TG Therapeutics (TGTX) CEO Michael Weiss On Q2 2016 Results - Earnings Call Transcript

| About: TG Therapeutics, (TGTX)

TG Therapeutics, Inc. (NASDAQ:TGTX)

Q2 2016 Earnings Conference Call

August 8, 2016 08:30 AM ET


Jenna Bosco - Vice President of Investor Relations

Sean Power - Chief Financial Officer

Michael Weiss - Executive Chairman, Interim President and Chief Executive Officer


Jonathan Aschoff - Brean Capital

Matt Kaplan - Ladenburg Thalmann & Co.

Joseph Pantginis - Roth Capital Partners

Yatin Suneja - SunTrust Robinson Humphrey

Reni Benjamin - Raymond James


Greetings, and welcome to the TG Therapeutics Inc. Second Quarter 2016 Earnings Conference Call. At this time, all participants are 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 now my pleasure to introduce your host, Ms. Jenna Bosco, Vice President of Investor Relations. Thank you. You may begin.

Jenna Bosco

Thank you. Good morning, and welcome to our conference call regarding TG Therapeutics second quarter 2016 financial results and business update. I am Jenna Bosco, TG's VP of Investor Relations, and I welcome you to our conference call today.

Following our Safe Harbor statement, Sean Power, our 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 Interim Chief Executive Officer, who will provide an update on the ongoing development of our novel, glycoengineered anti-CD20 monoclonal antibody, TG-1101, our novel once-daily PI3K delta inhibitor, TGR-1202, as well as a review of our recent achievements and upcoming milestones.

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 and uncertainties that can be found in our SEC filings.

This conference call is being recorded for audio rebroadcast on TG's website,, 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 second quarter of 2016, as well as the company's overall financial condition.

Sean Power

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

At June 30, 2016 we had cash, cash equivalents, investment securities and interest receivable of $75.8 million, which we believe will be sufficient to fund our operations into the second quarter of 2018.

Our net loss for the second quarter ended June 30, 2016, excluding non-cash items, was approximately $14.3 million, which included $3.4 million of manufacturing and CMC expenses for Phase 3 clinical trials and in preparation for potential commercialization.

The GAAP net loss for the second quarter ended June 30, 2016, inclusive of non-cash items, was $15.9 million, or $0.33 per share, compared to a net loss of $17.1 million or $0.38 per share during the comparable quarter in 2015. The decrease in net loss during the second quarter of 2016 was the result of a decrease in non-cash compensation expense related to equity incentive grants over the 2015 period, partially offset by an increase in clinical trial expenses related to ongoing and planned clinical registration programs.

Our net loss for the six months ended June 30, 2016, excluding non-cash items was approximately $26.4 million, which included $7.7 million of manufacturing and CMC expenses for Phase 3 clinical trials and in preparation for commercialization. We do expect that these manufacturing and CMC expenses will decrease in the second half of 2016.

The GAAP net loss for the six months ended June 30, 2016, inclusive of non-cash items, was $29.7 million, or $0.61 per share, compared to a net loss of $31.7 million or $0.73 per share during the comparable period in 2015. The decrease in net loss during the 2016 period was the result of a decrease in non-cash compensation expense over the comparable period in 2015, partially offset by an increase in clinical trial expenses related to ongoing and planned clinical registration programs.

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

Michael Weiss

Thanks, Sean and thanks Jenna, and thanks everyone for joining us this morning. While 2016 continues to be a very challenging year for our stock price, which many of you I am sure are keenly aware. Fundamentally we believe the company is stronger than ever with a lot of great progress made in the first half of 2016. Some of those highlights included the issuance of Composition and Matter Patents in the US for both TG-1101 and TGR-1202, providing protection through 2029 for TG-1101 and 2033 for TGR-1202. In both cases, plus up to an additional five years under the rules of patent term extension.

At the American Association for Cancer Research (AACR) Annual Meeting scientists from the Moffitt Cancer Center presented preclinical data describing the differential regulation of human T-cells by TGR-1202 as compared to other PI3K-delta inhibitors and close to presentation that may partially explain why we are not seeing the same autoimmune like effect with TGR-1202 as seen with other PI3K-deltas.

We also announced the commencement of the company’s first clinical trial of TG-1101 in multiple sclerosis, opening an entirely new area of potential value for the company. We also entered into a global collaboration to develop and commercialize novel BET inhibitors for the treatment of hematological malignancies.

