Avid Bioservices Inc (CDMO) 2013 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Peregrine Pharmaceuticals first quarter fiscal-year 2013 financial results conference call. At this time, all participants are in a listen-only mode. Later we will conduct a question-and-answer session, and instructions will be given at that time.

(Operator Instructions)

As a reminder, today's conference call is being recorded. I'd now like to turn the conference over to your host, Mr. Jay Carlson, Investor Relations department. Please go ahead.

Thanks, Allie. Good morning, and thank you for joining us. On today's call, we have Steve King, President and Chief Executive Officer; Paul Lytle, Chief Financial Officer; Joe Shan, Vice President of Clinical and Regulatory Affairs; and Rob Garnick, Head of Regulatory Affairs. Steve will begin by providing an overview of the Company's progress over the last quarter, and how these events paved the way for several important near-term clinical data and regulatory milestones. Joe and Rob will discuss our clinical and regulatory plans as we advance our three Phase II clinical programs for Bavituximab and Cotara. Paul will finish with a summary of our financial results for the first quarter of fiscal-year 2013 and to-date, including discussion of our recently announced $30 million debt financing. After our prepared remarks, we welcome your questions.

Before we begin, we would like to remind you that during this call we will be making forward-looking statements that are subject to risks and uncertainties that may cause actual results to differ. These forward-looking statements reflect our current views about future events and financial performance, and are identified by the use of terms and phrases such as believe, expect, plan, anticipate, on target, and similar expressions identifying forward-looking statements. These risks include, but are not limited to, the risk factors detailed from time to time in our filings with the Securities and Exchange Commission including, but not limited to, the annual report on Form 10-K for our fiscal-year 2012 ended April 30, 2012, and quarterly report on Form 10-Q for the first quarter ended July 13, 2012, which will be filed later today.

Investors should not rely on forward-looking statements because they are subject to a variety of risks, uncertainties, and other factors that could cause actual results to differ materially from our expectations. And we expressly do not undertake any duty to update forward-looking statements, whether as a result of new information, future events, or otherwise.

I'll now turn the call over to Steve.

Thanks, Jay. Since the beginning of last quarter, it has been an exceptional time for Peregrine, as we have seen two of the most important milestones in the Company history achieved, transitioning the Company toward late-stage drug development. The exclamation point for these milestones came just last Friday with the report that patients receiving Bavituximab plus chemotherapy in our proof-of-concept study in second-line non-small-cell lung cancer had double the median overall survival compared to patients receiving chemotherapy plus placebo. These are truly remarkable results that are not only great for the program, providing a clear signal to proceed toward a Phase III clinical trial, providing proof of concept that Bavituximab is an active drug when given with Docetaxel, but also great news for the non-small-cell lung cancer patients in the trial.

While moving toward this important data, we also strengthened our balance sheet with a $30 million debt financing at favorable terms, and continued to see good performance at our manufacturing subsidiary, Avid Bioservices, successfully navigating regulatory inspections and posting another solid quarter of revenues. We are continuing to deliver on the milestones we laid out earlier in the year. And have more important events coming throughout the rest of this year, including our continuing Bavituximab partnering discussions and due diligence, which remains a highly active area; preparing for an end of Phase II meeting for the Bavituximab program; and awaiting additional clinical results from eight ongoing clinical trials that will help further shape the program.

With that, I will now turn the call over to Joe for a recap of the exciting clinical data that was presented last week. Joe?

Thanks, Steve. I'd like to start by reviewing important details of the clinical data from our Phase II second-line Bavituximab non-small cell lung cancer trial that was just presented last Friday in the plenary session of the 2012 Chicago multi-disciplinary symposium in thoracic oncology. I also encourage everyone to listen to the pre-recorded Webcast that can be found on our Website for a more detailed discussion of the data presentation.

