Madrigal Pharmaceuticals Inc (MDGL) 2007 Q3 法說會逐字稿

Good day, everyone, and welcome to the Synta Pharmaceuticals Third Quarter 2007 Financial Results Conference Call. Today's conference is being recorded and webcast. At this time, for opening remarks, I would like to turn the call over to Rob Kloppenburg, Vice President of Investor Relations and Corporate Communications at Synta Pharmaceuticals. Please go ahead, sir.

Hello, and thank you all for taking the time to join us today. With me are Dr. Safi Bahcall, President and Chief Executive Officer of Synta Pharmaceuticals; Keith Erhlich, our Vice President and Chief Financial Officer; Dr. Eric Jacobson, Synta's Senior Vice President and Chief Medical Officer; and, Dr. Jim Barsoum, the Senior Vice President of Research. This morning we issued a press release that reported results for the quarter ending September 30, 2007. This release can be found on our website at www.syntapharma.com.

Before we go any further, I'd like to remind everyone that we will be making forward-looking statements during this teleconference call. Such statements, including statements relating to the timing and progress of clinical trials, reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such forward-looking statements.

Risks and uncertainties include the risks that the results of completed clinical trials may not necessarily be predictive of results in larger, later stage clinical trials and other risks and uncertainties described under Risk Factors in our Form 10-Q for the quarter ended September 30, 2007, as filed today with the SEC. Synta undertakes no obligation to publicly update forward-looking statements, whether because of new information, future events or otherwise, except as required by law.

I will now turn the call over to Dr. Bahcall, after which we will open the floor to questions. Safi?

Thanks, Rob, and thank you all for joining us this morning. Around this time last year, we set a series of ambitious goals for ourselves in 2007. These included completing initial public offering, initiating a global pivotal trial for our lead cancer drug, initiating a Phase I trial for our Hsp90 Inhibitor, and signing a major partnership. I'm happy to say that as of today, we have achieved each of these goals.

Before I describe some of these operational highlights, and turn to Keith to take you through financial highlights, I'd like to frame what we've done and what we're planning to do in the context of our overall strategy and priorities. Our first priority is to maximize the potential of Elesclomol, our lead cancer drug, which is now in a pivotal trial for metastatic melanoma.

Doing this means completing the pivotal trial as rapidly and effectively as possible so that we can be ready for project launch as soon as 24 months from now. In addition, this goal means demonstrating proof of concept in other tumor types, starting with indications where we believe the mechanism of action is most likely to work, which is high oxidative stress cancers, like melanoma. We'll have more to say about that in the coming months as we work with our new partner, GlaxoSmithKline, to finalize a global development program.

The second element of our strategy is building a top tier oncology commercial organization. We have two cancer drugs that we're excited about, following our lead drug, and more that we are working on internally. An important part of getting us to where we want to go is being able to fully capture as much of the cash flow from each program as we can for our shareholders. Having a top tier multi-product, multi-tumor oncology commercial organization is essential for achieving that goal.

At the same time, we want to manage our costs and overhead carefully, and therefore, we intend to slow build, keeping the ultimate goal in mind. We have built that into the mechanics of our co-commercialization agreement with GSK.

The third element of our strategy is to advance the other pipeline programs at the company. These include our Hsp90 Inhibitor, STA-9090 for cancer; our Vascular Disrupting Agent, STA-9584 for cancer, and our two oral agents for chronic inflammatory diseases, our IL-12/23 program and our CRAC Ion Channel Inhibitor program. We believe each of these programs has great potential. We're fortunate to have these programs, we're fortunate to own them 100% and we're fortunate to have the resources to advance them. We fully intend to realize their potential.

And finally, I would like to note that all of our drug candidates were invented internally by Synta scientists using our proprietary compound library and discovery capabilities. We intend to continue using our library and discovery engine to invent new drugs targeting first or best-in-class mechanisms that can transform the treatment of cancer and inflammatory diseases.

Those are the four elements of our strategy. Maximize the value of Elesclomol, build oncology commercial capabilities, get our next drugs approved and continue to generate new drugs. Each of our achievements this quarter, as well as this year, were important steps in advancing that strategy. Let me start by briefly summarizing where we are with the SYMMETRY trial, our global Phase III trial for Elesclomol in melanoma. This is a 630-patient trial, comparing treatment with Elesclomol plus paclitaxel, versus paclitaxel alone, which repeats the design of our prior successful Phase IIb trial.

