TG Therapeutics Inc

NASDAQ:TGTX

Earnings Call Transcript 2019-Q1

[Operator]

Greetings and welcome to the TG Therapeutics First Quarter 2019 Financial Results and Business Update Conference Call. At this time, all participants will be in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded. It is not my pleasure to introduce your host, Jenna Bosco. Please go ahead.

[Jenna Bosco]

Thank you. Good morning and welcome to our conference call regarding TG Therapeutics first quarter 2019 financial results and business update. I'm Jenna Bosco, TG's Senior Vice President of Corporate Communications, and I welcome you to our conference call today.

Following our Safe Harbor statements, Sean Power, TG's Chief Financial Officer will provide a brief overview of our financial results and then, turn the call over to Michael Weiss, the company's Executive Chairman and Chief Executive Officer, who will provide an update on the ongoing development of our lead compounds ublituximab and umbralisib, as well as a high level overview of our early stage programs and overall company's standing.

Before we begin, I would like to remind everyone that various remarks that we make about our future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. TG cautions that these forward-looking statements are subject to risks and uncertainties that may cause our actual results to differ materially from those indicated. Factors that may affect TG Therapeutics operations include various risk factors that can be found in our SEC filings.

This conference call is being recorded for audio rebroadcast on TG's website, www.tgtherapeutics.com, where it will be available for the next 30 days. All participants on this call will be on a listen-only mode.

Now, I would like to turn the call over to Sean Power, our Chief Financial Officer, to briefly discuss the financial results for the first quarter of 2019, as well as the company's overall financial conditions.

[Sean Power, Chief Financial Officer]

Thank you, Jenna and thanks everyone for joining us. As you may be aware, our financial results were released earlier this morning and can be viewed on the Investors & Media section of our website at www.tgtherapeutics.com.

I'll begin with our cash position. During the quarter, we were able to complete a public equity offering and debt financing to strengthen our balance sheet, leaving us -- leading us with cash, cash equivalents and investment securities of $92.5 million as of March 31.

To ensure that we remain well positioned to execute on our goals, subsequent to the quarter-end, we utilized our ATM sales facility to raise additional net proceeds of $24.2 million for a pro forma cash position as of March 31, 2019 of approximately $116.7 million. Our average price during this ATM campaign was $8.11 and total shares issued were approximately $3 million.

Inclusive of the capital raise during the first and second quarters, we believe our current cash position will be sufficient to fund our operations through mid-2020. Further, additional potential borrowing capacity under our venture debt facility would extend our cash runway through the third quarter of 2020.

Our net loss for the first quarter of 2019, excluding non-cash items, was approximately $33.3 million, while our GAAP net loss for the first quarter was $35.2 million, or $0.43 per share, compared to a net loss of $41.5 million, or $0.59 per share, during the comparable quarter in 2018.

As we've been saying for a number of quarters, our R&D spend would begin to decrease as our registration directed trials in both oncology and MS progressed into 2019, and we've now begun to realize some of that, which is a major contributing factor to a decrease in net loss versus the comparable period in 2018. We expected this -- that this trend will continue over the next several quarters.

With that, I will now turn the call over to Mike Weiss, our Executive Chairman and CEO.

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Great. Thanks, Sean. And thanks, Jenna, of course. And thank you all for joining us this morning. I know I can speak for everyone at TG in saying, we're all super excited about the developments thus far this year. With the achieving of many key milestones, top on the list, of course, has been the significant progress made with our Marginal Zone Lymphoma program, including the release of positive top line results and the receipt of breakthrough designation and orphan drug designation.

Moving forward, we believe further clarity on our potential MZL NDA filing, hopefully, by year-end, along with the presentation of final data also toward the end of the year has the potential to unlock significant value for our shareholders. And once that occurs, we believe the other layers of potential approvals and combinations within our robust B-cell pipeline will come into focus for investors, highlighting the value we are bringing to patients with B-cell cancers and further translating into significant additional value to our shareholders.