This trial for our lead indication is a randomized, double-blinded placebo-controlled Phase II trial evaluating Docetaxel with or without Bavituximab as second-line treatment in patients with stage IIIb or IV non-squamous non-small cell lung cancer. On study, all patients received standard second-line chemotherapy of up to six 21-day cycles of Docetaxel at 75 milligrams per meter squared. In addition, patients were randomly assigned to receive a blinded weekly infusion of placebo, which we refer to as the control group, or one of two Bavituximab doses studied, either 1- or 3-milligram per kilogram, until progression or toxicity. The primary end point of this trial is overall response rate, and secondary endpoints include progression-free survival, overall survival, and safety.

Between October 2010 and October 2011, 121 patients were enrolled at 40 global trial centers. No single center enrolled a substantial number of patients, and approximately 50% of the patients enrolled were enrolled in US centers, with the remainder enrolled in Europe and India. All patients were previously treated with one prior platinum-containing doublet regimen. Patient and disease characteristics were well balanced across the three study groups, with no differences in age, gender, race, ECOG performance status, stage of disease, or prior treatments, which could have significantly impacted the study results.

Bavituximab continues to demonstrate a favorable safety profile, with a combination of Docetaxel plus Bavituximab being well tolerated, with no increase in frequency or nature of adverse events compared to the control arm. Notably, no increase in bleeding or clotting adverse events were reported with the addition of Bavituximab, unlike the experience with other compounds which target blood vessels.

In terms of efficacy outcomes, let me start with the primary end point, overall response rate, or ORR, which was determined by independent central radiology reviews according to RECIST criteria, or Response Evaluation Criteria in Solid Tumors. As reported in May when the study was initially unblinded, the response rate in the Docetaxel plus placebo arm was 8% compared to 15% in the Bavituximab 1-milligram per kilogram arm. And 18% in the Bavituximab 3-milligram per kilogram arm. And 16.5% in the pooled Bavituximab arm.

Though the response rate of the Bavituximab-containing arms was double that of the control group, this trend favoring Bavituximab did not reach statistical significance, with P values in the 0.2 to 0.3 range. This was expected of the trial, as this trial had the power to detect an 8% versus 26% response rate, which is more than a three-fold difference, at a significance level of 0.15, not 0.05. This is expected also in a Phase II setting, as the main purpose of a trial this size is to determine whether a drug candidate is promising enough to move into a larger Phase III trial with more statistical power.

Next, progression-free survival also favored both Bavituximab-containing arms, with P values approaching significance levels. Again, based on independent central radiology review, median progression-free survival in the Docetaxel plus placebo arm was 3.0 months. In the Docetaxel plus Bavituximab 1-milligram per kilogram arm, median progression free-survival was 4.2 months, corresponding to a hazard ratio of 0.57, with a P value of 0.08. In the Docetaxel plus Bavituximab 3-milligram per kilogram arm, median progression-free survival was 4.5 months, corresponding to a hazard ratio of 0.65, with a P value of 0.19. In the Docetaxel plus pooled Bavituximab arms, median progression-free survival was 4.2 months, with a hazard ratio of 0.6, and a P value of 0.07.

Now turning to overall survival, another secondary end point in the trial, but the preferred efficacy end point which represents direct clinical benefit. At the time of this analysis, over 70% of patients in the control group had died, while less than 50% had died in either Bavituximab arm, and survival follow-up is continuing. The Kaplan-Meier graph illustrates a clear and persistent separation of the survival curves, favoring both Bavituximab arms, demonstrating that overall survival is clinically and statistically significantly prolonged in the Bavituximab arms.

Specifically, in the Docetaxel plus placebo arm, the median overall survival estimate is 5.6 months. While in the Docetaxel plus Bavituximab 1-milligram per kilogram arm, the median overall survival estimate is 11.1 months, with a hazard ratio of 0.51, and a significant P value of 0.029. In the Docetaxel plus Bavituximab 3-milligram per kilogram arm, the median overall survival estimate is 13.1 months, with a hazard ratio of 0.54, and a P value of 0.071. In the pooled Bavituximab arm, the median overall survival estimate is 12.1 months, with a hazard ratio of 0.52, and a significant P value of 0.015.

