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Verastem, Inc. (NASDAQ:VSTM)

Q4 2013 Earnings Conference Call

March 6, 2014 08:00 AM ET

Executives

Christoph Westphal - Executive Chairman

Robert Forrester - President and CEO

Joanna Horobin - Chief Medical Officer

Jack Green - CFO

Brian Sullivan - Director, Corporate Development

Analysts

Andrew Peters - UBS

Biren Amin - Jefferies

Richard Goss - Leerink Partners

Michael King - JMP Securities

Mara Goldstein - Cantor Fitzgerald

Brett Holley - Guggenheim Securities

Peter Lawson - Mizuho Securities USA

Operator

Thank you for holding and welcome to the Verastem Year-end 2013 Investor Conference Call on March 6, 2014. At this time, all participants are in a listen-only mode. There will be a question-and-answer session to follow. Please be advised that this call is being recorded at the Company’s request and will be available on the Company's website for a period of two weeks from today.

At this time, I’d like to introduce Mr. Brian Sullivan, Director, Corporate Development of Verastem. Please go ahead sir.

Brian Sullivan

Welcome and thank you for joining us to discuss Verastem's financial results and corporate highlights for the year-ending on December 31, 2013. My name is Brian Sullivan. I am Director of Corporate Development and I am joined today by Dr. Christoph Westphal, our Executive Chairman, Mr. Robert Forrester, our President and Chief Executive Officer, Dr. Joanna Horobin, our Chief Medical Officer and Mr. Jack Green, our Chief Financial Officer.

I hope you have had the opportunity to review the year-end results press release we issued earlier this morning. Before moving into discussion of the year-end results, please note that in this call, we will be making remarks about our strategy, future operations, future financial position, future expectations and plans and prospects for our Company that constitute forward-looking statements within the meaning of the Safe Harbor provisions of Section 21-E of the Securities Exchange Act of 1934.

All forward looking statements are subject to risks and uncertainties. We refer you to the risk factors section of the annual report on Form 10-K for discussion of important factors that could cause actual results to differ materially from these forward-looking statements.

We caution listeners not to place undue reliance on any forward-looking statement as there are no assurances that the matters contained in such statements will be achieved. In addition, these forward-looking statements represent our views only as of today. Subsequent events and developments may cause our views to change. Although we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so.

With that said, Dr. Westphal will make some summary comments on the Company's activities; Mr. Forrester will provide an overview of accomplishments for 2013 and discuss upcoming plans. Dr. Horobin will discuss recent clinical developments and Mr. Green will discuss the Company’s financial results for the year. Following some closing remarks we will then conclude today’s call with a question-and-answer session.

Please go ahead, Christoph.

Christoph Westphal

Thank you, Brian. My name is Christoph Westphal and I’m the Executive Chair of Verastem. In 2013 we made significant progress on our mission to provide new treatment options to cancer patients. We believe we’ve the opportunity to make a significant difference in many patients’ lives by specifically killing cancer stem cells.

As many of you know, patients undergoing cancer treatments often become resistant to standard therapies, which results in disease progression. At Verastem, we believe this is due to the presence of cancer stem cells and tumors. Cancer stem cells can resist chemotherapy and have the ability to seed new tumors, leading to disease recurrence following treatment.

Building on the research of our scientific founder’s professors Bob Weinberg and Eric Lander of the Whitehead and Broad Institute at MIT and Harvard, we’ve identified and are now clinically developing drugs that are designed to kill these cancer stem cells to achieve a more durable clinical response.

2013 was a year of strong clinical execution. As promised, we successfully initiated several clinical trials for our compounds targeting cancer stem cells. Looking ahead, we’re planning for multiple data readouts this year, the first of which occurred yesterday in Japan.

With that, I’ll turn the call over to our Chief Executive Officer, Robert Forrester to provide a more detailed overview of our corporate initiatives and accomplishments. Robert?

Robert Forrester

Thank you, Christoph. Good morning, everybody. Thanks for joining the call. In 2013, we made significant progress towards bringing new treatment options for cancer patients. We achieved numerous critical regulatory and clinical milestones and we now have three product candidates in various stage of clinical development including the registration-directed COMMAND study for patients with mesothelioma.

These small molecule compounds 6063, 4718, and 5584 have all demonstrated activity in killing cancer stem cells. Our most advanced therapeutic program is the focal adhesion kinase program where we’ve two small molecule inhibitors 6063 and 4718 in clinical development.

