TG Therapeutics, Inc. (TGTX) Q2 2017 Earnings Report, Transcript and Summary

Greetings, and welcome to the TG Therapeutics Second Quarter 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. Please go ahead.

Thank you. Good morning, and welcome to our conference call regarding TG Therapeutics second quarter 2017 financial results and business update. I'm Jenna Bosco, TG's VP of Investor Relations, and I welcome you to our conference call today. Following our Safe Harbor statement, Sean Power, TG's CFO, 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 novel, glycoengineered anti-CD20 monoclonal antibody TG-1101, our novel once-daily PI3K delta inhibitor TGR-1202 as well as a review of our clinical program. 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 at www.tgtherapeutics.com, where it will be available for the next 30 days. All participants on this call will be on listen-only mode. Now, I would like to turn the call over to Sean Power, our Chief Financial Officer, to discuss the financial results for the second quarter of 2017 as well as the company's overall financial condition.

Thank you, Jenna, and thanks everyone for joining us. As you may be aware, our financial results were released this morning and can be viewed on the Investors and media section of our website at www.tgtherapeutics.com. I'll begin with our cash position. At June 30th, we had cash, cash equivalents, investment securities and interest receivable of $86.5 million. Our pro-forma cash position, as of June 30th, 2017, was approximately $97.4 million, but including $10.9 million of net proceeds from the utilization of our ATM sales facility during the third quarter of 2017. Our net loss for the second quarter of 2017, excluding non-cash items, was approximately $26.9 million, including $8.1 million of manufacturing and c-Myc expenses for Phase III clinical trials and in preparation for commercialization and $2.4 million in expenses related to the commencement of the Phase III program for TG-1101 in MS. The GAAP net loss for the second quarter of 2017, inclusive of noncash items, was $28.4 million or $0.45 per share compared to a GAAP net loss of $15.9 million or $0.33 per share during the comparable quarter in 2016. Our net loss for the six months ended June 30th, 2017, excluding non-cash items, was approximately $48.6 million, which included $13.3 million of manufacturing and c-Myc expenses for Phase III clinical trials and in preparation for commercialization and $3.4 million in expenses related to the commencement of the Phase III program for TG-1101 in MS. The GAAP net loss for the six-months ended June 30th, 2017, inclusive of non-cash items, was $56.1 million or $0.96 per share compared to a net loss of $29.7 million or $0.61 per share, during the comparable period in 2016. I'd like to spend just a few more minutes providing some additional color on expectations for our burn rate moving forward and how the MS program fits within our historical cash burn. Over the last two quarters, our burn included a significant uptick in enrollment in UNITY-CLL as well as significant investment in MS study start-up costs and in manufacturing capacity and supply. Needless to say, all very positive developments for the company. Over the next two quarters, our expectation is that burn for UNITY-CLL will slow, as we complete enrollment and the MS Phase 3 study cost should slowly kick in. The net effect is that we don't expect to see a substantial increase in overall clinical cost as we launch MS, as those costs will largely be offset by the diminishing cost associated with UNITY-CLL. On the manufacturing front, we are projecting two more quarters of investment followed by two quarters of relatively modest burn. All in all, over the next 12 months, we expect our average burn to return to more modest levels, closer to the 15 million per quarter average burn we are more accustomed to, which we believe will allow our current cash position to be sufficient to fund our operations through 2018. To ensure that these accelerated costs did not impact our guidance, during late Q2 and early Q3, we added approximately $14.9 million to the balance sheet through the use of our ATM. Our average price was $10.87, representing nearly a 12% premium to the spot offering we did in March. Total shares issued during this campaign were approximately 1.4 million. With that, I will now turn the call over to Mike Weiss.

