Vericel Corp (VCEL) 2011 Q3 法說會逐字稿

Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Aastrom Biosciences third quarter 2011 Investor conference call. At this time, all participants are in a listen-only mode. After opening remarks, we will open up the call for your questions. Instructions for queuing up will be provided at that time. I would also like to remind everyone that this call is being recorded for replay purposes. I will now turn the conference over to Mr. Brian Gibson, Aastrom's Vice President of Finance. Sir, please go ahead.

Thank you, Karen, and good afternoon, everyone. Welcome to our third quarter 2011 conference call to discuss our most recent financial results, and the progress of our development programs. Before we begin, let me remind you that on today's call we will be making Forward-looking Statements covered under the Private Securities Litigation Reform Act of 1995, and all of our projections and forward-looking statements represent our judgment as of today. These statements may involve risks and uncertainties that are described more fully in our filings with the SEC, which are also available on our website. In addition, any forward-looking statements represent our views only as of today, and should not be relied upon as representing our views as of any subsequent date. Joining me on the call today is Aastrom's President and Chief Executive Officer, Tim Mayleben. Following our prepared remarks, we will open the call to your questions. Let me start with the review of our financial results.

For the third quarter of 2011, Aastrom had a net loss of $1.9 million, or $0.05 per share, compared to a net loss of $5.9 million, or $0.21 per share for the same period a year ago. The lower net loss in 2011 reflects the non-cash change in the fair value of our outstanding warrants. Our operating loss for the quarter, which excludes the impact of the warrants, was $7.4 million or $0.19 per share, compared to $5.9 million, or $0.31 per share a year ago. Research and development expenses for the quarter were $5.8 million versus $4.2 million for the same period a year ago. The increase in R&D expenses was primarily attributable to the preparations for the Phase III REVIVE clinical program for ixmyelocel-T, as well as an increase in non-cash stock based compensation expense. General and administrative expenses for the quarter remained flat with the prior year at $1.7 million.

At the end of September, Aastrom had $11.9 million in cash and cash equivalents. Our cash use of $6.6 million during the third quarter was below our previous forecast of $7 million. And for the fourth quarter, we also expect our cash spend to be in the range of $6 million to $7 million. That completes the review of our financial results, and I will now turn the call over to Tim.

Thanks, Brian. Since the FDA approved our special protocol assessment in late July for the phase 3 REVIVE-CLI study of ixmyelocel-T, we have been actively preparing for the commencement of this pivotal study here in the fourth quarter. Our preparations have included outreach to many US clinical sites, and I'm happy to report that we have nearly completed our site recruitment with more than 70 clinical sites planning to participate in the pivotal Phase III REVIVE trial. We are now working on site contracts, budgets, training for site personnel involved in the conduct of the trial, and protocol reviews with our medical staffs, and of course institutional review boards, or IRBs. Over the past few months, we've also conducted thorough testing of our cell manufacturing facility here in Ann Arbor to ensure its efficient and reliable operation when the pivotal study begins.

We believe the pivotal Phase III REVIVE study is well designed and properly powered to show the positive effects of ixmyelocel-T treatment in patients with critical limb ischemia who have no other treatment options. With a target enrollment of almost 600 patients, robust study design, and powering assumptions, we believe we're setting a very high bar for success, and we also believe that if the outcome of this large pivotal Phase III trial is positive, it will support a biologic license submission, or BLA, for US FDA registration at the end of this pivotal study. As I mentioned earlier, we plan to begin enrollment very shortly. Our patient recruitment efforts will be supported by next week's presentation of the final results from the Phase II RESTORE-CLI study at the American Heart Association's scientific sessions 2011 in Orlando, Florida. On Monday, Dr. William Marsten will present the 12 month follow-up results for all patients from this Phase II-B study. Recall that the RESTORE-CLI study was a double blind, randomized, placebo controlled Phase II-B clinical study, and the largest study of its kind ever conducted.

We believe that both the rigor with which the study was conducted, as well as the promising results, account for its acceptance for presentation at the AHA meeting, which, as many of you know, is the largest and most respected peer reviewed cardiovascular meeting in the world. Our program in dilated cardiomyopathy has also been progressing well. In September, we presented the final 12 month results from the IMPACT-DCM Phase II study at the Heart Failure Society of America meeting in Boston. The study showed that surgical delivery of ixmyelocel-T was well tolerated and consistent with improved heart function in patients with DCM, especially those with ischemic cardiomyopathy. We also reported top line six-month interim results from a second clinical study in DCM patients. This study showed that catheter delivery of ixmyelocel-T led to fewer adverse events and comparable efficacy results when compared to the results with surgical delivery.