We have performed extensive subgroup analyses on these data. And in both the 1- and 3-milligram per kilogram Bavituximab arms, subgroup analysis by age, gender, race, performance status and histologic subgroups showed a positive trend toward improved survival with Bavituximab. Also, the survival results were comparable between patients from the United States, Europe, and India, suggesting treatment benefit does not appear to be limited to a subset of particular patients, or where they were enrolled. Based on the positive outcome and overall survival, we're in the process of collecting available data on subsequent treatment at progression. And so far, there does not appear to be any differences across the groups.

It is important at this point to reiterate that this was a randomized, blinded, placebo-controlled trial in which no one knew what the patients were receiving in addition to Docetaxel. And the treatment and procedure schedules were identical in all three arms. We could not have conducted a less biased trial. The fact that the groups were well balanced coming into the study, and both Bavituximab arms showed similar benefit compared to the control arm, and that these significant interim survival results were not limited to a subset of patients, strongly supports that Bavituximab is an active agent which should be advanced into Phase III development.

As you can imagine, we are very pleased with these interim results, and look forward to announcing final results when available. Meanwhile, we're working towards the previously-stated goals of meeting with the FDA before the end of this year in order to initiate a confirmatory Phase III trial by the middle of next year.

I would now like to turn the call over to Rob for a regulatory update.

Thanks, Joe. As you have just heard from Joe, the data we announced last week has far exceeded our expectations. And I hope that you're as excited as I am over Bavituximab's potential. I feel strongly that Peregrine should be recognized for having the corporate courage to conduct the rigorous randomized, placebo-controlled Phase II trial that provided these robust data, and that provide the basis for us to plan for a pivotal Phase III program. We took an extraordinary amount of care in developing this Phase II trial design, and conferred with clinical experts and regulatory agencies, including the FDA, in the design of this rigorous clinical trial. Peregrine chose to conduct this trial to definitively establish the proof of concept of Bavituximab, and now plan to potentially include this data as part of a registrational package.

Having personally been involved in the evaluation of over 30 Phase II trials over my career, none of which ever achieved statistical significance, including many of today's blockbuster biotech products, I am personally extremely pleased with the quality of this data, and the clarity with respect to advancing Bavituximab into Phase III trials, which it provides. Our next steps are to present the data you saw last week to global regulatory authorities as part of formal end-of-Phase II meetings, from which we anticipate gaining concurrence into the planning and execution of a pivotal trial program. Normally it takes approximately 60 days to arrange such end-of-Phase II meetings, and following these meetings to submit IND amendments for the Phase III, and initiate the trial by mid-2013.

Touching on Cotara for a moment, Peregrine and the FDA are continuing to have positive discussions about the design and execution of a pivotal trial in GBM. We appreciate your patience as we strive to gain the most advantageous strategy for both parties for this novel and potentially important drug candidate.

I'll now turn the call over to Paul.

Thanks, Rob. Shifting gears now, I'd like to spend the next few moments covering a few financial highlights and our related financial goals. As I mentioned on the last call, it's important to understand that we operate a high-grid business model that includes a revenue-generating contract manufacturing business and an advancing drug development business. Let me first focus on our contract manufacturing business.

During the last quarter, Avid generated $4.1 million in contract manufacturing revenue, and we reiterate our revenue guidance of at least $15 million for fiscal-year 2013. In addition to the non-dilutive revenue we receive from Avid, on the last earnings call we mentioned that our next immediate focus was to secure a less dilutive debt financing vehicle similar to a term loan in the range of $20 million to $30 million. We recently executed on our stated milestone, and closed on a $30 million term loan with three extremely well-respected institutions -- Oxford Finance, MidCap Financial, and Silicon Valley Bank. Under the loan facility, we received initial funding of $15 million on August 30, and we have the option to receive an additional $15 million in funding.

This second tranche becomes available to us upon the attainment of certain pre-determined milestones, one of which was just achieved last Friday with the announcement of the positive overall survival data from our second-line lung cancer trial. The second related milestone pertains to having a positive end-of-Phase II meeting with the FDA, defined as our ability to move into the Phase III trial design. And we plan to have that end-of-Phase II meeting with the FDA before the end of this year.