Thank you, Sean and thanks to all of you for joining us this morning. I'm going to start this call by thanking our long-term shareholders for their continued support. Unlike many small companies that look to cut corners or take shortcuts, we have chosen a different path running large robust clinical trials, while pioneering novel -- novel combination therapy for B-cell malignancies. This kind of development takes time, but we are confident that all of our hard work and your patience will soon be rewarded. I can assure you your company has never been better positioned for success and your management team never more focused on creating long-term shareholder value by developing drug combinations that we believe will change patients' lives for the better. 2017 has already been an action-packed year with the achievement of many important milestones including, first and foremost delivering positive Phase 3 GENUINE data for the combination of ibrutinib plus our novel glycoengineered anti-CD20 monoclonal antibody with ublituximab also referred to as TG-1101. We received orphan-drug designation for our newly named U2 combination of ublituximab and umbralisib, which is also referred as TGR-1202, our next generation PI3K delta inhibitor for the treatment of CLL and diffuse large B-cell lymphoma. We also announced the results of the preplanned interim analysis by an independent Data Safety Monitoring Board or DSMB for the UNITY-CLL Phase III trial, which allowed us to close enrollment in both single-agent arms and also found that there are no safety concerns requiring modification of the study. We also had a busy summer, presenting at multiple large cancer and hematology meetings, including reporting positive data from the chemo-free triple combination of TG-1101, TGR-1202 and ibrutinib in both CLL and NHL. The overall response rates were 100% for CLL, Marginal Zone Lymphoma and Mantle Cell Lymphoma, all indications where ibrutinib is approved with substantially lower response rates. We also updated the all oral combination of TGR-1202 plus ibrutinib in patients with relapsed or refractory CLL and Mantle cell lymphoma showing the combination continuing to be well-tolerated and highly active. And finally, this summer, we presented data from the triple combination of TG-1101, TGR-1202 and bendamustine in patients with diffuse large B-cell and follicular lymphoma. We are very pleased with the high level of activity and tolerability profile demonstrated across both types of lymphomas. We've also been very busy building on our MS franchise and have moved this program rapidly towards Phase 3. So far this year, we've completed enrollment into our Phase 2 study of TG-1101 in patients with multiple sclerosis. We presented preliminary data from that Phase 2 study showing rapid and robust B-cell depletion utilizing a convenient one-hour infusion, which is significantly shorter than the competition. We were able to reach agreement with the FDA pursuing it as Special Protocol Assessment or SPA for our Phase 3 program, now named ULTIMATE I and ULTIMATE II of TG-1101 in relapsing forms of MS. Over the next month or so, before the end of the summer, we plan to launch the Phase 3 program in MS. In addition to these data presentations, we've been actively enrolling into our UNITY-CLL Phase III program this year, which has exceeded all of our expectations, putting us in the enviable position of being able to complete enrollment by the end of this year, which is almost six months earlier than our original guidance. All in all, I would say a very productive and action-packed year thus far. And if you thought that was exciting, just wait to see what we have planned to achieve over the next six to 12 months. Let's start with the GENUINE study and the potential BLA filing for accelerated approval. Recall GENUINE is a randomized Phase 3 trial comparing ibrutinib alone versus ibrutinib plus TG-1101 in the hard-to-treat patient population high-risk relapsed/refractory CLL. In the third quarter of last year, after consultation with the FDA, we amended the Phase 3 protocol to eliminate one of the two co-primary endpoints, leaving overall response as the sole primary endpoint following the amendment. We repowered the study solely for the overall response endpoint, which following the unblinding restudy showing almost 70% advantage in taking the combination, which was highly statistically significant. It is probably worth mentioning a point that I believe has confused some investors. At the moment, we amended the study, we and the FDA were well aware that we were no longer powered for the PFS endpoint. In statistical terms, that means the result of that outcome becomes less reliable unless weight can be given to the p-value, even if it is "statistically significant." The most common use for results from under-powered endpoints will be to help design and power a follow-up study, rarely would they be persuasive for FDA approval. We're quite pleased to see a trend for the very robust PFS advantage of the combination and believe given a highly statistically significant result for the primary endpoint, which was appropriately powered, the PFS benefit observed shows nice internal consistency of the data, and is certainly supportive of the belief that the overall response advantage is reasonably likely to lead to an increase in PFS, which is the regulatory hurdle required for accelerated approval. As noted previously, we plan to discuss with the FDA the possibility of filing GENUINE for accelerated approval in the fourth quarter. And if all goes well, we plan to file a BLA in the first half of next year. Assuming priority review, approval could come as early as the fourth quarter of 2018. We see the market opportunity for this combination in patients that have high-risk relapse/refractory CLL as somewhere between $250 million to $500 million, which is really a nice starting place for us as a company. That said, we continue to be most excited about our UNITY program and the blockbuster potential of the U2 regimen. So, let's focus on UNITY-CLL for a moment. The study is now a two-arm on study comparing U2 to obinutuzumab plus chlorambucil in frontline and previously treated CLL. This is a large randomized study and if successful, we would anticipate a very broad label for the treatment of CLL, setting up the U2 regimen as a flexible treatment option to use by doctors in any CLL setting. The robust rate of enrollment into the study continues to give us comfort of the significant role U2 will play in the care of patients with CLL. The timeline year is to complete enrollment by year end, announce topline overall response data next summer, and if positive, file for approval in fourth quarter of 2018 making approval possible in mid-2019. We will then continue to follow patients for a PFS outcome for a full approval. All in all, potential accelerated approval based on UNITY-CLL is only about six months behind a possible approval based on GENUINE. As inferred above, we think U2 has a significant market potential in CLL with peak sales potentially exceeding $1 billion. Next, let's review in more detail our UNITY-NHL program. There are now three parts to this study; first, the original part of the study, which is diffuse large B-cell cohort. From a timing perspective, we expect to hold the first interim analysis before the end of the summer, which could allow us to replace single-agent TGR-1202 with the triple therapy of U2 plus bendamustine. We would then expect to complete enrollment in this portion of the Phase 2b by the end of the first quarter next year. At that point, we can make a decision on filing for accelerated approval and the design of a Phase 3 trial. Next, we have the follicular cohort. We just recently started enrolling into this cohort and early enrollment trends are encouraging. We are not currently giving timelines, but expect to provide better guidance at ASH -- at our ASH Analyst Event in early December. By then, we should have enough enrollment experience and be better positioned to provide timelines. In this cohort, we are also anxiously watching the regulatory outcome for the pilaralisib and intravenously deliver dual PI3K alpha delta inhibitor, which recently filed for accelerated approval for follicular lymphoma. The PDUFA date should be later this year. If they are successful, which we really hope they will be, we should be well-positioned to be a fast follower of better regulatory strategy in the Marginal Zone Lymphoma cohort. Again enrollment has just begun, so we will defer guidance until ASH as well. As a point of reference, ibrutinib recently received accelerated approval for Marginal Zone Lymphoma with 63 patients and a 46% overall response rate, and is the only drug currently approved specifically for Marginal Zone Lymphoma. While it is an ultra-orphan indication, we would hope to be able to enroll at least 60 patients over the next 12 months or so. Once complete, and if overall response is comparable, we will be able to file the same regulatory strategy as used for the ibrutinib approval. As you can see, we have been hard at work at advancing our pipeline toward multiple approvals across CLL and NHL, and we're extremely pleased with the progress we've made thus far this year, in both our oncology and MS strategies, and look forward to an exciting remainder of the year. With that, let me turn the call 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.

