD patients. Four patients had acute lymphocytic leukemia, including three MLL-r patients and one had a myeloproliferative disorder.

The median age for enrollment for 53 years and the median number of prior systemic therapies was two. 14 patients had a prior allogeneic stem cell transplant, reflecting the extensive pre-treatment in these patients.

EPZ-5676 was well tolerated and adverse events were largely grade one or grade two. Adverse events assessed by investigators to be drug related or leukocytosis, nausea, hypomagnesemia and PR prolongation without associated QTc changes.

Two patients discontinued treatment due to adverse events that were potentially study related and no deaths were attributed to study drug treatment. 28 patients were evaluable for efficacy, 23 of them had MLL-r or MLL-PTD.

Among those 23 patients one MLL-r patient achieved a morphologic complete response and one MLL-r patient achieve a cytogenetic response. Several patients experienced resolution of cutaneous leukemia or a treatment related increase in neutrophils and/or monocytes consistent with a differentiation effect.

The identification of the MLL-r by split signal FISH in mature neutrophils suggest a differentiation effect on the leukemic clone. Pharmacokinetic exposures were dose proportional, and steady state plasma concentrations were reached on the first day of dosing.

The preliminary pharmacodynamic data show reduced histone H3K79 methylation from baseline in marrow and in peripheral blood mononuclear cells after 15 days of treatment at doses above 36 mg/m2/day. H3K79 rebounded towards baseline levels by day 28 in patients who received treatment for 21 of 28 days.

However, among patients who received treatment for the full 28 of 28 days, methyl-mark inhibition was maintained throughout the treatment cycle. Overall, we are pleased with the safety profile demonstrated by EPZ-5676 and given the finding of two complete responses in the 54 mg/m2/day cohort we are continuing to enroll patients in this Phase I study at that dose.

As a molecularly targeted enzyme inhibitor for patients with a genetically defined malignancy, the optimal dose for EPZ-5676 need not be at the MTD as would be the case for conventional cytotoxic agents. And also as we consider the possible options for further development of EPZ-5676 in our adult acute leukemia we are evaluating in preclinical studies combination regimens with various standards of care, and we will update you in the future when we have more information to share.

We also have a proof of concept study ongoing for EPZ-5676 in a third genetically defined acute leukemia pediatric MLL-r. The dose escalation stage of this Phase I study in pediatric patients with MLL-r leukemia is ongoing and currently enrolling patients in the US.

The abstract for the PK modeling for this study will be published today and we will be presenting the full model at ASH next month. As in the case with our adult study, we plan to carefully evaluate whether the optimal dose to progress into Phase II is at or below an MTD.

And we expect to report initial clinical findings from this study in the first half of 2015. Finally in October we terminated our agreement with Abbott, discontinuing development of a proposed companion diagnostic for use with EPZ-5676.

Based on dialogue with the FDA, we believe that the existing standard of care molecular testing used at the time of diagnosis will be acceptable to support characterization of relapse of refractory MLL-r leukemia patients in our clinical trial rather than requiring the companion diagnostic test previously under development with Abbott. Now turning to EPZ-6438, I share Robert’s excitement about the progress we’re making on this program.

The primary objective of this Phase I dose escalation trial was to determine the recommended Phase II dose. An additional objective of this clinical trial was to assess safety, tolerability and early evidence of activity for EPZ-6438.

At the Triple Meeting in late breaking oral presentation we will be providing updates on the 100, 200, 400 mg bid oral dosing cohorts, as well as data from the 800 and 1600 mg cohorts. This will include an update on the PMBCL patient who was reported as an objective responder in the August presentation, and who was still on study at that time.

As we look forward to initiating the first of our two – of our Phase II studies for this program in the first quarter of next year, we plan to evaluate EPZ-6438 in patients with DLBCL and follicular lymphoma, including patients with and without EZH2 in patients, as well as patients with non-germinal center NHL, including PMBCL. We are excited to study EPZ-6438 in this expanded NHL population in Phase II.

We are very pleased with the progress of the NHL program to date and look forward to sharing the updated Phase I data in two weeks. We also expect to initiate two proofs of concept studies in 2015, evaluating EPZ-6438 in patients with INI1-deficient tumors, following a planned IND filing this quarter.

One will be a Phase I study in pediatric INI1-deficient tumors, and the other will be a Phase II study in adults INI1-deficient tumors. Among the INI1-deficient tumors is a type of malignant rhabdoid tumor or MRT.

Characterized by a gene alteration that misregulates EZH2 activity, MRT typically affects infants and young children and currently the only forms of treatment are intensive chemotherapy and radiation. Even after multi-agent chemotherapy the survival rates for children less than three years of diagnosis is less than 10%.

