CTI BioPharma Corp.
Q4 2014 Earnings Call Transcript

Published: 13 Mar 2015

[Operator:]

Good day. And welcome to the CTI BioPharma Fourth Quarter and Full Year 2014 Financial Results Conference Call. Today’s conference is being recorded. And at this time, I would like to turn the conference over to Monique Greer. Please go ahead, ma’am.

[Monique Greer:]

Thanks, Matt. And welcome everyone to our fourth quarter and full year 2014 financial results conference call. This press release reporting our financial results can be found on our home page and in the Investors section of our corporate website at ctibiopharma.com and on the SEC’s website at sec.gov. We will be referring to page seven in recently filed form 10-K for the year ended December 31, 2014 which is also available in the Investors section of our website. Following formal remarks by management, the conference call will be open for questions. Joining me today are Jim Bianco, President and Chief Executive Officer; Nancy Boman, Senior Vice President of Clinical Development and Regulatory Affairs; and Matt Plunkett, Executive Vice President of Corporate Development; Lou Bianco, Executive Vice President of Finance; and Jack Singer, Executive Vice President of Global Affairs and Translational Medicine will also be available for questions. Before we begin, please note that during the course of the call, we will be making forward-looking statements based on current expectations. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. Additional information concerning these risks and uncertainties is contained in the press release reporting our financial results for the fourth quarter and the year ended December 31, 2014, the Risk Factors section of annual report on Form 10-K for the year ended December 31, 2014, and in the Company’s other periodic reports and filings with the Securities and Exchange Commission. I will now turn the call over to Jim.

[Jim Bianco:]

Thanks Monique. Good afternoon, everyone. Let me take this opportunity to thank all of you for joining us on today’s call. CTI BioPharma is clearly off to a great start in 2015. As you know, earlier this week, we announced that the PERSIST-1 trial of pacritinib met its primary endpoint in the intent-to-treat population with significantly more patients randomized to pacritinib achieving a 35% or greater reduction in spleen volume at Week 24 in patients randomized to best available therapy. Now a significant reduction in spleen volume was also demonstrated at Week 24 in patients who went through the study with moderate to life threatening disease related thrombocytopenia, a patient population that is very underserved with currently available therapy. Following the call on Monday, we spoke to many of you in the financial community and understand that there has been some confusion around the top line data that we shared, specifically around the primary endpoint. Now, as typical in this industry, we and our partner Baxter made a decision to share the most important information in the top line release such as the achievement of hitting our primary endpoint and the P value and save addition detail in order to preserve our ability to submit an abstract for presentation at a top tier medical meeting like ASCO. However, given that many of you have tried to use the data we’ve provided in order to figure out the percentage of patients who benefited from pacritinib and recognizing that you’re anxious to make comparisons between our data and the approved JAK inhibitor, we wanted to do the following. First, we want to clear up any potential confusion and secondly, make sure you have the appropriate context to understand what we’re trying to accomplish with pacritinib really versus the role of the approved drug plays in the current treatment paradigm. We believe ruxolitinib being the first-in-class JAK 2 inhibitor has and continues to make a significant difference in the lives of thousands of patients with myelofibrosis. However, based on what we believe that the percent of patients receiving lower doses of ruxolitinib in those study in the Phase 3 COMFORT trials coupled with a challenge of treating higher risk patients, we feel the medical and the patient advocacy community are asking for new agents that can address the wider cross-representation of the MF patient population that they have in their practices or in their constituency. So our goal for this PERSIST program was to evaluate pacritinib in two randomized Phase 3 trials in patients with myelofibrosis that would represent a true mix of patients that healthcare providers see every day in their practice. We believe in the potential for PAC to provide benefit not only to patients with fairly stable disease, but also for the 37% of patients with myelofibrosis who have mild to life threatening disease related thrombocytopenia which is a platelet count below 150,000 per microliter. So keep in mind, normal platelet counts range from 150,000 per microliter to 400,000 per microliter. Now, while it’s attempting to try to compare the results from PERSIST-1 with the COMFORT-2 trial, the two patient populations are vastly different. 44% of PERSIST-1 patients who received pacritinib had platelet counts below 150,000 with a medium platelet count of 168,500 and a lower end of the range at 7,000 platelets. In contrast, only 8% of COMFORT-2 patients had platelet counts below 150,000 with the medium count of 244,000 platelets. And you may recall patients with platelet counts below 100,000 platelets were excluded from that study. There are other important risk factors that are different like a much shorter time from diagnosis in the pacritinib study, the percentage of patients who are JAK2 negative, the percent of patients who had primary myelofibrosis or [lab poor] performance status or so called PS2 patients. The percentages of each of these parameters are markedly higher in the PERSIST-1 study than in the COMFORT-2 trial. Again, what we feel is the real representation of the myelofibrosis community that physician see and treat each day. Now unlike the blood cancer genome, MF is a chronic disease and like your patients, physician struggle to find effective treatments and are always looking for new options, particularly for patients that are hard to treat and have low platelets. So this difference between the respective patient populations and risk factors in the two studies really highlights the opportunity that pacritinib has to address a much broader patient population than is currently being served. We can achieve our goal by helping more patients and offering a potentially safer, more tolerable drug not by just mirroring efficacy or offering a drug that will be similar or second to market. As you may recall, pacritinib has Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis including but not limited to patients with disease related thrombocytopenia. Now that is the patient population that the PERSIST-1 trial addresses. Fast Track designation also included patients experiencing treatment-emergent thrombocytopenia on other JAK2 therapy or patients who are intolerant to or whose symptoms are sub-optimally managed on other JAK2 therapy. And this is the patient population we are targeting in our PERSIST-2 trial. And so with that background, let me ask Nancy Boman to provide you some additional detail around the study’s primary endpoint.