With that, let's start the call by highlighting some of the notable achievements thus far in 2019. In January, we received breakthrough therapy designation from the FDA for umbralisib for the treatment of Marginal Zone Lymphoma or MZL. Also in January, we announced publication of clinical data from the Phase 1 triple therapy combination of ublituximab, plus umbralisib, plus ibrutinib in Lancet Haematology.

In February, we launched a first-in-human Phase 1 trial of TG-1801, our CD47/CD19 bispecific antibody in patients with a relapsed or refractory B-cell lymphoma. And later that month, we announced the most important news of the quarter. The positive outcome from the UNITY-NHL Phase 2b pivotal trial of umbralisib monotherapy in patients with a relapsed or refractory Marginal Zone Lymphoma, following which as Sean noted, we secured approximately $85 million in equity and debt financings.

We then kicked off the month of March by announcing positive DSMB reviews of both the UNITY-CLL and the UNITY-NHL trials where no safety issues requiring study modification were reported and that the UNITY-CLL had successfully cleared a fertility PFS analysis.

We opened up April with the oral presentation given by Dr. Nathan Fowler of the MD Anderson Cancer Center at AACR annual meeting, reporting positive interim data from the MZL Cohort from the UNITY-NHL trial.

Shortly after, we received orphan drug designation from the FDA for umbralisib for the treatment of MZL. And just this week, we announced long-term follow-up safety data from the open label extension study of the Phase 2 trial of ublituximab in multiple sclerosis, demonstrating that ublituximab remains well tolerated with median duration of follow-up of 97.5 weeks, and no patients discontinuing from the open label extension study due to an adverse event.

Now, let me quickly provide some highlights from the ongoing pivotal trials. Again, let's start with the UNITY-NHL study, where Marginal Zone Lymphoma has taken center stage. The MZL Cohort includes 69 patients treated with single agent umbralisib, and the primary endpoint for this single-arm study is overall response rate as confirmed by an Independent Review Committee or IRC.

As I already mentioned, there had been a few very important developments with this program during the first quarter. And again, the most significant of which is that the overall response rate for the entire treated population of 69 patients met the study's primary endpoint as well as our internal target overall response of 40% to 50%.

Next step for us is to meet with the FDA to discuss a potential accelerated approval filing. If all goes well, our goal would be -- to be to file for accelerated approval by year-end.

Next, let me provide some highlights from our UNITY-CLL trial, which is a randomized study of U2, that's umbralisib plus ublituximab in patients with both treatment naive and relapsed or refractory Chronic Lymphocytic Leukemia or CLL.

The DSMB, as I noted above, recently met and reviewed safety from this study and again determined there were no safety issues requiring modification of this trial. It's worth noting that a significant portion of the patients in this trial are treatment naive patients with CLL, and there are no other PI3K deltas approved in first line CLL in large part due to safety concerns.

The primary endpoint for this trial is progression-free survival, which is an event-driven endpoint. Meaning, that we need to see a certain number of patients who have progressed or passed away before we can call the study complete and analyze PFS. This of course, makes predicting precisely when the study will complete somewhat challenging, which we've been talking about for several quarters now.

That said, our current estimate is PFS can read out before the end of this year if our original power assumptions of approximate 40% to 50% improvement in PFS are realized, and the control arm forms in line with recent studies using that same control arm. Otherwise, if events take longer than expected, the study could push into 2020. We remain extremely optimistic about this study and the prospects for a successful PFS result.

As mentioned earlier, the DSMB recently conducted a successful interim PFS futility analysis and recommended that we continue this study. We continue to believe U2 is a very attractive treatment option for patients with CLL, providing an important alternative to BTK-based therapies, especially in those patients who are not good candidates for or who otherwise have tolerability issues on BTK therapy.

Next, I'd like to highlight some aspects of our MS program, which we continue to believe is not fully appreciated by investors. Last week at AAN, we presented data from the open label extension or OLE of the Phase 2 trial, which continues to show that ublituximab is well tolerated now with the meeting follow-up of 97.5 weeks. Additional highlights from the final Phase 2 data included annualized relapse rate of 0.07 and a 100% reduction in gad-enhancing lesions.