We're scheduled to meet with FDA later this quarter to discuss end points and other issues relevant to the next phases of development for the DCM program. We want to be sure we understand how best to move this program forward in this orphan indication, and once we've completed the discussions with FDA, we'll incorporate their inputs into our development plans, and then initiate a Phase II-B study of ixmyelocel-T utilizing catheter delivery in the treatment of DCM some time in the first half of 2012. I'm also happy to report that we recently received a key composition of matter patent from the European patent office, providing protection throughout the European Union for various claims regarding the composition and production of mixed cell populations, which characterize ixmyelocel-T. This was our second patent award this year, and it significantly expands our patent estate for ixmyelocel-T.

I'm also pleased to announce that we recently redesigned and upgraded our website at www.aastrom.com. We have a number of new features there, and will be updating the site regularly, including some videos, so I encourage you to visit the site for the latest Aastrom information. So in summary, this has been another very productive quarter for Aastrom. We've advanced our 2 lead clinical programs, presented our clinical findings in multiple peer-reviewed settings, collaborated with regulatory authorities and key opinion leaders in severe, chronic cardiovascular diseases and regenerative medicine, expanded our intellectual property, and prepared for the launch of the pivotal Phase III REVIVE clinical trial. We recognize the importance of the CLI study to our company, to investigators, to patients, and to our shareholders, which is why we will be working diligently to ensure its timely and successful execution. And, of course, we'll look forward to updating you on our progress. So that concludes our prepared remarks and, Operator, we'd like to open the call to questions.

Thank you, sir.

(Operator Instructions)

Our first question comes from the line of Brian Lian from Global Hunger Securities.

Hey, guys, thanks for taking the question.

Good afternoon.

I was wondering what comfort -- if you could just remind us, what comfort you have received from the FDA that a single CLI trial would be sufficient for a filing? I know in the past you've talked about two, and I know you have an SPA for the first trial, but have you received any sort of a formal guidance that a single trial would be sufficient?

Brian, it's a great question, and I think, what we've said is we believe, based on the discussions that we've had with FDA, that it is possible for us to receive BLA approval with the single large Phase III pivotal trial in no option patients. Having said that, I think, as you know, the FDA typically requests, requires, I think, that sponsors have two Phase III studies, but I think if you look at the history, there's -- I think the studies that have been done in the CLI, in particular the no option CLI patient population, it's mostly been a single, large, Phase III clinical study. So I think we're looking at historical comparables, and I think we're also looking at the very high unmet medical need in that area. I think you also referenced that we've also had discussions historically with the agency about possible label expansion opportunities and a second pivotal trial in the poor option patient population, but I think it's -- we will continue those discussions, and certainly look to continue to talk to the FDA about it.

Thanks for the additional info. And then on the DCM Phase II trial, can you provide any additional info on the design? Would you be looking primarily at ischemic patients, and the size of the trial, and expected enrollment time lines, and so forth? And then if you have any information on the size of that sub-population.

Sure. Yes, no, good question. So again, with the DCM, again, just to recap, so we've completed our Phase I, Phase II studies there. These are studies with both catheter delivery and surgical delivery in a total of about -- I think it's about 60 patients or so. So moving forward, I think, as I mentioned in my prepared comments, we are planning a meeting with the FDA later this quarter to talk specifically about what the end point would be for this orphan indication. And, yes, I think what we're looking for right now for the next stage of development is, one, from a delivery standpoint, we want to be delivering the cells via catheter. Again, in our prepared comments, we had indicated that we saw better safety, no big surprise there, but better safety, better tolerance with the catheter delivery, and we also saw, as the data that we presented at the Heart Failure Society of America meeting showed, that, in particular, the patients with ischemic DCM responded better and so that, again, should not be a big surprise, because the mechanism of action that we've described for the ixmyelocel-T product lends itself particularly to what we call severe, chronic, ischemic cardiovascular diseases.

From a size standpoint, in terms of the next phase of development, I'd be offering you pure speculation at this point, until we've had the meeting with the FDA, but once we've completed that meeting, we will have much more insight into what that trial would look like. But again, I think, one, we've got some very nice Phase I, Phase II data. We've got some nice catheter delivery data. We've got some nice data, in particular, in the ischemic DCM patient population, and we have an orphan indication for the DCM patient population. So, I think with all of those at hand, we would expect to have, again, a rather small Phase II-B study, and something less than 100 patients, Brian. We're estimating 60 to 80, but we're speculating a bit until we have the opportunity to meet with FDA on that.