Thank you. The floor is now open for questions. [Operator Instructions] Our first question is coming from Yatin Suneja of SunTrust Robinson Humphrey. Please go ahead.

Hey guys. Congrats on all the progress and thank you for taking my question. Mike, on the upcoming meeting that you're going to have with the FDA regarding GENUINE. Number one, have you requested for that meeting? And then could you maybe also walk us through potential scenarios for -- or outcomes from this meeting? What sort of a confirmatory trial you're thinking of proposing there?

Sure. Thanks for the question. So in, terms of the timing of this meeting, our goal is to have the meeting sometime in October. We would expect it would take 30 days to receive minutes back; the official confirmation of what was discussed should take about 30 days. So, sometime in November, we should have clear guidance from the FDA on a possible filing. In terms of outcomes of the meeting -- I guess there's -- I can only think of two reasonable outcomes. One is that the FDA agrees that the filing is -- the package is sufficient for the filing or they will say, they don't believe the package is sufficient for filing, they would encourage us, I guess, at that point, to not file. But again, I think those are the two possible outcomes.

Got it. Then a question on UNITY-CLL, so you pointed out that enrollment is exceeding your expectations. So, what's driving that? Is it that physicians are aware of this? Can you just help us understand there? And one more question on that. What sort of a delta in ORR do you think is going to be meaningful in that particular trial given that you're enrolling a blend of newly diagnosed and heavily pretreated CLL patients?

