TG Therapeutics, Inc. (TGTX) Earnings Call Transcript & Summary

Good -- great. Good afternoon, everyone, and welcome to the 4:40 p.m. session at Day 3 of the Goldman Sachs Global Healthcare Conference. It's our last session of the conference, but I always like to say, save the best for last. I've got the pleasure of hosting a fireside chat today with TG Therapeutics. And with me, joining from the company is Michael Weiss. He's Chief Executive Officer. And so maybe before we get into detailed questions about the company, Michael, you and I have known each other for quite some time. You've helped cofound the company, actually, back in 2011, and we met sometime in 2013 or maybe 2014. So as we find ourselves here in mid-2020, maybe if you could start off by providing some reflections of kind of the vision for the company as you cofounded it, and where you've come -- from there, where you are now. So I'll turn it to you.

Yes. Sure. First, thanks for having us. And great to see you again. It's been a -- it has been quite a while. Yes. So what's interesting is when we started the company -- so we started to get the formation of the company together in 2011, and we were working on in-licensing ublituximab, the CD20. And one of the -- one of your original slogans or ideas we had, it was like ublituximab for the people, CD20 for the people, right? So we had this notion that we're going to be able to ideally come in with a very good price for our CD20 across some big markets that it was involved in. And then as we got through to the end of 2011, we started to -- we went to ASH, actually, ASH at 2011, and realized that CD20 is plus something else. We're really going to be an important treatment option, including CD20 plus a PI3K or plus a BTK. And so then we really started to narrow in on that combination strategy. We never really forgot the ubli for the people. And that still, if you come -- now if you go fast forward 8 years, what are we doing? What we have are double combination in finishing Phase III. We have the data and we're going to go file. And we have -- we'll be touching out for MS, where part of our idea is we're going to come in with a great price point. Right? So the 2 notions at which we started this company are still exactly the same. We've never -- we haven't wavered or changed literally since the very first days of this company. And so yes, we're obviously excited about where we are and where we've gotten to over that time. But we have held firm -- I mean you've seen -- you might remember some of those presentations back in the early days, and I can show you from even like concepts in 2011, we're very, very similar to where we started.

Right. So you find yourself now at a place where your assets have now come through clinical trials. You're at a late-stage right now. And with that said, we'll talk about the data in just one second about your assets. But as you find yourself here now, what's the vision in the next 5 to 10 years, perhaps?

Yes. So look, we are forward-looking for sure. We're in -- so as you said, we're coming on the other side of those clinical trials. We're looking at -- I think it's 5 labeled indications for 2 drugs over the next 2.5 years-ish? So if you look at 3- to 5-year time frame, we should be generating significant revenues across multiple products and multiple indications. The combinations don't stop at 2. It goes to 3 and 4. We have not just plans in place, so we have execution already ongoing for triple therapies that will hit the market potentially even in that same 3 to 5-year time frame. And then who knows, we could certainly expand some of these concepts as ancillary areas around the B-cell malignancy space that we're thinking about. And then there's also a bigger opportunity in autoimmune disease that we haven't even tapped into yet.

Okay. And well -- you've got some early-stage programs as well. And if there's time, we'll touch upon them. But maybe let's transition to your late-stage assets. You talked about your umbralisib and ublituximab, and you've reported data very recently. There's a lot going on. Maybe let's talk about the assets. You can talk about the assets first when you talk about the data. But 2 programs that have the U as the first letter. And I remember listening to a call of yours and you kept on saying U2, U2, I was like, what are they referring to? But I guess it's a combination of those 2. So was that just random? Or was there another story there?

So it's not perfectly random. So look, I'm not going to lie, U2 has been my favorite band since I was pretty young. I went to my first…

Me too.

First U2 concert, 1985.

Okay. You got me beat. You got me beat. I'm 1987.

That's pretty good. That's pretty good. So I'm a early U2 fan, and we inherited the name ublituximab from the licensor. We got to name umbralisib. So clearly, at that moment, when we decided to go with the double U, we knew where we were heading. Like, we were going to pick a little homage to our favorite band. So basically, U2.