Another potential source of capital we are focused on pertains to our unencumbered pipeline. As you can imagine, given the Bavituximab results that we shared with you on Friday, our partnering activities are continuing at a very active pace as we move closer towards the end-of-Phase II meeting with the FDA. Our stated goal is to have a partner onboard before we start the Phase III trial, and preferably before the end-of-Phase II meeting with the FDA, as we would like our future partner to be a part of that important meeting.

These are very exciting times for Peregrine. And we have been diligent in executing against our stated milestones. We look forward to keeping you updated on our progress. And we will now open the call up for your questions.

Allie?

(Operator Instructions)

Joe Pantginis of ROTH Capital Partners.

Congratulations on the great data. A few questions, if you don't mind, so bear with me. First, I just wanted to confirm something that I heard on Friday when Dr. Gerber presented the data. Can you confirm, did they say that the IDMC was the group that recommended pooling the data?

Joe, hi, this is Joe Shan. Yes, that's true. Typical on these blinded studies, you have an IDMC who can independently look at some of the results in advance of it being unblinded. The physical analysis plan is typical where you want to look at each group compared to the control separately. But because those two dose levels performed so similarly from each other, but better than the control group, it was recommended that we do a post-hoc exploratory pooled analysis.

Sure, that's helpful, thank you. And maybe just a couple quick nuance questions. First, thanks for providing the geographical breakdown update. That was really helpful. If you could maybe potentially further break down a couple nuances here. Have you or will you be looking at any of the potential mutation statuses of the patients in this study? And, also, have you looked at the outcomes of the patients, it was a range from 15% to 20% of patients, that received prior Avastin?

Geographic, I think we mentioned that there were really no differences. And the reason why we couldn't get into all of the details is there was a limited amount of time for David -- Dr. Gerber. As far as mutation status, that was not a requirement to enter the study. And, recall, PS is a broadly expressed target across multiple tumor types. So we did not collect that information on mutation, genetic mutation. And in terms of outcomes, we did look at the, for example, percentage of patients who received prior Avastin as part of their front-line therapy and there were no differences in outcomes with respect to that. There really were no other large enough groups to subset out.

Great, helpful again. Thank you. And then just two more quick questions. Obviously, you just alluded to also part of the mechanism of action for bavi. For this study or any of the current ISTs, and even the planned Phase III, what particular immune parameters will you be looking at, such as, say, infiltration of cytotoxic T-lymphocytes or any other parameters?

We're trying to build in some of that analysis, particularly into our investigator sponsored trials. They are a little bit cumbersome to build into large studies, especially large blinded studies that might be running in the future. But you're on the right track. The immune status of the particular immune cells that are inside the tumor through tumor biopsies. We're also building in tumor blood flow measurements. That's particularly in one of our other non-small cell lung cancer studies. So we're trying to really think about the mechanism of action and how it relates to preclinical studies. We're trying to really build in those same sort of analysis into some of our clinical studies.

Okay. And then just lastly. And thank you for your patience with me. Maybe a question for Rob or Joe. Rob, you did mention the fact that with your broad experience with multiple Phase II studies, highlighting the fact that Phase II studies are obviously not powered for statistical significance. And now you see these data here today. How do you think these data will affect the tenor, based on your multiple interactions with the FDA in the past with your upcoming end-of-Phase II meeting?

I think the regulators will be very excited. Certainly the FDA had a lot of input into our trial design. And I think they gave us some very wise counsel. And I think this is exactly the kind of study that they would like to see. And certainly it provides for us the clarity, which you rarely have in Phase II trials, to decide to go clearly into a Phase III study. And to actually really focus on replicating what we've just done. And I think that gives us, it derisks the program enormously, and really gives us a lot of confidence in how to go forward.

Great. Thanks a lot guys and congratulations again.

Charles Duncan of JMP Securities.

My congratulations on the positive results. My first question is, I'm wondering about the control arm experience. There's been a lot of bantering about, in terms of the median overall survival, it does seem like it's within the range. But do you think that 5.6 month number is low? And is it driven by the percentage of patients that are really Stage IV versus IIIb? And just what's your perspective on that?