Thanks very much.

You bet.

Thank you. And our next question comes from the line of Joe Pantginis from Roth Capital Partners.

Good afternoon. Thank you for taking the question. Tim, two questions. The first one is very short, but maybe more of a more complex answer. How are your ongoing discussions with the FDA going with regard to your second SPA for the poor option Phase III. And then the second question is, I don't think it could be under-touted, the fact that you've reached 70 sites ready to go for this study. So I was just curious, what can you say has been somewhat of the behind the scenes activities, both, past activities and ongoing activities that have been able to get you to that 70 sites so fast? The education process that you guys have been going through and the types of processes you will be going through to enhance enrollment as well. Thanks a lot.

Yes, sure. No, thanks, Joe. So on your first question about the discussions with the agency on the SPA, I think, what we've tried to do is -- I think you've heard me say before, we don't want to negotiate publicly with FDA or collaborate publicly with FDA on the poor option patient population or the poor option SPA. So we've been trying to keep those discussions between the company and FDA on that. So I don't want to comment too much on that. I think what you can count on from us is, when we have additional insights and information from those discussions, that we will be out communicating to folks about that. Again, I think you've heard us say our goal in any of this is to be as transparent with you as possible, because that's the culture that we're trying to cultivate here at Aastrom.

Sure.

In terms of the sites,I've said before, we have a very experienced team here and, I think they deserve the credit for getting out and talking to the sites, qualifying the sites, and it's not necessarily glamorous work, but it's operational execution, and so I think that all the work that they have done, and will continue to do, quite honestly, is paying off. So they very much have been in head stone mode, will continue to be, and, I think to your point, or to your question, rather, about, some of the things that we're doing, I'll just tick them off briefly here. I think one of the things that we've tried to do with this study, again, learning from those that have gone before, is we're making sure that we're only doing this study here in the US. Our goal is to have 80 sites across the US and part of the reason for that is the CLI patient population is elderly, as you know. If you recall from our Phase II, the average age of our patient in that study was in the late 60's. So we want to make sure the sites are as close to those patients as possible, so that means having more sites, but that should reduce the amount of travel time that any one patient has to have to participate in the trial. I think secondly, we're doing a lot of qualification of the sites. So we've got a very extensive questionnaire to qualify these sites, but I think the fact that, as you know, we've got 70 of them already indicates the enthusiasm, and I think it's at least in part data driven and, in part, reflects the fact that there's not a lot of other options out there for these patients.

So physicians and sites that treat these patients are looking for options for these patients. The other things that you've heard us talk about, we have a specialty recruitment vendor that we've brought on, and has been working with us, because our goal is to start aggressively right from the start with enrollment, and so we will be prepared to do that with site-specific recruiting strategies. Because, again, just to think through this with you, recruiting patients in a large central metropolitan area is fundamentally different from recruiting strategies that are going to be successful, perhaps, in rural Alabama. So we're developing in conjunction with this, again, very experienced vendor strategies for each site that are going to pay off. And, of course, other things; to ensure we have a homogenous patient population, we have a centralized eligibility review committee that will make the determination of which patients to include in the study and which not and, again, I think we've been very thoughtful and very execution oriented with respect to the operational aspects of this study.

Great, thanks so much, Tim.

Thank you, Joe.

Thank you, sir. And our next question comes from the line of Jason Napodano of Zacks Investment Research.

Good afternoon, everyone.

Hi, Jason.

Quick question on the site. How many of those 70 sites, or I guess of your 80 goal sites, were part of RESTORE?

That's a great question, Jason. If you recall, we had 20 sites participate in the Phase II and, it's -- I think it's about 60% of those sites are coming back into the Phase III. So, 12 or 13. But the other thing I'd highlight is that a number of these sites have participated in some of the other trials that have been run, biological trials. So, again, most of those have been gene therapy studies, as you know, but they do have experience treating these kinds of patients with biological therapies, which is, again, very helpful.

Got you. And as far as the data that we're going to see in 2 weeks at AHA, I assume we're going to see a subset analysis of just Rutherford 5 patients?