We also enrolled our first patient in our registration-directed UNITY Diffuse Large B Cell Phase 2b clinical study, and finally we presented an integrated safety and efficacy analysis of 165 patients treated with TGR-1202 both alone and in combination with TG-1101 at the American Society of Clinical Oncology (OTC:ASCO) Annual Meeting as well as at the European Hematology Association (EHA) Annual Congress.

Some highlights from this presentation included that TGR-1202 alone and in combination with TG-1101 continued to demonstrate a favorable safety profile. Discontinuations due to TGR-1202 adverse events were limited at 8%, and to put that into perspective data presented also at ASCO this year on the combination of [Indiscernible] in previously treated CLL, stood at 39% discontinuation rate due to adverse events.

Additionally grade 3, 4 adverse events most commonly associated with PI3K-delta inhibitors were relatively rare with pneumonia at about 5%, pneumonitis at less than 1.5%, ALT, AST elevations at approximately 3%, and colitis below 1.5%. This equates to two cases of colitis, both of which occurred at doses exceeding the Phase 3 dose and did not appear to be time dependent, one instance occurring at four months and the other at 24 months after the initiation of therapy.

Overall of the 155 patients treated with TGR-1202 between the two studies, 80 patients were on drug for greater than six months, 43 patients were on for more than 12 months, and the longest patients have been on daily TGR-1202 for greater than three years.

The presentation also showed encouraging efficacy, particularly at the Phase 3 dose of 800 mg, including an 88% overall response rate in the 16 patients with CLL, including two CR, plus an PR in an ibrutinib refractory patient; 57% overall response in seven patients with Diffuse Large B Cell, and a 53% overall response in 17 patients with follicular and marginal zone lymphoma.

Additionally from a safety standpoint, specifically for the 800 mg Phase 3 dose, grade 3, 4 adverse events, most commonly associated with PI3K-delta inhibitors, was similar to the entire safety population, and continued to be relatively rare with pneumonia at about 2.5%, penumonitis at 0%, ALT, AST elevations at approximately 5%, and colitis at 0%. These data were not presented at ASCO or EHA, but were developed in response to some questions we received at and after the conferences.

We are highly encouraged by the data presented, which further confirms our belief that TGR-1202 has a unique and differentiated safety, tolerability and activity profile as compared to other deltas. With the recent high-profile setbacks that [Indiscernible] we believe more than ever there is the need for a PI3K-delta with a wider therapeutic index.

We recognize that some investors and possibly some clinicians are not yet convinced. They are firm to paint all deltas with the same negative brush. We will continue to update our safety profile on a regular basis with the goal of elevating those concerns. In the meantime, let me provide some positive news from our Phase 3 clinical trials. I'm happy to report that we currently have over 60 US sites open to enrollment in our UNITY-CLL study. Our plan is to open approximately 100 sites in the US and approximately 50 sites in Europe and Israel by the end of this year.

I'm also extremely pleased to report that enrollment into UNITY-CLL study is tracking well and meeting our expectation. As anticipated, enrollment seems to be easier than in GENUINE and with enrollment already strong and many high enrolling sites soon to be initiated, we are feeling extremely optimistic that we can meet or exceed our enrollment goals for the UNITY-CLL study.

With that let me turn to our GENUINE Phase 3 trial, which is evaluating TG-1101 in combination with ibrutinib in patients with high risk CLL. We launched this study with the hope and intention that this would be a fast and straightforward approach to getting TG-1101 approved. Recall at the time we designed this study, we were very uncertain of what the FDA would require to get two novel drugs approved simultaneously. As a result, we only started discussing with the FDA the concept of a UNITY-CLL study after we completed our SPA discussions for GENUINE. We still believe that GENUINE’s goal of improving on ibrutinib therapy represents an important treatment goal. There is no question that ibrutinib is a very good drug, but few if any patients are cured with single agent ibrutinib.

Our Phase 2 study demonstrated increases in overall response as well as a deepening of responses with 25% of the patients on the combination of ibrutinib plus TG-1101, obtaining either a complete response and/or MRD negativity. Any time you leave residual disease you enhance the chance of the cancer mutating and advancing. Based on early [PFS] curves with single agent ibrutinib, we believe the patients that might benefit the most from this multi-modality approach were those with high-risk disease.

We continue to believe that it is a worthwhile approach. But as we have highlighted in our recent calls, recruiting these high-risk CLL patients has posed a greater challenge than expected. One issue we identified was that many of our sites were not screening for high risk features on relapse. To address this issue we implemented a very simple screening protocol, which we have previously described.