Yes, I think I can start off and then turn it over to Joe. With regard to the stage of patients, I think in all of the arms it was around 90% Stage IV. So I don't think it's in any way related to that. I think clearly, if you look historically at the experience of docetaxel, that we are well within the range of that 5.6 months. It may be on the low end of the range but it's certainly consistent with some of the prior clinical trial results. And in effect if you even look at some of the interim data that's been presented from some of the other clinical trials involving docetaxel, it's very consistent with those results, as well.

And I think it's important that, while there's talk about it's on the low end, let's keep in mind that this is the reason the gold standard type of study to run is a double-blinded, placebo-controlled study. Because this is a patient population that is consistent with the entry criteria for all of the arms. It is meant to be a solid control for this particular study. Otherwise, you could compare with historical results for docetaxel and say that well we beat the previous record for docetaxel and so it must be a good result. But really, this is the gold standard study. It's meant to remove all the bias, make sure you have a similar patient population, receiving the same dosing regimen, with the same criteria and the same standard of care.

And I think, with that said, I think it's a clear result. I think it's actually remarkable that it's read out as a statistically significant result in overall survival. But, again, it's what the FDA would expect. And as we think about what's the next trial going to look like, the Phase III, obviously it's going to look very similar to this trial. In fact, with as few deviations from this trial design as possible, because that is what will give us the highest probability of success. Joe, I don't know if you or Rob want to add anymore to that?

Yes, I think, Steve, you already hit the nail on the head. This is the reason why randomized clinical trials are conducted, as you really shouldn't compare across studies. You do that early on when you have limited experience just as a benchmarking exercise. But you have to run randomized clinical trials and interpret the data in that context of that study, that subgroup. And we've already said that this is a smallish trial. It's not statistically powered to show major significance. But we did see that. And when we looked at the subgroups and the balance of patients coming into the study, it was well balanced. So there really isn't anything else we can say, and try to compare the number we saw in the docetaxel arm to other published studies. If you run enough studies and you can do some sort of meta analysis, it's certainly a good fit in on the control results.

Joe, Steve, I absolutely agree, and I appreciate the rigor of the design. And clearly compelling, at least in my mind, clinical proof of concept. I'm wondering what you would do, if anything, different as you go into Phase III. I know you haven't had your end-of-Phase II meetings yet with the Agency. But can you share with us, if you would, in terms of powering how much would you discount these results in terms of the magnitude of benefit that you would look for in Phase III? And what would you do different, if anything, in terms of geography or the entry criteria that Steve mentioned with regard to defining these patients and what they have?

Sure. I can address that. As we stated, we feel the results from this Phase II are so clear and compelling, we want to change as little as possible going into a Phase III. And really replicate hopefully these results. And recognizing that usually Phase II data look better than Phase III, so it's a little bit of the chicken or the egg. We are not going to be overly ambitious in the statistical assumptions going into a Phase III. And we've stated before that we would like to keep this study, a Phase III study, in the 300 to 500 patient range. Working backwards, you can imagine it's going to be a hazard ratio of less than 0.8 but not as low as 0.5. So somewhere in between there. And of course, significance of at least 0.05 with probably 8% or 9% power. So these are very standard assumptions for Phase III. And I think we have the Phase II data to really support that type of assumptions.

And again, just to follow on to what Joe said, I think the standard for approval for a drug in second-line non-small cell lung cancer will be another trial that would replicate this one. And as Steve said it's (inaudible) possible, I'm not sure what else we would do different, other than increase the N of the patients. And once we have that data, the combination of information between this trial and the next one, the pivotal Phase III, should really be, the plan would be that that would be the data that we'll need to achieve an approval. And I think if we achieve anywhere near the degree of clarity that we just obtained, I think this will be a pretty straightforward approval process. I'm sure the FDA would agree with me. But this is something -- and the FDA as well as other global regulatory authorities would agree that this is a pretty straightforward design. And we really just need to obtain concurrence on it and then to begin our execution by mid 2013.