[Nancy Boman:]

Thank you, Jim. I wanted to take a few minutes to share with you some additional details around PERSIST-1 and provide a quick overview of the program in general. I refer to you again to the table on page seven in our 10-K that Monique referenced at the start of this call. The table shows the proportion of patients randomized to pacritinib or best available therapy to achieve a greater than or equal to 35% reduction in spleen volume from baseline at Week 24 or up to Week 24 in the intent to treat population or the evaluable patient population. So just that we’re on the same page, I’d like to define ITT in evaluable patient population. The ITT population is the primary analysis which included all randomized patients on pacritinib or best available therapy. There were 220 in pacritinib arm and 107 in the best available therapy arm. Patients without scans at baseline or at Week 24 are considered as non-responders for this primary analysis. In contrast, the evaluable patient population includes only patients with both baseline and Week 24 scans. For the pacritinib arm, this was 168 patients and for the best available therapy arm, this was 85 patients. This parameter provides a good estimate of treatment effect size. If you look at the left hand side of the table, you’ll see the following. The ITT at Week 24 which measures a difference in spleen volume at baseline compared to spleen volume at Week 24, there was a 19% effect in pacritinib arm and 5% in the best available therapy arm. Next, if you look at the ITT up to Week 24, this includes patients with a baseline scan and a scan between Week 24 and 48 weeks. There is an effect of 24% in the pacritinib arm and 5% in the best available therapy arm.

[Jim Bianco:]

Week 12 and Week 24.

[Nancy Boman:]

