Achieve Life Sciences Inc (ACHV) 2005 Q1 法說會逐字稿

At this time I would like to welcome everyone to Sonus Pharmaceuticals first quarter conference call. [OPERATOR INSTRUCTIONS] Thank you, Miss Dull, you may begin your conference.

Thank you, and good afternoon everyone. Welcome to Sonus Pharmaceuticals first quarter conference call. I'm Pamela Dull, Director of Investor Relations. To begin the call, I'd like to remind everyone that some of the statements made today, may include predictions, estimates, and other information that might be considered forward-looking. These statements are based on current expectations and assumptions that are subject to risks and uncertainties. Actual results could differ materially from our predictions and estimates as a result of various risk factors including those identified in our form 10-K for the year ended December 31, 2004, and other SEC filings all of which can be accessed on our Website. With that, I'll turn the call over to Mike Martino, President and CEO of Sonus.

Thanks, Pam. Hello and welcome, everyone. Joining Pam and me on today's call are Alan Fuhrman, our Chief Financial Officer, and Dr. Michael Stewart, our Chief Medical Officer. Since we last talked with you a short eight weeks ago, we've moved steadily forward with the implementation of our strategy for TOCOSOL Paclitaxel and I believe that we are on track to achieve our objective. We're focused on moving TOCOSOL Paclitaxel into a pivotal Phase 3 trial in 2005 and have made good progress on that objective. We have had further substantive discussions with the FDA to finalize the Phase 3 special protocol assessment, or SPA, and I'm delighted to report that we now believe we have a clear path to complete that process. We'll get into the details on that in a few minutes.

We'll use the following format for today's call. First, Alan will provide a brief summary of our financial results, next I'll review our first quarter progress. Michael will then review the status of our clinical and regulatory programs for TOCOSOL Paclitaxel. And finally, we'd be happy to answer any questions you may have. With that, I'll now turn the call over to Alan.

Thank you, Mike. Let me briefly review the financial results for the quarter, which we reported in our press release this afternoon. We reported a net loss of 4.8 million, or $0.22 per share for the first quarter of 2005 compared with a net loss of 3.6 million, or $0.20 per share for the first quarter last year. The planned higher net loss primarily reflected an increased level of R&D spending as we continued to execute the clinical and regulatory plans for TOCOSOL Paclitaxel, as well as higher G&A costs related to business development activities and the termination of the Synt: em acquisition.

On the balance sheet, we ended the quarter with 15.1 million of cash and no debt. We continue to expect that our cash burn during the first half of 2005 will be 1.5 million per month on average, increasing to approximately 1.6 million per month on average for the full year. However, this base burn rate does not include the cost of the Phase 3 pivotal trial for TOCOSOL Paclitaxel. As you know, our goal is to secure corporate for TOCOSOL Paclitaxel to fund all or a portion of our Phase 3 trials. Once we have that partnership in place, we will be able to provide additional guidance on the cost of the Phase 3 study for Sonus as it relates to our projected 2005 cash burn.

I also want to note that as previously announced, we filed an S3 shelf registration statement on April 1, of this year. The SEC has recently cleared the S3 and the only step remaining for the S3 to become effective is for Sonus to send the SEC a letter requesting acceleration. That completes the financial overview and I'd like to turn the call back to Mike.

Thanks, Alan. Let's move right into the highlights of our first quarter progress. First, we continued the dialogue engaged with the FDA on our December 2004 end of Phase 2 meeting and, proceeding through the SPA process that began earlier this year for our Phase 3 registrational trial. In addition to the study protocol, an FDA includes agreements about how the study will be conducted, how end points will be evaluated and how results will be analyzed statistically. In our SPA application, we also asked the FDA to agree on the basis for approval of our NDA, based on this pivotal study with supportive data from our other clinical and non clinical studies. As we've mentioned in the past, it typically takes up to six months to get an SBA in place. At this point in our discussions with the FDA, we are hopeful of meeting our goal of securing the SPA approval by the end of the second quarter.

Second, we had mentioned on our last update that we had a successful meeting with the FDA in March about the chemistry, manufacturing, and controls, or the CMC information that will support the NDA for TOCOSOL Paclitaxel. The CMC information essentially details the product, its specifications, including stability, as well as our processes and methods for manufacturing it in a repeatable, predictable, and reliable manner within those specifications. We were delighted with the outcome of this important meeting as the FDA agreed that the manufacturing process, analytical methods, and stability testing programs for TOCOSOL Paclitaxel are sufficient to initiate Phase 3 testing, and that the data we intend to include in our NDA would be sufficient for FDA review.