The details of the trial's design are in our press release from yesterday, and are unchanged from the description we have presented over the past several months that is available on our website, so I won't repeat them on this call. I will say that we have had an extensive dialog and reviewed all of the aspects of the protocol with the FDA. We have incorporated the agency's comments and that is reflected in the announcement we made yesterday in the completion of the SBA process.

Metastatic melanoma, like myeloma and non-Hodgkin's lymphoma several years ago, has been a very tough cancer to treat. We have two critical features that differentiate us from prior attempts in melanoma. Number one, while none of the traditional anti-cancer mechanism categories, such as chemotherapy or vaccine therapy, have worked for this disease, melanoma is a tumor type with a particularly elevated level of oxidative stress. Melanoma appears to be particularly vulnerable to the mechanism of action of Elesclomol which is to further elevate oxidative stress in cancer cells beyond the critical breaking point.

Number two, and this is important, this is the first Phase III trial for a new agent in melanoma that is confirmatory rather than exploratory. In other words, this is the first Phase III trial for this disease that is preceded by a positive, blinded, randomized study for that same agent in the same disease. That has been very encouraging for us and for our investigators and that's been reflected in the enthusiasm we have seen from investigators globally for this trial.

So, again, the answer to what's different; number one, the mechanism we believe is particularly well suited for melanoma, and number, two, the first confirmatory rather than exploratory Phase III trial. As of today, we have initiated just over 20 sites and have treated a number of patients. We expect an interim analysis for safety and non-futility in the second quarter of next year, and are targeting completing enrollment and the primary endpoint analysis, that's PFS, by the end of next year, with an NDA filing in the first half of 2009. We expect to report more on our operational progress over the course of this coming year.

In September, Elesclomol was highlighted in the melanoma session and at a press conference at ECCO, the European Conference on Clinical Oncology, with the emphasis on the strength of the Phase IIb data and the potential of the novel mechanism. ECCO is the leading cancer meeting in Europe and the prominence of our presentation in the media and at the conference was an indication of the growing interest in Elesclomol among European opinion leaders.

In October, Synta presented new mechanism and combination agent preclinical results at the AACR-NCI-EORTC meeting in San Francisco. These results detailed the pathway by which Elesclomol kills cancer cells and demonstrated that the drug has both single agent activity and enhances the efficacy of other widely used first line anti-cancer agents, including Rituxan, Taxol, and Gemzar.

Very importantly for clinical application, Elesclomol, unlike other chemotherapies, appears to provide this enhanced activity with minimal added toxicity. This is very important for both clinical and regulatory implications, as well as commercial implications. It's very different having a drug that you add on top of first line therapy that has minimal extra toxicity as opposed to adding a drug that has very, very high toxicity.

These results paint a full picture for how Elesclomol is killing cancer cells which Synta, our partner, GSK, and our collaborators believe is an exciting new approach that has broad potential, multiple tumor types, combined with widely used first line agents. We believe this is tip-of-the-iceberg time for oxidative stress in cancer, and we will all be hearing a lot more about this science over the coming years. In fact, Jim has told me that the number of papers published relating to oxidative stress in cancer has grown exponentially with over 3,000 papers published last year on this subject.

This past quarter, we also advanced STA-9090, our novel Hsp90 Inhibitor, into a Phase I dose escalating trial. In preclinical studies, 9090 has demonstrated potency ten to 100 times greater than other Hsp90 inhibitors, as well as potent activity against highly resistant cancers. We're very excited about initiating this trial, and we believe that 9090 is a strong addition to our clinical pipeline. We expect to present more data on this program at a scientific meeting in 2008.

Finally, as I noted earlier, on October 8, Synta and GlaxoSmithKline entered into a very substantial partnership for Elesclomol. Synta and GSK will jointly develop and commercialize the drug in the U.S. and GSK will have exclusive responsibility outside the U.S. We will receive an up front payment of $80 million, which we expect shortly, having just cleared (inaudible). We will also be eligible to receive over a half billion in pre-commercial milestone payments. These include payments both for operational progress and payments for positive clinical outcomes.