We believe the Phase 2 results are highly supportive of our ongoing ultimate Phase 3 program and I believe that ublituximab can deliver a best-in-class profile that includes comparable to better efficacy, comparable safety, convenience and price over available MS therapies. As a quick reminder, the ultimate one and two Phase 3 trials in MS are comparing ublituximab to an active control of teriflunomide in subjects with relapsing forms of MS known as RMS.

The primary endpoint for each study is annualized relapse rate following 96 weeks of treatment. Both trials have completed enrollment, and we expect data in mid 2020. It's also worth noting that we had some great KOL meetings at AAN, and there was great interest in ubli and its value proposition. We continue to be impressed with the enthusiasm for the one-hour infusion and the potential we have to strategically price ubli to enhance access to patients.

It's worth noting that ofatumumab, the only city 20 currently approved for MS is anticipated to generate approximately $4 billion in revenue in 2019 and only its second full year of launch. Clearly, this represents a very large market potential for CD20 in MS and even a small portion of this market would result in significant value to shareholders.

And finally, as mentioned earlier in addition to our exciting pivotal data, we currently have and continue to build a robust portfolio of early clinical drug candidates that in combination with U2 -- we can believe -- we believe can drive us closer and closer to our goal of curing certain populations of patients with B-cell cancers, adding another layer of growth and value for our shareholders, including -- included in an early pipeline, our TG-1501, our anti-PD-L1 antibody, TG-1701, our novel BTK inhibitor and our most recently licensed compound, TG-1801, our novel anti-CD47/CD19 bispecific antibody. We plan to share more about these compounds as the year progresses and it is possible that one or more of these compounds can advance into pivotal trials in 2020.

With that, I'd like to turn the call over to conference operator to begin the Q&A session, following which I'll return and provide some concluding remarks.

[Operator]

Thank you. We'll now be conducting a question-and-answer session. [Operator Instructions] Our first question today is coming from Alethia Young from Cantor Fitzgerald. Your line is now live.

[Alethia Young, Cantor Fitzgerald]

Hey, guys. Thanks for taking my questions. Congrats on the progress over the quarter. On the NHL study, can you just discuss how you're thinking about reading out maybe the follicular arms? Now, I know you've obviously have the MZL data published on that, but just wanted to make sure I was clear on the timelines.

And then, also on the MZL data, I guess I'm just curious, how you guys think about what the potential probabilities are around how much follow-up may be needed. I know you have that the conversation with the FDA. So, I'm sure you're working through some scenarios in your head, so just want to hear a little bit more about that? Thanks.

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Sure. So I'll start the margins and we'll work backwards with follicular. So in terms of follow-up needed, right now, we believe we will have a good nine months of follow-up on all patients. Even if the FDA asks us for 12 months of follow-up, I still believe we can have the filing in by year-end. But again, it's hard to know exactly what they're going to look for until we sit down with them. But our feeling is nine or 12 a follow-up and each patient gives us a median follow-up of significantly more than that. I think it's a 15 to 18 months depending on the two timelines, both of which would be reasonably consistent with the follow-up of ibrutinib when it was approved to Marginal Zone.

So we're in the range. I think we're -- it's relatively tight, but will in terms of what the alternatives are, but we'll see. Again, I don't want to get out over my skies until we have that conversation. And once we do, obviously, we'll make people aware of the timelines from there. So I think that's an important next step for us to get that clarity.

In terms of the follicular arms, as we were saying to a lot of folks, we've been guiding since the Marginal Zone. We’re really focusing all of our resources right now on getting the Marginal Zone data cleaned and ready for potential filing. Again, that also depends on how much follow-up is required. We’ll also add to the workload required to clean that database.

Having that, once we finished that and get that filing in, we’ll turn our attention to either CLL follicular and work on cleaning those. Again, if the CLL data is not available, we’ll turn the team's attention to cleaning and getting the follicular data ready for presentation and filing. So our best guess at this point is that follicular is closer to the end of the year or into 2020 in terms of top-line with a potential filing for follicular middle of next year.