Sure. So, the positive enrollment, and again, allow me to speculate, so take this as our speculation. But it does appear that the ease of use of the combination, the ability to enroll any type of patient, whether it's frontline or relapse/refractory or high-risk or ordinary risk, makes it quite easy to enroll. So, we think it's just the open enrollment criteria, which again, as noted in the prepared remarks, will ideally lead towards an open-label as well, right. So, we -- our expectation is that the study is positive, which we certainly believe it will be, and if it is positive, we would have a label that says, the treatment of CLL. So, in essence, the way they are using it in this clinical trial, they would be able to use it in practice, which is very flexible, wherever and whenever they need a treatment option for the patient, whether it's upfront or in relapsed patient, someone who has been previously treated with ibrutinib, someone who is naive to ibrutinib, someone who doesn't tolerate ibrutinib, whatever setting is necessary at the moment, the patients -- the doctors seeing the patient, U2 combination can be used assuming again we get the front-label. But certainly in this clinical trial, for the most part, that's the case. There's very few exclusions, obviously, it can't be resistant to obinutuzumab or chlorambucil, but that's pretty close to the only restrictions in the study. So, that's our impression that again even enrollment due to open access and, again, we think that translates to later use on the market as it really is a flexible treatment option for patients with limited options, and I know that there's a lot of -- people think there is a lot of treatment options out there. But once you've had ibrutinib, you had -- you really don't have much choice, particularly in the community where venetoclax is very challenging to offer to patients. So, again -- and a lot of patients don't tolerate ibrutinib as we know, so, it is great news for this kind of an option, we could see it in enrollments. And then to your second part of your question, you asked about the expected delta in the overall response or what we knew to be successful?

Yes, what do you think is meaningful?

I think, in this setting, anything that is statistically significant, I think, will be clinically meaningful. I think we're probably -- I think it's approximately 15% is what we're powered for, which probably a minimum detectable difference into the 12% or 13% range, all of which are under the SPAs, we're looking for a statistically significant answer. So, I think we've got it pretty well set up. Our expectation is that we haven't chosen that for MS arm. We'll have a response rate that's lower than the one that's labeled, the label is for only frontline patients, and I think it's about 78%, 79% overall response rate. That's going to be pulled down by the percentage of patients that are on study with relapse disease. Then [Indiscernible] Rituxan, I think is somewhere between 50% and 55% overall response in relapsed patients, and my guess is -- will be in a similar range, and again it just depends on the proportion of patients that will be relapsed/refractory to get that blended overall response, but I think there is plenty of room for us to be approximately 15% better. Our ibrutinib plus 1101 study shows that in CLL -- relapsed patients with CLL and those are the high-risk patients, we should see about an 80% response rate, our expectation is that in relapsed patients, we should be pretty close to that with 1101, 1202, or U2. And then in frontline patients, we think they're going to be very high in terms of overall response rate. So, I think there's plenty of room for us to be successful in the overall response endpoint, certainly, the higher the proportion of relapsed/refractory patients that enter the study will bring down the blended average of the control arm. It will also bring down the blended average of the progression-free survival endpoints, and that will shorten the length of the trial. Our hope has been, we've guided towards that 25% to 30% in relapsed/refractory setting would be great, anything better than that -- or anything higher than that would be even better, and even if it goes a little bit lower than that. We've powered the study surely off the frontline numbers. So, anything that comes in a relapsed/refractory side, we think is just incremental benefit to the trial design.

Got it. Very helpful. Just one question, this one for Sean. Sean, help me with the SG&A spend. This is a second time I was way off. How should we model it in the second half? I know the press release says that it's going to be constant. Can you just help me there, please?

Sure, so when we refer to a constant SG&A expense, we pull out the non-cash comp number, which we disclosed separately because that tends to be a little bit lumpy from quarter-to-quarter. So, I do believe that the SG&A spend was consistent with prior quarter, if you take out the non-cash comp and would expect that it would remain constant in the future quarters as well.

Got it. Thanks guys.

Thank you. Our next question is coming from Matt Kaplan of Ladenburg Thalmann. Please go ahead.

Hey guys good morning.

Good morning.

Congrats on the great progress. Just wanted to dive into the SPA that you just received for the MS study. And can you help us understand the design of that study, specifically with including the comparator arm of teriflunomide as the active control?

Sure. So, the program itself is two studies, ULTIMATE I and ULTIMATE II, they're identical studies. So, both of them will compare with rituximab versus teriflunomide, which is an oral agent, so it would be a double-dummy study. So, patients who wish to receive dummy infusions will also receive placebo pills titrated by double-dummy design, excuse me. So, the other aspects of the trial, again, I think we've noted they're both about little over 400 patients in each trial. And overall, the design -- the endpoints are all quite consistent with the study -- the OPERA studies for Ocrelizumab. Any other details or specifics, Matt?

Yes, the expectation with respect to annual relapse rates and how you powered for that in terms of the size of the study?