Let me use this opportunity to clarify this a bit since I know there are some questions out there. By operational progress, we mean, for example, progress on enrollment or initiation of trials and other indications. These are not contingent on clinical outcome. In our release this morning, we guided that we expect to receive between $40 million and $50 million in operational milestone payments from GSK in 2008.

These are payments that are expected before we unblind the Phase III melanoma data, and do not depend on the outcome of that trial. These payments will more than cover our Phase III trial cost for the year and will leave us with substantial resources to develop the other products in our pipeline.

This is a very strong deal for Synta that advances each of the four elements of our strategy that I mentioned in the beginning of this call. The additional resources and expertise from GSK will allow us to more rapidly expand into other tumor types. The product launch experience reduces the number of our operational risks. Both of these increase the potential value of the programs at Synta.

Second, this is a true co-commercialization agreement in that we have carefully constructed in the agreement a key role for a Synta oncology sales and marketing force in the United States. We expect that to benefit not only our lead drug, but our subsequent cancer drugs. Finally, the economics are very attractive, providing us a reduction in costs, a meaningful share of profits, and through the upfront and milestone payments, freeing us from the need to raise capital through product launch and beyond. The increase in resources allows us to set ambitious goals for advancing the rest of our pipeline programs, the four others we have commented on publicly, and others we are working on as well.

I will now turn the call over to Keith Erhlich, our Chief Financial Officer, for a review of financial results for the quarter, after which we will open up the call for questions.

Thank you, Safi, and good day, everyone. For the quarter ended September 30, 2007, we reported a net loss to common shareholders of $14.9 million, or $0.45 per share, compared to a net loss to common shareholders of $14.7 million, or $0.66 per share for the same quarter during 2006. For the nine months ended September 30, 2007, we reported a net loss to common shareholders of $106.6 million, or $3.35 per share, compared to a net loss to common shareholders of $45.8 million, or $2.06 per share, for the same period during 2006.

Included in the net loss to common shareholders for the nine months ended September 30, 2007, is a non-cash charge in the amount of $58.6 million for the beneficial conversion of preferred stock in connection with our initial public offering in February, 2007, and in the same period of 2006, there was a non-cash charge for accrued preferred stock dividends in the amount of $1.1 million. The net loss before these non-cash charges was $48.0 million and $44.8 million in the nine months ended September 30, 2007 and 2006, respectively, or an increase of $3.2 million.

Research and development expenses in 2007 decreased by $1.3 million, principally due to non-recurring costs incurred in connection with the 2006 completions of our Phase IIb trials in Elesclomol for metastatic melanoma and apilimod for Crohn's disease, as well as for the cost of preclinical efforts leading to our recently initiated Phase I trial for STA-9090. These decreases were partially offset by start up costs incurred during 2007 in preparation for our global, pivotal Phase III Symmetry trial for Elesclomol.

General and administrative expenses increased $5.1 million during the nine month period, principally as a result of the incremental legal, accounting, compliance, insurance and other related costs incurred in connection with operating as a newly public company in 2007, the creation and operation of investor relations and business and commercial development functions, and costs incurred in connection with negotiating our partnership with GSK. The corresponding changes in research and development costs and general administrative expenses for the third quarter of 2007, as compared to the same period in 2006, were principally due to the same factors.

The Company ended the third quarter of 2007 with $48.3 million in cash, cash equivalents and marketable securities, compared to $46.8 million at the end of 2006. We will receive our $80 million non-refundable upfront payment from GSK early in the fourth quarter of 2007, strengthening our balance sheet considerably with an estimated year-end cash balance of approximately $110 million. In addition, based upon our current operating plans, we expect operational milestone payments from GSK to range from $40 million to $50 million in 2008.

While we have not concluded yet on all of the details of the accounting for our partnership with GSK, we would like to provide some guidance. Beginning in the fourth quarter of 2007, we expect to recognize the $80 million non-refundable upfront payment over the agreement performance period, which we estimate to be approximately 15 years. Milestone payments are also expected to be recognized over the performance period, beginning with each milestone achievement date.

I will now turn the call back to Safi.

