Celator Pharma Conference Call to Discuss Phase 3 Trial Results for VYXEOS: Full Transcript

Operator: Welcome to Celator Pharmaceuticals Conference Call to discuss the Top line Results of its Phase 3 Trial of VYXEOS, also known as CPX351. At this time, all participants are in a listen-only mode. An audio webcast of this call is available on the Investor Section of Celator's website at ir.celatorpharma.com. This call is subject to copyright property of Celator Pharmaceuticals and recordings, reproduction or transmission of this call without the expressed written consent of Celator Pharmaceuticals is strictly prohibited. As a remainder, today's call is being recorded. I will now turn the call over to Fred Powell, Chief Financial Officer of Celator Pharmaceuticals. Fred M. Powell: Chief Financial Officer: Well, good morning everyone and thank you for joining us to sharing this existing news for AML patients and for Celator. The press became available at 4.00 P.M. Eastern time yesterday, March 14, 2016 and can be found on the Investor's section of the Company's website. There are a number of people participating on the call this morning. From the Company are Scott Jackson, Chief Executive Officer; Dr. Arthur Louie, Chief Medical Officer; Dr. Lawrence Mayer, Founder President and Chief Scientific Officer; Derek Miller, our Chief Business Officer; and Lisa Deluca, our Vice President, Regulatory Affairs. We're also diluted to have world-renowned leukemia experts on the call. Dr. Gail Roboz from New York-Presbyterian Hospital and Weill Cornell Medical Center and Dr. Jeff Lancet from the H. Lee Moffitt Cancer Center & Research Institute. Both have considerable experience treating patients with VYXEOS, having been involved with a number of our clinical trials. Dr. Lancet is the Principal Investigator for the Phase 3 trial. Please note that today's conference call and webcast may contain certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. To the extent that any statements made on this call contain information that is not historical, these statements are essentially forward-looking and are subject to risks and uncertainties detailed in the company's filings with the SEC such as Form 10-K, Form 10-Q and Form 8-K reports. I will now turn the call over to Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals. Scott? Scott Jackson: Chief Executive Officer: Thank you Fred. Good morning everyone. While this is the day we've all been waiting for and working so hard towards, I am very pleased to report that the Phase 3 trial for VYXEOS has met its primary endpoint demonstrating a statistically significant improvement in overall survival in patients with high risk or secondary acute myeloid leukemia. In addition, the trial demonstrated statistical significance in secondary endpoints of induction response rate, both the CR+CRi rate, as well as the analysis of CR alone. VYXEOS also resulted in lower 60-day mortality and similar rate for grade three or higher non-hematologic and hematologic adverse events. It is very exciting and gratifying to be in a position to report today that VYXEOS significantly extends the lines of older patients with high risk or secondary AML compared to the 7+3 regimen. I want to thank Arthur, our entire clinical team and the independent parties who worked with us in the trial for the outstanding job they did in conducting this trial. Working with AML key opinion leaders and internal colleagues, Arthur is the architect of the clinical development program from phase 1 through phase 3 for VYXEOS. I also want to thank the Leukemia & Lymphoma Society for their support in developing VYXEOS, which started back in Phase 2 and continued into Phase 3. Lastly but importantly, I want to express the gratitude of everyone at Celator, to all the patients and clinical investigators along with their teams at the sites in the United States and Canada who participated in this trial. With their courage and dedication, we look at this trial in high risk AML patients as the first step to potentially becoming a new standard of care in AML, sub-plant 7+3 the standard of care for roughly the last four decades. Now, let me turn the call over to Arthur to provide more detail about the Phase 3 trial. Arthur? Arthur C. Louie, M.D. :Chief Medical Officer: Thank you Scott. As Scott mentioned, we are very excited about the results of this trial and what this could mean for older, high risk or secondary AML patients. Before I discuss the specific results, let me quickly review the trial design. The trial was conducted at 39 sites in the United State and Canada with patient enrollment beginning in December 2012 and completing in November 2014. This was a randomized controlled clinical trial in patients aged 60 to 75 years with untreated high risk or secondary acute myeloid leukemia. Patients were randomized 1:1 to receive either VYXEOS or the 7+3 regimen, which is conventional cytarabine and daunorubicin treatment. An independent nonopathologists reviewed each patients information prior to randomization to confirm the diagnosis. The nanopathologists on a blinded basis assessed each patient's results to determine whether the patient achieved a respond after treatment. The trial was designed to enroll 300 patients. A total of 309 patients were actually randomized for the trial, with 153 patients on the VYXEOS arm and 156 patients on the 7+3 arm. Patients were stratified to balance accrual to each arm of the study by age and AML type. The AML types included were treatment-related AML, AML with documented history of MDS with prior treatment from hypomethylating agent, AML with documented history of MDS without prior treatment with hypomethylating agent , AML with documented history of CMML and de-novo AML with characteristics of MDS. Patients were well-balanced between the two study arms based on age and AML type. The primary emphasis of the endpoint was overall survival. We will also be discussing a few of the secondary endpoints as well as top line safety assessments. These include induction response rate where response was defined as complete response, referred to as CR, and complete response with incomplete hematologic recovery, referred to as CRi. Both the CR rate as well the combined CR+CRi rate will be discussed. Rate of stem cell transplant was an endpoint, 60-day mortality and adverse events. Overall survival is measured from the date of randomization to death from any cause. Patients not known to have died at last follow up are sponsored on the date they were last known to be alive. Overall survival was analyzed on intent to treat basis with all randomized patients analyzed. A stratified log rank test was used to compare VYXEOS to the 7+3 arm, and was performed after 236 death occurred. The median overall survival for patients treated with VYXEOS on the trial was 9.56 months compared to 5.95 months for patients receiving 7+3, representing 3.61 month improvement in favor of VYXEOS. The hazard ratio was 0.69 and the p-value was 0.005. This represents a 31% reduction in the risk of death versus 7+3. In addition, it was quite compelling to report the percentage of patients alive 12 months after randomization and that was 41.5% on the VYXEOS arm compared to 27.6% on the 7+3 arm, representing 50% relative improvement. The percentage of patients alive 24 months after