[Alethia Young, Cantor Fitzgerald]

Just some of you now evolve from CLL, with this, I got a good 60/40 split between the naïve. How do you -- what's your confidence level on kind of being able to get like in my earlier lines versus kind of maybe like a second and third line label there?

[Sean Power, Chief Financial Officer]

Yeah. So this study is designed for both first line and relapsed/refractory. Again, there's 60% of the patients are in treatment naïve patients. So I think we -- our full expectation is that the label would be broad enough to cover both treatment naïve and relapsed/refractory. I don't see a scenario where we are -- we do not get the first line, and we get the second line instead because again the majority of the patients are first line. Yeah, I think if the study is successful, which we expect it will be. We expect to have both groups. The only caveat that we know about is that if the -- if directionally or there is -- or rather internal consistency of the two groups is not the same then potentially we don't only get one group.

But again, thinking about the question of front line versus relapsed/refractory, it would be almost impossible to imagine a situation where the relapsed/refractory were so positive that it carried the entire trial. And so that -- thus, we only receive the relapsed/refractory. It's potentially more likely that the front-line carries and the relapsed/refractory doesn't get there. But again because of the split, which is almost even both groups really need to contribute to have a successful outcome.

So I just -- I don't envision a scenario where both are not on the positive side of things. Again, they don't -- each group doesn't have to be statistically significantly better than its counterpart group. But the expectation is that both groups will be contributing to the ultimate successful outcome.

[Alethia Young, Cantor Fitzgerald]

Okay, great. Thanks.

[Sean Power, Chief Financial Officer]

Thank you.

[Operator]

Thank you. Our next question today is coming from Ren Benjamin from Raymond James. Your line is now live.

[Ren Benjamin, Raymond James]

Hey. Good morning, guys. Thanks for taking the questions. Mike, can you talk a little bit about sort of your confidence regarding the PFS timeline. And I guess, you mentioned the DSMB met, but every time they meet, do you get a sense as to how many events have taken place and do you have a sense of how many patients remain on therapy, because I think the way the design of the trial is they can remain on the experimental combination therapy for as long as they're responding versus the control arm?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Yeah. So patients will stay on therapy as long as they're gaining benefit and are continuing to have benefit and are not having tolerability issues. So yeah, the patients in the control arm as you've described are getting a six-month course of therapy and then, we see how long it takes for them to relapse. The vast majority, of course, will relapse at some point and the median for the control arm is expected to be for front line patients anywhere from 19 months, which is what we saw in the ILLUMINATE trial to 26 to 27 months, which we saw in the CLL 11 trial.

And relapsed/refractory patients is not a good measure. But you can, sort of cut almost in half the expectation of PFS from first-line to relapsed/refractory and it's just a ballpark. So yeah, I mean, I think -- so in terms of predicting the end of this thing, again, we believe and it's -- this is our belief -- we believe that the control arm is well-known enough that the probability that it's going to dramatically shift is relatively unlikely.

So again, between ILLUMINATE and CLL 11, you've got a bracket of 19 months to 27 months in front line patients. Again, if you assume approximately half of those two numbers is what you'd expect to see in relapsed patients. You've got a pretty well fixed PFS and we've modeled within a relatively good range there from 18 to 22 months I think of total PFS. We've modeled that out. It doesn't -- it's not very sensitive to those kinds of changes when you're out. Our follow-up is pretty good at this point and getting better. By the end of this year, we will have an almost 20, 30 months of median follow-up. So again, if you think about in potential PFS for that group of 18 to 22 months on a blended basis at 30 months of follow-up, it's hard to imagine that, that entire population hasn't reached their median right.

So assuming that group is fixed then the only potential variable is whether our performance is better-than-expected, right, in terms of benefit over the control arm. The study, as we've described a few times as powerful about a 40% to 50% improvement in progression-free survival, if in fact the control arm performs as we've described relatively in line with the numbers and we have a 40% to 50% improvement, the study should be over by the end of this year. Again having said that, assuming the control arm is well fixed. If our arm is performing better than 40% to 50% improvement over their PFS, then it will go into 2020.