Thanks, Keith. Before I open the call to questions, I'd like to say that this has been an extraordinary year for Synta, with the IPO, partnership, survival data, Phase III initiation and new drugs advancing, it has been very busy and very successful. We've been able to deliver, entirely because of the very hard working and talented group of people we've assembled across the Company and the discipline we've always aspired to, and always will aspire to, of setting, meeting and exceeding ambitious goals.

I'd like to take this opportunity to thank all of our employees for their hard work and their dedication that has made it possible for us to achieve so much in our first year as a public company. We'll now open the call to questions and discussions.

Thank you, Dr. Bahcall.

(OPERATOR INSTRUCTIONS)

Thank you. Our first question comes from the line of Ajim Tamboli with Lehman Brothers. Please proceed with your question.

Hi, good morning. With the signing of an SPA with the FDA, can you confirm their agreement on the ability to file on the primary PFS endpoint, and also what does the FDA want to see with regards to overall survival? And also, what are the powering assumptions for a final overall survival analysis?

Sure. Let me go through those one by one. Yes, as part of the SPA, we do intend to file on the primary endpoint which is PFS, progression free survival. Two, there are no hard and fast guidelines about exactly what criteria you need to meet in PFS, before approvability. Our expectations are that approvability, based on the primary endpoint, would be the subject of review by panel -- informed panel, probably from the melanoma community.

We have been given no guidance that any benefit in overall survival is necessary. In fact, if you look at the minutes of an ODAC meeting from a couple of years ago, the FDA posed that question to an ODAC panel specifically, whether approval based on some benefit in PFS, with no benefit in OS, in overall survival, should be allowed, and the ODAC panel at the time, voted 13 to zero, yes, even in the absence of any OS benefit, the drug should be approved on PFS. Does that answer your questions?

It does. Thank you. And then, on the guidance you gave today, in terms of financials, you mentioned that you'll be receiving $40 million to $50.0 million from the GSK collaboration next year with regards to milestones, which should more than cover Phase III trial costs, I'm just wondering what incremental spend you expect on top of that for your other programs? And then, based on the year end cash guidance, how long is that sufficient and do you have any financing plans right now?

Well, that's a lot of questions for one. You might want to leave some for some other people. But let me kind of go through those one by one, starting from the last one. We have no near term financing plans. We think the $110 million that we'll end this year with, with the $40 million to $50 million of operational milestones, more than covers our needs.

Should the Phase III trial outcome be positive, we expect substantial additional cash and the combination of all of those payments in cash are more than sufficient, in our view, to take us through product launch. So we certainly have no near term financing plans. In terms of guidance for 2008 on expenses and other programs, that's something we'll provide on our next conference call, which would be in conjunction with our 10-K filing and be expected in the first quarter of next year.

Thanks for taking the questions.

Thank you. Our next question comes from the line of Mike King with Rodman & Renshaw. Please proceed with your question.

Good morning. Thanks for taking my questions. Just trying to get a little more clarity on the amortization of GSK payments. Are they all -- is there a date certain in the future 15 years from now that all payments have to be amortized up until, or are they just 15 years from whenever you incur them?

Let me turn that over to Keith.

Yes, generally the point that we're considering for the duration of the development and commercialization agreement, which, of course, is the Company's clear plan to see through and maximize as much as possible. The date that we've estimated would be approximately the earliest -- expiration date of the earliest patent in connection with Elesclomol.

Okay. And do you mind sharing that with us?

And that's about 15 years out.

From?

Today.

Today as we speak?

Yes, that will be about 2022.

Okay. So we should take that in mind whenever we want to project other amortization?

That's correct.

Okay. And just turning to the stock purchase option. I know we're not at that point yet, but should you agree to sell stock to GSK, have you decided how those payments are going to be amortized? Will they need to be amortized?

That element of accounting we haven't really considered yet. I don't know if there's any amortization associated with that, though.

Okay, great. I assume if there is, you'll update us at some future point.

Yes, I think in the 10-K it will be very clear what all of the details of the accounting would be.

Okay. And then the -- a pipeline question. Apilimod. When do you think we'll see data from CVID?

We should have some data by either the end of this year or early next year.

Okay. And could you, Safi, remind us what the endpoint is on the CVID?