randomization was 31.3% for the VYXEOS arm versus to 12.3% for the 7+3 arm, more than 150% relative improvement. This is the first time an overall survival benefit has been demonstrated versus 7+3 in this patient population. This is great news for patients and their families. You'll remember that last year, we announced that VYXEOS showed an impressive 43.2% relative improvement in induction response, which was CR+CRi. We only report CR+CRi in our responses realizing that this may be conservative compared to other reports, but we are not aware of any evidence that suggests partial response or something less than a partial response translates to improved overall survival. The observed induction response rates with CR+CRi were 47.7% for VYXEOS compared to 33.3% for the 7+3 arm. This was a statistically significant benefit with a p-value 0.016. I want to point out that the rate of CR alone was 37.3% for VYXEOS compared to 25.6% of 7+3. This was also a statistical significant outcome with the p-value of 0.040. The rate of stem cell transplant was 34% for VYXEOS arm versus 25% from the 7+3 arm. I will now move on to discuss top line safety information. A key indicator of safety is early mortality. Results for the 60-day all-cause mortality was 13.7% with VYXEOS arm compared to 21.2% on the 7+3 arm. No substantial difference in Grade 3 or higher adverse events was observed between VYXEOS and 7+3. In the intent-to-treat population, Grade 3 or higher, hematologic adverse events were similar for overall infections, febrile neutropenia, and bleeding events. In the intent-to-treat population, Grade 3 or higher, non-hematologic adverse events were similar across all organ systems, including cardiac, gastrointestinal, general systems, metabolic disorders, musculoskeletal, nervous system, respiratory, skin and renal systems. It's established that a significant efficacy improvements provided by VYXEOS had not come at the expense of significant additional or new toxicities. In summary, VYXEOS met the primary endpoint of the trial, significantly improving overall survival and achieved statistical significance for induction respond and also resulting favorable early mortality. This is terrific news for newly diagnosed patients with high risk or secondary AML. At this time, I would like to introduce Dr. Lancet and ask him to comment on his results and his experience with VYXEOS. Jeffrey E. Lancet, M.D.: Senior Member and Chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center: Thank you Arthur. As you know, I have been involved with the CPX-351 with the VYXEOS program for close to 10 years now. So I have a lot of firsthand experience in utilizing this drug and seeing its benefits over the years ranging from the original Phase 1 trial to the current Phase 3 trial. Because you mentioned, this in my opinion, this represents an important breakthrough in AML in general, but in particular for a group of patients that really is very difficult to treat, primarily patients with secondary AML, meaning that it's AML that came from the prior hematologic disease such as myelodysplastic syndrome or a myeloproliferative myelodysplastic overlap syndrome, but also patients that have received prior chemotherapy for another cancer and subsequently developed AML. And as a group, these patients do very poorly. We recognize through historical data and inclusion in other trials that this patient population really stands out as a group that does exceptionally poorly when it comes to responses to chemotherapy namely 7+3 and overall survival. And these findings of poor outcomes have been replicated time and time again throughout multiple clinical trials for the years. But having said that, I think it's also important to recognize this group represents a large proportion of the AML population. We recognize now that probably in the range of 30% to 40% of all cases of AML have a secondary designation meaning that 30% to 40% of these AML cases have arisen from a prior myelodysplasia or secondary hematologic disorders. So it's a significant proportion of the overall AML population and it's particularly important in the older age group of patients, mainly over age 60. And in general, the over age 60 population comprises the majority, the large majority of newly diagnosed AML. So you can see that it's an important, a very important and large sub-group of the overall AML population that does very poorly. So this represents a real breakthrough I think in the fact that we have a therapy that is effective at extending survival and improving response rates in these patients. So it's great news all around. My personal experience with this drug is that it's well tolerated and we can see that evidenced by the lack of any increased serious toxicity rates or early death rates in the patients treated with the for CPX-351. It's typically been administered in the hospital as an inpatient setting. It can also be administered on the outpatient setting, in particular in the consolidation regimens that we use post-remission. Again, in my experience, it's been well tolerated, at least is well tolerated as the traditional 7+3 and I think Dr. Roboz can probably attest to as well, patients don't seem to lose their hair on this regimen for the reasons that are not completely clear to me, but it's a very welcome I guess lack of side effect that patients don't expect going into this. So, it's kind of fun, a little fun point to emphasize. But in general, more importantly, it's been well tolerated there. We haven't observed earlier excess death rates and the infection risk in general doesn't appear to be any worse than it would be with 7+3 regimen or in the setting of neutropenic patients with AML who are already at an increased risk of infection. So, I have been very pleased with the overall efficacy that we've been able to demonstrate in this trial, the safety profile and the fact that it really represents the very important group of patients that to this date have never really had any type of effective therapy, and in my opinion, is in a great need of novel treatments and I think we took a major step forward in this direction with this study. Arthur C. Louie, M.D. : Thanks Jeff. And I'd like to ask Gail Roboz to talk about what she thinks of the totality the data that we've collected and where it might fit into the treatment paradigm for AML? Gail Roboz, M.D.: Professor of Medicine and Director of the Leukemia Program at the Weill Medical College of Cornell University and the New York-Presbyterian Hospital in New York: Good morning everybody. Well, this is a fun call and it's fun day in acute leukemia land. I think that many of us have felt a bit jealous of our colleagues in other areas of the hematologic malignancies as we watched sort of one breakthrough after another, and we are feeling a little bit left behind and lost in acute leukemia and it's fun to have what I view as a clean wind. It's better and it's safer than what we currently have as the decades' old standard of care and I think it's important that we don't have to breakout the textbook and statistics and try to take a crash course in advanced complicated statistics in order to understand what's happened here. The CR rates are better, the overall survival is better, which we were hoping would be the case and predicting would be the case based on the fact