In September last year, we initiated COMMAND which is a registration-directed study of 6063 in patients with mesothelioma, a highly aggressive form of lung cancer with a high percentage of cancer stem cells. Unfortunately the incident mesothelioma continues to rise worldwide and will post significant health risk for years to come. There is only one approved treatment Lilly’s ALIMTA, which is used as first-line therapy in combination with cisplatin.

Mesothelioma is an orphan disease where we maybe able to rapidly deliver a new treatment option to patients. Yesterday we reported a successful data from our Phase 1 study of 6063, in Japanese subjects. We went from conception to our first patient on trial in less than five months.

We now have reported data only six months later. We achieve this fast timeline due to the efforts of our team and our collaborators in Japan. It does of course rose my expectations for all future trials and looking ahead. Ms. Joanna, who is now smiling and so I think probably reminds me of the no good deed goes unpunished.

Strategically this trial is important to support our application to Japan’s pharmaceuticals and medical devices agency for the potential initiation of additional COMMAND clinical sites in Japan. If approved, we currently anticipate adding these sites in the second half of 2014. Our goal is to parallel development of 6063 mesothelioma in many countries worldwide, including the U.S., Europe and Japan.

To achieve our mission of developing new treatment options for patients by being leaders in the cancer stem cell field we have assembled an extraordinary team of people around the world. We recently appointed Dr. Jose Baselga, as Senior Medical Advisor. Jose is Physician-in-Chief at Memorial Sloan-Kettering Cancer Center and is one of the most innovative translational researchers in oncology.

We also recently extended our research collaboration with Eisai to generate novel inhibitors of Wnt/beta-Catenin signaling. 2013 was an incredibly productive year for us. Thanks to the extraordinary efforts by our team.

Our focus for 2014 will continue to be on clinical execution for each of our product candidates. It is our goal to change the way cancer is treated to deliver a more durable clinical response of patients.

Now I’d like to turn the call over to one of our wonderful team member, our Chief Medical Officer, Dr. Joanna Horobin to provide more detail around our ongoing clinical programs.

Joanna Horobin

Thank you, Robert, and good morning, everybody. 2013 was indeed a very busy year. We initiated clinical trials in multiple indication and multiple geographies and we’re expecting several data readouts from these trials in 2014. As Robert mentioned, the COMMAND study in mesothelioma is now well underway with our lead FAK inhibitor VS-6063.

COMMAND is expected to enroll approximately 350 to 400 patients at clinical sites in 11 countries including the U.S., the U.K., Australia, Canada, South Africa, New Zealand and countries in Mainland Europe and of course as you just heard we hope to be able to add Japan to that list as well.

The COMMAND study is enrolling patients immediately following first-line therapy with Alimta plus platinum. Currently there are no approved therapeutic options following first-line treatment. So patients essentially wait with no further therapy until their disease progresses. We hope to prolong the disease pre-period for these patients following that front line therapy as well as potentially the period of overall survival.

COMMAND is a double blind placebo controlled trial that incorporates the opportunity to enrich for patients with tumors that are low in the biomarker, Merlin. Researchers demonstrated that FAK inhibitors such as VS-6063 have increased activity in tumors with low Merlin level.

The COMMAND study therefore stratifies patients according to the Merlin status of that tumors. The design of the study also incorporates an interim analysis which may result in the selection of patients with Merlin low tumors as the primary patient population. So at the time of the interim analysis based on the absorbed effect on progression free survival the independent data monitoring committee will recommend whether the accrual should continue with either old patient that is with both Merlin low and high tumors or continue with patients with Merlin low tumors only.

If the trial continued with patients with Merlin low tumors only, the sample size will be re-estimated and this is to ensure that there will be adequate power for the primary analysis of progression free survival.

Now while the exact timing of the interim analysis is of course dependent on enrollment and the response to treatment, we’re currently expecting it to occur approximately in mid 2015. And we will give an update on our projections for this R&D date later this year in July -- on July 10th, in New York.

Prior to commencing COMMAND we met with regulatory agencies to discuss our plans for 6063 in mesothelioma. These interactions were very collaborative and they all agree that there is a large unmet medical need in this disease. Based on these discussions, we elected to choose the co-primary endpoints of both overall survival and progression free survival. But we were encouraged to seek accelerated approval on the PFS outcome if the data are supportive of that.