Between Week 12 and Week 24. And lastly, if we look at the patients that were evaluable at Week 24, there is an effect of 25% to pacritinib arm and 6% to the best available therapy arm. Needless to say, these are all highly significant. While we’re sharing any additional detail today outside of these numbers, I will say that the magnitude of treatment effect for the low platelet subsets less than 100,000 and less than 50,000 per microliter, they’re comparable to or greater than these numbers and are also highly significant. In addition, consistent with our Phase 2 experience, while a cohort of patients has yet to reach the Week 48 time point, preliminarily data suggest the treatment effect size for patents on pacritinib will continue to increase at 36 and at 48 weeks. All patients will continue to be followed until mature data become available. We look forward to reporting additional data at an upcoming scientific meeting. We believe that these data put us on a strong path towards approval because we met the primary endpoint of the trial and we believe we have a potential viable commercial candidate that can address the unmet need that exists today. We are delighted to now build on this positive momentum and typically completing enrollment in the ongoing second Phase 3 trial known as PERSIST-2 and intend to potentially commence the regulatory submission to the FDA and/or the EMA as early as the end of this year. The Baxter is responsible for the submission of the MAA in the Europe. We believe pacritinib kinome profile suggests its potential therapeutic utility beyond myelofibrosis. In December of 2014, we announced the presentation of the pacritinib data at the American Society of Hematology Annual Meeting. A preclinical study demonstrated a unique kinome profile for pacritinib among patients in development for myelofibrosis and suggests potential therapeutic benefit across the spectrum of blood related cancers such as acute myeloid leukemia or AML, myelodysplastic syndromes or MDS, chronic myelomonocytic leukemia or CMML and chronic lymphocytic leukemia or CLL. We are confident that together with our partner Baxter, we will be able to more rapidly advance to development and availability of pacritinib for patients with myeloproliferative neoplasms, AML, and other cancers around the world. I’d now like to turn the call over to Matt Plunkett to review some of the key achievements for 2014.

[Matt Plunkett:]

The fourth quarter and full year 2014 were productive for us. We accomplished many corporate goals, not the least of which was the completion of enrollment for PERSIST-1 which triggered a $20 million milestone payment from our partner Baxter. As we discussed, we reported top line results for this pivotal trial this week. In addition, we achieved another of our stated corporate objectives for 2014 when we entered into an exclusive license and collaboration agreement with Servier to help expand the product reach and commercial potential of PIXUVRI in territories where we presently do not have a commercial presence while also retaining U.S. rights. PIXUVRI is the first and still the only therapy approved for patients with aggressive B-cell NHL who have failed two or three prior lines of therapy. The transaction has the potential for approximately $133 million if all milestones are achieved as well as royalties on product sales. The next milestone is based on completion of enrollment in connection with our ongoing post-marketing commitment PIX306 Phase 3 trial. This trial is intended to support the conversion of our EU conditional marketing authorization to full marketing authorization and label expansion to include second line therapy and use in combination with rituximab. We expect this trial to complete enrollment in the fourth quarter of 2015. The arrangement with Servier provides a 50-50 cost sharing for future and agreed-upon development efforts including both registration-directed trials and what we term ISTs or investigator-sponsored trials of which a number are currently in progress or plan to begin this year. On the global expansion front, we are pleased to report Servier have received reimbursement approval for PIXUVRI in Spain. PIXUVRI will be included in the national list of available reimbursed products. Servier holds the commercialization rights for this territory and will be responsible for the launch of the drug in Spain. As part of our agreement, we received the €1.5 million milestone payment from Servier. We continue to raise awareness for PIXUVRI in the EU and physician experience with it continues to grow. We believe that having Servier on board will significantly enhance recognition and the power of PIXUVRI given their significant resources they have on the product and the enthusiasm for this drug. Tosedostat is our third promising product candidate that I wanted to briefly mention. Tosedostat is a first in class product candidate in oral inhibitors of aminopeptidases, a family of metalloenzymes that clip and free up amino acids from peptides and polypeptides, allowing them to be the building blocks for new proteins essential for tumor cell survivor. In 2014, we acquired worldwide rights to tosedostat and assisted in the initiation of a randomized Phase 2 trial evaluating tosedostat plus low-dose cytarabine for older patients with AML or high risk MDS which is being conducted by the UK’s National Cancer Research Institute AML Cooperative Group. We expect to report whether tosedostat met the initial efficacy hurdle to enter into the Phase 3 component of this Pick a Winner trial. Depending on the results, we would plan to consult with the FDA and the EMA regarding potential registrational strategy upon availability of data from this trial. Clearly, tosedostat fits nicely in our portfolio of novel agents specifically targeting blood related cancers. Finally, in January 2015, we appointed Dr. Alan Burnett to serve as the strategic leader for development of agents targeting myeloid malignancies. Dr. Burnett most recently served as Professor and Head of the Department of Haematology in the Institute of Cancer and Genetics at Cardiff University and is highly regarded internationally for his work in the treatment of AML and MDS. Dr. Burnett will assist in the development strategy of tosedostat and other product candidates moving forward, given his vast experience and connection in this area. Now, I will turn the call back to Jim to review the financials and the key objectives for 2014.