that in intensive retreated patients that has historically been a predictor of overall survival in acute leukemia, we actually have a difficult to treat patient population which has more patients than CR, more patients able to go on to transplant and more patients living longer without excess toxicity. So for a change, this is not complicated. I'd also like to comment though that I do not view this as only statistically significant. So these are clinically significant data. The improvements that we are seeing are not measured in hour in terms of overall survival. These are real improvements for AML patients and I think what it does is open up the platform of a new standard of care on which to build going forward into the future. Chemotherapy is far from dead in acute leukemia. It has still and continues to still get more patients into remission than anything else. And I think that it should have been predictable that just like new technologies and new ways of making almost anything, and in this case, drugs should translate into something better for patients, this finally did. I have a slide that I've maybe become a little bit known for that, that I started quite a few years ago in talking about this agent that if you can't beat them, join them and there is a conceptually and intellectually found to have wanting to make chemotherapy better to want to improve on what our best treatments is. And it looks like that's happened. So, now there is a platform on which to consider this as what can be added to it, what among additional novel agents can potentially be joined with this one, given the favorable toxicity profile that makes it extremely attractive for combinations. Even if it's not to be combined, I just want to emphasize the point of what I view as again a clean win with both statistical and clinical significance. Arthur C. Louie, M.D. : Thank you. Thanks to both of you. I will turn the call over to Scott. Scott Jackson: I would also like to thank Drs Lancet and Roboz for sharing their perspectives on the results this morning. At the conclusion of our opening comments, they will be available to answer questions. Based on the clinical data from the phase 3 trial along with the data phase 2 trials, we believe we have a clear path forward for regulatory filings in the United States and Europe. Based on the trial results, Celator plans to submit a new drug application for VYXEOS to the FDA later this year, our current expectation is by the end of third quarter. Upon receipt of the positive data, we have submitted a pre-NDA meeting request, but the meeting has not yet been scheduled. We also intend to compete a marketing authorization application or MAA with the European Medicines Agency in the first quarter of 2017. We are submitting the findings from the Phase 3 trial to the American Society for Clinical Oncology 2016 Annual Meeting. In addition, we will present additional aspects of the trial at future medical and scientific conferences to allow the AML medical community to fully appreciate the findings. Meanwhile, in anticipation of making the product available to patients, we continue to prepare for commercialization of VYXEOS in the United States on our own and we plan to partner VYXEOS outside of the United States. If approved, VYXEOS would be well-positioned to take the first step towards becoming a foundation of care for AML patients. To explore the full clinical potential of VYXEOS, we are proceeding with additional clinical development in other AML patient populations and other blood cancers. This is being done by investigator initiated trials, oncology cooperative group trials, and company-sponsored trials. We expect to make additional announcements later this year regarding other trials. Lastly, we believe the Phase 3 success with VYXEOS provides definitive clinical validation of the CombiPlex platform, which we think will create opportunities to apply this technology to new combinations of drugs, not only chemotherapeutics, but also molecularly targeted agents. And we believe the work conducted to-date positions the company to pursue R&D collaborations with other pharmaceutical companies. Now I'd like to turn the call over to the Operator for any questions. Ryan. Question & Answer Operator: Thank you. [Operator Instructions] Our first question comes from the line of Joe Pantginis with Roth Capital Partners. Your line is now open, please go ahead. Joseph Pantginis: Roth Capital Partners: Hi, good morning. Thank you very much and congratulations on this historical event. It's like you said, it's a long time coming and thank you very much for all the feedback today on the call. So my first question is, I guess, if you look forward and we hope for the eventual approval now of VYXEOS, how easy do you think the transition would be in the practice now to be able to transition or sub-plant from 7+3? Scott Jackson: Joe, well, good morning and thank you very much. It's great to be talking to you. You've been -- you initiated on us, you were the first and a long-time coverer and supporter of the company. So it's great news. I'm going to ask Derek to comment in terms of the potential adoption of VYXEOS. Derek Miller: Chief Business Officer: Hey Joe, thanks for the question. Hopefully you can hear me okay. So that's a great question. I think the first thing I would want to point out is that from our market research and from talking with investigators, the primary place of treatment for AML patients is in the hospital or near hospital setting. So we conducted research in the US and in Europe with institutions, with hospitals that were near institutions or affiliated with institutions and also private practice and share the profile. And based on the profile that we shared, which is very similar to what Arthur walked through today, we feel that the adoption of VYXEOS for these patients would be I think pretty quick actually. They feel that the benefits they've seen from the -- not only response rates, but the survival is very compelling and because it is a head to head study, I think it blended itself well for sort of a transition from 7+3 to VYXEOS for the patients that are in our trial. Scott Jackson: What I'd also like to do is at this moment ask Dr. Roboz, your perspective on that. Gail Roboz, M.D.: Yeah, I mean I think that that's going to be falling off a log actually because there is a lot of -- I think their hearts fall when we have to give 7+3 and that's not really fair to the regimen because it really has emerged as still the one to be, but because that is giving newer, better, smarter, faster in a manner that is both uncomplicated and actually easier for patients, I think is actually a pretty straight forwards shot. There is nothing particularly new for the treating oncologists to learn here. And that makes it pretty easy to adopt and again, as I sort of, the time to allude to the time to alluded to before, it's not particularly complicated to receive this. So you see the population, it includes a lot of AML patients, they are difficult to treat. There is a fatigue I think in giving what is viewed as an old treatment and here you have something which is quite easy to explain to a patient that now looks like we may be able to test better because you chances of remission are higher, your chances of overall survival are better and your chances