Third, during the quarter, we continued to evaluate the anti-tumor response rate and safety data from our Phase 2b study of TOCOSOL Paclitaxel and patients with metastatic breast cancer. And those results are fully in line with our expectations. Michael will go into a little more detail in a moment.

Fourth, as you know, we completed patient enrollment in the Phase 2a studies of TOCOSOL Paclitaxel almost two years ago. And those studies generated encouraging initial data on safety, and anti-tumor activity. We have continued to follow patients for survival duration in those studies, and we're pleased to have an update on those results today, which Michael will also cover in just a few minutes.

Finally, in the first quarter, we continued in our discussions with perspective partners for TOCOSOL Paclitaxel. As we previously indicated our overall goal has been and remains to maximize the value of TOCOSOL Paclitaxel. A good corporate partnership or partnerships are a means of this goal. We believe that completing the Phase 3 SPA agreement with FDA and parallel with corporate partnership discussions puts us in a stronger position to realize appropriate value around the terms of a deal. Our goal remains to finalize the SPA and to secure a partner in order to initiate the Phase 3 trial for TOCOSOL Paclitaxel. Let me say that we are pleased with the nature and progress of our partnership discussions, we are also at the stage where it is important not to presume the details of the outcome until the terms are finalized. I'll now turn the call over to Michael Stewart to provide further details on the clinical and regulatory progress with TOCOSOL Paclitaxel. Michael?

Thanks, Mike. As Mike mentioned we've had ongoing interactions with the FDA on our registrational Phase 3 trial plan. We submitted a request for a special protocol assessment including the study protocol and formal written plans for how the study will be conducted, how study specified end points will be evaluated, and how results will be analyzed statistically. Securing an SPA agreement is a complex process, but we continue to be pleased with the content and speed of our progress with FDA. The communications have been straight forward, and we believe that all details remaining to be finalized are understood. And the final agreement will be confirmed before the end of the second quarter.

As with we have previously stated, we do not control the timing of FDA review, or their response on any specific issue. As also previously stated, we believe it is most appropriate to wait for the final agreement before discussing publicly the design of the study. We have chosen to invest the time required to secure this SPA agreement with the FDA before starting enrollment. In order to potentially reduce the regulatory review issues, that are commonly encountered in review of an NDA submitted without an SPA agreement.

When we submitted our SPA application to the agency, we also asked them to address the proposed basis of approval for our NDA. They have indicated that approval of our NDA under 505 B2 would be based on the results of the single Phase 3 study that we will conduct, along with supportive data from our other clinical and non clinical studies and CMC information. It could also be related to modification of the current Paclitaxel label to include a weekly dosing schedule. Based on the discussions with the FDA, we do not believe that would affect the timing on our NDA submission, nor the period of time required for its review.

We've also continued to make progress in the ongoing Phase 2b study in breast cancer. Data continue to come in both for anti-tumor responses and for tolerability of TOCOSOL Paclitaxel which is being given weekly at a dose of 120 milligrams per square meter in this trial. At this point, the investigative reported response rate is at least 51% after 16 weeks of treatment. With a current 95% confidence interval of 36 to 66%.

Data continue to come into the database every week as monitoring a study site and collection of case report forms progresses. The CT scans obtained on each patient at eight week intervals to assess response and the confirmatory CT scans obtained four weeks after each response is identified, are being transferred to an independent radiologist for review. We expect that we will have final independently confirmed response assessments, more complete safety data, and an initial estimate of time to disease progression, in time for presentation at the San Antonio breast cancer symposium in early December of this year.

Turning to the ongoing Phase 2b study in bladder cancer, progress has continued to be slow in the U.S., because fewer and fewer patients are being referred to cancer center for second line treatment of this disease. That pattern of practice started a few years ago and has continued to develop in the U.S.. It is different in Europe, where many patients continue to be sent to large specialized cancer centers. Regulatory approval for our study are in the final steps in Spain and the UK and we will begin enrolling patients in about a half dozen countries there in the next several weeks. Because this is a relatively rare disease, as we have discussed before, progress is not rapid, but we continue to believe it is an important area where effective more tolerable treatment is needed. And TOCOSOL Paclitaxel appears to offer a meaningful alternative to currently used therapy.