Yes, so we basically work from -- we have more conservative assumptions than you find in the actual results for OPERA, but we basically worked from the OPERA data looking at their annualized relapse rates for the drug and also for the comparator arm, we also looked at their study that have compared teriflunomide to Rebif and in those trials they basically look almost identical, particularly at the higher dosages, the one that we're using of teriflunomide. So, basically just worked from the power assumptions from those trends and the results from those trials to build in -- more conservative than I think the benefit seen in the OPERA I and OPERA II studies was 46%, 47% decrease in annualized relapsed rates. It is showing something little bit more conservative than that. But we definitely have an expectation of a wide margin of victory of rituximab over teriflunomide.

Okay, that's very helpful. Thank you. And then just shifting gears to your UNITY trials. UNITY DLBCL study in terms of the interim analysis, what should -- how are you going to announce the results there? And what should we be looking for?

We'll announce them very carefully. I think the expectation -- we're just going to start off by announcing that we're not able to close one or both of the arms, I guess both go through attesting for the first stage of the trial. The hope and expectation is that the single-agent 1202 arm will be coming out at the first checkpoint, which we'll be doing shortly. Once that occurs, we will be replacing it with the U2 + Benda. So, I think the first release will just be that we conducted the interim analysis on A or B, whichever it's called, will be now converted from potentially a single agent to U2 + Benda regarding the extent of probably announcement at that point, any data will have to be at a proper [Indiscernible].

And then when you say you can complete enrollment by the end of first quarter, does that include the U2 + Benda arm as well?

Yes, that's our expectation. Enrollments used to be picking up quite nicely right now. So, our hope is that we'll have reached our target enrollment for both the U2 arm and for the U2 + Benda arms by the end of the first quarter.

Okay. Thanks. And then a final question with respect to, you mentioned that you used the ATM during early third quarter. What are your plans, I guess, in strategy for accessing the ATM going forward?

Yes, so, obviously, I think people who've invested in the company previously have been around us, they know that we opportunistically will tap into the ATM usually to overcome any what we see as lumpy or extraordinary expenses. We had some CNC and startup costs that crossed the wire this past quarter. So, we decided to tap into the ATM. It's -- for us it's a very flexible tool. We're super careful when we use it, we typically limit to sell the remaining -- very small percentage of the trading volume, I think our typical sales were somewhere between 25,000 to 50,000 shares of the higher end and usually half of them are cumulative shares traded for days. So, it's a pretty quiet program, which has spread it out over a number of days and I think we got a nice average price as Sean mentioned almost $11 to add about $40 million to the balance sheet. So, I think very successful campaign, the one we completed. Right now, we're not in a campaign. We'll obviously just see where we are during the quarter and the expenses that come in and we'll make an assessment. But we do like to keep the tank full, have the money, run closer to empty or half full. So, I think if it makes sense we would tap into it again, but I think it's just subject to where we're at expenses, what's going on in the marketplace and, of course, we're I'd say happy to not have to use it, but when we do use it, we're quite happy with the results. The last point I make is that the shares that were issued during the quarter 1.4 million shares, I think Sean mentioned represents about 2% dilution. So, I think modest levels of dilution that gave us a lot of extra runway and again, we just really don't want to get the local tanker too low. So, that's our overall strategy. Any more details on that Matt?

No, that's great. Thank you. Thanks for taking the questions.

Okay. You got it.

Thank you. Our next question is coming from Ren Benjamin of Raymond James. Please go ahead. Mr. Benjamin your line is live, do you have questions today?

I do. Can you hear me now?

Yes, please go ahead.

Ren help [Indiscernible] the mute button.

Yes, thanks. I -- sorry about that. good morning and congrats on all the progress. So, a couple of questions. I probably missed this one when you're answering Yatin, but the confirmatory study and the potential for confirmatory studies in terms of when you're talking with the FDA, did you talk about that? Or can you just review that for us please?