of toxicity are better. So it's tough for me to understand what the barrier would be to adoption of this. Joseph Pantginis: That's very helpful. Thank you so much. And then a quick question that I will have is I know you talked about potential or at least guided towards potential pricing in the future or where you might look to do this. But the other question that I have that talks more to the data is talking to really the importance of these additional months towards potential curative therapy and I couldn't tell before if Arthur made any comments about the follow-up transplant rates. Thanks a lot guys. Scott Jackson: Why don't you talk about the clinical benefit aspect, Arthur, and then we will sort of transfer it over to Derek in terms of pricing. Arthur C. Louie, M.D. : Sure. I think the clinical benefit comes quickly in the form of getting a higher response rate and that reduces you risk of early death due to the AML. But also it comes in the form of making a substantial proportion of patients eligible for procedures like transplant. So that of course occurred and a lot of the -- one of the aspects of this trial that we will have to look at when we have all of the data and can go over in real detail is to look at the impact of the induction treatment on the way of transplant, the kind of patients. What we do know right now is that the substantial number of the CR patients became eligible for transplant and were transplanted. And we have the data for those patients which will come out later, showing the benefits in term of their survival. So, yes we have all that. Scott Jackson: So, Joe, the only other comment I would add on that and one of the comments that Arthur had made earlier, in this particular trial, 34% patients who received VYXEOS went on to receive stem cell transplant versus 25% on the 7+3 arm. That's the only data that we're in a position to comment on at this time as we've submitted the additional data such as that along with information like event-free survival, duration of remission etc. To ASCO, should say, it's going in today as late breaker to ASCO, and we want try and preserve the opportunity to present as much of that information as possible at the conference. And with that I will turn it over to Derek to answer the latter part of the question, which was about pricing. Derek? Derek Miller: Hi, Joe. So clearly we are pretty far out, ahead of filing let alone launch, so, we haven't set price. I think what we've been saying all along and I will continue to reinforces is that in this day and age, it's critical to establish the value proposition and I think with the profile that we've just shared today, we think we have a very compelling profile that delivers value to all the key stakeholders: patients, providers, and healthcare system. That being said, we have enough research in the US and ex-US to get a sense of whether or not a premium price would be acceptable and reimbursed in all of the different countries, and the answer is yes, but the specific price bands, if you will, are still under review and we're still doing work to assess what the pricing will be. So we're not at a point where we can disclose that yet, but we do believe that's if the profile does warrant a premium price and that we will deliver really, I think, important and compelling value to patients and providers and providers and health system. Joseph Pantginis: Guys, thank you for the answers and congratulations again. Scott Jackson: Thank you Joe. Operator: Thank you. Our next question comes from the line from Mike King with JMP Securities. Your line is now open, please go ahead. Mike King: JMP Securities: Thanks for taking my question and let me add my congratulations as well. My first question is, did you guys sleep last night? Scott Jackson: Not well. Mike King: Yeah, I was going to say I'd be pretty stoke myself. But anyway seriously, Scott, I know you answered Joe's question about the rate of transplant in both arms, but I missed it, unfortunately I am jumping between phone calls this morning. So if you wouldn't mind repeating that for me? Scott Jackson: Sure. In the Phase 3 trial, 34% of the patients on the VYXEOS arm went on to receive the stem cell transplant versus 25% in the 7+3 arm. And what I was commenting on is that is additional information along the line for stem cell transplant, event-free survival, duration of remission were examples I gave of additional information that we are submitting to ASCO as a late breaker later on today. Mike King: Okay got that. And... Scott Jackson: But one thing I would say though that I neglected to say, Mike, sorry, I neglected to say when I was responding to Joe's. One thing we feel very good about is that the data are consisting across all metrics that we've looked out so far. So, everything is going in the right direction. Mike King: Yeah, right. I was going to say, if you could just remind us what -- how you treated transplant, did you stratify by whether patients were transplanted or not and I assume that mortality statistics that you're excited are intent to treat, whether -- irrespective of transplant, correct? Arthur C. Louie, M.D. : Yes, that's correct. The primary efficacy is overall survival and that was by intent to treat. We stratify patients by age and AML type. We expected that with the higher response rate we should have more patients do transplants, we did. So all of that is expected and then there is a whole series of other things that we will get into as we get deeper into the data a little bit later. And so, we will take a very close look at the patients who qualify to transplant and their outcome. Mike King: Okay, terrific. And can you say anything about dose intensity in both arms or is that going to be embargo for ASCO? Arthur C. Louie, M.D. : We don't have that data now. I can tell you that historically dose intensity has been excellent, the best and true with both arms in the sense that the onset of the adverse events occurs really after you give and has completed the induction treatment and that's true in both arms. So most of the cytopenia-related events occur a little bit later after you have chance give all the drugs. So that is the intensity of not affected. Mike King: Okay, great. And then finally, did you give the rates of febrile neutropenia? Arthur C. Louie, M.D. : We have it, it's not released. But the rates -- what I can tell you is that the rates were comparable in both arms and they were in the 65% to 70% range in both arms. Mike King: Okay. That's fantastic, thanks very much guys. Looking forward to seeing the data at ASCO. Scott Jackson: Thank you, Mike. Operator: Thank you. Our next question comes from the line of -- with Cantor Fitzgerald. Your line is now open. Please go ahead. Analyst: Thanks very and congratulations on the data. Just a question, I know that trial was very well powered and -- but I am just curious as to the differences that you -- that have been observed just at least on a numerical basis between Phase 2 trial and the data set that we're seeing here and in particular with relation to sort of 60-day mortality as well as OS because there are some differences between Phase 2 and Phase 3. Arthur C. Louie, M.D. : Sure. In the Phase 2 trial, we had one, a randomized trial in patients of the same age, 60 to 75, and the Phase 2 trial took on all comers so