Next, as Mike mentioned a few minutes ago, we continue to monitor the long-term value of treatment with single agent TOCOSOL Paclitaxel in the Phase 2a trials of ovarian non small cell lung and bladder cancers that began in 2002, and completed enrollment in mid 2003. All consenting patients have continued to be monitored through their treating physician. And we expect to have final data on all available patients before the end of this year. Data review, confirmation, and analyses are ongoing and data bases have not yet been locked. But median survival in each of the three studies has now been estimated based on information reported by the investigators as of early May.

In the ovarian cancer study median survival is estimated to be 74 weeks. With a 95% confidence interval of 49 to 116 weeks. In the non small cell lung cancer study, median survival appears to be 35 weeks. With a 95% confidence interval of 19 to 48 weeks. In the bladder cancer study, we are currently estimating median survival at slightly longer than 57 weeks with a 95% confidence interval of 27 to 95 weeks. We believe these numbers for median survival, following treatment with TOCOSOL Paclitaxel are in each case in the ball park of published survival duration after combination chemotherapy regimens, used in the second line treatment of patients with these diseases.

Finally, as a reminder, I'd like to mention that the results of the clinical pharmacology study conducted last year, comparing TOCOSOL Paclitaxel and Taxol will be presented at the upcoming ASCO annual meeting on Sunday May 15, at 8 a.m. This study included analyses of the amounts of Paclitaxel in the circulation over time, following single doses of TOCOSOL Paclitaxel and Taxol. Both drugs were administered at the standard Taxol regimen of 175 milligrams per square meter separated by at least three weeks. This is one of the most comprehensive studies ever done for Paclitaxel pharmacokinetics and we look forward to sharing the full results of that. As we have previously disclosed, the results show that the Tocopherol formulation is able to deliver substantially more unbound of active Paclitaxel into circulation over time than is achieved with Taxol. It is our belief the greater anti-tumor activity may result from treatment with TOCOSOL Paclitaxel as the result of higher exposure to active drugs given on a sustained basis. And we look forward to confirming this hypothesis in our pivotal Phase 3 trial. Mike, I'll turn the call back to you, now.

Thank you, Michael. This is outstanding progress. We're excited to be moving closer to realizing our goal of performing the Phase 3 registrational trial for TOCOSOL Paclitaxel. We're eager to confirm the potential benefits of the product, and believe that our development program has the potential to differentiate TOCOSOL Paclitaxel from other products in this class and to increase its value to cancer patients, physicians, and shareholders. Our strategy remains to position TOCOSOL Paclitaxel as the Taxane of choice in an attractive and growing market. And I believe that we are squarely on track to implement this strategy.

Before wrapping up, let me quickly summarize expected milestones with TOCOSOL Paclitaxel for the balance of this year as follows. Complete the SPA process, secure a corporate partner, initiate a pivotal Phase 3 trial, predicated on completion of the SPA process and on available resources. That completes our prepared remarks, and we'd be pleased to answer any questions that you may have. Michael, would you please open the line for any questions.

[OPERATOR INSTRUCTIONS] Your first questions comes from Matt Kaplan.

Good afternoon, guys. Just a quick question in terms of the progress towards the start of the initiation of the Phase 3 trial, previously you had indicated that it was a third quarter goal for the Company, is that still if case and is that still achievable?

That remains our goal based on discussions to date with FDA, we believe that is achievable, however as Michael has said we don't control nor can we manage the pace or the content of FDA's responses. So we'll be in a better position once we have the SPA finalized. We believe as of now we're on track to do that by the end of June. But that, again, depends upon both the pace and content of our interaction with FDA.

Sure. That's obviously hard to predict, bureaucracy. But, with respect to -- are there any issues or things you can point to that are holding up the FDA process or -- ?

No, it's really proceeding as we expected. I think the difficulty for business people is we're used to a business environment where we can have informal discussions and move forward very quickly from there. The process of interacting with FDA is a very stylized and formalized one. I want to say that we continue to be very pleased, as Michael said, with both the content and pace of those discussions but we simply have no way of predicting if that will continue.

And, just a final question, then I'll jump back in the queue. In terms of your partnership discussions, it seems as though, have -- has the taste of discussions or the content of discussions there changed over the last quarter? Is there progress being made there that's tangible? Or can you give us any sense?

Well, I think there is very good progress being made there. And those discussions have changed in terms of both pace and complexity from the perspective that we have continued to be in discussions with people that have been at the table for a while and those discussions have picked up pace, and in addition as we signaled, I believe, on our last call about eight weeks ago, we have had new people express interest, and that has continued to occur, in fact since that call eight weeks ago. So, we continue to understand that concluding our first partnership in a major geography is a priority for shareholders, it remains a priority for us as well. And I think we're making good progress towards that goal.