We believe this screening protocol has solved this problem and we have seen an up tick in screening. However, we are still finding that the patient population is more challenging to enroll than we originally thought. Our plan is to continue to work on ways to accelerate the trial for use as an early registration pathway for TG-1101 as it was originally intended.

The positive enrollment trends we are seeing in the UNITY-CLL study are extremely encouraging, and may provide a more rapid path forward for approval of TG-1101 and TGR-1202 than we originally anticipated. This in turn is having the unexpected effect of lessening in a very positive way some of our original rationale for running the GENUINE study in the first place, i.e., to get that rapid early approval.

With that I would like to switch gears and discuss a very exciting new area for us. In May, we announced the launch of our MS program. We are excited about broadening our pipeline into autoimmune disease and think there a significant market potential for our compounds in MS, which has a prevalence of approximately 400,000 cases in the US and approximately 2.5 million cases worldwide.

As noted on our last call, B-cell depletion therapy has proven to be highly efficacious in the treatment of both relapsing and progressive forms of MS, and we feel confident from our experience on the cancer side that TG-1101 is a potent B-cell depleting compound with a favorable safety profile and we believe TG-1101 to remain an exciting differentiated treatment option for patients with MS.

While we have a substantial data set for TG-1101 in oncology patients, we have recently launched Phase 2 dose finding study. This is designed to determine the optimal dosing regimen for TG-1101 in MS patients. Patients will be monitored for safety and tolerability at each dosing cohort and we will be evaluating B-cell depletion as well as establish MS efficacy endpoints.

The study will also evaluate accelerated dosing regimens to reduce infusion times similar to the way we have done in our cancer studies. While very early enrollment into this trial is running ahead of schedule and we do anticipate completing enrollment in the pre-specified cohorts, excluding any extension cohorts before year-end.

Over the next six months or so we believe we will have enough data from our MS phase 2 study to commence our Phase 3 registration program in the first half of next year. Towards that end, we have already begun a dialogue with the FDA to understand their expectation and believe that that process should conclude in the same approximate time frame.

Finally, we have noted in the past that we have received interest in this program from potential partners and we can say that there is continued interest and discussions are ongoing. However, whether or not we enter into the transaction is subject to many variables, importantly we do believe we can add significant value to the program over the next six to nine months as we demonstrate activity directly in patients with MS and demonstrate an ability to infuse TG-1101 safely in a shorter infusion time than competitor products. And finally as we define the regulatory pathway, which could lead to study designs that are highly manageable for us to execute on a go alone basis.

With that, let me now turn the call back over to the conference operator to begin the Q&A session, following which I will return to make some concluding remarks as well as reiterate our goals for the remainder of the year.

Question-and-Answer Session


[Operator Instructions] Our first question is coming from Jonathan Aschoff of Brean Capital. Please proceed with your questions.

Jonathan Aschoff

Thank you. Hi guys. Good morning and nice to see the clinical progress and the continued 1202 differentiation.

Michael Weiss

Thank you.

Jonathan Aschoff

I wanted to ask how the recent pivotal results in diffuse large B-cell impacts your thinking regarding TG-1101 in that indication?

Michael Weiss

Yes, that is a good question Jonathan. So that study particularly we thought was the one study of that registration program and their [rituxan replacement program] was the most likely to be negative. This is front line patients with aggressive diffuse large B-cell lymphoma. You would expect, one should rituxan perform quite well in a frontline patient population, where there is high expression of CD20. So the ability to differentiate the difference between those two drugs I think is and clearly was a challenge.

So we really I think all along though that that was the toughest place for them to demonstrate that they could show that [Indiscernible] was better than rituxan in that front line patient population, and was absolutely zero. There is no question that in a head to head basis they have proven it twice now, both in follicular and CLL that glycoengineered CD20s are better than non- glycoengineered CD20s or rituxan. So I think it is just one of those situations where the trial design was set up that was very challenging and probably [failure] from the very beginning but I think they had to try as part of their replacement. It seems like they will probably be R-CHOP or remain diffuse large B-cell, but they will be able to replace rituxan across indolent lymphomas and CLL.

Jonathan Aschoff

Okay, thanks and I guess that it is simply too difficult to presently estimate genuine trial time, and I guess, since you have the coverage from UNITY for both drugs you almost don’t care?