[Ren Benjamin, Raymond James]

Got it. I just want to confirm though that you don't have, sort of, updated advances as every time the DSMB meets that you have an idea of how it's progressing. It's still based on model. You're blinded completely to the trial results so far?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

We are completely blinded to the trial results.

[Ren Benjamin, Raymond James]

Got it. Just following up with MZL that the landscape continues to shift, we get questions regarding lenalidomide and rituximab approval or potential approval, can you just talk about how you're seeing. I'm sure, you're seeing the landscape just as we are. How that might impact your application timelines chances for approval and then, I guess most importantly, use in the commercial setting?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Yeah. So in terms of Marginal Zone, it doesn't look like a lot. A lot is changing in – as far as we can tell. So we do feel like we have a pretty good path forward to approval. In terms of the commercial application, look there's a need for non-chemotherapy options in the treatment of patients with Marginal Zone Lymphoma. Ibrutinib overall is a very good drug. Obviously, I think I would argue it's a better drug in CLL than it is in Marginal Zone, but it's a good drug overall, but it's – as we've described in many situations, it's not perfectly tolerated. It's not for everybody. We think that umbralisib, the profile that we've seen thus far in the 42 patients that we've presented at AACR and if that profile were to continue, we think that it is a more attractive profile for patients on – with Marginal Zone Lymphoma, we think we have a very good opportunity that we would be the first chosen small molecule non-chemotherapy for patients with Marginal Zone Lymphoma. We have – it appears to be at least a -- on the surface a higher response rate. But more importantly, are the differences in complete response rates and the median time to onset of response. So if you're patient and again, assuming the data holds up through the final analysis, if you're a patient and you have a choice between the two options, one has a median time to response of about 2.5 months and one has median times response about 4.5 months, so you get to know sooner. If you're getting a good reaction to the drugging, you have a higher probability of getting a complete response rate.

So, yeah -- and we think it's an attractive profile. Obviously, it's not a head-to-head comparison because they were never studied against each other, but we think we've got it. We will have a nice and label to talk about just our drug, and we think it's attractive for Marginal Zone patients.

[Ren Benjamin, Raymond James]

Got it. And just one final question for me, I think in your responsibility, I just want to make sure the UNITY-NHL study. I thought we had two read-outs expected in the middle of the year, The DLBCL cohort and the FL cohort. And I think you mentioned that the FL cohort is likely to be delayed or un-blinded later this year. And that's the Company's choice. It's not like we're waiting for events right. The decision is when you guys make that decision to pull the trigger. Is that the same thing with the DLBCL and do we expect a similar timeline?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Yeah. Diffuse large B-Cell has been for at least almost a year now. I'd say at least nine months has been de-prioritized given our feeling about the unknowns in the diffuse large B-Cell market. So that data is maturing, but in terms of corporate resources to analyze that data, there's a lot there and kind of excited some point to dig into it. Unfortunately, we just don't have the resources to dig in today. So at some point, again, as we get closer to the end of the year, we'll see what we have in front of us. Again, if we have CLL, all focus will be on CLL. If we don't have CLL, the focus will turn toward follicular and then to diffuse large B-Cell.

[Ren Benjamin, Raymond James]

Great. Thanks very much for taking the question.

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Yeah.

[Operator]

Thanks. Our next question today is coming from Ed White from H.C. Wainwright. Your line is now live.

[Ed White, H.C. Wainwright]

Good morning. Thanks for taking my call. So Mike, you had mentioned that – 1501, 1701 and 1801. One of more of those could move to a pivotal in 2020. I just wanted to see if we can get a little bit more information on that as far as timelines go. When can we expect to see data from each of those trials? And then just on the BTKs, 1701 -- we also have 1702. We haven't spoke about that -- I was just wondering if that's in development or if that's on the sidelines waiting for you to see what's happening with 1701s. Thanks.

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Sure. So I think the easy question was 1702 is a backup compound to 1701. Right now, things are going pretty well with 1701s -- I don't think we're moving very aggressively on 1702 at this point.