6063 has received orphan drug designation in both the U.S and Europe for the use of -- for the use in treatment of mesothelioma and there is also designation is designed to help us encourage development of drugs, which may provide significant benefit to patients suffering from such rare diseases.

Now I’d like to discuss the results of our Phase 1 study of 6063 in Japanese subjects, which were announced yesterday and presented here at the Targeted Anticancer Therapies Conference, in Washington DC. This Phase 1 study which enrolled nine patients is an open-label dose escalation trial, designed to assess the safety and pharmacokinetics of single agent 6063 in Japanese subjects. The study results demonstrated that 6063 was well tolerated at all dose levels. There were no serious adverse events or dose limiting toxicity.

Pharmacokinetic results from the recommended Phase 2 dose of 400 milligrams BID which is the dose being used in all of our other studies of 6063 were consistent with previously reported data in non-Japanese subjects. Side effects were consistent with previously reported results from the U.S Phase 1 trial.

The Phase 1 trial is still ongoing with three patients continuing on study drug, including actually one patient who has mesothelioma and according to the investigator this patient with mesothelioma is currently in cycle seven has been on study therefore for approximately 20 weeks and has disease stabilization and improvement in symptoms. Recall in the placebo-controlled Phase 3 trial of vorinostat in a patient population with recurrent mesothelioma.

The reported medium time to progression was just six weeks whereas in the Phase 1 study as the GSK FAK inhibitor in a similar patient population, investigators reported a medium time to progression of 18 weeks. So positive outcome of this Phase 1 trial supports our application to the Japanese PMDA for the initiation of COMMAND clinical sites in Japan during the second half of 2014.

6063 is also being evaluated in the Phase 2 trial in Kras-mutated non-small cell lung cancer. Now Kras-mutated non-small cell lung cancer is a highly aggressive disease for which there is no specific targeted therapy. Patients with Kras-mutated tumors typically progressed extremely rapidly and derive limited benefits from chemotherapy.

Our collaborators at University of Texas Southwestern generated intriguing preclinical data demonstrating that tumors containing a mutation of the Kras-gene along with an accompanying secondary loss of function either through a deletion or mutation in either p16 or p53 or particularly sensitive to FAK inhibition. So our Phase 2 study is designed to test the hypothesis, the tumors with mutations in Kras and the loss of function of p53 or p16 are most sensitive to FAK inhibitor treatment.

In the study there are four arms. The first arm includes patients with non-small cell lung cancer and a Kras-mutation only. The second and third arm includes patients with non-small cell lung cancer with tumor has a Kras-mutation and loss of function in either p16 or p53 respectively. And then the fourth arm includes patients with non-small cell lung cancer tumors containing a Kras-mutation and loss of function in both p16 and p53. The trial is currently accruing in patients at nine sites in the U.S and is expected to enroll up to 44 patients, potentially 11 per arm in the first stage of this Simon two-stage trial design.

I do think it’s important to say that this trial has a very high hurdle for success due to the aggressive nature of this disease. However, if we see a signal of activity in any of the arms it would be tremendous first for the patients and would also provide a clearly defined development cost forward in this indication. The trial is also important for overall development of 6063 because it will add to our safety base -- database for any potential NDA filing based on the results of the COMMAND study in mesothelioma. We expect to report interim results for this Phase 2 study in lung cancer in the second half of 2014.

In 2013 we also reported the successful completion of the dose escalation portion of a Phase 1 study evaluating 6063 in combination with full dose weekly paclitaxel in patients with ovarian cancer. The dose escalation reach the anticipated dose of 400 milligram BID in combination with weekly paclitaxel without any dose limiting toxicities. In total six patients were treated in the dose escalation portion of the trial and we saw encouraging signs of clinical activity, including a patient with a complete response as we’ve previously reported. This patient was on study drug for a total of 37 weeks.

The Phase 1b expansion phase of this study is now fully approved and we plan to report preliminary data from these patients in the second quarter of this year. The primary goal of this trial is to provide the necessary safety information for us to expand into additional tumor types in combination with paclitaxel. Paclitaxel is a commonly used agent in many solid tumors where cancer stem cells may play a role in disease progression.

We believe the combination of a cancer stem cell inhibitor with existing therapies maybe a more effective treatment than just existing therapy on its own as we will be targeting both the cancer stem cells and the bulk tumor cells.