Michael Weiss

I would say almost – I wouldn’t say exactly, again I think we are still working with GENUINE. We think it is an important study design. We think it is important to show the benefit of ibrutinib, but yes, there is some sense that with the UNITY-CLL study enrolling quite nicely and a lot of – most of our major academic sites are not yet open in the US and we have a lot of interesting and exciting sites in Europe, both Western and Eastern Europe where there has been a lot of enrollment in these studies.

I think the big CLL 11 study, which was the Gazyva CLL study, I think almost of the enrollment came from Eastern Europe or a lot of it. It was the major enrollers, and we have a lot of those sites ready to get them involved in hopefully by the end of year have them up and running. So, enrollment right now is strong. We still have the major academic centers to get up and running in all of Europe. So, yes, I think we are feeling very optimistic and that obviously will set us up for approval for both drugs, but again we do think having data from the combination of TG-1101 plus ibrutinib is still important. We still think it would be great if we can figure out how we can make that happen fast enough, so that it gets done before we get any further with UNITY-CLL.

Jonathan Aschoff

Great. Thank you very much.

Michael Weiss

Thank you.


Thank you. Our next question is coming from Matt Kaplan of Ladenburg Thalmann. Please proceed with your question.

Matt Kaplan

Good morning guys.

Michael Weiss

Good morning.

Matt Kaplan

Thanks for the update in terms of the profile for 1202 and breaking up I guess the Phase 3 [plus too], I guess given the differentiation of 1202 versus idelalisib and duvelisib, one of the things that we heard at ASCO and ASH was excitement from investigators in terms of combining it, can you update us on your plans for additional doublets and triplets with 1101 and 1202, and also 1303 and then also the ongoing combos?

Michael Weiss

You kind of lost me in there a little bit Matt, but I will say that our hope is that we will have some really nice presentation at ASH this year for some of the triple combination work we have been doing both with TG-1101 and TGR-1202 plus ibrutinib, which has been conducted in CLL and NHL. We also have 1101, 1202, and 1303 plus [Indiscernible], which we are studying in lymphomas. And I think there is a few other novel combinations that we are looking at 1202 plus ibrutinib as an oral, and I think there is one another oral combo that we are looking at as well. So, we are hoping that at ASH we will have some pretty interesting data on some of those next-generation combinations.

Matt Kaplan

Okay, great. And then with the MS for 1101, the Phase 2 ongoing, what are you looking to share I guess in that study and then what do you think I guess at this point the Phase 3 could look like?

Michael Weiss

Well, in terms of what we want to show from the Phase 2 study, the most important information that we are trying to get so that we can move on to Phase 3 is really just the B-Cell depletion information. We just want to get comfortable that at those doses we are looking at, we are depleting the B-Cells in sufficient quantities. We are pretty confident we are going to do that, but until you actually do it you still don't know with certainty. So that is the big part of the program.

We will continue to follow patients over a two-year period to look at certain aspects of MS efficacy, including GAG lesion reductions but that kind of information would not hold us up to start the Phase 3 program and that will be data that will come out nicely during the conduct of our Phase 3 trial. So first is the B-Cell depletion data. The other part that is important to us is our ability to show we can infuse in shorter time frames. Right now I believe [Indiscernible] is a three to four hour infusion every six months. We would like to see our infusion come down closer to one hour. As you know, on the cancer side, after the first one or two doses we are able to get 900 mg into a patient in an hour and a half, and our anticipation is that the Phase 3 dose for MS will be less than 900 mg.

So that is what we are looking for both B-Cell depletion and infusion times data, and then in terms of what a Phase 3 design should look like, I think if you look at OPERA I and OPERA II, which were the Phase 3 trials run by OPERA, I think that's a pretty good sense of what these studies could look like and they are pretty straightforward. It will be 1101 versus an active comparator, Rebif was the active comparator used in the OPERA study. I think our goal would be to use either Rebif or some other compound that has equivalent activity profile, but again that part we are working with the investigators to figure out exactly what the best comparator arm will be. But certainly we will be looking for something that had an activity level in and around the same level as Rebif.

The other thing we said is if you look at those trials, they had – each one OPERA I and OPERA II they had approximately 800, I think even over 800 patients in each one of those trials for a total program size of [1,500] patients that if you look at the feed values that resulted from the studies, feed values had three, four zero before you got to a number. So we believe that a significant smaller study design to be completed that would provide a highly efficacious result and that’s really part of our conversation a dialogue that we’ve and we’ll continue to have with the [FAR] in the next six to nine months and that was the finding of what that program in terms of size look like. And I think the end points will be the same and you’ll realize straight at two years.