That's a good point. He did ask that as part of his question, I'm now looking at my notes and I didn't get to that. He had like a four-part question. So, I did miss that part, so good catch for Ren. Let's talk about that now. So, our going in position would be -- we'd like to offer the FDA the UNITY-CLL trial as the confirmation trial for GENUINE. It's obviously a large randomized well-conducted study, well-controlled study. So, we think there is a really nice large trial sitting in the wings that we've been working on for two years under SPA. If that study is not acceptable to the FDA, then our plan is to work with them to try and identify a study design that will make them comfortable with the results. So, I think we're definitely open to conversations. The FDA has been greatly helping us design the original -- the UNITY-CLL trial as well as the GENUINE trial. So, our goal is to go in there in a collaborative fashion, we'd like to discuss with them first the UNITY-CLL trial, we think it is an appropriate confirmation of the GENUINE results when it's complete. It will provide approvals, if it's successful. It will provide full approvals for both ublituximab and umbralisib in combination of each other. It has a certain validation of showing that you can take a CD20 monoclonal antibody and a B-cell receptor antagonist, put them together and get to an outcome which is quite similar to using 1101 plus ibrutinib. We know that the confirmation study that's in the works for venetoclax for their 17p study, which is a single agent approval of venetoclax in relapse/refractory 17p patients, I believe that their confirmation trial is venetoclax plus bendamustine plus Rituxan versus bendamustine/Rituxan. So, again somewhat of a similar situation, not the exact scenario where we use venetoclax in combination with other agents to provide the full approval. So, again, it's not perfectly analogous, but we do think that there's -- it's a reasonable discussion to have about whether the UNITY-CLL, we'll also try plus the confirmation tried. Again if it doesn't, we're more than happy to work with the FDA and design a trial that would make them happy.

Got it. Okay makes sense. And just sticking with the UNITY-CLL thing for a second, do you plan on presenting the data from the single-arms of the study. And just as we talk about a robust enrollment, what's the breakdown between academic versus community sites that are currently enrolled?

So, in terms of presenting the single-arms, we haven't -- I think at some point we'll probably discuss that -- well, I think the study will be completed before the end of the year. I think it all will be presented together at some point. I don't think there is any way for us to really do before the study has completed enrollment at that point, it's probably the next conference available, everything should be available close to. So, we don't have any plan, if we want to try to do it before we'll break the blind on the trial part of it, we need to have a chat with the FDA about that. And that really hasn't been a high priority for us at this moment. So, it will, obviously, be presented, assumption is, it's going to be presented all as one package at some point.

Got it. And in terms of the breakdown?

Yes, in terms of the enrollment breakdown, it's probably between probably 65% to Anderson community, 30%, 35% academic. So, it's pretty well balanced considering we have -- the vast majority of the sites are community sites. So, in terms of numbers, I'd say the enrollment is very well distributed across the U.S., certainly concentrated in large networks. We know some colleges in Sierra Canyon, the folks down in South Carolina, the Ovarian Cancer Group which is a huge academic half-community group. So, those are again distribution. But it's been pretty well balanced. We recently pretty much closed off most of European enrollment over the last month to two months. So, this -- the enrollment that we're getting today is primarily U.S. based.

Got it. And then regarding UNITY-DLBCL. I guess a couple of questions. Just one, the delta that you're looking for in this study that could potentially allow you to file for accelerated approval. And then maybe, just your thoughts on what many perceive to be a changing landscape with the CAR-T therapy is entering, just this kind of how you're thinking about this landscape?