These are biomarker analyses. It's a handful of patients where we've been looking at change at different biomarker capabilities. And just as a reminder, we've guided expectations low on this program. While we're very excited about the target, and I think there's been some spectacular data from other companies who are targeting the IL-12/23 protein complex, we believe this first generation compound, based on the data we've seen to date, needs improvement in pharmaceutical properties to make it a real viable drug candidate, so we don't have high expectations for taking this program forward.

Okay. And then just one final question is -- remind us how you guys measure levels of oxidative stress, and can you also help us understand the biology of that a little bit better in terms of whether it's related to stage or prognosis, etc? Thank you.

Sure. I'll turn this over to Jim.

Sure. There are multiple ways to measure oxidative stress and one way is to measure the expression on the gene expression pattern. So when a cell is under oxidative stress, a variety of genes and proteins are produced which are response to that stress. And there is a classic oxidative stress expression signature which is induced by Elesclomol and that's what we have seen in multiple different tumor types.

The other thing one can do is directly measure the elevation of reactive oxygen species. You can use dyes such as DC-FDA, which directly measure super oxide and hydrogen peroxide, and we've seen that induced at very early times after Elesclomol treatment. And in terms of how that relates to cancer and different clinical trials that we might do, it's known that broadly across the board, many cancers have elevated reactive oxygen species relative to normal cells, and are very susceptible to increases in reactive oxygen species leading to apoptosis.

So in further development, we're considering those cancer types that are particularly susceptible to this pathway, have very high oxidative stress, such as -- besides melanoma, that includes breast cancer, prostate, pancreatic, ovarian cancer and certain leukemias like CLL.

Did that answer your questions or --?

It does. Thank you very much.

Thank you. Our next question comes from the line of Robyn Karnauskas with Bear, Stearns. Please proceed with your question.

Hi, guys. Thanks for taking my question. Just some more questions regarding the Symmetry trial. First of all, regarding the powering. What is the P value that we're expected to reach for the primary endpoint? And what is the powering assumption for maybe -- is it PO1 versus PO5 and that sort of thing?

This is -- the powering assumption is based on a P of 0.05. It's a two-sided alpha of 0.05, which is pretty standard. This is a two-in-one trial design, so, in fact, the 630 patient number has been chosen so that we have a good powering for the secondary endpoint of overall survival. As you know, you need a lot more patients to see a good delta, a good improvement in overall survival, than you do for progression free survival.

So, in fact, the powering for the primary endpoint is very, very high. It's well over 95% powering, the way we've done the trial. And in terms of the number of patients that you would expect, it's event driven. So we would expect, at some point in 2008, we would see sufficient number of events to give us quite a bit over 95% power to see a two-sided alpha of 0.05.

What is the number of events? Can you release that?

We haven't provided those details yet. It's in the ballpark of 200.

Okay. And then, how often are you conducting scans for progression?

It's at a minimum of every two cycles, which is every eight weeks, or more frequently if the investigator would like to see a scan from the patient.

Okay. Then another question on the trial. So how do you plan to maintain there won't be any treatments after progression to maintain powering for survival?

With any PFS study, as soon as the patient progresses, per the RECIST criteria, they are unblinded and open to any treatment. Metastatic melanoma, unfortunately for patients, has no agent which has ever been shown to survival. In this disease in particular, therefore, you're somewhat less concerned with the issue that you're referring to, the post-study treatment issue confounding survival data, because whether they were on the control arm or the treated arm, after they have progressed, they're going to get some agent and there really isn't any other agent out there that's shown to improve survival.

So in this disease, and in this trial, we have somewhat more confidence that the overall survival data will not be as susceptible to the post-study treatment issue. But that issue that you mentioned is true for every study in cancer that's trying to look at overall survival.

Okay. And last question, so what is the powering assumption for survival? How much power is there for survival?

We're at about a 80% power to see, again for the two-sided alpha of 0.05 to see an improvement from nine months in the control arm, to 12 months in the treatment arm.

Okay. Great. Thanks a lot.

Thank you. Our next question comes from the line of Joel Sendek with Lazard. Please proceed with your question.

Hi, thanks. I just wanted to go over -- I'm just looking at the release in your commentary. It looks like there are a total of four looks in all. And the first look, are you going to be looking at PFS at all or is that just a safety look?