There is lot of stuff that is pretty well established in the MX world and so if you offer one study in basic design will be copied almost identically obviously, lot of them the end in the study, the number of patient subjects studied will be different and possibly will make these a different compared on one then certainly as well proven to have activity in around the same range as we rebate, if we don’t use rebate.

Matt Kaplan

Great, thanks for the [indiscernible].


Thank you. Your next question is coming from Joe Pantginis of Roth Capital Partners, please proceed with your question.

Joseph Pantginis

Hi guys, good morning, thanks for taking the question. Michael, can you provide a little color with regard to your earlier prepared comments on 1202 with regard to efforts that you’re going through right now with regard to the broader physician population and I guess the way you put it was painting the PI3Ks with the broad stroke as, they’re all the same versus the safety call filing, efficacy profile that you’ve provided?

Michael Weiss

Yes, I mean, anyone has ever touched that drug doesn’t see it that way and we’ll take we’ve one investigator and we’ve a lot of investigators now that touch that drug and talking about hundreds who have purchased – anyone has ever given the drug to the patient and has also given one of the other drugs to the patient, feels the same in terms of their tower zoning safety profile there – but it’s a big country, it’s a big world and is so as of others, you’re not – I’ve always felt and believe that any physician who has in touch to drug to – actually touched the drug it’s negative until they use it. And we do have a pretty effort onto expand the user base of the drug 1202, like I said unit you’ll study, the 60 site that are currently opened only handful of those are major academic centers and the next 40 without a good number of major academic centers that will be opening as part of that next tranche they take as you know six to nine months to a launch of a large academic center into clinical trials of, this is why they're in the second half of this year, but the more people that can touch [indiscernible] the more people are going to be believers, you just have to keep getting more people involved, so we have an active effort to get them into the UNITY-CLL study, and we have active efforts to get them into UNITY-DLBCL, and we'll continue to actively try to get them into molecular studies.

We've been talking to them about even anyone who is -- some of the major academic, kind of who want to do their own things, so we've even have an outreach program, and more offering sites to do trials and demos interested in. And I think we'll hear about a few more of those over the next few quarters. So I think, our goal, we have to get more people to cut drugs and I think we will do that through UNITY program.

Joseph Pantginis

It’s very helpful. Thank you. And then my next two questions are relatively brief. I was just curious with regard to MS Program, are you still looking to present B-cell depletion data by yearend. And second, what is the status of the IRAK-4 program?

Michael Weiss

So in terms of B-cell depletion data, we'll certainly have plenty of B-cell depletion data before yearend, just the question is what the appropriate venue for disseminating that information. The way we end that conferences go out, as ACTRIMS, is big ones in September. Clearly, we won't have any a net data there. We will have [indiscernible] data there. And then the next major conference I think is actually AAN, which is in April, so I think in between those two time points, we'll come up with certainly present some of the information, possibly with corporate presentations, that I don't think we're going to just throw a PR out there with some random B-cell depletion data, but we will have plenty of B-cell depletion data long before the end of the year for sure.

Joseph Pantginis

Okay. Great. And IRAK-4?

Michael Weiss

IRAK-4, we're still trying to figure out exactly what we want to do with that program. It has a pre-clinically as a tight therapeutic window and we're just not sure if given all the other activities we have ongoing in the preclinical with both PD-L1, GITR, now we have BET in house. We're looking at some other agents as well, we're just trying to prioritize and see where it makes the most sense. It could be in a position to put it into the clinic if we wanted to, probably within the six month period once we turn the system to do it, though I just said, I think preclinical has been a pretty tight therapeutic window and we're just trying to figure it out.

Joseph Pantginis

Okay. Great. Thanks a lot.


Your next question is coming from Yatin Suneja of SunTrust Robinson Humphrey. Please proceed with your question.

Yatin Suneja

Hi guys, congrats on all the progress and thank you for taking my question. Just a couple of questions on UNITY CLL. Could you remind us when you might be able to complete enrollment and how many patients per center are you guys targeting for that trial?