Yes, so, we'll work forward to backwards. So, let's talk about the landscape a little bit then we'll talk about what we'd hope we could see with the agents and the different combinations that we're using. So, the landscapes -- so CAR-Ts are great for a very limited purpose. Let me size the scans [ph] today. So, the patient that fits into -- a patient that will get a CAR-T or should be getting a CAR-T is a somewhat unique patient. It's a patient that has diffuse large B-cell, but can wait almost 30 days before getting treated, that in and of itself is an interesting patient. So, they have to be healthy enough to be perceived to not pass away or not become so debilitated in 30 days. Many of these patients are diverted in, treated multiple times where they failed stem-cell transplant, are not really capable of waiting 30 days, so I think the landscape for CAR-T is going to be, obviously, highly restricted to locations where I guess the transplant sites primarily, we'll be using it. I don't know how many centers across The United States will be up and running at the early stages. But usually have to be very well-trained sites and may have a number of well-trained sites from the clinical trials. But you also have to imagine that these patients not only are they healthy enough for the 30 days, they have to be healthy enough to travel to some location that's not necessarily near their home. It is not a treatment for the masses. It is not a treatment for most patients. It is a treatment for, again a very select group of patients, which is probably okay given the manufacturing constraints of the CAR-T industry today, it's probably okay that it's only eligible for new script of patients. Having said that, if you look at the -- what we're trying to accomplish we're treating patients that are too sick to go on CAR-T trails. Two of our sites are major participants in CAR-T trials, and we're getting patients that aren't healthy enough to make it into the CAR-T trials, and we're giving them, particularly, with the -- this triple therapy, giving them -- most of them, 50% and up, really nice responses. So, it's -- we'd like to look at our treatment options and we've done this -- we've seen this for a very long time. We're developing treatments for all patients, right. So, if you look at UNITY-CLL, it's for all patients. As we look at diffuse large B-cell, we are taking in all-comers, no matter how sick they're. They're going on to our study. It's easy to use, off-the-shelf. It's the treatment; again let's stick to U2 + bendamustine for a moment. It's off-the-shelf, easy to use. Tolerability has been quite good. To my knowledge, no patient has died from treatment and a lot of patients are gaining -- are getting long-term benefit. We had -- as we described in our paper, I believe, its Lugano, we had 50% of the patients that were true refractory patients. These are patients that are as close as we could define, the patients that were in the CAR-T pivotal trial. We had about a 50% response rate, of which 42% were CRs and another 8% were PRs. But the PR was, I think, out almost 12 months. So, very durable PR in that setting. And then if you look at a very -- another very interesting setting there, U2 + Benda was probably used in patients that were deemed to be relapsed from prior therapy, but not necessarily refractory. That is the largest market opportunity in relapse/refractory CLL, with the patients who have taken R-CHOP and come back and they had better response but they come back and then need another treatment, those patients, they had a 100% response rate in that patient population. Again, still small number. So again, I caution that still small numbers, which is why we're doing diffuse large B-cell Phase 2b. And now we're excited to get that U2 + Benda arm opened once to see what that looks like in a more rigid environment. But to us, the biggest marketing -- we're facing the hodgepodge of chemotherapy that you might get, if you're not -- if you're not transplant-eligible and you have relapsed or you relapsed from a transplant -- again, not transplant-eligible, you come in, you're going to get either Gem/Ox, BR, R-squared or any number of alphabet soup with chemotherapy, of which most of them don't have a great outcome for the patient. That is the largest population, again, of patients with relapse/refractory diffuse large B-cell. That's where we'll be participating. We'll also be in the heavily refractory patients, most of which won't be eligible or won't be able to get through CAR-T therapy. So, it's a very long windy answer. Hopefully, that's all that, but if you have any follow-up on that, please ask.

No, that was a great answer. Thank you very much and I'll let Matt ask the next one and I'll jump back in the queue. Thanks very much.

You got it.

Thank you. Our next question is coming from Matthew Andrews of Jefferies. Please go ahead.

Thank you. Hey, good morning Mike.

Good morning.

First question can you discuss the rationale for an SPA in the MS setting? What's it related to, is it the size of the study relative to Ocrevus? Why pursue an SPA?

Yes, I mean, for us, we -- whenever possible we prefer to have an SPA. It's -- as a small company, we are subject to a lot of questions. I think if we would have showed up with two studies of 450 patients, the world would have said, definitely their ticket is too small. So, that was one major reason, which we identified. Others are just making sure again how we're doing our statistics and how we're calculating any relapse rates and other aspects of the protocol are embedded and the FDA is comfortable with them are important. There is a lot of statistical discussion on how we've handled certain data. So, for us, it's whenever possible, again, it is not always possible. The FDA was very kind and worked with us to build out these two trials and give us an SPA. Sometimes it's not possible, and so you go without it. But whenever possible, particularly as a small company, and again, if Merck showed up with these two studies, no one would question. But they were registration eligible, but we always have to be on top of our game. And we feel the SPA just gives the extra assurance that we went the extra mile with the FDA to make sure that we pre-vetted every aspect of this protocol and locked both the size and how we were managing the trial statistically and otherwise was acceptable to the agency.

Got it. Thanks. Transitioning to ubli for high-risk CLL and the upcoming FDA dialogue in the fall. Where are you with manufacturing c-Myc? And when would you expect potential FDA inspection of your CMO? Would that be first half of 2018 event?

Yes. So, it wouldn't be until after we filed. So, again, if we're -- it may actually, ultimately, the second half of 2018, if we file in the first half some time and with six months' timeframe after that they'll really come in and inspect the CMO.

And then, just curious, with the EHA and ICML meetings, can you share with us just some of the feedback from the European CLL KOLs as it relates to the GENUINE data? And any update on how U.S. investigators and KOLs are looking at the evolving and improving data set, if you will, for GENUINE?