In terms of data from each of these trials and potential for pivotal trials sometime in 2020, so look, we're moving along, I think, the BTK as it stands today is probably the furthest along in large part, because it got started first and we've seen activity at the first dose level. So, it makes it a lot easier. Now, we're just around the margins trying to identify what is the optimal dose both as a single agent and also in combination with U2.

So I would hope that during the remainder of this year, we'll be able to identify a dose that we could take into pivotal trials from both single agent and in combination with U2 for 1701 BTK, which ideally would put us in a position sometime in 2020 to start a pivotal program with that compound.

Beyond that, the TG-1501 or PD-L1. We have some really good confirmation from the solid tumor studies conducted by checkpoint that the drug is highly active. The profile looks great. It's a really neat compound in terms of its ability to both engage T-cells and K-cells. So, it's really the only antibody in that class that has that dual capacity. The Pfizer, Merck AG compound also has that capacity, but it also has -- that drug has a bit of a challenge in its short half-life. So, the ability of this compound to have a full two-plus week, half-life plus it has the maintenance of its FC domain, which gives it ADCC. So, it's really a very unique PD-L1.

Again whether that makes it the best PD-L1 that's ever been created, that's obviously not what we're trying to say, but it's a very unique and it's an interesting PD-L1 and I think the solid tumor data that we've seen just so far, which is recently presented, gives us high level confidence that we're dealing with an active agent. So, we're really at-dose right now. We're starting with the dose that they left us in the solid tumor studies at 800 milligrams every two weeks.

We're just getting going on our heme study. But again, it's -- we're in May, six to eight months from now. We should have a pretty good population of patients to understand what's going on and I think that one may be toward the second half. If we're going to get in. If -- obviously, in each of the data and so, it's going on. But if everything is going well, certainly 2020 second half, late second half to get that into pivotal studies is also not out of the question.

And then, the bigger wildcard is the 1801, the CD-47, CD-19 bispecific is a very novel first-in-class agent. We have to start very low in the dose escalation, so that's ongoing. So, I think it's too early for me to assess what the timeline will be there, but obviously, super excited to get that going in combination with the rest of our portfolio as soon as we can.

[Ed White, H.C. Wainwright]

Okay, great, Mike. Thank you.

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Yes. Thanks, Ed.

[Operator]

Thank you. Our next question today is coming from Pete Lawson from SunTrust Robinson Humphrey. Your line is now live.

[Pete Lawson, SunTrust Robinson Humphrey]

Yes. Thanks for taking the questions. Just on MS, what's the physician feedback been like say AAN and just can you remind us on the timeline, is that still potentially a 2021 product?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Yes. So, in terms of physician feedback, we had multiple meetings at AAN. We spent pretty much the better portion of a full day with back-to-back meetings with KOLs. And also community-based KOLs, it was really enlightening great meeting. The excitement for the product is we think -- what we heard was very high. I think there's enthusiasm.

I think one might be surprised at the attractiveness of a one-hour infusion, but the folks think it's a big deal. It's not only just a patient convenience factor. The economic effect of freeing up that chair as quickly as possible and the infusion suite cannot be underestimated. So, yes, we've got a lot of great feedback, and we were -- again just reaffirms our excitement and enthusiasm for the profile of ublituximab in MS.

In terms of timelines, yes, the studies should – we should start to see data from the studies in mid-2020. Our goal is to have a filing in. This would be a supplemental BLA. If all goes well with our expectations for ublituximab in CLL, so this would be a supplemental BLA. And our expectation is try to get that in before the end of 2020 or early 2021 with approval in 2021.

[Pete Lawson, SunTrust Robinson Humphrey]

Great. Thank you. And then just on 1501, you'll see a differentiation. There is a benefit -- here, the differentiation or is it just more so the ability to control pricing?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

So we won't know until we test it fully. I think there's a few pieces to the puzzle of 1501. One is the differentiation and again, the nice part about PD-L1 is it's in -- it's a tumor target, right. So PD-L1 sits on the cancer. PD-1 sits on your T-cells. All the PD-1s were engineered to remove any ADCC effect, so that they would avoid the possibility of actually landing on their own -- on your body's T-cells and having the body, then kill the T-cell, which would destroy the point of hitting it with PD-1.