That's our plan. And just -- it's only six days now, so we've been waiting, it seems like, obviously, since early June to be at this point. But AHA starts this weekend, and just to remind everybody, Dr. Marsten who is a principle investigator, one of the principle investigators in the RESTORE-CLI study, is going to be presenting the data next Monday, next Monday the 14 at the American Heart Association meeting.

I said two weeks, but I don't even know what date it is today, so I apologize.

I'm with you on that. I'm with you.

Okay. So as far as that subset analysis, I'm sitting here thinking about what to expect from those patients, and I guess I could see it maybe going either direction, but it seems to me like when you have a sicker population, you might have a greater opportunity for separation between ixmyelocel and the control. Am I thinking about it correctly?

I think you are. Again, the exact results, or the precise results will be available next Monday, but, yes, I think you're thinking about it the right way and, again, I don't want to say more than that in terms of specific numbers, but I think you've heard us say qualitatively we're encouraged, very encouraged by the data. And again, you and others can take that a lot of different ways, but we'll just keep saying, we're very encouraged by the data. We've only got six days now before everybody can take a look at that themselves, and confirm that we should be encouraged.

Got you. Okay. And then REVIVE, it's a 1 to 1 randomization, correct?

That's right, Jason, 1 to 1.

Okay. So patients start at bone marrow aspiration, if there is an event between that time period and re-injection, you're still doing an aspiration for the control population, correct?

That's right. Yep.

Okay. So there's no -- barring some statistical anomaly, we shouldn't really be too concerned about events that are going on in that two week period, because assuming we get a normal 50-50, the statistical hit should happen on both the control and ixmyelocel.

I think that's the right way to think about it. Keep in mind, as we've talked about, this is a chronic cardiovascular disease. These are not acutely ill patients and, in fact, one of the exclusion criteria is specifically, if the patient -- and again, it's not perfect. No physician is going to be perfect on this, but if a patient is acutely ill, and they're going to experience an event, or they're likely to experience an event in less than 3 months, then they really shouldn't be in the trial. And again, just part of the disease is that this is generally a chronic disease that -- atherosclerosis, as you know, is a chronic disease that builds up over time, and periodically there are acute events, but generally speaking it's a long-term chronic disease that builds up over time.

Got you. I appreciate the answers. Thank you.

You bet. Thanks, Jason.

Thank you. And our next question comes from the line of Jason Butler from JMP Securities.

Hi. Thanks for taking the question. I'm just going back to the CLI, the potential to file in a single trial in no option patients, have you had discussions with the FDA focused on a magnitude of benefit that you would need to show to pursue a single trial filing, and if so, do you think that the trial design, and your assumptions for magnitude, and your statistical powering for the Phase III trial would satisfy the FDA's view on a sufficient magnitude?

I will answer that, I guess, with the -- so first of all, Jason, thank you for the question. But, I think the right way to answer that is, we're experienced, but we're not the FDA, and so we're speculating a bit about how the FDA might look at this. But just to sort of walk down the path here, I think the way that we have thought about it is that if we're able to replicate, see similar results in our Phase III as we've seen in the Rutherford 5 patients in Phase II, then we think that that will be very compelling to the regulatory authorities in reviewing the data. That, I think, is -- probably from your experience you know that being able to provide the regulatory authorities very compelling, very statistically significant results, that not only the primary end point, but the other end points, the components of a composite end point, are all pointing in the right direction, that we're seeing good wound closure or wound healing in patients.

All of those things, I think, have to line up in order for -- and again, the standard that the agency would apply to us is no different than they would apply to any other sponsor, that generally speaking the FDA would want to see very compelling, concordant results to rely on a single study. Having said that, again, I think that we've powered this study very conservatively. I think the powering assumptions we've disclosed, that we're expecting a 22% treatment group event rate, and a 34.5% control group event rate, which provides a relative difference of about 35%. That's a very conservative control group event rate assumption, given the historical data, that is the historical US data. So we feel like we very conservatively powered this study, Jason, and we're going to run the study. As you heard me say earlier, we've done a lot of things to ensure a homogenous patient population in this Phase III study, so I think anything that anything that can be done, we've done, and we're going to continue to execute on that.

Okay. Great. And then maybe switching over to DCM for a second. And again, sorry for likely asking you to speculate a little here, but you mentioned a couple of times the fact that this is an orphan indication. Based on your conversations with FDA so far, do you think there's any potential for the Phase II-B you plan to run to serve as a pivotal trial, either alone or in combination with another pivotal trial?