Our second FAK inhibitor VS-4718 is currently being studied in the Phase 1 open-label, multi-center, dose escalation trial that is designed to assess the safety pharmacokinetics, pharmacodynamics and look for initial evidence of clinical activities in patients with advanced solid tumors. The results of this study should give us the necessary information to determine the future course of clinical development for this drug candidate.

We currently anticipate giving an interim update regarding this study in the latter part of 2014. In addition to our FAK inhibitors we are also developing VS-5584, a dual PI3K and mTOR1, 2 inhibitor. In 2013 we presented preclinical research at the AACR, NCI, EORTC, Molecular Target Meeting on 5584s ability to preferentially target cancer stem cells.

The data demonstrated VS-5584 has relative equipotency against all four human class I PI3K isoforms and both the mTOR1 and mTOR2 complexes of the mTOR kinase. 5584 decreased cancer stem cells across multiple in vitro and in vivo cancer models including triple negative breast cancer, small cell lung cancer and ovarian cancer. These results were significant because standard of care treatments like chemotherapy increase the proportion of cancer stem cells which can lead to treatment with (indiscernible).

So in late 2013 we initiated a Phase 1 trial evaluating VS-5584, an already available compound in patients with advanced cancer. This Phase 1 open-label dose escalation and schedule finding study is designed to assess the safety pharmacokinetics, pharmacodynamics and the initial clinical activity of single agent VS-5584 and we anticipate being able to provide an interim update for this study in the latter part of 2014.

I will now hand over to our Chief financial Officer, Jack Green, to provide an overview of the year-end 2013 financial results.

Jack Green

Thank you, Joanna, and good morning, everyone. I'll recap the financials announced today beginning with our cash position. As of December 31, 2013 Verastem had cash, cash equivalents, and investments of $123.7 million as compared to $91.5 million on December 31, 2012.

Net loss for the year -- year ended December 31, 2013 was $41.2 million, as compared to $32 million for the year ended December 31, 2012. Net loss for 2013 includes non-stock-based compensation expense of $10.4 million as compared to $7.4 million for the year ended December 31, 2012.

Research and development expense for the year ended December 31, 2013 was $25.9 million as compared to $21.7 million for the same period -- same prior year period. General and administrative expense for the year ended December 31, 2013 was $15.4 million as compared to $10.5 million for the same prior year period.

In summary, we are well capitalized and have the resources and momentum to execute on our corporate objectives. Based on our current operating plan, we believe we have sufficient cash to fund the development of our programs and operations into the first half of 2016.

Now, I'll turn the call back over to Robert, for an overview of our upcoming milestones and closing remarks.

Robert Forrester

Thank you, Jack. So, as you can see 2013 was an important year for Verastem. There continues to be strong support for and growing interest in targeting cancer stem cells. So looking ahead to 2014, we believe we have the product candidates, the capital and team in place to execute on our goals. In particular we are focused on achieving the following clinical milestones this year.

First, considering the clinical execution of the COMMAND study. We will update the projected timing of the interim analysis at our R&D Day on July 10, in New York City at 12:30 p.m. Eastern Time at the NASDAQ MarketSite Center in Times Square. I do know people will join us. We are hopefully going to be able to ring the bell at the end of the day; it will be a fun day as well as a good update from the Company.

Secondly, assuming approval from the Japanese authorities, we will hopefully initiate the COMMAND study centers in Japan in the second half of 2014. Third, we were announcing preliminary data from the Phase 1/1b trial of 6063 in combination with weekly paclitaxel inpatients with ovarian cancer during the second quarter of 2014.

Fourth reporting preliminary data for the Phase 2 study of 6063 in patients with Kras-mutated non-small-cell lung cancer in the second half of 2014, and then finally reporting interim data on the Phase 1 trials for 4718 and 5584 in the later part of 2014. So, it's going to be a very busy year.

We achieved so much in 2013, but we still have much more to do this year and beyond. We are passionate about our mission to change the way cancer is treated and we look forward to updating you on our progress as the year unfolds.

I will now ask Zhou, our specially flown in British operator to open up our call to any questions you might have.

Question-and-Answer Session

Operator

Thank you. (Operator Instructions) Your first question comes from the line of Matt Roden of UBS. Please proceed.