PD-L1 on the other hand lands on the tumor and engages the T-cells, while it's sitting on a tumor. But while it's there, it might as well try to kill the tumor itself, right. So we have that FCs opening and ready for business. So it has a tumor. So yes, will that be a differentiator of significance? We'll only know as we go through the clinical program. But it's also a function of the use of PD-1s and PD-L1s in liquid tumors to date is relatively limited and the experience broadly is relatively limited, right. So we have approvals in Hodgkin's disease, so push that off to the side just a little bit. You've got an approval in primary mediastinal Diffuse Large B-Cell, which is a very rare form of Diffuse Large B-Cell.

And then after that, we've only have -- there's literally a smattering of data available. So, one part of having 1501 is not just the package pricing later. You can't really run trials -- the trials you run around without permission from someone else, if you don't have your own PD-L1 in hem malignancies. So for us, it's about research flexibility about building the combinations that we won for best care for patients exploring them broadly, which is really impossible today. If you don't have your own or you don't get an agreement with someone to give you a free drug, but that always, always, always comes with strings attached.

So, again, it's research flexibility. It's possibly learning that the differences in how this molecule works, really make a difference clinically and then, its future package pricing for sure.

[Pete Lawson, SunTrust Robinson Humphrey]

Great. Thank you. Just in CLL, since MZL is kind of potentially wide open, who are you thinking about as kind of the potential first adopters in CLL as a particular subsets of either patients or the community versus academic, just kind of -- I'm just trying to work out your game plan?

[Sean Power, Chief Financial Officer]

Yes. So our game plan is relatively straightforward. We see -- we do see the market as being divided between the community and the academic centers. In academic centers, you're going to have a lot more options, particularly with venetoclax being well used and well liked in academic centers, whereas in the community, venetoclax is much more of a challenge. So we see the community oncology space being dominated by a ibrutinib. But again, as we've noted multiple times, ibrutinib is a very good drug, but it's not a perfect drug.

And second generation BTKs are honestly only moderately appear at least from the data we've seen, only moderately better on the tolerability toxicity profile of "BTK" toxicities. So you need an alternative to BTK therapy. There's no question and we think that alternative represents up to almost 40% of the market. Probably 20% of patients before they'd go on ibrutinib would be candidates that are not good candidates for ibrutinib, which would be good candidates for us.

And then, on the other side of going on BTK therapy, you're going to get another 20% of the patients that are going to fall off over a year or two based on tolerability, not resistance that will also be very good candidates for U2 therapy. So we think across lines of therapy, we have a really good opportunity at anywhere from 20% to 40% market share of a very, very large market. If it's a $10 billion market, we think there's plenty of room for us to add value to patients and then, that's just -- that to us is the foot in the door.

Once you realized that you can get the same outcome using U2 and perhaps you have a better experience with it from a tolerability standpoint, then you start to use it more often first line, then you would just in the patients who don't tolerate or are not good candidates for ibrutinib. So we think there's growth built into that, but certainly we think the beginning market is for patients who are not good candidates or who don't tolerate BTK therapy, we think that's a pretty large portion of the market.

Like I said, I think once you move into the academic centers, you're going to find that there's a lot more options and maybe a little more confusion on how the treatment options and cascade will go. But I think ibrutinib-based therapy is venetoclax-based therapy is all being in the mix for a front-line therapy even in the academic centers.

And ultimately, the academic centers will converge to -- in our opinion, the academic centers will converge on two basic potentially curative first-line treatment, which will be an ibrutinib plus, venetoclax, potentially plus or minus eziebah [ph] on the one hand, and inpatients who are not good candidates for that because of ibrutinib potential toxicities, they would go on something like a U2 plus venetoclax.

And again, both of those treatment options will be potentially curative in a reasonable number of those patient. So the market is moving in the direction both academically and in the community that you need an option that sits right next to BTKs that you can offer to patients when they're not good candidates or don't tolerate BTK therapy.