Thank you.

]] Thanks, Mat.

Your next questions comes from Vinnie Jindall.

Hey, guys, it's Vinnie. Mike Martino, I had a quick question for you regarding the pace of the negotiations with potential partners. Roughly how much longer, based on the pace of current discussion and how close you guys are in terms with the most serious potential partners, ball park, how long after you get an SPA In place would you at least expect to have a final deal done with a partner?

Well, Vinnie, unfortunately, I think the best answer I can give you at this point is what I said in the conference call. I believe we're at the stage of discussions where it simply does not serve us well for me to speculate on that. I want to reiterate that I think we're making good progress and we are confident that that is an objective that we will meet and one that we will meet to put us in a position to initiate the Phase 3 trial on schedule.

Fair enough. Not to put words in your mouth at all, but, if it was on the order of say, two months, or something that wouldn't be unexpected?

Well, I really don't want to bite on the timing aspect of it except to repeat again, that I think we're on a pace to put us in a position to initiate the Phase 3 trial on schedule, and conclusion of a partnership is a necessary ingredient.

Fair enough. And I have another question for Michael Stewart, actually.

Yes. .

Michael, roughly, what is the general response rate that's out there for Taxol used once weekly? In metastatic breast?

I think that you have to look at whether it's first line or second line. Probably the largest study that has been reported recently was one done by the CALGB that Doctor Andy Seidman from Memorial reported early last year at ASCO and in that study which was a comparison of weekly Taxol versus Taxol used on the labeled regimen of 175 every three weeks, the patients who were assigned to receive weekly Taxol, about 80% of them I recall, it's 5 or 80% were first line patients and the others were second line, so it was a mixed population. But overall, they had about a 40% response rate, which is what you would expect if you look at Phase 2 studies of smaller populations. 40% percent at first line diseases, 30% at second line disease is not unreasonable.

Given that mix, how do you explain the roughly 25% increase in response rate that you're seeing with TOCOSOL formulation?

Well, I hesitate to add that this is, again, a single arm study it's multi-institutional, but it's single arm open label and although the x-rays get measured not only by the radiologist, at the study sites, they get measured by an independent mass radiologist who has no knowledge of the patient's treatment or other issues. He just feeds stones and measures target lesions. Obviously, my speculation is, that if you get more drug in on a sustained basis, and we know that we can do that. TOCOSOL Paclitaxel is very well tolerated. And most doses are delivered on time at full dose. And I think that that may go a long way toward explaining why we're seeing a higher response rate. If you use another drug, where because of toxicity you have to back off on the dose or skip a lot of doses, there's no chance for that drug to reach its maximum effectiveness.

And of that 51% can you give us a break down of what are PRs, versus CRs?

0h, dear. I don't -- I'm afraid I don't remember -- it's early on, most of them are PRs, obviously, but it's early on and I don't have the numbers in front of me. I think that the real issue was we wanted to get out some information for you guys today, so you know where we're heading but it's not uncommon at best response is what we will eventually be talking about rather than the current level of the case forms we have in house. As I mentioned, they're incomplete. We don't have all of the data in on all of the patients.

Got it. Thanks, guys.

Sure.

Thanks Vinnie.

Your next question comes from Allen Long.

Can you tell us which disease indication the Phase 3 is targeted at and if you can't yet be specific, can you provide us some color in your thinking with regards to choosing the pivotal indication?

Well, what we have said is that the lead indication will be one in which Taxol is approved as a single agent therapy. That pretty much says that it's second line metastatic breast or second line ovarian, and there are a variety of factors that we've considered in the decision including regulatory factors, clinical factors, and commercial factors. Clearly we have made a proposal to FDA and as Michael indicated, we're in the process of iterating our communications on that. We believe that we have a very clear path forward, and we'll look forward to discussing the specifics of the study once we have that final SPA.

For your Phase 2b trial on breast cancer, might you be releasing some interim data like progression before December, and if so, through what venue?

Well, it's hard to predict when data will be available, of course, and I don't want to speculate on that. I will say that our philosophy and indeed our policy has been to release data at scientific meetings such as ASCO or the absence of that to provide material updates on our quarterly calls and that will continue to be our policy and our practice.

One more question, can you provide some color at this time of what you're looking for in a partner?