Andrew Peters - UBS

Hi, guys this is actually Andrew in for Matt this morning, congrats on all the progress this year. Couple of quick questions, the first is I have noticed that GSK started a Phase 1 combo study with their FAK inhibitor with their MEK inhibitor. I was wondering if you see a rationale for combining the two and if you have any thoughts on what other mechanisms you think would best combine with FAK, I guess both in mesothelioma and other tumor types. And then just related to the Japanese study, it looks like most of the patients were pre-treated, but do you know if the mesothelioma study received Alimta prior to coming on drug. And do you have any biomarker data on any of the patient’s Merlin status on the mesothelioma and Kras-mutation on the lung cancer patient? Thanks.

Robert Forrester

Andrew, I think you had a couple of questions there. The first was around combinations, GSK, MEK inhibitors other potential combinations. So, we actually think the idea of combining a FAK inhibitor with a MEK inhibitor is a really, really good one. We have seen very, very strong synergy with those two compounds classes. And so we’re enthusiastic as GSK is moving forward with that combination. So, I think that’s a great idea and we look forward to them completing that trial and publishing, so I think we’ll learn a lot from that. Secondly, what other combinations, where we see synergy with a number of different classes of drugs and obviously we are doing a paclitaxel trial right now so we see some synergies with some existing therapies. We also see very, very strong synergy with the PI3K/mTOR pathway. And so I think at some stage in which we very much like to do something with 5584 one of the FAK inhibitors nothing planned currently, but in the future that could be a very interesting combination to pursue. Now the second set of questions were around Japan, and I will hand that over to Joanna.

Joanna Horobin

Thank you, Robert. Yes, thank you Andrew. So first of all the patients that were treated in the Japanese Phase 1 were very typical patients in a Phase 1 study and so all that one of these patients that had actually no prior treatment. Specifically there was your question about the mesothelioma patient, that patient had received Alimta with platinum previously and had been progressed, and at the time of progression came into our Phase 1 study.

Andrew Peters - UBS

And any biomarker data?

Joanna Horobin

We hope that, that will be forthcoming but we haven't got that yet, but we will certainly look into that and if we have it we will report it at some point in the future.

Andrew Peters - UBS

Okay, great. And congrats again on all the progress.

Joanna Horobin

Thank you.

Robert Forrester

So, Andrew our normal process will be to report data like that at scientific conferences. So hopefully later on the year we will have some data to do so.

Operator

Thank you for your question. Your next question comes from the line of Biren Amin of Jefferies. Please proceed.

Biren Amin - Jefferies

Hi, guys. Thanks for taking my questions. I’ve been noticing some clinical trials that you recently started a trial with 6063 in the new adjuvant setting in mesothelioma. I just wanted to understand objectives of this trial and whether you’re looking at Merlin status for this study? Thanks.

Joanna Horobin

So thank you Biren for picking that up, obviously you’ve got eagle eyes. Yes, we have got a small proof of mechanism study that’s ongoing in patients with newly diagnosed mesothelioma. And really the opportunity here it's that what we would call a window study. So the opportunity here is to get the drug to patients before undergoing surgery that allows us to do biopsies before and after receiving the drug and really helps us understand in correlative studies the effect of the drug potentially on various biomarkers of interest to us. So, investigator initiative study but I think one that’s quite interesting and presumably at some point in the future again that data will be forthcoming and will be presented at a medical meeting.

Biren Amin - Jefferies

Okay. And if I could have a follow up on the Kras-mutation study, I understand that the company is planning on interim data in the second half of this year; will the company also make a decision on the dose expansion cohort and proceeding to a dose expansion cohort in second half this year as well?

Joanna Horobin

I think it's likely the-- because of the prevalence and the lack of treatment options for this particular disease. This is a study that we anticipate will accrue quite quickly. And as you know there are predefined criteria for making the decision on expansion. So we will be following the protocol definitions for that. But as we mentioned before we do anticipate that that will happen later on this year.

Biren Amin - Jefferies

Great. Thanks.

Operator

Thank you for your question. Your next question comes from the line of Howard Liang of Leerink Partners. Please proceed.

Richard Goss - Leerink Partners

Hi, this is Rich Goss calling for Howard, thanks for taking my question. I was wondering if you could give us a bit more detail on the three patients (indiscernible) on the Phase 1 study. I think you said that one is mesothelioma patient, but what tumors did the others have? And also, do you expect enrollment sites in Japan to affect the timing of the COMMAND trial interim readout? Thanks.