Sure, so I think, overall, the -- in Europe this summer, we had a lot of incredible, both one-on-one and group KOL meetings, which has led to the expansion of sites interested in UNITY-NHL. That was a really big part of what we accomplished. I think people were excited about not only U2 + Benda, but I think there is a lot of excitement about U2, generally, in patients with Follicular Lymphoma. And there's also a nice level of enthusiasm for 1202 Marginal Zone. There's a big Marginal Zone Consortium in Europe and they were very excited -- the members of that group, I would say, are excited about working on our Marginal Zone Lymphoma performance. So, overall, I would say it was a hugely successful program for us over the summer in Europe, which I think will enhance our overall normal trends, which we're already doing quite well with pretty much a U.S. only enrollment. We think Europe is going to start to contribute in a very material way over the next six months. In terms of the U.S. investigators and KOLs, into ASCO we had this number of KOL meetings. We had a lot of meetings at ASCO itself. I'd say net-net; folks are intrigued by the GENUINE data. I think many folks were surprised, which again surprises me that they were surprised by the strength of the data. And I think, overall, even in PRLs which is a subject of interest in conversation between academics and others, but the PRL was not part of the response criteria, it does not appear that there is any indication that the iwCLL is actually going to change that, but there is still a focus from two KOLs on PRLs. I think they were quite, again, intrigued by the fact that we did show the PRL data. There is still the separation between the two groups even if you include PRL. So, I think, overall, we had a very positive feeling about the data. Again I think -- and it's not unfair to ask for PFS advantages. And, obviously, the only amendment to the study that kind of took that away from folks, but I think, again, people were intrigued by the PFS advantage that was observed. And again, I say, observed because once we repowered the study, we took away the powerful endpoint. But I think, the overall data set definitely impressed folks, and we think that it's hard to refute. It's a very -- it's a randomized trial. So, we have both arms sitting right there. We have all the data and it's hard to refute that by adding rituximab to ibrutinib. It did not enhance the overall response rate, and I did not enhance CRs and MRD negative in the peripheral blood, all of which are internally consistent with each other and with the trend in PFS. And we think it's a very solid data set, obviously, we look forward to chatting with the FDA then, hopefully they feel the same way.

Yes. Thank you for that. And just lastly, so by the end of this year you'll have feedback on the FDA on GENUINE and then if my math is correct six pivotal/registrational studies ongoing across MS and blood cancers, is that right?

So, by the end of the year, for GENUINE, hopefully all goes well, we'll have a good answer from the agency. We'll have that study, actually it will be ongoing, that's true. We'll have UNITY-CLL, which will be completed along, but ongoing, and then we'll have the three arms to the UNITY-NHL study, those are Phase 2b, so more, as we call them registration-directed, all of which have the potential of being used for accelerated approval, each of them has a model -- regulatory model to follow, Marginal Zone as we mentioned earlier, will follow the ibrutinib model for accelerated approval if we have the data that supports that. Follicular, we're waiting on the FDA decision on [Indiscernible] if they do accept their regulatory pathway, then there is a regulatory pathway we can walk through for accelerated approval as well, again, assuming the data supports that. And diffuse large B-cell, we're anxiously waiting to see what the label looks for [Indiscernible] and really help us to find what the hurdle is for accelerated approval in diffuse large B-cell. So, that's five and then the MS, so there will be six pivotal trials.

Got it. Okay, great. Congrats. Thanks a lot.

Thank you.

Thank you. At this time, I'd like to turn the floor back over to management for any additional or closing comments.

Great. Thank you very much. And again, thanks all for joining us. Let me just wrap-up the call by briefly reviewing some of the key goals and objectives for the remainder of the year so we're all on the same page again. We're going to have the commencement of our global Phase 2 trial on MS, hopefully, in the next few weeks under our SPA ULTIMATE I and ULTIMATE II. Again, also, in the very near-term, we'll do the first interim analysis of UNITY-NHL and hopefully, we'll be able to announce that we're dropping the single-agent 1202 arm and replacing it with U2 + Benda. We're looking forward to meeting with the FDA and hopefully, having a positive outcome of those discussions, and being able to file GENUINE for accelerated approval. We plan to report additional clinical data from our MS Phase 2 study and we, before the end of the year, plan to complete enrollment into the UNITY-CLL trial and, of course, at the end of the year, at ASH, we will be updating a number of our ongoing CLL and NHL studies. So, with that, again, on behalf of all of us at TG, I'd like to thank our investigators and the patients as all well as our loyal shareholders for their continued support. Thanks again everyone for joining us and do have a great day.