that essentially anyone that was newly diagnosed and previously untreated was eligible. And in that trial, approximately 40% to 45% of the patients had high risk disease as defined in the Phase 3 trial. So, it was a subset of about 58 patients out of the 125 that were treated. And very fortunately, that trial actually was really representative of the population out there. When we designed the Phase 3 trial, we focused on the subset of patients. And the differences between the Phase 2 trial and the Phase 3 trial really are reflected and having in the Phase 3 trials a slightly higher risk patient group. And I can say that because when we -- in fact, if we look back at the data that was presented when we discussed the CR and CRi rate this past summer, we showed the demographics and the characteristics of the patients in Phase 3 trial have higher risk with it, a higher percentage of patients had myelodysplasia with prior hypermethylating agent. And that group actually we thought would likely be hardest to treat, something we have more of them. And I think that really contributed to the median survival in the control arm being less on the Phase 3 than it was on Phase 2. If you remember, in the Phase 2, it was about 6.3 month, in the Phase 3 it was 6 months. That actually contribute a lot of difference, and it increases the rate of -- so forth and so on. So that's sort of the principal difference in patient population. Analyst: Okay. And if I could just ask, since the clinicians are on the phone today, I mean, in the past I think certainly doctors always speak to the idea of having a drug approved for AML and being able to sort of feel tested, if you will. And so, I am just curious as to without committing too awfully, where you see the most potential for VYXEOS in beyond what we're seeing in this data set here? Gail Roboz, M.D.: Well, I can certainly start with that. So, I think that yes, I have definitively spoken a lot of about getting a drug out there so that we can then figure out how to use it. It's tough for me to believe that these data would be in the end restricted to this AML population. And I think that there is still -- a lot is used in chemotherapy broadly throughout acute leukemia and I think that we are just starting to understand, yes, there are, for example, molecular subgroups to patient who may benefit from additional agents, but what has not been made clear is that there are subgroups who don't need chemotherapy. So we're just starting to have data to look at to see maybe there are actually molecularly defined subgroups that are particularly responsive to this agent or that would have -- by one plus something else, so that would be, the drug is well tolerated, I see no reason why much older patients couldn't get it and we certainly have what my side has an IST already that is ready to launch and others are as well, that there is no particular, so the old school of frail elderly versus fit elderly, this is all have to change. This has been a losing strategy for years. Right now you've got a lot of patients with the really deadly disease and a really good drug that's well tolerated. So, I think one has to throw out age restriction, throw out biology restrictions because we don't really know what we are doing yet. We know we have a win in this particular population, but if you think about the biology here, and the subgroups within secondary AML that were included, there is still a lot to figure out, who might benefit, younger patients, much older patients. I really think that the field is wide open. Jeff, I don't know if you want to say it a little differently or add to that. Scott Jackson: No, I agree completely. I'd just make the additional point, that I think the drug really optimizes delivery to the target organ and has a lot of potential in the sense that you are getting the drug primarily to the bone marrow and we're getting it into the cells at the - as we shown in some preclinical studies, at the optimal ratio. And in addition, the drug delivery is very an important aspect of successful cancer therapy, in that there are multiple mechanisms of resistance that occur prior to the drug ever really getting into the cell and that can occur through enzymatic polymorphisms that occur primarily within the liver which this drug may very well bypass, multi-drug resistance phenotype or Pgp, for example, that we think and hope that this drug may be able to overcome. So these are not issues, they are really specific just to the older MDS related AML population although they may be more enriched in population, but I can see a vehicle delivery systems such as this really being applicable across the board in SGL to -- when we get more understanding as to some of the molecular mechanisms to fine-tune it. But there is no shying away from the fact that effective drug delivery should be effective across all venues. Analyst: Okay. Thank you very much. I appreciate it. Scott Jackson: Thanks. Operator: Thank you. Our next question comes from the line of Phil with TCA Financial. Your line is now open, please go ahead. Analyst: Hi, good morning and thank you for taking my call. Scott Jackson: Good morning Phil. Analyst: I would like add to the long list of congratulations on not just the data you presented yesterday, but also it seems to be a long period of good executions from here. Scott Jackson: Thank you very much. Analyst: When Dr. Roboz mentioned a term about adoption as being I think she said, used the phrase falling off a log, and I appreciate her using terms that even I could understand. In kind of follow along with the previous caller's question, assuming approval for the Phase 3 patient subgroup, how much could or would we see adoption outside of that patient subgroup of other AML in advance of requiring other trials to be completed? Gail Roboz, M.D.: I don't know, Scott, did you want to -- I didn't hear, in my take, who is doing that. Scott Jackson: Yes, I was passing it over to you, Dr. Roboz, so, perfect timing. Gail Roboz, M.D.: Okay. So okay, so thanks for putting me firmly in the land of now I guess the -- with that even having on label, I am already off-label, it's oncology. So I guess we can conceptually talk about that. I mean, I think that look, it is certainly the case that we are starving for good things in acute leukemia and one can certainly imagine a scenario where their clinicians would not feel enormously restricted to follow rules if that would be a possibility. And I am being oblique there because I certainly don't want to imply anything about recommendations that would be outside of a potential label. But just speaking about the science and the clinical care, there is no reason why the drug should be restricted to the bounds of what we've been talking about in terms of either clinically or biologically. And I think what we're hoping is to actually go forward with additional studies and additional work to demonstrate this. So, we don't feel restricted, certainly the docs who have been working on this are not thinking of this at all as limited. We want the data out there and I tried to make this points before that I don't see that there is nothing that tells me and 82-year-old can't get it, there's nothing that tells me a 28-year-old can't get it. We want this to be optimization of the prior standard of care and getting it out