Joanna Horobin

Thank you. So, the investigator chose to highlight the patient with mesothelioma in the Phase 1 study. At this point we haven't actually disclosed the diseases that the other patients have. But I think Dr. Shimizu was particularly intrigued by this particular patient and therefore highlighted it in the poster. In terms of the second question with respect to the inclusion of Japanese subjects in COMMAND, this was obviously part of our original plan and so I don’t think it is likely to speed up in any way the planned accrual which is actually progressing on target at the moment, and so I don’t think it's likely to impact dramatically the timing of the interim analysis. What's important though for us of course was to try and make sure a major market like Japan was included early in the study so that the patients included in the interim analysis would be representative of major markets and major territories.

Richard Goss - Leerink Partners

Great. Thank you.

Operator

Thank you for your question. Your next question comes from the line of Mike King from JMP Securities. Please proceed.

Michael King - JMP Securities

Good morning guys, thanks for taking the question. I just wanted to ask a couple of questions about NF2 and whether we’ll see data this year that speaks to the prognostic aspects of NF2 in first line response to Alimta, and then I have a related question that I wanted to ask as a follow-up.

Joanna Horobin

So it's a really good question Mike. Obviously in the longer term I think we’ll be able to get that sort of information from the results of the COMMAND study, but that’s a little way off. However we are working with the worlds leading experts in mesothelioma many of whom have significant tissue banks of tissues taken from patients previously treated with standard of care or Alimta platinum. And so we are aware that there are some pre-clinical projects ongoing at the moment to actually look at the mutation stated to those patients. So, while I can’t speak for those investigators we do have the -- and we try every second year meeting of the iMig, the International Mesothelioma Interest Group that’s going to be later on this year, and so I think it's quite likely that some of those investigators would be trying to get that information out. But as I said I can’t really speak on behalf of them, but I do think it's a possibility.

Michael King - JMP Securities

Okay. And then, we are starting to see NF2 and Merlin pop up in other tumor types with respect to resistance in prognosis, and so I was just wondering is there any thought about either specific clinical studies ahead of COMMAND readout to sort of survey other NF2 or Merlin-low tumor types for further expansion?

Joanna Horobin

That’s a really interesting question Mike, and we are aware of some ideas that are in development but might try and link patients with specific mutations to specific target therapies that would be done through (indiscernible) property group structures for example. So nothing definitive on that at the moment, but I think your idea is one that many others are thinking about I think it's possible that we will see such protocols emerging and if it's appropriate for our drugs to be put into those protocols and then obviously that is something we would consider.

Michael King - JMP Securities

Okay. And then there’s two quick follow-ups on 6063 and Kras lung. I don’t know if you can give any thoughts to the current sort of enrolment progress. There seems to be a lot going on with lung these days especially with respect to immunotherapeutics, so just wondering if you can speak to your expectations for enrolment goals there?

Joanna Horobin

Obviously this is a common disease. Kras-mutation is a common problem as well. There are lots of these patients. We have a number of the big academic sites that are involved with doing these specific mutational driven studies in our protocol. So, we’re not anticipating an easy (technical difficulty) with the enrolment of this study.

Michael King - JMP Securities

Okay.

Joanna Horobin

I think it's a separate section of the disease. I think it's unfortunately all too easy to (technical difficulty).

Michael King - JMP Securities

Yes, true that. All right, and then one final question, on 4718 do you believe when we have got the interim Phase 1 data in the second half that we’ll start to see the true differentiation of that molecule?

Robert Forrester

Yes, that’s our goal. We’re not ready to talk about differentiation until we can get it through Phase 1 if you have a good therapeutic window. So we’ll talk more about it later in the year.

Michael King - JMP Securities

Okay. Thanks very much.

Robert Forrester

Thanks Mike.

Operator

Thank you. Your next question comes from the line of Mara Goldstein of Cantor Fitzgerald. Please proceed.

Robert Forrester

I think we’ve lost Mara. Zhou, do you want to go to the next question?

Operator

I’ll go to the next question which is from the line of Brett Holley of Guggenheim Securities. Please proceed.

Robert Forrester

This is very weird.

Operator

I do apologize there’s a slight technical problem, bear with me one moment. Yes, thank you for your patience, Mara Goldstein’s line is now live in the call.

Mara Goldstein - Cantor Fitzgerald

Yes. Can you hear me?

Robert Forrester

Welcome back.

Mara Goldstein - Cantor Fitzgerald

Thank you. I thought you're trying to send me a message.

Robert Forrester

I thought you were sending us a message.