Well, we're looking for someone who is committed to oncology. We're looking to someone who is committed to the vision of TOCOSOL Paclitaxel as a taxane of choice. With a clear understanding of the requirements for the ongoing life cycle management of the product that is inherent in that vision. And we're looking for someone who can provide resources of course, money, but as importantly, clinical, regulatory, as well as the commercial resources necessary to complete development and launch the product.

You're not necessarily looking at just that big pharma then?

That is correct. I would continue to to say that players at the table, potential partners, while they do include big pharma, also include companies that at least Wall Street would probably characterize as specialty pharmaceutical companies.

Thank you very much.

Thank you, Allen.

Your next question comes from Mark Monane.

Couple questions here, in your press release you nicely outline why -- what the limitations are of Taxol. Could you go over for us how TOCOSOL potentially addresses those limitations and therefore, talk about its potential in the real world?

Sure. I'd like to hand it over to Michael to discuss that from a clinical perspective and then I'll give you the flavor of some primary market research that we've completed. Michael.

Mark, I think the two broad categories are one, the toxicities of the chromophore ethanol formulation, whether it's Taxol or the generic equivalent they have the same formulation. And there are a number of toxicities that are associated with chromophore. Neurotoxicity is certainly among the leaders there, but there are cardiovascular toxicities as well. Probably more vascular than cardiac. The other major area is the area of difficulty views. Taxol injection has to be diluted, has to be done in a pharmacy under a hood. An IV add mixture prepared and that is labeled to be given over three hours. TOCOSOL Paclitaxel is a ready to use product. It's drawn into a syringe and given directly intravenously in 15 minutes. And so I think that it's a very different kind of -- you don't have to have a pharmacy, you don't have to have an infusion clinic, you don't have all the associated with that and most importantly the patient doesn't have to sit there for three hours watching one drop after another go in.

That's fair.

Now, Mark, in terms of the primary market research and, this has been a pretty extensive study for us talking with not only oncologists, and in that category, not only the thought leaders, but the community practitioners, as well as the pharmacist, and the results are consistent with previous surveys that we've completed. Although those previous surveys haven't been anywhere near as extensive or statistically rigorous as this one. And I think the top line of results would say that number one remain, efficacy remains the trump card in oncology, however in this taxane space, we believe that even if TOCOSOL Paclitaxel is approved as a noninferior Taxol on an objective response rate as the initial claim, if that is against a Taxol control arm response rate that is viewed as in line with the practitioners' previous experience with Taxol as well as the label and multiple published studies, that that will be viewed as a strength of the product.

Secondly, regarding safety and tolerability, as Michael indicated the side effect is at the top of the list for oncologists, and at the top of the list by a wide margin is in fact peripheral neuropathy. And the reason is because there is simply no intervention available today to treat that condition to save time. And what that means is the therapy has to be interrupted for the patient to try to recover from that side effect and unfortunately the tumor is also recovering from the effects of the drug.

Sure.

Finally, with those things in place we believe that our features and advantages on convenience and ease of use provide a solid platform for differentiation. Now, if we are able, in the design of our study to prove superiority over the long run in terms of time to progression, and/or survival, again, we believe that those will be very very competitive to manage the life cycle of what would already be a competitive product.

That's very helpful. I have a question and it's an offshoot of your answer and that is a little bit about the pharmacokinetics and the pharmacodynamics. We can get a very high level of Taxol but that's not necessarily good because with extra efficacy one can get extra side effect profile. Can you talk about, without giving the results of the ASCO presentation, can you talk about those issues of release and leakiness and blood concentrations and how we should think about that in treating the cancer and preventing resistance?

Yes. I think that the easiest way to go back to it is to look at is look at what we've previously recorded and what we see and it coming out of the Phase 2a studies and now we're seeing the same thing out of the Phase 2b work and breast cancer and that is, when you give this drug on a weekly basis at the doses we're giving it, it is very well tolerated. People are able to get almost all of their intended therapy on time at full dose. They don't have to have it interrupted for toxicity, they don't have to have it delayed, they don't have to have dose reductions for the most part, and I think that that's the critical issue. We're able to get more in, we're able to get it in on a sustained, consistent basis, that's the key to efficacy and it's being done without toxicity that requires interruption or dose reduction.

Got it. And the last questions has to do with the CMC. You highlighted nicely in your press release, but can you talk about some of the issues addresses we know in biotechnology, CMC issues are becoming more and more important. I think they were always there, but be it seems to be more and more important. How -- what should we get -- what should we understand after a meeting from the FDA and your ability to moving forward into the Phase 3 trials?