[Jim Bianco:]

Thanks Matt. Total revenues for the fourth quarter and full year ended December 31, 2014 were $17.8 million and $60.1 million respectively compared to $32.9 million and $34.7 million for the same periods in 2013. For the fourth quarter and full year 2014, net product revenues of PIXUVRI grew to $2.5 million and $6.9 million, respectively, and that compared to $500,000 million and $2.3 million for the same periods in 2013. Total revenues for the full year 2014 included license and contract revenue of $53.2 million, which was primarily attributed to the following

[Operator:]

Thank you. [Operator Instructions]. And at this time, we’ll take a question from Charles Duncan with Piper Jaffray. Please go ahead.

[Charles Duncan:]

Thanks guys for taking the question. And congrats on the recent positive pacritinib data. Jim or perhaps Nancy, I’m just wondering if you could speculate a little bit on the competitive landscape in myelofibrosis. Some investors have compared on the recent PERSIST-1 top-line results for COMFORT-2 with those for COMFORT-2 with RUX; and I know you kind of addressed this in your prepared remarks but I’ve been travelling and haven’t had a chance to take a look at that data in your 10-K. But I’m wondering, if you could comment further on whether or not you believe the data in your study in terms of the percentages of patients that have achieved significant spleen reduction is similar to, better than given the patient population or not as good as the 28% or so that was observed in the COMFORT-2 trial?

[Jim Bianco:]

Great question, Charles. I just want to point out one of the differences. We talked about the difference in risk factors. I mentioned on the call on Monday that the patient -- time from diagnosis to entering PERSIST-1 was very short that we had commented in the PAC arm that it was less than a year. In the COMFORT-2 trial it was 4.9 and in COMFORT-1 trial it was 4.9 years from time from diagnosis. So clearly, that difference in the acceleration of their disease as extent of their disease between the two studies. And that’s why we keep saying cautioning not try and look at the two trials in terms of comparative. And we’re not looking and saying that we’re superior to ruxolitinib; it’s a totally different patient population and it’s actually what we feel and we think we’re going to hear this loud and clear at ASCO, this is what everyone’s been waiting for, a real study of real patients, not a study to hit a primary endpoint, but a study that actually can do good in terms of the treating community. So that having been said, if you look at our Phase 2 results and what we’re seeing now in the Phase 3 study, pacritinib increases spleen size reduction over time, so that our 36-week and 48-week percentages for best responders is actually higher than what it is that we see at the 24-week time period. If you look at the COMFORT-2 study the reverse is true. Their best response in terms of effect size occurs at Week 24 and by Week 48, as you said, it was 28%. And we feel at that time point at 48 weeks that the percent effect size between these two compounds will be comparable if not overlapping. And so we’re confident, we have a very active drug. And probably one of the most important parameters that didn’t come up on the call is that we have 45% of the patients out 21 months on therapy, including patients who have very low platelet counts. And we haven’t calculated our median or so called dose intensity, but we mentioned on our phone call on Monday that dose reductions and dose discontinuations were very low. And so we think that we’re able to maintain maximum dosing over very long periods of time irrespective of their platelet count. And as you know from the published studies, even though the patient population was significantly better, they had dose reductions and ultimately dose discontinuations because of anemia and thrombocytopenia. Jack, do you want to add anything to that or...