There is a clear and urgent unmet medical need for these patients, and we are working diligently to initiate this proof of concept study. In summary, we are excited about the clinical momentum and look forward to building significantly on this progress as we move into 2015.

Robert will now walk you through the financial and business performance for the quarter.

Thanks Peter. I will begin with our current and forecasted end of year cash position.

We began 2014 with $157.2 in cash, cash equivalents and accounts receivables and ended the third quarter of 2014 with $213.8 million. This position reflects our successful follow-on offering in February 2014, with $101 million in net proceeds and collaborative non-equity of $20 million in the nine months ended September 30, 2014.

We continue to expect to end 2014 with more than $170 million in cash and cash equivalents, and anticipate that the cash, cash equivalents and research funding under our collaboration will fund the company through at least mid-2016, prior to including any potential future milestone payments. Turning to our first nine-month results, collaboration revenue for the nine months ended September 30, 2014 was $31.1 million compared to $32.2 million for the same period in 2013.

Our collaborations including our retained US rights are important drivers of our strategy to become a commercial oncology company. To-date, we have earned approximately $189 million in non-equity funding from our therapeutic collaborations with Celgene, Eisai and GSK and we expect our collaborations to continue to be important sources of non-equity funding for us.

Our next potential major milestones include $10 million from Eisai for an EPZ-6438 Phase 2 initiation. Research and development expenses have increased largely driven by the expansion of our product platform and the advancement of our 5676 clinical trial and related DOT1L programs.

Expenses were $55.1 million for the nine months ended September 30, 2014 compared to $41.9 million in the same period in 2013. We anticipate research and development expenses in 2014 to be approximately $75 million.

Epizyme continued to execute on our strategy of creating personalized therapeutics for patients with genetically defined cancers. We are very excited by our recent advancement; particularly our clinical progress and we remain well-positioned to deliver on our goals.

I will wrap up here by thanking all of our employees for their innovation, execution and dedication in helping us advance towards our goal of building value for shareholders by bringing transformative new therapies to patients. We will now open the call up to Q&A.

Candis?

Thank you for taking the question. I was just wondering if you could help us understand, I think everybody recognizes that maybe the MTD may not be the optimal dose, but that is typically because of the tox.

If you have substantial efficacy, can you help us understand why the 80 milligrams of the higher dose of your drug for DOT1L may have a differential effect on what the core goal is which is methylation hitting the methylation of the target versus the lower dose. Is there some kind of self inhibitory kind of effect as you go higher because it seems like you said you have methylation, are you hitting the methylation at with a continuous dosing with all dose cohorts?

So can you just help us understand why the higher dose may have less efficacy than the 54?

Thanks Jonathan. Yes, I think there is a couple of potential hypothesis.

One is in the field of epigenetic and depending on the target various families of gene expression can get induced and so among the possibilities are that the higher doses were actually effecting the gene expression patterns that is counteracting the effect that we are seeing at what appears to be effective dose based on the two complete responses that we saw 54 milligrams per meter square plus the evidence in the continuous leukemia patients and so that's one possibility that we are exploring that is there is a bell shaped curve if you will or differential effect of higher doses on gene expression and then there is at the effective doses. The other possibility is that 5676 has as you say has self inhibitory effect either on its uptake into the cellular environment or on other gene expression.

And we are exploring both of those possibilities at this time. Nonetheless we do want to explore further activity or the activity that we saw 54 milligrams per meter squared and parallel with those preclinical experimentation.

Great and then I mean with these findings is this something that could theoretically also apply to the EZH2 program and are you going to kind of maybe alter the approach with the remaining dose escalation to see if you capture similar observations in that trial?

Yes, we have completed the dose escalation with 6438 that is the 100/200/400/800 and 1600 milligram doses and as you will present in the November 28 at the triple meeting and in anticipation of initiating our phase II study early in 2015 we are confident that we will be able to select the phase II dose from that dose ranging study. In the 5676 data we saw saturation of the inhibition of the methyl mark at the 54 milligram per meter square dose.

So, we believe again that that’s the rational for extending our experience at that dose. Similarly with 6438, with the data that we have shown today, we are seeing activity at the 100/200 and 400 milligram doses and we will be presenting data at the 800 and 1600 milligram doses.

That will provide insight in the doses that we will be selecting for our phase II.

Great. I have additional questions but I will get back in the queue.

Thank you.

Thank you.