Michael Weiss

So the original guidance was that we figured it was about a 24 month enrollment period. The study got up and running March April of this year. So 24 months from now, sort of first half into first quarter and second quarter of 2018, but as I said in my prepared remarks, I think we can turn a neat work seal that time frame, which the way we're seeing it today. And in turns of patients per center, if we have globally about 150 sites up and running that would imply about three patients per site, so I think pretty modest. We're expecting -- I mean, as a study, there is 150 sites that's going to enroll at all, and there will sites, I don't know -- we already have many sites that are already above three enrolled patients at this point.

Yatin Suneja

And then in terms of the end point, I think the PFS was the primary endpoint. If we had to push an accelerated approval, could you tell us that what the bar would be? And when can we see that data?

Michael Weiss

So basically the study is designed with, say, three checkpoints, the first is to remove the two single agents on, so we had a contribution interim analysis. And that will be after approximate 200 patients have been enrolled into the trial. Once we view that and hopefully we'll be able to turn move the two things, raise an ARM, the study will continue as a head-to-head. All the patients enrolled prior that will obviously maintain and be part of the study, and enroll as a one-to-one randomization [indiscernible] versus 1303. And then once we get to the end of enrollment there is another interim analysis for HRA approval with overall response rate. And we're now at the end of enrollment. And then we'll continue to file patients for PFS.

I think the overall response was part of the minimum of six months of follow up since that's the time frame, which we give because I have [indiscernible] that's when we could do the overall response. My guess is that the PFS will probably be close to really lie it around the same time as [indiscernible], and we can't be completely 100% sure, but I think if we assume that somewhere between 25% to 30% of the patients are going to be also re-factoring and the remainder will be frontline, we're going to see some reduction in the overall PFS from the desire of the Phase III trial, which was I think past 26, 27 months.

So we'll see what happens first. We're accepting very strong PSF curves from the study or setting the free ARM, but it’s kind of possibly, it’s a free option for us to have a little response, but maybe that the PFS difference is still great with the studies earlier.

Yatin Suneja

And just maybe one more question on GENUINE. So the challenge that you are facing, is it because that the centers have not been screening patient appropriately or are we just overestimating the legible patients pool, because my guess would be like there should be a lot of patients out there who are refractory or who have already taken ibrutinib?

Michael Weiss

Well, I think it’s a combination of both, which is I think there are definitely lot of momentum and sites were not rescreening these patients, so I definitely I think broke some early some momentum there we're having. And then obviously went back and we've implemented the screening protocol, but we're still seeing that there is lot of patients that just don't qualify. So I think the incidence maybe slightly smaller than we expected.

And then there is an always an efficient -- even if it were a 50% natural screening, meaning 50% of the patients will be high risk and 50% will not be, that's a relatively accurate estimate, which is obviously quite below. But then there is always some very potential reasons why patients won't qualify for trials, even if they know they're 10% or 15% degradation from there, so that definitely creates the challenge.

When we talk to doctors about it, they say, yes, I mean, in their mind they view it as a real niche setting in terms of finding high risk patients, so I think it’s a combination of both. I think the incidence of high risk is probably slightly below the 50% projected target, and then you lay on top of that, just any other reasons why patients will fail to be eligible for trial or will openly decide not to enter the trial, there is always some reason that always comes up that, certainly if it is fused together, it’s definitely a lot more challenging than something like said, where it’s wide open. The only real restriction is having team desire to work around we saw previously.

In the U.S., generally for [indiscernible], so that's not an issue. And for relapsed/refractory patients, not many of them that seen under this two drugs, so that has not been a challenge. We always deal with a more open design, easier to enroll to, and its clearly chosen to be the case.


Thank you. Our next question is coming of Reni Benjamin of Raymond James. Please proceed with your question.

Reni Benjamin

Thanks for taking the question. First, can you talk a little bit how an anti-CD20 and a PI3K inhibitor kind of fit into this world where you have IVR, you have Venetoclax, where do you think this gets sort of relegated to and who are the docs that are ideally using it?

Michael Weiss

So I think that's a good question, Reni, because I think most people just believe that this space is very crowded, but if you really break it down it’s not as crowd as a space as one might think. And there is always room for a very good, well-tolerated treatment option, but again, let's assume all positive thoughts that UNITY-CLL is a positive outcome trial that we see benefit in both frontline and lots of refractory patient, and its approved across all of CLL, so we would have the first real utility regimen that could be used in basically almost any setting for CLL patients.