And, Charles, I forgot to address your comment about geography in the Phase III. I think clearly we want as many of the patients in the Phase III to be enrolled where we would like to eventually market the product. So obviously US, Europe. We recognize the skepticism of the clinical trial results coming out of emerging clinical trial regions such as India or Eastern Europe. However, I think we demonstrated that in the study there really were no differences. But we, of course, are going to keep a close eye on actual enrollment and perhaps cap the enrollment if any particular country is enrolling a lot faster than others.

Yes, and I think that this is one of the -- just a quick follow on is -- as we're thinking about partnering discussions, and one of the reasons we feel it would be a big benefit to have a potential partner onboard in time for the end-of-Phase II meeting, is it really gives you an opportunity to think through the strategy. Because, again, we are viewing this as a global registration trial. And certainly the US, Europe and potentially other territories will be involved naturally. But really, it's the benefit of being able to ask all the questions that you want to ask at end-of-Phase II meeting. And to think through things like where you want to enroll the patients, as Joe mentioned. Because ideally you want the majority of those patients to come from the territories in which you are actually seeking approval. That's obviously a big benefit. It's one of the reasons we're really trying to move along the partnering discussions in the same sort of tempo as we are the end-of-Phase II meeting preparations.

Steve, that's a great segue to my final question, which was on partnering. If you can provide any additional color in terms of the strategy. Would you ideally seek an indication-specific partner? Or do you think that this could prove to be a broader platform accessing type partnership that might result in development of the drug across different indications?

I think we view this as a an oncology partnering exercise. So, clearly there is bavituximab in which we have the clinical data and the program more generally as it relates to treating cancer. But I think essentially, our strategy hasn't really changed. It's ideally an ex-US partnership. I think it will be all indications within oncology. I think it's just too difficult to try to split up different oncology indications. But certainly, geography is a way to split up the partnering exercise. With the goal of at least having some sort of a co-promote at the end of the day. We still have considerable upside left for preparedness as we continue to advance this program toward what we hopefully will be eventual product approval. So still primarily focused on ex-US partnering, but with the realization that in order to achieve our broader goal of also bringing in the capital that allows the Company to be financially secure through the end-of-Phase III readout, we think is an important part of that partnering discussion. So, like I said, probably ex-US partnering with some sort of a co-promote in the US is a reasonable outcome. There's been quite a number of good comparables out there for deals recently.

Okay, thanks for the added color.

George Zavoico of MLV & Co.

Thank you. And, again, let me add to the congratulations to the results of the Phase IIb trials. It's really quite extraordinary. Congratulations. My question relates to the platform technology that bavituximab represents. Charles alluded to it a little bit, as well, in his question. The mechanism of action actually suggests that it could be effective in most other cancer -- in many other cancers. But Peregrine, you guys had to choose to do the trials in those that were most likely to succeed based on prior data. And now you're pursuing some of these other leads with ISTs. These results obviously provide considerable confidence, certainly in lung cancer. But could you speak to how it affects your plans for other indications? In the partnering discussions, for example, are you looking for companies that might expand on the indication or just want to do the Phase III trials? So could you speak to that, please?

Sure, yes. I think that clearly our goal is to bring on a partner with the partnership to then move the program not just into a Phase III study but a Phase III study with additional clinical trials that will help explore the broader potential technology platform. Because, you're right, from our pre-clinical modeling and what we believe we'll extrapolate to the clinic, we believe most solid tumors, if not all solid tumors, will be PS positive. And that chemotherapy, again across many different types of chemotherapy, will up regulate that target.

I think the other aspect of running as broad of a program as we can -- and, as you alluded to, we have currently eight ongoing studies, we'll look at many different combinations and indications -- is that, more than likely, we're going to find combinations that work better than others. And those are the ones who want to really follow on. So, as you can imagine, as we're thinking about future clinical trials, additional trials combining docetaxel are attractive because we had the earlier Phase IIa results with docetaxel in which we had the very nice overall survival data in the breast cancer patients. The data from this study is obviously extremely positive, and we couldn't be happier with that. But, again, we think that there will be other combinations and indications that are particularly hot areas for development. And on the other counterpoint of that is the fact that we'll probably find some combinations that just don't look as a attractive. And that's part of the purpose of running the clinical trials we're running, is to really guide the program into those areas we're going to have the best benefit.