[Jack Singer:]

I just want to make one additional comment. I totally agree with Jim’s stake on the differences between the populations. We were definitely treating more aggressive disease and further long in the disease as well. But aside from the comments that Jim made, I just also would remind you that although it was the approvable endpoint and a primary endpoint, spleen size reduction is not a clinical benefit in and of itself; it has to be accompanied by other parameters of benefit. And I would say that one of these biggest issues we have in myelofibrosis is cytopenia is not only for platelets but for red cells. And if you look at the data on other JAK2 inhibitors, most actually increased anemia and ruxolitinib actually increases the red cell transfusion requirement. As mentioned in our press release, we are starting to see data is not fully analyzed, but it’s very clear that a reasonable percentage of patients, who are transfusion dependent at the beginning of PERSIST-1, became transfusion independent starting at about 24 weeks and increasing over the first year. This is very impressive and is not seen with other JAK inhibitors and we look forward to a full analysis of the benefit on cytopenias and I would be very surprised that we don’t have similar data on platelets.

[Jim Bianco:]

And Jack brings up, Charles a very good point that everybody on the call and who listen to this transcript, we are just one week into knowing this data and there are a number of protocols and step plan driven analyses. And as we continue to see more and more information, I mean, this is becoming a very impressive story for this drug in a patient population that we think will open the eyes when the data are presented including the magnitude of effect size and the benefit of course some of the other endpoints that are being followed in this study. So, we’re really anxious to share that with everybody but we want to make sure that we do it in a very forum like ASCO where this what we consider paradigm shifting agent in the JAK2 world, we really show that what it can do for a whole course representation of this patient community.

[Charles Duncan:]

That’s helpful, Jim and Jack in terms of that added color. I appreciate that. Let me ask you one additional question regarding some of the indications beyond myelofibrosis. I think you mentioned earlier in the week couple of ISCs and AML and MDS, I am wondering if you anticipate any visibility on those studies this year perhaps at ASH or even before it?

[Jack Singer:]

Let me just tell you what we’re planning to start within the next -- either have started or will start within the next couple of months. We’re doing a study in low risk MDS, pre-hypomethylator post-Revlimid, so these are patients that severe cytopenias including red cell transfusion requirements in which clinical benefit can be measured as metabolic improvement and that actually is improvable endpoint. So these are signal searching studies. A signal there would be unique because nothing has a signal in that phase and there will be two studies in that space, one in Europe and one in U.S. We’re starting the study in first line AML in the elderly combining pacritinib with the hypomethylator and there will be two studies such as that as well. We’re also hoping to put together a consortium to start a clinical trial which could lead to an early approval file in CMML but that is not as established as the others. So, there is going to be a lot of news and I can’t guarantee when clinical data will be available, taking to scratch to consider that a clinical data will be presented at ASH because that needs to be the top line results within three months.

[Jim Bianco:]

As you point out Charles, there is a study that’s ongoing with three positive relapsed AML. If there is any data in AML that would be the study that may readout by yearend as we’ve been noting. One thing that Jack didn’t mention was some very exciting ex-vivo data in CLL in terms of understanding again how pacritinib can disrupt the stromal clonal environment in that disease; hopefully we’ll see a publication sometime this year. But clearly that has led to a lot of interest in looking at PAC in CLL plus and minus vaccine in combination with the BTK inhibitor.

[Jack Singer:]

Just to comment a little on that, this hopefully will be submitted for publication shortly. The data suggests that pacritinib actually has an effect upstream of a group at CLL by interfering with the stromal CLL interaction. And we are expecting protocol from a major center looking at pacritinib running to a group and then the combination we have refractory CLL. I think that will be the fascinating study and should be early readout.

[Jim Bianco:]

It’s becoming clear that pacritinib is a pipeline in and of itself and we’ve heard that across from our Baxter colleague as well in terms of as we start to see these data come out.

[Charles Duncan:]

We’ll look forward to seeing the full analyses hopefully at ASCO or EHA in later end 2Q. Thanks for the added color.

[Jim Bianco:]

Thanks Charles.

[Operator:]

And now, we’ll move to Bert Hazlett with Ladenburg.