And if you think about what line treatment does start, you're going to have, I don't know, 60%, 70% of the patients are going to be started in the community, the remainder will be started in academics center. And in the community, they're going to look for drugs that they can easily provide to the patients with the least amount of toxicity, and they're going to make a decision whether they want to start with BTK base first line treatment or they're going to start with a PI3K delta phase treatment and we'll be the only one of that class, so we will be competing with the BTK base treatment. There will be BTKs plus Gazyva, which are running through the clinic as we speak.

There is going to be some portion of the patients that do not tolerate. Again, we'll start from the worst case scenario now, which is everyone believes that the BTK is a better and we're not going to be as competitive. But there'd still be 15% to 20% of the frontline patients that go on in BTK therapy and don’t tolerate it well and come off for some reason. So, I think we're starting in the worst case scenario with a 15% to 20% in patients that just don’t really tolerate well, the BTK base treatment. Layered on top of that, there is patients who can't afford potential co pays that could be differential in co pay's between us and them. The one advantage we will have is that we will be able to come to the market with very competitive pricing for our combination.

We said that before but we continue to believe that 1303 will be the best priced combination therapy out there in the marketplace. And we think that will help to drive some additional use for frontline. So, again I think we can push forward and assume that there is going to be another 10% or 15% of the patients from a cost standpoint or maybe more. But a conservative estimate, another 10% or 15% of the patient that will end up on 1303 frontline for cost reason. So, now we're pushing 35% 40% market share in frontline and that does not include the biggest wildcard which is what happens if the data continues to develop and evolve that treating a BTK failure is extremely challenging.

Right now, PFS and survival from BTK failure is quite low and they're very hard to treat these patient. And that may give a lot of pause for folks to use a BTK therapy in upfront setting. So, I think in the community an upfront setting, I think we're going to do quite well. I think we're going to sit in with a good amount of market share. We have options where we could be the number one frontline regiment in the community but we're certainly not, not assuming that as a base case. But we think that we will be a highly competitive and well used regiment in the frontline setting.

Academics will have access also to NEDA IRAK [ph] which will not be very popular in the community for years to come. So, the NEDA IRAK combinations in the frontline will have another wrinkle to academic positions and how they want to treat their patients in the frontline and again in that 30% to 40% bundle, we do think we'll be competitive as an activation active combination and we'll be competitive on price. Again, once you move into the second line setting, anyone who did receive a BTK inhibitor in the community is very likely to go on to a 1303 therapy after BTK therapy in the community. Again, its' a easy straightforward approach, one that could have activity from 25% to 50%, we only have a tiny number of patients that we treated but definitely had some responses and some patients that look like they were doing well.

So, might be able to do so. I do think that folks will try it after BTK therapy if that's what they go with first and so I think it will be really nice option for patients in the relapse refractory setting. And then again I don’t think in the community for years to come as going to be a very popular treatment option for those docs. And then in the academic setting again I think it's going to be what would you like to use and what order, given the fact that the NEDA IRAK single agent MRD negative raise are pretty nominal. I think there is a lot of early excitement that you're going to get really high levels of MRD negativity using NEDA IRAK alone, both in last year factor patients and probably upfront.

In the 17 key patients in the label, I think it's quite less than 2% or 3% MRD negative. So, I think some of that that excitement that you can use NEDA IRAK to create these MRD negative patients is possibly off the table. And again just opens up the door, we're seeing some interesting results to 1303 both with CR's and MRD negative. So, I think it's going to wide open. I certainly think people who are assuming that 1303 is going to get lost in the shuffle are going to certainly mistaken, but people are in side of an opinion.

Reni Benjamin

And then do you guys have a program, maybe evaluating a triple combination with the NEDA IRAK, like here?

Michael Weiss

We haven’t announced anything but as part of our outreach to physicians that may not be interested I working on anything that we've developed but they have their own ideas. I'd say that is definitely in the work.

Reni Benjamin

Got it. Just switching gears to GENUINE. Are there, at least when I look at both trials, I almost besides GENUINE being in my view the low hanging free trial and probably the most straightforward and easiest to succeed for a study. Are there any trial modification whether it's entry criteria that you might be able to institute and I guess just reading kind of the language in today's call. Is there at any points maybe this year or next year where you just look at the enrollment rates and you say what we have to call it and kind of fill the study for to conserve resources and the like.