So again, that is a very interesting question. It's one, Jason, that we've thought about internally and, I think there's part of us that certainly hopes that if we run the Phase II-B in sort of what we call internally a registration quality Phase II-B study, that it's possible because it is an orphan indication, that that could be considered a trial that could be added to the registration package for the DCM indication. So, again, I think it's possible, but again, we'll know more sometime this quarter here, and be back talking to you and others about what we've learned. But we're certainly hopeful for that, but we're not counting on it as part of the development plan. If we're able to do that, if the agency allows us to take that tact, then obviously I think there's some nice economic advantages there.

Okay. Great. Thank you very much.

Thanks, Jason.

Thank you. And our next question comes from the line of Jason Kantor of RBC Capital Markets.

Thanks. I think I was the third Jason on this call. A little bit of a psych out on me the first two times around. So a couple of -- a lot of my questions have been answered, but -- I might have missed it, but could you give us your latest thoughts in terms of the time line for enrolling the study? When -- how long do you think it will take?

Yes, good question. So what we've been projecting is that the study, about 600 patients will take about 18 months to enroll, and maybe just to take that a step further, the end point is a 12 month amputation-free survival end point. So, if we meet our enrollment goals and then follow the last patient for 12 months, we expect the entire study to run about 30 months. And the only other caveat that I'd -- while that's our assumption, Jason, I think we will know, about six months into the enrollment, how we're doing with that assumption. Again, I think you may remember me saying previously that on our quarterly updates, we will be providing enrollment updates on that trial.

That would be very helpful.

So people won't have to guess.

Okay. And you mentioned that in preparation you were doing some kind of thorough testing of your process, your manufacturing process. I was just wondering if you could kind of explain what you meant by that?

Yes. Yes. Some of the things that we've been doing with the facility and the team here is to, actually -- as you may know, you can buy bone marrow, just like you can buy blood and other products, and so we've been acquiring bone marrow, and ramping up the volume in the facility to make sure that all of our processes and procedures are working effectively at higher volumes. So it's really just shaking out the facility and making sure that all the processes and procedures are working at volume. So we wanted to make sure that we tested it, obviously, before we got into the actual trial volumes, which, again, I think it's just a little bit of belts and suspenders, but a good process to go through.

I just had a couple of other questions. You have this -- I think there's some kind of eligibility review committee that's looking at making sure people are the right kind of patient. How selective is that committee going to be, and how -- what's your expectation for how many people you have to screen to actually enroll one patient? Is that a possible bottle neck for you in terms of enrolling the study? Also, what criteria are you using to make sure that somebody is not too far gone, in terms of losing a limb or being close to death from some other cause?

Yes. So we've been very -- I think this really goes to the inclusion, exclusion criteria, which we've been incredibly thoughtful about. And not only, obviously, leveraging our expertise, but leveraging the expertise of our external steering committee, and, as you noted, the eligibility review committee. These are very experienced clinicians, very experienced vascular surgeons. So I think we've been very thoughtful about the inclusion, exclusion criteria, which I think nicely addresses the question of how do we ensure that these patients are sick enough, but not too sick. I think the eligibility review committee, the way I like to think about it, is that rather than having 80 physicians and 80 sites interpreting the inclusion, exclusion criteria, no matter how much training you do at an investigator meeting, or subsequent investigator meetings, or any of the other site training or video training that you do, you're bound to get different folks' interpretations of that.

So, we thought it best to rigorously train the handful of physicians that are going to be staffing the eligibility review committee, who themselves are very experienced vascular surgeons and interventional cardiologists, who have experience with this particular patient population, and so their determination is final. They will be making the final determination of which patients come into the study and which don't. In terms of how many we think that we'll have to screen to get patients into the study, because we're working -- most of the sites that we're working with are experienced in working with these patients, and so when we talk about tissue loss patients, or Rutherford 5 no option patients, they've got a very clear idea of who those patients are. And so there is some subjectivity to it, but I think our expectation is, because we're working with very experienced sites, and -- one of the interesting experiences that we had is, interviewing a lot of these sites and asking them to complete these site qualification questionnaire, that we were able to, we think, really hone in on the experienced sites that understand this patient population best.

Thank you.

Thanks, Jason.

Thank you, sir. And our next question comes from the line of Stephen Willey of Stifel Nicolaus.

Hey, guys. It's actually Amol Pawar sitting in for Steve today. How are you?

Good. How are you?

Good. Most of my questions have been answered. I just have a couple of questions, if you don't mind. Could you remind us what the baseline characteristics of this Phase III trial will be compared to? For example, the Phase III TAMARAS trial.