Well, I think the major take away from that is that we have a stable product that is well, characterized, validated at a scale that is suitable to support launch, and with a process that is reliable, repeatable, and predictable i.e. all the good code words that exist to ensure GNP manufacture of products. More simply, we have a manufacturable product. And we feel good about that progress.

Sure thing. Thanks for the added information.

Thanks Mark.

Thanks, Mark.

Your next question is a follow up question from Matt Kaplan.

Hi, just a quick follow up question from -- on Mark's. Focusing a little bit on the neurotoxicity. If you look at the toxicity profile of potentially two of your competitors, one that's on the market and one that's not there, specifically Abraxane, on a weekly basis, they had a 10% weight of grade three neuropathy and Diopax had a rate of neuropathy in the 30 -- occurrence in the 30 to 50% range and a grade three of 4 to 19%. How does your -- obviously, you only have weekly data, but how does yours stack up to those competitive products? Which look like they have higher rates of neuropathy than Taxol, perhaps?

Higher rates of neuropathy than Taxol on a weekly basis? I don't think so because --.

No, no, no, no, those products look like they have a higher rate of neuropathy than Taxol. How does yours stack up?

Well, as we previously reported, we've got a 9% incidence of grade three neuropathy and no grade four neuropathy and that's on patients who have been on treatment for a year, in one case up to two years. The reason I was questioning you is because the data the Taxol data that Andy Seidman reported last year for weekly Taxol showed in all -- look at all patients, there was a 23% incidence of grade three peripheral neuropathy. When they looked at those patients who were dosed starting at 80 milligrams per square meter or less. There was still a 19, 19% incidence of grade three peripheral neuropathy. So I think we're seeing neuropathy rates that are favorable compared to what's been reported for Taxol.

We would conjecture based on the data that one of the features, advantages, and benefits of this product is going to be a favorable neuropathy profile. Now, obviously that is one of the points that will have to be proven, holistically in our total integrated safety database of all the studies and specifically we'll get our first head to head view of that at least versus Taxol in the Phase 3 study.

Okay. Thank you, that's all.

Thanks, Mat.

Your next question is a follow up question from Vinnie Jindall.

Hey, guys. Just had a quick question for you. In order to be able to reference the data that you guys produced for median survival in the ovarian non small cell and bladder trials for Phase 2s? Michael Stewart, like what generally are the median survivals you expect for those patient populations receiving either Taxol or another therapy standard of care?

Well, and that's why I mentioned the -- when I said that the trials we're doing are single agent TOCOSOL Paclitaxel and I think if you look at second line populations, whether it's ovarian or lung or bladder, they tend to be treated with combination chemotherapies, and they range depending on the size of the study and there are several review articles that have listed a number of these, but what we're seeing for ovarian in terms of a survival duration of, what is 16 -- 74 weeks, so it's 16, 17 months something like that, it's certainly consistent with what's been reported for combination therapies which is usually and other platinum plus or minus something else. May include Taxane. Taxane plus platinum is sometimes used as second line therapy in ovarian in patients who are -- do not have primary resistance. And 18 to 22, 24 months is certainly reasonable for combination therapy. And non small cell lung, a seven or eight months survival with combination therapy for second line is thought to be very good and we're seeing a simulated thing with single agent, again, with bladder if you get a 13 or 14 month survival, that's really where the numbers have been, and it's kind of locally advanced inoperable metastatic disease. So what we're seeing with single agent I think is certainly consistent with what's been published for combination regimens and second line treatment of patients with those diseases.

Great, thanks.

There are no further questions at this time. Gentleman, do you have any closing comments?

Yes, Michael thank you. If there are no further questions, we'd like to thank all of you for joining us today. As Michael indicated earlier, we will be presenting the results of our clinical pharmacology study and a poster presentation at ASCO on the morning of May 15, that's a Sunday, 8 a.m. and we would hope to see you there. Our next opportunity to speak formally with you will be at our annual shareholders meeting on May 23, in Belleview Washington, in addition we'll be presenting at the Needham & Company annual biotechnology conference on May 26, in New York City. Both the annual meeting and our presentation at the Needham conference will be broadcast live and archived on our website at www.sonuspharma.com. Sonus.Com. As always we appreciate your continued support. We look forward to sharing our progress with you in the months ahead. Thank you, Michael, that concludes the call.

This concludes today's Sonus Pharmaceuticals first quarter conference call. You may now disconnect.