Michael Weiss

Look. I think any and all of those are practical responses to what's going on and obviously if it's obvious to you, it's probably obvious to us that those are the things that we need to consider and are considering. So, yes, I think we're keeping our eyes wide open, we're watching the enrollment of both studies. We're trying to figure out what makes the most sense. Again I think we'd like to be able to continue to use GENUINE for accelerated approval of 1101. But we just have to see again whether you're right, whether there is something we can do with the inclusion exclusion criteria or whether we just in some way modify the study or terminate the study as you described again and save resources all those are on the table. Like I said as they're too intuitive to you as they're intuitive to us as well.

Reni Benjamin

Got it. And just one final question. Can you give us a sense as to the Checkpoint program status and why you feel your checkpoint PD-L1 and GITR that's being developed is different than what's already out there. And I presume that’s part of your pre-clinical testing, you are testing at against other products that are being evaluated around the market. Could you just give us some color on that program?

Michael Weiss

Yes. So, I think in terms of the profile of the actual PD-L1 antibody for one and I think GITR probably we could say the same about is that we're looking for certainly best or near best-in-class in terms of potency, binding affinity, all those attributes, I mean, we're coming in with a very strong antibody products. We're confident of that. I think on the PD-L1 side, where they are lot on the market, I think the key differentiators for us will be we will maintain some level of ADCC in the first product and we are evaluating glycoengineered versions of our PD-L1 which would basically create the first and only dual action PD-L1 where we can engage both T-cells and NK cells. And so we do think that actually provides some interesting additional activity for PD-L1 as a class.

So, that will be very novel and interesting. And again we've always felt that we wanted have a own products as that we can continue to build on those pricing advantages that we touched on briefly on 1303 as we continue to add antibodies on top, I think we can do it in a very cost effective manner and be able to come in with triple and quad therapies that are priced closer to what you pay for one half to two drugs that you have to buy in the open market. So, we do see a lot of advantage that again we're hopefully adding activity and not adding a lot of toxicity and a lot of cost. I think those that's kind of the goal of having these things internally. So, we definitely want to have comparable to best in class antibodies that come out of that program and we have a great team working on them.

And then being able to use them efficiently in the clinical trials to create extra benefits for patients without adding extra toxicity and without adding extra cost. Or marginally extra toxicity and marginally extra cost, I mean, there's always going to be some level of toxicity that will come with new drugs.

Reni Benjamin

Got it. Thanks for taking the questions and good luck going forward.

Michael Weiss

Thanks, Reni.


Thank you. At this time I'd like to turn the call back over to Mr. Weiss for any closing comments.

Michael Weiss

Great. Thank you very much. And thanks everyone for joining us in this call today. I thought what I would finish with was just a few of the key catalyst over the next six to nine months. I do believe that we have some exciting things coming up. And again I know everyone wants to be negative in this market but I did think they have some really interesting and important catalyst that will be coming forward. So, I think in terms of the Phase 3 trials, we are looking to continue to provide enrollment updates and both GENUINE and UNITY as we move forward both in third quarter conference call and then probably again early January. Hopefully, enrollment trends will pick up in GENUINE and continue to be aggressive and moving quite well in UNITY-CLL and we'll be able to give again even just more clarity on where we are.

We will approach by clarity on actions, again that we're taking to accelerate GENUINE towards a more rapid approval of TG-1101 again consistent with those original goals that we have discussed here today. We do expect to complete enrollment in our MS Phase 2 trial for the end of the year. Again, that's in the pre-specified cohorts if we add additional expansion cohort just to get more information. Obviously that could that continue into next year. And again, we'll like to present preliminary a Phase 2 clinical trial results. And again we plan to start the Phase 3 in the first half of next year. As part of which we believe that results of our discussions with the FDA in defining the repertory pathway and the exact sizing of that clinical trial that we talked about earlier will be quite important. I think could add a lot of interested to what we're doing.

And then last but not least, again we touched on in some of the Q&A. We're hoping for a very impactful ASH meeting in December. And last track I think went in last week, so not clear what actually will be accepted. But on the dark, it could be presentations on our triple therapy program including a combination of 1303 + Ibrutinib in both CLL and NHL and the combination of 1303 plus must seen in NHL as well as data from the all double combination of Ibrutinib + 1202 and there's some other novel novel combinations that maybe presented at that conference as well. And we really think that these presentations will highlight our leading position in creating novel well tolerated and efficacious next generation combination.

So, with that, let me thank everyone for joining us on the call. I like to thank the team at TG Therapeutics, our investigators, our patients, as well as our shareholders for their continued support. And I thank everyone again for joining us on the call. And have a great day.

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