Yes, so again, that's a great question. The TAMARAS study, as you may remember, included Rutherford 5 patients with existing tissue loss. I think the big difference between TAMARAS and our planned study is that the TAMARAS study was run in, I think it was 30 or more countries, across five continents in the world. And, of course, I think you heard me comment earlier that our study is going to be run at 80 sites in one country, that is here in the US. So, some of the geographic variability that Sanofi saw in the TAMARAS study, we certainly don't expect to see. The control group variability will be substantially different. But the patient population will be very similar. It will be the no option CLI patients with existing tissue loss, or what are, in the vascular community, known as Rutherford 5 patients.

Okay. Thanks. And probably the last question. Is there any anecdotal evidence now that you've had patients that have been out of the trial for a while, any anecdotal evidence for any events post the one year period? Do the benefits seem to wear off, or do they seem to last long term?

It is a great question, and unfortunately the protocol for the RESTORE-CLI Phase II-B study didn't provide for the opportunity to follow these patients past the one year time point. So the answer is we just don't know. We -- anecdotally, we have had patients contact us after the unblinding of the study, and are very happy. Some of the patients that were treated are obviously very happy with the results. So, we have -- I guess you did ask whether we have anecdotal, so, yes, we do have anecdotal data that the effect is lasting well beyond one year, but we don't have definitive data, is where I was going with my initial comments. We don't have definitive data, but we certainly have anecdotal indications that the therapy is lasting a while. And, of course, you may recall, we have some patients where the open label DCM studies that have similarly had very good results, lasting two years or more, so far And then probably exhibit A has been a compassionate use patient that was treated with upper extremity CLI more than four years ago, and has never had to be treated again, one, and, two, has not had further progression of his disease, which, as I mentioned earlier, CLI generally is a chronic, progressive disease and, by all accounts, he should have seen further progression of this disease. So, we're very encouraged by it, but we're also cautious because it's just anecdotal data at this point.

All right. And is this something that you would be able to perhaps record after the REVIVE trial, especially if they would like to -- as part of the package, instead of running another pivotal Phase III trial?

Absolutely. Our intention is to follow these patients. Again, we'll have to go through the protocol process and IRB approvals for that, but there's no reason to think, at this point, that we wouldn't be able to follow these patients past, not only the one year efficacy follow-up, but, also, we're going to follow the patients for at least an additional six months for safety purposes.

Okay. Great.

All right. Thanks for the questions.

Thank you. And our next question comes from the line of George Zavoico of MLV & Company.

Hi, Tim. How are you? And congratulations on a good quarter.

Thank you, thank you.

Just got a couple of quick questions. It sounds to me, from your prepared remarks and from some of the answers to the questions, that the DCM trial, the catheter DCM trial that you're preparing to start early, or in the first half of next year, it sounds like to me that pretty much the protocol design is set, that you've pretty much decided on what patients, how to do it. What exactly is left with the FDA to discuss in the fourth quarter meeting?

I think the two big things, George, are, one, we want confirmation that the agency is okay with our proposed design, and in particular, we haven't settled on two features; one is the size of the trial and, of course, the size of the trial will be driven by the second factor, which is the end point. We don't know at this point what end point the agency would like us to use in the Phase II-B and the Phase III. We have some ideas, we've submitted those ideas to the agency, but we need to have the discussion with them to understand how they think about those.

Okay. Is the choice of catheter pretty much set as well? I know there are a number of options you could use for a catheter.

Well, in terms of the specific catheter, no. But, as you pointed out, there's an abundance of catheters out there, but we'll finalize that in the coming months here, and, again, there's no technical feasibility issue there. It's just picking the catheter that the physicians would most like to use.

Okay. And with regard -- actually, this sort of refers to both trials, the II-B coming up with DCM, as well as the CLI trial. Can you give a ballpark range of what you expect the costs will be per patient in each of these trials?

Yes, we can. And again, I think we have -- part of the reason for our comfort with the estimates here, in terms of numbers is we've run the large Phase II-B study in CLI, and in DCM we've got 60 patients worth of data, and know what features we're going to carry forward into the next phase of the program. So for the CLI program, we're estimating that that trial will cost somewhere between $45,000 and $50,000 per patient. So, with the 600 patients we've been saying, a total cost of that trial, including manufacturing costs of about $25 million to $30 million. And for the DCM program, it's a little bit less than that. We're still in that range, probably in the $40,000 to $45,000 per patient.