Let me clarify what those four looks are. So between now and the final primary endpoint analysis, there's a total of two looks, including the final analysis. There's one interim analysis which we'd expect in the second quarter. That's something that we are blinded to. It's an independent data safety monitoring board. They will be looking at safety, but they will also be looking for non-futility. So that is the first and only interim look at PFS before the final PFS data. It's by an interim board which is blinded and the charter calls, specifies only for a non-futility analysis.

The second look, which we would expect by the end of next year, is an unblinding and the final analysis of the primary PFS endpoint. At the time of the second look, we will also look at OS, and we would expect that to be an interim, because we would expect to not have achieved enough events for the full OS analysis. That would be, let's say, end of next year. We would have the primary endpoint analysis and an interim look at OS, and if the primary PFS analysis were positive at that time, we'd proceed with filing an NDA, which we'd target for the first half of '09.

There are two subsequent looks, which are -- one additional interim OS analysis and then one final OS analysis, which we would expect to take place over the coming year after that. Does that answer your questions, Joel?

Yes, so you don't need -- like you said before, you don't need the overall survival in order to file, so that's kind of gravy if you hit that. How about the other scenario, that's obviously pretty unlikely, but let's say for some reason you miss PFS, you have the opportunity to wait to see if you have an overall survival benefit?

That's something we'd consider at the time, working closely with the FDA and the medical advisors. As you say, we think that's probably an unlikely scenario, especially given our Phase IIb data where we show such a striking improvement in PFS.

Yes. Okay. And then, just doing the math on the enrollment -- so, you think it's going to take about 14 months. Can you help us with some of the assumptions about how many sites you have to get up and when in order to meet that goal, and is it an aggressive goal or do you think it is conservative, given the interest in the drug?

Eric, do you want to talk to this?

We plan to have approximately 150 sites worldwide to enroll this trial. We do believe this is an aggressive goal, but we also think there's a lot of enthusiasm from the investigators, given the strength of our Phase IIb data, and we're doing everything in our power to assure that we achieve this goal.

Okay. All right. That's all. Thank you.

Thank you, our next question comes from the line of Jason Kantor with RBC Capital. Please proceed with your question.

Thank you. Most of my questions have been answered. I'm just wondering if you could tell us if there is any change in inclusion or exclusion criteria between this Phase III and the previous Phase II study.

Eric?

Most of the inclusion criteria are the same -- [so this is] Stage IV metastatic melanoma patients. We exclude people with known brain metastases. The one change is that in the Phase IIb study, we looked at both chemotherapy naive patients, as well as patients who could have received one prior standard chemotherapeutic regimen. In the Phase III trial, we chose to go with chemotherapy naive patients as the primary populations of study.

We also had some minor changes in the stratification, so in this study, we're prospectively stratifying for key prognostic variables including LDH.

And what percentage of patients in your Phase II were chemo naive?

In the Phase II, roughly 40% were chemo naive and 60% had one prior standard chemotherapeutic regimen.

And have you presented the results broken down by those various groups?

Yes we have, and there was a strong trend towards marked improvement in PFS in the chemotherapy naive patients. If you look at the hazard ratios for both groups, the drug was beneficial in both. But given the very impressive improvement in the chemotherapy naive patients and the fact that we're also looking at overall survival as a key endpoint in this study, we and our advisors felt that the chemotherapy naive patient population was the ideal patient population to study in this trial.

Okay. Thank you.

Thank you. Our next question is a follow up from Mike King with Rodman & Renshaw. Please proceed with your question.

Sorry. I had the phone muted. Thanks for taking this follow up. Apropos of the previous question, remind us whether the chemotherapy included patients who had received biologic therapy, or was that an exclusive criteria?

In both the Phase IIb study as well as our Phase III trial, we do allow prior biologics.

Okay. You have not, as far as I can recall, showed the differences, if any, between patients who had received prior biologic therapy versus not, have you?

I don't think that we've presented that subset analysis.

Okay. Is there a plan to do so, or no? I know you're stratifying for that in the Phase III, correct?

We are, given that some patients will have received prior biologic or other nonstandard chemotherapies in the Phase III, we are going to stratify for that. We have looked at this and we did not feel that the prior biologic was an important variable in our Phase IIb study.