Hi guys thank you for taking my questions. First question is on 5676, can you tell us how many patients have you currently treated at the 54 mg dose and then it looks like you have not achieved or you have not establish an MTD and there it doesn’t seem to be any DOT.

So, will you pick the 54 mg into the phase – will you consider that as the phase II dose, thank you?

Right. Well, thank you very much.

So the full details of course of the study will be presented at ASH and this was – this is a standard 3+3 dose escalation study with expansion at the doses that we feel are to be explored and so at the earlier doses again it's a standard 3+3 design. But now as we have discussed we will be expending at the 54.

Okay. Thanks.

Hey guys. I wanted to maybe pick up where Jonathan left off.

I am just wondering at doses above 54 mg meter square can you talk about what first of all other than differentiation effects, what other effects we are seeing in differentiation effects of biologic effect but that may not have any clinical relevance whatsoever so I would think that – where the action is at number one. Number two can you also talk about time of follow-up or average time on therapy because I am just wondering if these patients have had adequate period of time on drug in order to see some kind of benefit from 3676?

Sure Mike. Thanks for the question.

So with respect to chemotherapy and duration that data will be presented at the time of ASH in December. We are not to be going outside the balance of the abstract now.

But that data will be available. With respect to our interest in the 54 milligrams per meter square dose, of course it relates to the two complete remissions that have been seen in those patients which clearly we feel represents biological activity that is of clinical relevance and in addition, the differentiation effects you mentioned as well as resolution of senior peers that has – all come into play in terms of how we view both the biological activity and the potential clinical activity as well.

Okay. If I could maybe follow-up, I am just wondering if maybe introduce the comment made by Robert in the answer to the previous question about the methyl mark, I am just wondering if do we need additional set of pharmacodynamic markers to get a better picture on what's happening here or do you feel that 54 you have got what you need as far as hitting the methyl mark, but yet not inducing these other changes and I don't know if you can be more specific about those other changes and how you are measuring and whether we will see that dotted ash?

Hi Mike, this is Bob Copeland. Thanks for your question.

So with respect to the pharmacodynamic biomarkers, we been using the H3K39 methyl mark as measure of the ability of the compound to get into tissue and to have bio-chemical effect and as I have reiterated at multiple meetings, we view that as a semi quantitative read out. We are not using that in any way to define a specific level of enzyme inhibition that would translate into a specific kind of typical effect.

That said, at this point I think our clinical experience allows us to continue to go forward driving on the basis of patient response as the key read out.

Okay. I will get back in the queue.

Thank you. So on 6438, if anyway you talk through any of the side effects you are seeing on how they have chosen from the last day to release and then of biomarkers or diagnostics you have been looking for to select?

Thanks Peter. So, in terms of the side effect profile we continue to be really encouraged by the side effect profile that we are seeing and on November 28 when we have the oral presentation at the triple meeting, we will be showing you some of that – we will be showing you all of that data that we have.

But really we continue to be really encouraged by that side effect profile. In terms of the biomarkers, particularly for the biomarkers for the extended phase II study that we are talking about, we’ll rely on two different sources of biomarkers.

One of the biomarkers that determine what’s called the (inaudible) or COO for short but that (inaudible) enables one to not only obviously identify the NHL patients by standard diagnostics but also divides patients into the germen center sub types and the non germen of center sub types and that established diagnostic procedures to make that distinction. So, we will us that for the initial division of the NHL patients into the germinal center or non germinal center population.

Then furthermore, in dividing between the wild type and mutant patient populations within the germinal center patient we actually have couple of approaches going on there. That is a fairly standard PCR based diagnostic and a number of lymphoma centers have local centers that are able and capable and in fact are using PCR lab developed test locally to characterize those patients as either having mutant or wild type cell populations and in addition I will remind you that we are developing a diagnostic in collaboration with our diagnostic partner Rosh molecular again a PCR based diagnostic to identify patients with non-wild type EZH2.

So it's going to be a combination of PCR based for the EZH2 and (inaudible) and algorithms for the initial separation of the patients.

Thank you and just again on 6438, two phase two trials you are being initiating which you think -- the data fastest on NHL subset?

So just – we are actually initiating three trials. So in the INI 1 population we will be initiating a pediatric trial first and then we will be initiating an adult trial following that.

The INI 1 deficiency tumor present themselves slightly differently than the pediatric population for it tends to be dominantly predominately malignant tumor MRT or related tumor ATRT where the adult population, it tends to be more of a soft tissue sarcoma like synovial sarcoma, so those will be two separate trials and then we will have the larger NHL trial that we have talked about. The speed and time to registration is really going to be determined by the level of activity and efficacy that we see in those various populations.