Mara Goldstein - Cantor Fitzgerald

Just a question, I mean I know there’s small number of patients in the Japanese study in the Phase 1 study, but it looks like two out of the three stable disease responses were in the higher group to 600mg group, so as it relates to COMMAND that study is being dosed at 400mg, are you able to speak to that at all?

Joanna Horobin

So the first thing I would say Mara is we’re talking about a very small group of patients, with only three patients per cohort because we did not have to expand any cohort, as I said we didn’t see any dose limiting toxicity. So, there are four numbers first of all. I think there’s one thing to point out of course is that the patient who’s been on study longest, the patient who is now in cycle seven with mesothelioma is actually at the 400mg BID dose. So, I think it's most unlikely that it's related to a dose effect, so I think we have previously demonstrated doses certainly above a 100mgs BID and certainly above 200mgs BID biologically active. So, I think it's probably more the affect of small numbers.

Mara Goldstein - Cantor Fitzgerald

Okay. And then just on Merlin, I know there’s only, rather on the adaptive trial design I know there’s only so much information you can disclose at this point, but patients are screened at entry and then they are -- and then do you -- I guess at whatever that interim trigger point is, is the biomarker data collected then and is the biomarker data collected along the way such that you might be like looking at different time horizons?

Joanna Horobin

Yes, now that would be really interesting wouldn’t it to be able to follow any changes in the biomarker. I think that’s really not practical in a disease of this -- in a study like this which is being done in a multi-sense basis and in fact in the disease where repeat biopsy is actually quite challenging. So, the way we do in the biomarker piece is that we’re collecting either archival tissue or in patients who don’t have that we are able to get a new biopsy -- we’ll take a new biopsy and it is that original biopsy then that forms basis of that stratification into either Merlin-low or Merlin-high. We don’t do any further biopsies along the way. And then at the interim analysis of course the company will not see the effect by biomarker status, the interim -- the data monitoring committee will see that and they will make a recommendation based on predefined an algorithm basically as to whether or not we enrich into the Merlin-low patients.

Mara Goldstein - Cantor Fitzgerald

Okay.

Joanna Horobin

Did I clarify that?

Mara Goldstein - Cantor Fitzgerald

Yes. Thank you.

Joanna Horobin

Thank you.

Operator

Thank you. Your next question comes from the line of Brett Holley of Guggenheim Securities. Please proceed.

Brett Holley - Guggenheim Securities

Hi. Can you hear me?

Robert Forrester

We certainly can Brett. Welcome back.

Brett Holley - Guggenheim Securities

Thank you very much. I just have a question on what’s kind of the projections are for peak mesothelioma incidence in Japan based on their very late removal of [asbestos] [ph] from their country, I mean should it model out very similar to the United States and I guess comment on Europe as well as when we might see that actually peaking out?

Robert Forrester

That’s a great question. We know that in Japan they only controlled asbestos in ’06, and so we have seen basically a tripling of the number of patients over the last 10 years. There are about 1,500 new patients a year and it is increasingly rapidly. They have a very similar problem in Japan as in the U.K. where asbestos is being used so widely in housing stock, in hospitals, in schools. And it's just basically endemic in every building and it's really, really hard to get out of a system. So, our expectation is for something similar to in the U.K. where we haven't reached the peak yet in the U.K. and we’re at to like 2500, 3000 new patients a year, just similar to the U.S. which is a frightening thought in it's own rhyme. So I think the answer is in Japan, I think we’re still in the early part of that curve and the peak is probably not for another 10 to 20 years. So, I think the Japanese market is unfortunately from the patient perspective a really good market for this drug which is why we’re so enthusiastic about the progress that we’ve made in Japan and the speed at which we’ve made that progress. And again I mean it's like a great credit to join out [Mitch] [ph] and the team in Japan for moving this trial along so amazingly quickly. I have never seen the trial go so quickly nowadays, particularly it’s the other side of the world. So, it's a very interesting market for us.

Brett Holley - Guggenheim Securities

And I guess should the incidence in Japan be disproportionate to the population as it was in U.K. based on the prevalence of this business?

Robert Forrester

I think you’re probably right, but Joanna.

Joanna Horobin

Yes, I mean I think as Robert pointed out, I think it's more that the problem asbestos is just more endemic. I mean I think certainly at the moment we believe that the U.K. leads the -- essentially leads the pack in terms of per capita incident. And I think Japan is probably -- Australia is probably not far behind and then Japan is probably moving up in the rank sadly.