Okay. So, it didn't have an effect on outcome?

No.

Okay. And then just as far as, Safi, the stated goal for filing in the first half of '09, perhaps you can walk us through it. I commend you for having such an ambitious goal, but maybe walk us through how you plan on getting there. There's going to be a lot of data points, a lot of patients, a lot of centers. So, how does Synta set it up so that that can happen?

Sure, Mike. We've run over 20 clinical trials at the Company. We have a very experienced clinical operations group. Jeremy Chadwick has run clinical operations at Vertex, at GlaxoSmithKline, at PAREXEL. He's worked with a number of -- many of the top pharma companies, and he's built a very strong branch underneath in terms of data management, biostatistics, medical monitoring. So we've, in the past, have been very, very successful at meeting or exceeding all of our enrollment targets.

We're working with a very experienced CRO and I think, especially, the fact that our partners, including the partner that we have signed with at GlaxoSmithKline, who came into the Company, audited the Company in great detail, looked at our experience and capabilities, and said, don't let us slow you down and left us entirely in charge of the process of running the clinical trial and filing the NDA, is a reflection of the capabilities we have internally in being able to meet strong operational goals for the trial. Does that answer your question?

Yes. And then, if I may, in order to get the -- you said 14 months or roughly, in answer to Joel's question as far as the target enrollment timeline?

That's correct.

So when would the last patient -- would have to be enrolled by March?

We're targeting the last patient enrolled by end of next year.

By end of --

Right. By end of '08, but to have data by March of the following year.

Well, we're targeting filing the NDA, so we would -- the way we have structured this trial, again, with a two-in-one design, is that you could enroll your last patient and then you do the primary PFS analysis right around the same time. And of course, the primary PFS analysis doesn't need to be a full 630. It's a -- it's the first, call it 300 or 400 patients, not the full 630.

Right. Okay, thanks.

We would -- just to follow up, I think you asked how it would work. You would enroll -- just to kind of map this out for you -- the timeline-- you would enroll all your patients. Let's say you finish it by end of next year. Right around that time, you do the primary endpoint analysis, which is on the first 300 or 400 patients. You get that data. You've completed your manufacturing, your registration batches, your non-clinical studies. You assemble that full package over the next couple of months and file that NDA with the FDA in that first half of '09. That would, because this has a fast track and a priority review --

Right.

-- that would put you in a position to launch in the second half of 2009, which is our goal.

And you're not planning to enroll -- to file on a rolling basis?

We haven't made a decision about that right now.

Okay, thanks.

Thank you. Our next question comes from the line of Ajim Tamboli with Lehman Brothers. Please proceed with your question.

Thanks for taking the follow up questions. Just to confirm, in terms of conducting the primary analysis on PFS, that won't occur before completion of enrollment to allow for sufficient patients for the overall survival analysis.

That's correct. Our intent is to complete enrollment and then do the primary PFS analysis. That would allow us the benefits of doing a PFS study, which is very, very highly powered and very clean, but at the same time, as we go ahead and proceed and file on PFS, we're still collecting data on OS, so that by the time we get to market, we can, if the drug repeats what it did in our Phase IIb study, go with both a highly significant PFS benefit, as well as hopefully show us an OS benefit.

And then with regards to enrollment, we actually saw a couple, or a few centers come online a couple of months ago. So what are the goals in terms of getting all 150 sites up and running? And then can you confirm that there are no competing agents in Phase III trials right now for melanoma?

Our goal is to get all of our sites initiated and operational by the first quarter of next year. In terms of Phase III studies, the agent that has probably been getting the most visibility or press are the CTLA-4 antibodies, and those trials are winding down, they're not yet all done but they are winding down. There are one or two other studies that are out there that are in the process of winding down, but we really haven't heard, in all our communications with investigators, both in the U.S. and in Europe, much significant competition other than a focus on the CTLA-4 antibodies.

Thanks for taking the question.

Thank you. That concludes the question and answer session. I would like to turn the conference over to Dr. Bahcall for closing remarks.

Thank you all for your time today, and we are all looking forward to making 2008 as exciting a year for Synta and for our shareholders as 2007 has been. Thanks again.

Ladies and gentlemen, this concludes the call. You may now disconnect. Thank you for your participation.