And so until we start to collect that data in a larger population it's a little bit hard to predict which of those trials will proceed the quickest.

Right. Thank you so much.

Thanks for taking the question. A question really thinking about the future development of both of these agents 3676 and 6438 were there any particular combination that you think might be promising in terms of looking at reducing count initially and then taking care of the rest of the glass essentially with the 3676 compound and 6438 are there anything that are you are seeing in preclinical studies and then also any way to think about maybe speeding up the clinical program or initiating the fast as possible clinical program with the combination?

Thanks.

Sure. Thanks for the question.

So I will take them in sequence. For 3676 we have been exploring pre-clinically as has been described combinations with both standard care agents as well as the noble agent in this arena and so we are excited by the results that have been obtained and will be published soon.

And certainly in this area as we know the standard of care for AML includes agents such as (inaudible) and then in the relapse refractory setting, DNA hypo methylators like -- so those are things that were interested in exploring based on both preclinical data and as well as clinical opportunities. For 6438, what has been published and described has been synergy with the various elements of chemotherapy and we are particularly excited by the synergies seen with steroids in the case of what we have looked at already Prednisilone as well as the Dexamethasone of course those are key components of the chop regiment.

So I think those offer exciting avenues for combination development.

And if I could just follow-up quickly is there particular scientific rational for hypomethylator for 5676 and then thinking of the clinical development is there something obvious here like or more obvious like a clinical trial program or something where you use standard of care and then your agent to -- who is response and then enrich that the cohort kind of pickle or design or anything like that? That you’re thinking about?

Yes. That's truly two part question.

I will take the first part. We have seen very strong synergy with both (inaudible) as well as with hypomethylating agents and I think that in the case of -- while there is less of a clear molecular hypothesis we have noted that both MLC and 5676 lead to differentiation effects and what maybe happening this is a little bit speculative for what maybe happening is that we the synergy is synergy of driving differentiation effects.

In the case of the hypomethylating agents, obviously there is well documented interplay between DNA methylation and histal-methylation and so by having agents that block is specific histal methylation site together with agent that broadly block DNA methylation, you are having synergy at the level of the transcriptional control due to chromate remodeling.

Okay and let me follow up on the second part of your question regarding the clinical development in combination. Two areas, basically in design and pick the winner, certainly with respect to pick the winner type design so those are one that we are actively considering.

In order to arrive at what we feel would be the most optimal combination with the most optimal doses of each of the components of the combination so absolutely. With respect to basin design certainly they have been used in base one studies and starting off on a combination we will certainly want to first determine the doses of the drugs used in the combination and for that base-in designs are a little less optimal for that.

I think the good news there is that based on the safety profile that we have observed thus far and will be reported out in much greater detail at the triple meeting and ASH, both 5676 and 6438 have safety profiles which will allow them which we hope will allow them to combine well with other agents be that standard care of noble so my suspicion is that more complex statistical designs will not be necessary as we move forward because of the favorable safety that we have seen thus far for both agents.

Okay great. Understood.

Thanks.

Thanks for taking the question and follow-ups. So I guess the additional questions I would ask is one was there any indications of this kind of U shaped in the preclinical models and then the second part would be given that methyl marks certainly is an important biomarker given the fact that there could be U-shaped curve if you go to higher doses are there other biomarkers or things you could measure to figure out the second question of when it's too high?

Thanks for the question Jonathan. This is Bob Copeland.

What we saw in overall preclinical models both in (inaudible) we are pretty standard dose response so we didn’t see any evidence of the U or bell shaped dose response and the empirical data in the clinic is that we saw the greatest responses at 54 milligrams per meter square whether that indicates the bell shaped curve or not, it is clear at this point that is one hypothesis. So I wouldn't put too much credence on that descriptor right now.

The second part of your question are there things that we could look at beyond the methyl mark, there are specific transcriptional effects that would be expected to derive from inhibiting H3K27 diamethyl in the context of MLOR and we are looking broadly at different data but there is not a specific biomarker that I can point you to today.

And so what you guys mentioned earlier about observing certain things in the patients to kind of understand if there is kind of up regulation of other genes or gene families, is that something you can do with existing samples that you have from patients from this trial or is that something you would have to do prospectively in the follow-up trial?

Now fortunately we have material from the current phase one dose escalation that we can use for that purpose.

Great. Thank you so much.

Thank you everyone for joining us this morning. As a final note I would like to mention that in our ongoing efforts to keep our investors up-to-date on our science and our clinical programs, we will be hosting events at both EORTC in Barcelona and ASH in San Francisco and we hope to see you either or both cities.

Thank you.