Robert Forrester

And Holland is not far behind.

Joanna Horobin

I mean the countries where we’re not conducting a clinical trial as we discussed before but those are markets which in the future will unfortunately become I think rather important for mesothelioma.

Brett Holley - Guggenheim Securities

Great. Thanks very much.

Robert Forrester

Thanks, Brett.

Operator

Thank you for your question. Your next question comes from the line of Peter Lawson of Mizuho Securities USA.

Peter Lawson - Mizuho Securities USA

Hi, just around the COMMAND study and the data monitoring [bold] [ph] decision. If they go for the low Merlin sub-population, do you have to re-access the patient side, is that likely to delay the trial?

Joanna Horobin

That’s a really good question. I suppose, it depends on a number of things, I mean it obviously depends on just how many patients would be needed to be added. We will have -- we would expect by the time of the interim analysis to have all the sites opened including of course the ones that we’re adding that are coming on later just because some sites take longer. So, the base of sites that we’ll be accruing will be large. I think the other thing is that I think the -- as we’ve already discussed not only is the insidious of this disease increasing in some of the places where we’re doing the study, but the awareness of the study is becoming increasingly well understood and well known. For example, just last week in the U.K. where Rare Disease Day focused specifically on mesothelioma, there was extraordinary coverage about the problem of mesothelioma, but also about the prominence of this study to the extent that there were interviews with our lead investigator, one of our second investigators in the U.K. on evening news on multiple-channels on February 28. There were also radio interviews with those individuals which were syndicated I think more than a 140 times, and in fact Dean Fennell who’s the principal investigator -- or the lead investigator for the U.K. was also at the House of Lords talking on behalf of the bill that’s been sponsored there to try and get better access for new drugs to patients with these rare diseases. So well on the one hand the patient population would be slightly smaller that would be targeting if we have to move to the enrichment or if we chose to move to the enrichment. I think the awareness of the study and the number of sites that would be open by that time would probably mitigate the fact that we would need to extend the accrual for those particular patient. So, I don’t think it would necessarily extend the duration of the study that long actually.

Peter Lawson - Mizuho Securities USA

You had assumed, if I look this right 50-50 split of Merlin-low, Merlin-high for the recruitment or is it just in a way from that?

Joanna Horobin

No, that is exactly what we are anticipating. All the literature would suggest that the incidence of Merlin-low is in that sort of 40% to 50% of the total patient population and then additional data that we generated together will collaborators certainly confirms that.

Peter Lawson - Mizuho Securities USA

And then for the four arms with the Kras 6063 study. I know that’s a high risk and a high return study. Which arms do you think would be more likely to show a clinical response?

Joanna Horobin

So it's a very good question. So, the preclinical data would suggest that the patients with Kras-mutations only are actually unlikely to benefit. The preclinical data would suggest that if the patients that have the second mutational deletion of either p16 or p53 that would get benefit. And frankly we think that the double loss of p16 and p53 is unlikely to be seen very often. So we think it's unlikely that we will necessarily even accrue that fourth cohort. So I think we should think about this operationally as a three cohort study in which we see two cohorts having the highest potential for benefit.

Peter Lawson - Mizuho Securities USA

Then just, is there anything being presented at AACR?

Robert Forrester

Yes. Yes, lot of preclinical data, yes there is.

Joanna Horobin

Because there’s preclinical data that’s being submitted.

Robert Forrester

Yes.

Peter Lawson - Mizuho Securities USA

Okay, and then the timeline for the Wnt, any update there?

Robert Forrester

Yes, we announced today we have extended the collaboration with Eisai, which seem to be very interested in that pathway, the Wnt/beta-Catenin pathway and hopefully in due course over the next few years maybe there’ll be some, the candidates are going to come out of that work that we could consider bringing into the clinic.

Peter Lawson - Mizuho Securities USA

Okay. Thank you so much.

Robert Forrester

Thank you very much as well.

Operator

Thank you. Ladies and gentlemen, that concludes our question-and-answer portion of the call. I would like to turn it back over to management now for additional closing remarks.

Robert Forrester

Thank you, Zhou. Thank you all very much indeed for joining us this morning. We look forward to catching up with you in due course. Have a good day. Bye.

Operator

Ladies and gentlemen, that concludes your conference call for today. We appreciate your participation. You may now disconnect and have a very good day.

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