there and understanding exactly what it does for all populations. That said, it's better for everybody when there are clinical data from studies supporting this rather than people just -- whatever they want with it, I do think so that again clinicians have certainly -- happy and can trained with limited options available in its very deadly disease. And I know are going to be itching due to test is delayed. Scott Jackson: Yes, I would that just add on top of Dr. Roboz's comment. Obviously the company is restricted in discussing within the labeled indication. Again, we are assuming moving forward as the product is available, we think it's very important to demonstrate and generate the clinical data in other patient population. One of Phase 2 studies was conducted in patient with first relapsed AML and we saw some strong data from that Phase 2 study, but we have about half a dozen clinical studies up and running that are investigated or initiated or oncology cooperative group studies at this point in time, which helpfully will generate data that will support that potential utilization. Analyst: Okay. Well, thank you for taking my question and congratulations again. Scott Jackson: Thank you Phil. Operator: Thank you. Our next question comes from the line of John Sullivan with Leerink. Your line is now open. Please go ahead. John Sullivan: Leerink: Hey guys, good morning and congratulations. Scott Jackson: Thank you, John. John Sullivan: I wanted to know a little bit more about whether there is information that you can share with us regarding the different age subgroups. I know you stratified for age in the study. Can you tell us anything about the difference between the 60 to 69s versus the 70 to 75s. Scott Jackson: In terms of the outcome or just the number of patients? John Sullivan: Yes, in terms of outcomes. In terms of -- yes, both actually. Arthur C. Louie, M.D. : We can't tell you much at this time. We will have the data shortly and we will analyze it thoroughly. I mean, the most we can tell you really comes from the Phase 2 data, which will pretty soon become obsolete. And basically I mean, in the earlier trial, we were getting responses and actually good movement in the high risk patients in both age groups. So, it's not particularly restricted. Scott Jackson: Yeah, the one thing -- sorry, Arthur. The one thing I would add is that at our analyst day this past July, we actually shared some of the demographic information and it's about 60% to 65% of the patients are between the ages of the 60 to 69. The remaining patients are 70 to 75. And it was balanced between the two arms. One of the things that was point of emphasis although it's difficult to follow along on a conference call, but from the analyst day is that when you look at the patient demographics, gender, race, age, performance status, very well balanced between the two arms and when you look at strata, the five different types of AML patients, patient populations that we included in the study, again, very well balanced between the two arms. John Sullivan: Helpful, thanks, congrats again. Scott Jackson: Thank you very much. Operator: Thank you. Our next question comes from the Stephen Willey with Stifel. Your line is now open. Please go ahead. Stephen Willey: Stifel Nicolaus: Yeah, good morning guys. Just also wanted to extend my congratulations on the data. I guess maybe just a question for the physicians. We talked about I guess the better profile from a side effect perspective and obviously the lack of alopecia, something that will appeal to patients as well. But I am guessing, there is also an opportunity I think just based on the dosing regimen to perhaps move consolidation therapy to the outpatient setting. And I guess to the physicians, this is still a fairly fragile patient population, even post-induction. So, just kind of wondering what you think the prospects of that transition might be and how that actually might drive either physician or patients adoption? Jeffrey E. Lancet, M.D.: Yeah, that's a good question. I think we recognize that recognized post remission therapy I think is kind of what you're alluding to and transition to that. That post remission therapy is an important aspect of the therapy to AML in general and we feel that most patients, they go through initial therapy successfully will require some degree of consolidation therapy. And many centers right now, including our own are adopting outpatient-based consolidation therapy successfully and safely because the patients are in better shape, the duration of neutropenia, thrombocytopenia, the infectious risk in general and to be shorter patients want to be out of the hospital because they have been spending so much time in the hospital. And our own experience again, the outpatient consolidation typically in the form of higher intermediate dosage therapy is well tolerated and safe. So there really shouldn't be any barriers to CPX-351 having that same type profile. In fact, patients have been treated on the outpatient side during the consolidation phase. I can attest to that, and have done very well. And again, being in remission, these patients are generally more stable, feeling better, they have lower risk for complications and not to say that this is light or easy therapy, in that there is still a requirement for intensive monitoring and follow up. But in general, the transition would not be anticipated to be difficult and in my own personal experience, has been quite simple and easily adopted and readily adopted by the patients. Scott Jackson: Thanks, Jeff. I'm going to ask Derek to comment on this as well. Derek? Derek Miller: Hi, thanks. That's a great question. One of the things that I would do is to draw your attention to the ASH poster that we've presented this past ASH in Orlando, where we looked at Phase 2 data and conducted a health research utilization study. And essentially what that showed was just under 50% of the patients treated with VYXEOS in consolidation were treated on an outpatient basis. And so I would expect that as experience and familiarity grows with the management of side effects and understanding which patients are best suited for that type of approach, I think that number could potentially increase and we will certainly be looking at that in the Phase 3 analysis as well, but we don't have a data yet. Stephen Willey: Okay. That's helpful, thank you. And then, it is just a question for Scott. Just I guess on the bandwidth side. I am imagining you and your team would be pretty busy on the regulatory front for most of the next 12 months and I think the physicians have spoken to the need to develop this drug in other subpopulations at a minimum. So, just kind of wondering if you kind of feel like that's something that the company as of right now will be able to handle and it's not kind of where you need to grow to be able to handle both ends of that equation. Thanks. Scott Jackson: Yeah, no, no, thank you Steve. And from a regulatory perspective, while we've been working on the NDA submissions in advance of actually having the positive outcomes, we were obliviously assuming and hopeful that it was going to be what we've seen. We are on track for the end of third quarter NDA submission. As I mentioned in my opening comments or my concluding comments, excuse me, that we requested a pre-NDA