[Bert Hazlett:]

Thank you for taking the question. And again, well done on the progress. Could you just remind us, you mentioned that you will be starting additional studies as you just in the second indication formally with Baxter by year-end 2015. Could you just remind us of whether or not that study start actually triggers a milestone? And Jim, if would be so kind as to remind us the economics of indications beyond myelofibrosis? Thank you.

[Jim Bianco:]

Right. So, yes, if they initiated registration directed trial, we are in a mid-teens million dollar payment from Baxter, if we put that in the conditional release. In addition, if they submit their MAA, we earned a $12 million milestone from Baxter as well. In terms of other indications Bert, is that -- didn’t get the second half of your question.

[Bert Hazlett:]

Yes, the other indications please.

[Jim Bianco:]

Right now, there is I will say -- I won’t say critical development but certainly an investigator development in the space of looking at p-vera in terms of what make sense, what’s the real unmet need in that disease. As we mentioned, Jack said there’s several studies in AML plus and minus hypomethylating agents plus and minus PAC if we get an early signal there that is clearly a direction that might of interest. Personally I think probably the most exciting data that I’ve seen is the CLL data.

[Jack Singer:]

Well the earliest, easiest regulatory growth in CLL?

[Jim Bianco:]

That’s true.

[Jack Singer:]

There is an approved therapy but it currently doesn’t work that’s why they’ve decided it.

[Bert Hazlett:]

I was really focused on the economics that would be with regard to the additional indications; in the U.S., it’s profit split but internationally, there are higher royalties associated with those different indications beyond myelofibrosis.

[Jim Bianco:]

That’s correct. I think we said it’s above the teens in the mid range and we said that for indication outside of MF that’s with the royalty rate would be in addition as you know the cost sharing if it benefits both territories at 75% Baxter 25% CTI, so European only it’s 100% on their expense and if it’s U.S. only, it’s shared 50-50 as are the profits and losses for the product. I can tell you that people are geared up, people are real excited now with positive data in hand. It’s their organization as well, so enthusiastic about bringing this through the regulatory process and to market it to patients as quickly as we can.

[Bert Hazlett:]

Perfect. Actually that dovetails into my next question which is, when do you anticipate commercial preparations actually beginning if there is a potential for the filing to commence around year-end 2015?

[Jim Bianco:]

We started here last year as Matt said. So launch year minus two is when the work started kicking in. I could you tell you that the team, the planned strategy all those components, market research, market analysis, we’re very familiar with what’s going on in the space in the U.S. and Europe and we understand what the unmet needs are kind of where the holes in the marketplace are. So we’re just real excited about getting this to market as quickly as we can. And we think that the reception in the clinical and patient advocacy community would be a relief because again having choices especially for patients we don’t have a choice right now or can’t stay on drugs for longer periods of time is really kind of the pent up unmet need and demand that we think will be out there. So as our partners at Baxter said of course we always share data with the regulatory agencies; we’ll take guidance from them. Clearly our goal is to finish the second trial and then get the NDA underway. We’re on target for all the other components of that NDA to get in place in the fourth quarter.

[Operator:]

And at this we’ll take the question from Reni Benjamin with H.C. Wainwright.

[Reni Benjamin:]

Thanks for taking the questions. I guess just a quick one Jim, can you just remind us again, what’s the delta that you’re looking for and persist to? And is there anything in the study that skews patients that skews the enrollment for patients for a more thrombolytic patient population, as they continue to enroll, some sort of an adaptive component?

[Jim Bianco:]

One thing that we can tell you is we now have some really good insights into how patients with 100,000 platelets or less will react to this drug both in terms of treatment effect, duration of effect, et cetera. So, we’re pleased with that in terms of what our assumptions were going into the trial. We also expect to see about the same proportion between below 50 and above 50 and below 100, if you will. And so you know that does have two dose arms for pacritinib 200 BID, 400 once a day and then of course the BAT arm where we would expect to see a good proportion of patients who are on Jakafi coming off Jakafi and then getting on BAT of which some may again get back on Jakafi. So we don’t have an adapted design in place where we’re actually monitoring real time, if you will. I think it’s clear that we’re doing; it’s the things that we learn, the lessons learned on PERSIST-1 are already been implemented on PERSIST-2. And we feel we have a really good shot at not just winning on that trial but winning demonstrably and in terms of compared to BAT. So, Reni maybe you can elucidate little bit what you were specifically getting at?