And how many patients for the DCM are you looking for again?

We've said we think it will be --

The size of the trial.

We think less than 100 in the phase II-B, somewhere in the 60 to 80 range. But again, we'll get confirmation of that once we've had the discussion with the agency.

I'm sorry. You did mention that earlier. I'm sorry.

That's okay.

Finally, there's been a lot of interest among some of the other stem cell type companies in acute coronary syndromes. There seem to be some pretty good results that some of these trials are showing. Could you comment a little bit on your views toward expanding ixmyelocel into that? I know you're going to be very, very busy with DCM and CLI, but I'm wondering if that's in the back of your mind, and when you're going to be able to pull the trigger on something like that, if you're going to be able to pull the trigger at all?

That is a great question. We have some good ideas. As I think we've mentioned before, we have some pre-clinical work that we're not talking much about at this point, because we, obviously, have 99% of our focus on the Phase III REVIVE-CLI trial, and then secondarily, the DCM program, which is soon going to be late stage clinical as well. But having said that, we are exploring a number of other indications. We've said our focus is severe chronic cardiovascular diseases, and certainly there's aspects of the ACS patient population that fit nicely into that category. But I think it's premature for us to be talking about anything that we're planning there at this point, because we are so focused on the late-stage clinical programs in CLI and DCM.

Something to look forward to perhaps down the line. In that regard, I imagine with the successful trials you've had already, you've probably also -- and I think you may have mentioned this somewhere along the line, that there's been some interest among investigator sponsors to do trials on their own. Is that something that's perhaps going to happen?

It's a great question, George, and we do have folks that have contacted us. But I come back to, gee, all of those things require people's time and attention, and we are just so focused on the CLI and DCM programs. We've had a lot of success as a result of that focus, and so until we are well into the Phase III program, I think are you going to see any of us start to pick our heads up and look at something different. I think we feel like we've got to make those -- the late stage programs are going to drive the most value for our shareholders, and I think it's, too, it's what partners, potential partners are most interested in as well because, late stage programs are obviously not far from commercialization, and commercialization drives revenue and profit. So that's going to be where our focus is.

Quite understandable. Thank you very much. I look forward to seeing you all in New York next week.

Sounds great. Thanks, George.

Thank you. And our next question comes from the line of Boris Peaker with Oppenheimer.

Hello, and thank you for taking my questions. A lot of questions have been addressed, but I just want to ask a few more follow-ups regarding clinical sites, and specifically, what are your criteria for accepting clinical site into a trial? Can you put it in a context? You mentioned earlier, I think, about a third of the clinical sites from the Phase II are not going to be included in the Phase III, so I just want to kind of understand the reason behind that decision.

A lot of it is, I think, some of the sites that were in the Phase II study, Boris, just didn't enroll patients, or didn't enroll actively, that is screen and enroll. So I think it is in our best interest to exclude those from the study going forward, because as you've heard us talk about before, we understand the Phase III CLI program is all about enrollment, enrollment, enrollment. So we want to get sites into this, and we have. We've been very assertive in making sure that sites have access to these no option CLI patients as part of their practice. So I think that's been one of the most important criteria. But I think the others -- some of the ones that I mentioned earlier, I'll just note again. One is certainly prior experience, weighs importantly, prior experience with either cell therapy or gene therapy studies. And then access to, like I said, access to the patient population. We want to make sure that the sites are geographically close to where we know, and where the ICD-9 codes indicate that the CLI patients are living and working.

And in terms of the physicians themselves, do you interview them? And I know that you're focusing specifically on the US to reduce the variability in the standard of care, but I'm just curious in terms of the physicians themselves, how variable are their approach to treating these patients, and how are you accounting for that?

Yes. Well, that's a very interesting question, Boris, because, as you note, even within the US there is geographic variability in how CLI patients are cared for. Different wound treatment protocols, for example. And I think one of the things that we've tried to do, as I mentioned earlier, is to ensure a homogenous patient population coming into the study. Even though there may be practice differences, having the centralized eligibility review committee is, I think, really the key to making sure that we get a homogenous patient population into the study, and then we obviously can't tell the doctors how to practice medicine, but they have to meet certain basic requirements in terms of making sure that they have wound care capabilities at the site.

I see. And as you speak to these physicians, and you bring them on board in the clinical sites, which you've had a lot of success recently, I'd want to get a sense of how much interaction you have with them and, also, what is the feedback that you're getting from them? Particularly since you're talking to physicians that have experience, that have had some experience with cell therapies and gene therapies and so forth. How do they view ixmyelocel-T?