So I think we're going to continue to cast a wide net, find all of those indications and combinations that are particularly attractive, and then really take advantage of those. And, again, I view this as a very similar approach to what has been used for other highly successful drugs. Avastin is one that comes to mind. And Rob might be able to add a little color to that. But bottom line is we're really trying to follow a strategy we think will give the best shot at having multiple indications for this drug at the end of the day.

Yes, I think following on to what Steve said, one of the things that's always attracted me to bavituximab is the fact that it does have such a potential plethora of possible indications. And, as we pointed out, we really went into non-small cell lung cancer based on the signal-seeking data that we had originally gotten in early Phase I and Phase II studies. And I think that was a very wise way to go forward. And just like Avastin is, you'll remember Avastin was first developed in colorectal cancer. And then, once having a broad mechanism of action anti-angiogenesis, we then were able to develop that drug into multiple other cancers where theoretically its mechanism of action would still apply. And, of course, it's gone on to become an extremely profitable and valuable drug in the oncology arena.

So I think we're thinking about a very, very similar strategy for bavituximab. Basically use these ISTs to guide you in terms of where you're most likely to succeed and in what combination of drugs to combine with bavituximab. I think luckily we're seeing very good safety signals with the drug. And that's a really an important aspect that helps us to decide how broad the drug actually can be applied. So, using the ISTs and then potentially other signal-seeking Phase IIs, we plan to really maximize the benefit for this particular product. And I think we've got a broad potential and a bright future.

As a follow on to that, one of the things you guys pointed out a little bit earlier was that this was broadly stage IIIb, IV, and non-small cell lung cancer. You didn't really need to have any mutational status prerequisites here. Which also suggests a broader implication for this drug. And not only that -- maybe you can speak to that, as well -- but not only that, it also suggests that it might also be active in the front-line setting. You had equivocal results earlier this year. But the hard data really coming out of the front line is the overall survival, which we expect later this year. So how does that change your view? And does this give you added confidence that perhaps the front-line data will also turn out to be more positive than first reported this year?

Yes, I think a few points and then Joe might want to add a little on to that. I think that, obviously as we're thinking about the mechanism of action, this modulatory activity of bavituximab, its ability to turn on the immune system, that clearly that's something that could, at the end of the day, show the biggest benefit in overall survival. As patients who are on treatment long enough are able to elicit a strong immune response, which then helps hold the disease in check for an extended period of time. And certainly that factor fits right in with the second-line non-small cell lung cancer data where we're having the biggest impact on overall survival. And, again, it's not unexpected with immunotherapies and it's been seen with other immunotherapies that are in the clinic or have earlier reported results. So I think that that's something we could see across the board.

I think every clinical trial is an individual study in order to look at a particular combination and a particular stage of disease. Some are going to work, and, undoubtedly, if we run enough studies, some are not going to have positive results. And I think we're anxious, like everybody else is, to see the data from the front-line study. But in addition to the carboplatin-paclitaxel combination randomized study, we're also exploring pemetrexed in a front-line setting. So we do believe that front-line non-small cell lung cancer should be a target, and still has a good probability of success for the Company.

It's just a matter now of, again, studying it in these individual studies, And, again, taking the hot lead into a pivotal trial at the end of the day. And we'll take the same approach with other solid tumor indications also, where often the shortest route to the market is in the high unmet medical need, which is typically in the second-plus line of therapy, as we've done in non-small cell lung cancer. And, again, we want to continue to explore that in other indications, as well. Joe, I don't know if you want to add anything about the mutational status?