[Reni Benjamin:]

I guess where I am going with it is, as the trial enrolls, if the patient population is skewed more towards the let’s just say the $100,000 -- sorry 100,000 platelet count versus let’s say less than 50,000, you might expect one type of drug effect from the control arm versus not. And so I was trying to get a sense as to, based on the enrollment that you saw in PERSIST-1 about how many patients might you see less than 50,000 platelets and could you modify that given your findings as enrollment continues so that you have more patients who are let’s say less than 50,000 in platelet count?

[Jim Bianco:]

Yes, we certainly could. We follow those metrics weekly and monthly as patients come in both by region, by strata, et cetera. So it’s certainly something that we look and I understand what you’re saying for patients between 50,000 and 100,000 if they’re on Jakafi, you may have a different treatment effect size than you would have there, below 50,000 where they’re not getting Jakafi. I think this trial will make a big statement in and of itself in terms of when physicians have a choice to give ruxolitinib, would they do it in this patient population and that will be a resounding answer when the trial is completed, especially since a substantial proportion of the patients will be enrolled here in the United States where ruxolitinib is readily available to patients and physicians. I think all of these are things that we look at real-time. And so yes, the answer would be if you had a higher proportion of patients than what you’d expect getting -- coming in between 150,000, would you make some changes, we’re not planning on it in fact. Again I really do think that the issue for docs today is that they’re sub-therapeutically managing patients who have platelet counts of 100,000 or below. And they’re looking for a better treatment option. And they have two out of three chances of getting one of those better treatment options in this trial, which is why I think that that’s why they would choose to participate in.

[Operator:]

David Lebowitz from Janney Montgomery Scott has the next question.

[David Lebowitz:]

My first question is actually on the top-line guidance. Is there any way you could give us a somewhat of a bit of a guidance on how this might breakdown between milestones and PIXUVRI?

[Jim Bianco:]

I think we did it at the beginning of the year right when we gave the number 55 to 70 was the range; we said that PIX was going to be in that $10 million to $12 million range for gross sales. I think we had PERSIST-2 milestone that we mentioned would be in that number; the start of an additional trial was in that number and then we had in that number the sales from TRISENOX and other sales milestone payment from Teva. And then on the upper end of the range if the MAA should be filed in this calendar year that that would take us through the upper end of the number. And then we add them up that it comes up between contract license revenues, milestones and product sales are the major components, if that helps.

[David Lebowitz:]

Thank you very much. And jumping over to completely different subject with respect to tosedostat and also I guess further with Opaxio, given that the clinical trials where one is by the Gynecological Oncology Group, the other is being at another physician sponsored study. What are the range of possibilities for how those two drugs could proceed given that these were physician sponsored studies?

[Jim Bianco:]

So, let me start with GOG. The GOG is the largest cooperative group network for gynecologic malignancies in the United States, 195 sites. Cisplatin’s approval in ovarian cancer was their cooperative group study that Bristol took the data and submitted it to the FDA when it was used in combination with -- I’m sorry, paclitaxel combination with carboplatin, sorry. That’s what I meant to say. So, they actually were the ones who hold the IND for this indication. They were the ones that interfaced with us and the FDA with regards to the initial discussions about protocol and endpoints. And so, we feel that this trial, especially since it’s a survival endpoint, could serve as the basis for approval in that indication, should the data be robust enough and in terms of survival effect. With regards to the L1 study which is what I think you are referring to tosedostat MRC randomized trial at low-dose cytarabine plus or minus tosedostat. That study is successful and in Pick the Winner and there were several other compounds, I think Vosaroxin, you go on the website and look a series of other investigational agents. And so the one that has the best combined CR rate and/or effect size rate would go forward into -- there is a large randomized trial. We would negotiate with them, obviously access to that data if the data were to be successful and we would have that discussion with the FDA on the utility of that trial as the potential registration study in frontline high risk elderly AML/MDS. And so the answer is yes, the FDA has done that in the past. GOG path has already been defined clearly that many years ago and the L1 trial would be something that we would do prospectively once we know whether or not we hit -- we were the winner in Pick the Winner and we get to go forward into the randomized controlled trial.