It's a complex question and I think that the general feedback that we've gotten is enthusiasm for the fact that we're running the Phase III study with a focus on helping patients that have no treatment options today. You may have heard me say in prior calls, when we think about the treatment options for these patients today, once they've exhausted the revascularization procedures, first the endovascular procedures and then the open bypass procedures, the only remaining treatment option is amputation, and I think all of us today would say that, amputation is just not a great option.

It's not a good option for anybody. We wouldn't wish that on anybody, and yet that's the only option left for these patients in order to save their lives. So again, I think, physicians, as you know, are caring. They get into the profession because they care, they want to help patients, and I think having an option like ixmyelocel-T available to their patients is, I think, really what's driving the enthusiasm for being involved in the study. I think the other one is actually more scientific, Boris, and that is that we're pioneering here. This is -- being part of a large pivotal study like this is exciting to a lot of physicians to be part of changing the practice of medicine.

I see. Okay. Well, thank you very much for taking my questions and congratulations on your progress.

Yes. Thanks, Boris.

Thank you, sir. And our next question is a follow-up from the line of Joe Pantginis from Roth Capital Partners.

Thanks for taking my follow-up. Tim, it's not me looking to be controversial, but this is a topic that comes up every once in a while when I talk about this concept. I'm looking at different indication, different technology altogether. If we're going to bring in what I would describe as the Dendrion drama that has been going on for the last several years, I'm just curious, if you look if there are any potential spillover with regard to discussions with your physicians on the CLI side, with regard to any potential push back about autologous therapies?

It's an interesting question, and I don't think it's controversial at all. Again I think, as you indicated, especially with some -- a lot of the discussion about what's been going on with Dendrion. I think there was a lot of enthusiasm initially for that program, and I think, obviously, again, we're not close to it, but we certainly heard some of the repercussions of that. But I think to draw a couple of important differences, as I was mentioning earlier, I think one of the real issues here is -- at least as I understand the indication that Dendrion is pursuing, that either was or has become a very crowded, or much more crowded therapeutic indication.

Sure.

And so as a result, patients and physicians, in particular, have other options. And so I think, when we look at CLI, and in particular the no option CLI patients, as I was emphasizing earlier, there are no treatment options for these patients. And so that, fundamentally, is a very different market, a very different physician mind set about treatment options. Again, if your choice is to amputate a patient's leg, or to use an autologous therapy such as ixmyelocel-T, it's a -- we hear from physicians it's a very easy choice. On top of that, I think you've heard us say, the fact that we're starting with the patient's own cells, we're starting with their bone marrow as our raw material for making the product gives a lot of comfort to the physicians from a safety standpoint. And, of course now we've got -- I think you've heard us say, more than 200 patients now have been treated without consequence, without serious adverse events. So it's safe, it's an option in a market and in an indication for which there are no options, other than amputation and so we're actually getting, I think, again, as indicated by the number of sites that are interested in participating, we're getting a lot of physician enthusiasm, because there aren't many folks that are wading into this water, and we are. And so, again, we're getting a lot of support from the vascular community for that.

No, that's great. Thanks so much for the follow-up.

Appreciate the question, Joe. Thank you.

Thank you, sir. And that concludes our question-and-answer session. I'd like to turn the conference back to Mr. Mayleben for any final remarks.

Thank you, Karen. I just want to thank all of our callers for your questions today. Our listeners, for your continued interest in Aastrom, and in particular, our shareholders for your continued support. This is undoubtedly the most exciting time in the history of Aastrom, and we look forward to updating all of you in the weeks ahead. In particular, I'd highlight the presentation of data by Dr. Marston at the American Heart Association meeting next week. Also, I just want to note that we're finalizing plans for what we're calling an R&D day webcast that we expect to hold next week. That will be after the presentation of data at AHA, but once we finalize the plans for that, we'll make sure to get the details out to everyone so that you can tune in if you're available. So thank you very much.

Ladies and gentlemen, thank you for your participation in today's conference. A replay of the call will be available after 7.30 PM Eastern Time on November 8, 2011 until 11.59 PM Eastern Time on November 12, 2011. You may reach the replay by dialing 855-859-2056, or from outside the United States at 404-537-3406. The pass code for the replay is 17046596. Thank you for your participation, and you may now disconnect. Everyone have a good day.