meeting that went in right after we received the positive data announcement. We've shared the information we've talked about today with the FDA, are awaiting that pre-NDA meeting. But we are very confident that we can hit the end of the third quarter. And then, as far as the MAA, because we have limited resources with the new organization, we've staggered the submissions and the MAA application is targeted for submission in the first quarter of 2017. Stephen Willey: Okay. Thanks and congratulations again. Scott Jackson: Thank you very much Steve. Operator: Thank you. Our next question comes from the line of Boris Peaker with Cowen. Your line is now open. Please go ahead. Boris Peaker: Cowen: Great, thank you for taking my question. I'd like to add my congratulations to this significant development. I guess I just wanted to expand on what was discussed earlier in terms of usage in potentially other settings. If you look at the NCCN guidelines, the secondary AML and primary AML are very similar. So, maybe for the physician experts, what would it take, if it gets approved in secondary AML, what would it take to get it in the NCCN guidelines for primary AML or maybe some of the other settings? Scott Jackson: Why don't I ask Jeff to take a lead on that? Jeffrey E. Lancet, M.D.: Yeah, I mean, you all can comment on this too. I feel that there is AML in general, not just secondary AML, is an area of great need and where I think we can probably agree that there is not a very effective standard of care, if you're going to want to call it a standard of care 7+3. To answer the question, what it will take to get incorporation into the guidelines, I think we are going to have to see evidence that there is some unique activity of the drug within certain populations of AML in order for that to happen and again, off label use isn't something that I would typically want to condone or offer because we don't have proof of it yet. But I think that there is the opportunity through multiple trials that our investigator and initiated and company sponsored to investigate these types of questions, maybe not necessarily on a Phase 3 basis, but on a smaller scale for proof of principle to identify areas of need and areas of opportunity where the drug may be especially active that can come from that in order to get NCCN approval. I don't think it's going to happen just by waving our hands and saying we have new drug, but there is going to have to be some level of evidence, not necessarily a large randomized trial, but some level of Phase 2 evidence that suggests you make the activity in subsets of patients in order to move the needle with the NCCN for the non-secondary AML population. For the secondary AML population for sure, as Gail said, it's clean win in this population and should be no question in my mind that this group would benefit from that drug in that particular arena. But outside of that, I think we are going to have to wait for some of the evidence to come in and I think it will come in. But that will be the key in driving NCCN guidelines outside of the original indication. Gail Roboz, M.D.: I would just add also to that that I am not -- I am very hopeful that this isn't going to require serial 800-patient study. That's not where we're going and if you think about it, the way the guidelines were constructed. I mean, what is primary AML, what is newly diagnosed AML, there's plenty of subcategories already within that where we know that standard 7+3 is extremely limited. So the question will be that I think it's becoming clear when you look at the pi-charts, the dividing of AML into two subcategories, either including or not including molecular data, I think that we are moving forward into a zone of understanding that sort of pumping everything together in AML is hazardous, shall we say, from a guidelines point of view. So I would just being a little bit oblique, but I would say that it is unlikely that every single subgroup is going to have to be carved out and have a huge randomized trial. And I think that once we the Phase 2 and other clinical data are coming in, showing those, let's say, older patients or young patients with complex carrier type or patients with TP53 mutations or other groups that it's not that they -- those who haven't been explicitly addressed, that there haven't been standards of care that need to beat in the standard type of Phase 3 setup. And I think that as the drug gets more play and as we are hoping to demonstrate that the continued superior efficacy and safety go forward, I think it becomes more of a challenge to explain -- what we want to have happened is to have it be a challenge why you are not using it. And I think that does have to come into consideration where you have difficult to assess subgroups that have very high unmet medical need where you can demonstrate that the standard of care is failing the patients. As you show that you have something which is demonstrating superiority in other settings, I think that does put on a pressure and I think that one have to look at AML a little bit differently and even hope for things like a little bit of patient advocacy and physicians advocacy that it's something has other feature to it that are consistently emerging and that are to put a little bit pressure on adoption of something that looks better. And I would just bring that out of sort of my hope for the future in AML as we have a good choice to play with, what are some of the ways that we can push forward out of the last 20 years of trial development and in to maybe new territories. Scott Jackson: My only comment to add to what Jeff and Gail said is just to remind folks that we have a very long patent life in the US. We have patent protection now till 2029, which really gives us the opportunity to further develop the asset in some of these other patient populations. Boris Peaker: Great. I just want to follow up maybe with Dr. Roboz, you mentioned several times on the call but the current guidelines or the current segmentations of patients sounds like is outdated and may not be fitting certainly with newer option coming on board. I am just curious from the logistical perspective, are you aware of specific consorted efforts based on some relevant working groups to potentially reclassify AML, re-stratify patients and really approach it more on a molecular basis or whatever is more fitting than the more traditional age-based in primary and secondary disease? Gail Roboz, M.D.: Yeah, I mean, I think the issue is, yes, this is receiving more discussion than anything else in all of our meetings. But the hazard is that you don't want to be either a lumper or a splitter. You have to lump when it's good to lump, and split when it's good to split. And that is a challenge because what we don't want is anecdotal medicine of having 85 different subgroups of patients each with -- subgroups of AMLs each with 2 patients in them. That doesn't help. But at the same time, you don't want to throw everything together in one group because that has been certainly amongst relapse patients that has been grossly unsuccessful. And even with the newly diagnosed patients, we already have core-binding type of patients separated out completely. APL is a totally different disease. The TP53 mutated patients we know biologically are very different and yet we haven't