[Jack Singer:]

Just the color on the L1 study, this is not just a British study but it is an international study following many of the European sites as well as most of the other sites as Australia and New Zealand. So, this is newly well set up to be a Phase 3 program in terms of their approval rates are very high and it could be done quite rapidly. And as mentioned earlier, Alan Burnett was the Former Head of this group; has excellent working relationship with them. And where in the study to meet this primary endpoint in the Phase 2, he would work them as well as regulatory agencies to define a Phase 3 program that could be implemented rapidly. Also comment on tosedostat, has been very interesting abstract, a frontline study in the [indiscernible] at EHA, very positive study which duplicated the frontline data from University of Washington and was presented at ASH last year. So we’re very -- I think this is going to be an extremely interesting drive in frontline, [elderly] and in MDS and anxiously await the data.

[Jim Bianco:]

And always -- I kid Alan and I say that’s why he joined CTI because he was looking at the L1 trial data.

[Operator:]

We have time for one more question. This will from Bob Ai with WallachBeth Capital. Please go ahead.

[Bob Ai:]

My question is about PERSIST-2. So, I just want to make sure to first of all, so you have patients with platelet counts more than 100 will not be allowed to enroll?

[Jim Bianco:]

Correct.

[Bob Ai:]

And so, can you tell us a bit more about titration with Jakafi work I think is starting with 5 mg dose then want happens if the patients found dose is well tolerated, does the dose increase or stay at the 5 mg?

[Jim Bianco:]

Okay. So you’re talking for the patients with thrombocytopenia and looking at their label. So, we look at three patient streams that will come into the PERSIST-2 trial. There are going to be patients with disease related thrombocytopenia who are not candidates for Jakafi who are not doing well on their BAT. There will patients who are on ruxolitinib who are redeveloping treatment emergent thrombocytopenia and as they taper their dose, they redevelop splenomegaly and their symptom scores go up. So that’s a second patient stream, probably the least frequent patient stream that we would see. And then there is those patients who have disease related thrombocytopenia who are on the appropriate dose of Jakafi meaning 5 mg or 10 mg dosing, again depending if they’re above 75,000 or they’re below 75,000. And you think of it if they’re on that dose and they have a lot of symptoms and a big spleen and low platelets from their disease then we feel that group is not optimally treated at those sub-therapeutic doses and therefore that is our potential control arm. Now when they have a washout period, they get randomized and the physician can start them back on the appropriate dose of ruxolitinib if they choose as BAT. And as I was mentioning to one of the other questions that in and of itself will be a very telling parameter in terms of how many physicians would choose to use rux again when they had essentially modest treatment effect in this segment of patients who have disease related thrombocytopenia.

[Bob Ai:]

Also in the design of the PERSIST-2 trial, what percent of the patients do assume that will get Jakafi?

[Jim Bianco:]

Do you remember Jack? What percent of control arm, was it 30%? I am trying to think about the number first. It’s probably too granular to have on a call Bob. It gets into all of our sizing assumptions under us. So, we prefer just to neither way we stated it.

[Operator:]

That does conclude the question-and-answer session. At this time, we’ll turn it back over to our speakers for any additional remarks.

[Jim Bianco:]

Thank you folks. Thank you operator. Thanks everyone for joining us on the call. I hope we provided a little bit of transparency on the top line data to at least clear up any potential confusion that was out there. And we’re really excited about the product, we’re really excited about the opportunity for patients as well as for all of us here at CTI and at Baxter. And we look forward to sharing these data with you hopefully in the late breaking session at ASCO in June. And that ends our presentation for today folks.

[Operator:]

And again that does conclude today’s conference call. Thank you all for your participation.