Yes. I think, George, you're right. We did not select based on that. However, I think bavituximab, in theory, could work though, even with some of these ultra-targeted molecular drugs. It's just that was not the purpose of this particular study. In the future that's something I think we would be interested in studying those combinations, as well. As far as differences across different studies, even of our own, basically Steve already mentioned, every study is a different experiment. They share some similar traits in trial design but, at the end of the day, you just have to see what the data says. In our front-line study, I think the surrogate readouts, the response rates in PFS, went very clear in terms of any difference. But those are surrogates and not direct clinical benefits. So, we are hopeful that we might see something in survival but not yet reached that point. But I think that certainly is a possibility and at this point it just isn't here.

One last quick question. On your imaging program, I-124 PGN650, you're enrolling patients in this trial. Could this be also part of the pivotal Phase III? Do you think you could track tumor response in the Phase III with I-124 PGN650?

Yes, I think that given the current timetable of the end-of-Phase II meeting and beginning of study, it's just probably not in the cards for the Phase III. Certainly, I think, as we think about future development, and I think that this is something that also partners like very much, is that I think that that really could be a very valuable tool as we go forward in selecting the right combinations and the right stage of disease. And really being able to have almost like a biomarker that would allow us to guide the development of the bavituximab program, rather than having to run hundreds of randomized Phase II studies to pick the hot leads, is we may be able to get a really early read on that through the imaging program. And the utilization of that in our bavituximab program in the future. But as far as being ready for the Phase III, unfortunately the time line's too tight and that ship is already sailing along.

And, quite frankly, with the survival results we're seeing in the, quote, unselected population, there really is not a need to select patients in order to enrich results in the future. I think that often that's a strategy that's necessary if across the board you're not seeing positive activity. But maybe in a particular subset. For example, some mutational status. That certainly makes sense. I think bavituximab is broad enough that that's not a requirement. But we are developing imaging platform, as Steve said, potentially a tool for selecting different combinations or such.

Okay, thank you very much. Appreciate you taking the questions.

(Operator Instructions)

Greg Wade of Wedbush.

Let me add my congratulations to the very strong data set. Joe, with respect to concordance with disease control and response, can you tell us whether you've had a chance to interrogate the data to see whether there is some concordance there with response in overall survival? Thanks.

We have not looked at that extensively because, again, historically, response rates are a very poor prognosticator for survival. In this case, and obviously we had seen overall within our cross groups a similar trend of increased response rates and prolonged PFS. And now certainly the survival prolongation. But short answer is no, we've not really tried to correlate those two because it's not necessarily a shrinking of tumors on radiograph that leads to this. And, in fact, it actually brings up an interesting point, is that there was a comment from the session chair about the applicability of really resist-based definitions. And if you evaluate drugs such as bavituximab, that might have an immune component, and that may not be the best way to evaluate. And certainly, again, we're looking at the survival end point as related to one that's determining the activity, the meaningful activity, and not really relying on a surrogate.

And with respect to time-to-best response, there's been some observations that other immunologically active agents have a much delayed time-to-best response. Was there any difference in the time-to-best response in either the control or the bavi arms?

I don't know the exact results at the moment. But I can say that, by and large, no, there were no differences in when patients responded. Keep in mind, they were only on chemotherapy for up to six cycles. And that's one of the reasons why, in a study of this design, that you actually cap it. Otherwise there could be imbalances in the number of chemotherapy cycles. That really comes down to interpretation. So the response is they have to basically achieve very quickly in the first few cycles.

Great. And then lastly, with respect to survival. Have you had a chance to review the narratives around death? Do you see any differences in the site of failure or ultimate cause of the demise of the patients between the control and the bavi arms that might be informative as to how the drug's working in the study? And thanks for taking my questions.

Sure. No. I think we haven't done statistical analysis. Certainly, we view all FAEs that result in death. Generally, these are disease progression. That's the primary cause of death. It's an outcome of their disease process and not so much a toxicity or something.

Great. Thanks.

I'm showing no further questions at this time. I'd like to turn the conference back over to Mr. Steven King for any closing remarks.

I'd like to thank everyone again for participating in today's quarterly conference call. We certainly look forward as we continue to advance the bavituximab program, make other advancements in our overall corporate activities. And look forward to discussing that at our next earnings call in December. Thank you very much.

Ladies and gentlemen, this does conclude today's conference. You may all disconnect. And have a wonderful day.