[Pete Lawson, SunTrust Robinson Humphrey]

Great. Thank you so much. Congrats on the progress.

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Thank you.

[Operator]

Thank you. Our next question today is coming from Matt Kaplan from Ladenburg Thalmann. Your line is now live.

[Matt Kaplan, Ladenburg Thalmann]

Hi, good morning guys. Thanks for taking the questions. Matt, just wanted to zero in on Marginal Zone a little bit more given the relative near-term filing of the NDA, can you give us a sense in terms of where you are in the preparation for the filing in terms of CMC, manufacturing preclinical tox package. I guess, what's the rate limiting step for filing?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

So I don't have a current update in my hand, but I know the team is working on all aspects and I've been informed that they feel like they can get it all done by the end of this year. So I think if -- assuming that, we are coming to an agreement with the FDA and what the package looks like and the timing of follow-up and everything else that's required, the team tells me that they will be ready for any of your filing.

[Matt Kaplan, Ladenburg Thalmann]

Great. Thanks. And then commercialization plans for Marginal Zone in the U.S., what are your thoughts there?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Yeah. So, we hired Adam Waldman from Celgene. He is unbelievable, fantastic commercial person who has been in this area for quite some time, and he is going to help build the most gorgeous commercial team this side of the Mississippi maybe even both side of the Mississippi. Obviously, there has been tapes of obviously, a little bit of exaggeration, I'm sure he is going to – he will create a great team. But yeah, the plan is to build a really top-notch commercial organization. We think that there's a lot of great talent available in the marketplace to join us. We've got a lot of inbound interests from folks who were following what we're doing and unlike what's going on. So I think we can and we'll be able to put together a really talented team to commercialize umbralisib and U2.

[Matt Kaplan, Ladenburg Thalmann]

Great. Thanks. And the last question I guess with the number of medical conferences coming up at ASCO EHA, ICML, what type of presence we have there? Are you going to have any presentations at those upcoming conferences?

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Yeah. So we have several oral presentations in Lugano. We have an oral presentation at ASCO, and we have just opposed to presentation at EHA.

[Matt Kaplan, Ladenburg Thalmann]

Congrats on the progress, and good luck.

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Great. Thanks, Matt.

[Operator]

Thank you. We reached end of our question-and-answer session. I'd like to turn the floor back over to Mr. Weiss for any further or closing comments.

[Michael Weiss, Executive Chairman & Chief Executive Officer]

Great. Thank you. And again, thanks everyone for joining us today. As I wrap-up the call, let me just review some of the key goals and objectives for the remainder of 2019. I think we've talked quite a bit about these in the Q&A and in the prepared remarks. But first and foremost, of course, we'd like to have a nice meeting with the FDA to discuss our filing for MZL and hopefully following that will boilable that we'll be able to provide the clarity that we'd like to give to investors on the regulatory path for Marginal Zone. And again, the goal is to – if all goes well to get that filing and by year end. Additionally, we're looking forward to presenting the final MZL data by year-end hopefully at a major conference.

Next up, importance, of course, is getting to that top line progression free survival data for UNITY-CLL. Again hopefully, we'll have that data available to us by the end of the year. And again, the goal is for that to support approval of U2 in combination for all lines of CLL both treatment naive and relapsed refractory. Beyond the key events, we'll have multiple data presentations across the year as we've just talked about, both on single agent in combination.

We've got the summer conferences coming up, ASCO, EHA, Lugano. Also this summer, there's EAAN, where we will present additional MS data and then, we'll have an opportunity toward the end of the year. We will have -- we are hopeful present more MS data and at ASH -- hopefully, we'll be presenting a lot of exciting data on both umbralisib single agent, as well as some of the newer compounds and combinations.

So, on behalf of all of us, here at TG Therapeutics, I'd like to thank, of course, our investigators and their patients who will continue to participate in our trials and help move science along and of course, our shareholders for their support and our employees who work hard every day to make it all happen. Thanks again everyone for joining us and have a great day.

[Operator]

Thank you. That does conclude today's teleconference. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.