officially separated them out yet. So, I don't want to make it seem like an obvious thing that is going to happen that there is going to be a plain, old, new classification coming out next week. But I will say that the discussions at least that I am participating in are rooms that are very clearly trying to figure out how to avoid being categorized in the same way the things have been in the past. And for example, if you are looking at patients, and I take the TPs of these re-mutated patients, because they do bad with all therapies even with our transplant, and yet, if you ask, okay, what would the new therapy do randomize to? Well, I mean, it would be randomized to, I don't know, 7+3, or to hypomethylators in older patients. This is where people start hand waving because the question hasn't been put that before. So, you can pick something that's available that that hasn't been defined as a standard of care for that molecular subgroup. It's just what exists than what we have been using. So there definitely will be change in the future that doesn't have -- in hopefully to randomizing on novel therapies against therapies that we know are ineffective, but just what's out. That certainly has to change and having a novel chemotherapy choice, again, which is predicted to be applicable for multiple different groups, because again, it's not -- this is the advantage of having a drug isn't targeted, but you can apply it to multiple groups. I think it offers that really new opportunities and I know that this the direction of many of the ISPs in trying to pick out those subgroups, both molecularly and age-defined. Scott Jackson: I think I would just that to that. Like Gail said, I think we are moving towards molecularly-defined subgroups in general, recognizing that no two leukemias are alike, but at the same time, our treatments haven't caught up with the molecular complexity of the disease and the treatments that do exist that are targeted specifically, at least the single agents are not very effective in the broad sense. So we're still able to categorize diseases molecularly, mainly for prognostic purposes, but at the end of the day, there is still a very large need. And I think this maybe to the crux of the question, and I think there will be a very large need for broad-based generalized therapy to service the backbone for more specific targeted therapy given the unbelievable complexity of the disease and the fact that there are so many different drivers of this disease that it's going to take time to select that out and it's, I my opinion, very unlikely that we're going to find magic bullets that are going to apply to the overall population of leukemia patients that does not include a more generalized therapy, that is able to at least cell kill and site of reduction in general. Gail Roboz, M.D.: It definitely does not heal -- that chemotherapy is over and all are on the clinical side, in fact, may be just beginning. Scott, and also I am actually going be killed if I don't go into -- Scott Jackson: Gail, we've already exceeded the time. Gail, I appreciate you being on the call very much. We're going to take one more call, but we understand Gail, you have to drop off. Thank you. Gail Roboz, M.D.: And my congratulations too and look forward to much more data. Scott Jackson: Thank you, Gail. So, operator, time for one last question before we wrap it up. Operator: Yes sir. Our last question comes from the line of Michael Mullen with National Securities. Your line is now open. Please go ahead. Michael Mullen: National Securities: Thank you. Scott, the entire team, congratulations, phenomenon work, phenomenon results. I really appreciated the comments by Dr. Roboz and Dr. Lancet as well. I mean, they are frontline in this disease and to hear their thoughts and appreciate their thoughts regarding having a new tool to offer, a better outcome for their patients was really exciting. The my question is about the pipeline potential. And I practice my question by fully understanding the company's timeline this year and their focus on getting the US and European filings done. But I believe this was the first time any company has successfully combined two very different drugs inside of a single liposome. So, could you perhaps give some guidance regarding CPX-1 in colorectal and when you anticipate releasing data on that potential application as well? Thank you. Scott Jackson: Sure. Thank you Mike. One of the things that I'll comment on CPX-1 and then I will ask Lawrence to comment more on our platform. We do have a limited amount of resources, we focus primarily on CPX- 351 or VYXEOS. What we've also embarked on was really further developing the technology platform to demonstrate its application to not only traditional chemotherapeutic drugs, but also molecularly-targeted agents and that was really more of a priority of CPX-1. With respect to CPX-1, we see the development would in all likelihood require us partnering with another company to further develop CPX-1. We have completed a Phase 2 study on colorectal cancer. We do believe that there is a path forward, but our resources were prioritized, the VYXEOS as well the technology platform demonstrating its application, as I mentioned, with targeted therapies. And with that, I'll ask Lawrence to comment briefly on what's happenings with platform. Lawrence? Lawrence Mayer, Ph.D: Founder, President and Chief Scientific Officer: Sure, thanks Scott, I'd like. Yeah, we've made some really exciting progress in the past as we announced last -- in third quarter 2015 and that presented data in November at the EORTC AACR Meeting in Boston that we applied, successfully deployed the technology using our nanoparticle delivery systems, and applied it to combinations using molecularly-targeted agents. Given the wide-spread development focus from the pharmaceutical industry on these type of agents, we wanted to ensure proof of principle. And now I think it's opportune with this validation of the CombiPlex technology platform with the Phase 3 results from VYXEOS, we think that's really -- we are doing some groundwork getting outreach to various companies, we think we're now in a great position to go back out and really established some research collaborations. We have exciting pilot data and with this validation, I think it positions us to be very successful in 2016 on the path of growth. Michael Mullen: Wonderful. Well, thank you much for taking questions, Scott, team, great job, phenomenal day and I appreciate all your efforts. Scott Jackson: Thank you Mike. Operator: Thank you. Ladies and gentlemen, this is all the time we have for questions today. I would now like to turn the call back to Scott Jackson, Chief Executive Officer for closing comments. Scott Jackson: Thank you Brian. This is truly a tremendous day for patients with high risk or secondary AML. We are excited to be able to communicate this positive Phase 3 outcome. Many products have been studied on AML, but the standard of care has not changed in decades and we're delighted to take this step towards possibly becoming a new foundation of care. It's certainly as promising for patients. And thank you for your participation in today's call. We look forward to updating you again soon. Operator: Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect. Everybody have a great day.