Well, with that said, maybe we'll start off with the assets in themselves. And then in the context of the UNITY-CLL trial, I mean, there's a lot going on with the company. Maybe we'll start with the assets themselves. And maybe we'll start with the PI3. So why don't we find out -- there's a lot out there about the class. There are some approved agents. You feel you have a differentiated assets. Let's talk about that.

Yes. So the class is active, right, known to be active across both CLL and indolent lymphomas. And the problem has been that tolerability has been an issue. And so we believe that we have a compound that overcomes those tolerability issues. And I can go through the science behind that, but the short answer is it's the most selective for PI3K delta of all the competitive products. And it is the only product that hits CK1 Epsilon is an unknown target, new but known now to protect T-regs and a lot of the toxicity associated with the first gen molecules is related T-reg dysfunction. So the basic science supports the concept that this should have an overall better tolerability profile. And then the data -- we've treated, I think, over 1,500 patients. I mean, the safety database is quite robust, study to study. It's very consistent. We see -- and what we try to do is, look, you could -- we have these KOL calls quite frequently. We had one today again. And you can point on this tox or that tox or whatever tox, but the bottom line is, how are patients overall tolerating the drug? And the bottom line is you look at patients that drop off the drug for AEs, right? That is really the compilation of what's going on with the drug. And consistently, we see a drug -- we see with our drug that about 10% to 15% of the patients over the course of the trial will drop due to AEs. That is pretty well in line with some of the best TKIs. I mean I think you can find some that are better, but it's pretty well in line with very well tolerated TKIs. And that's where -- I mean when you look at our compound, for the most part, it doesn't really have a safety profile that's consistent with PI3Ks. It has a consistent profile with most TKIs. There's -- you're going to see short-lived, but you have to see some GI Tox and that kind of thing. But overall, the [ IDAses ] that have plagued the prior generation are relatively not seen. Again, we do see them, but they're very rare.

And maybe just a quick follow-up here on the class. And given that there are other approved products, you did give us some perspective of KOLs. But do you think for the broader community, there's going to be this class effect that will require a significant amount of education to get them comfortable with the mechanism?

Yes. So I think it's not a significant amount of education. Or let me say it this way, every new drug that wants to be successfully launched requires a significant amount of education. You want to make sure people understand the profile of the agent, regardless of the mechanism. Every one of them requires a significant amount of education. I don't think we are going to be challenged to get people comfortable with the molecule. The nice part about our clinical development program, which I think different than most other compounds in this class. And in fact, even ibrutinib, venetoclax, the vast majority of our studies were conducted in the United States, and the vast majority of those were in community sites. So we already have a lot of community centers that have already had experience with the drug, and that's the #1 issue with new drug launches. If you haven't used it before, there's a lot of education and there's some tentativeness. So the fact that we have inroads into many large community centers and many small and mid-sized community centers. Puts us in, I think, a very good position for people to understand and advance what the attributes of the drug are, and what to expect.

So with that in the context and maybe putting the PI3K delta aside for a second. Let's talk about your anti-CD20, right? And so the original vision of the company was anti-CD20 for the people, and that's like maybe 8-plus years ago. There have been advancements in the space. There are multiple anti-CD20s either on the market or coming to market. So maybe we can just talk about the profile that you've seen with your anti-CD20 and then transition to that until -- into what does the combination do, and then we can lead into kind of the UNITY-CLL trial.

Yes. So as you know, there's a mixed question there because we're obviously using the CD20 for MS. About those attributes because they are slightly different. The drug is the same, but the dosing is different, so it has a different profile. But on the oncology side, in terms of the competitive landscape of CD20s, there's not a lot out there in terms of CD20 specifically, right, or engineered CD20s. There's GAZYVA or brentuximab and us. Ofatumumab, I'm pretty sure is going to be taken off the market or is already off the market. What's coming down the pike are engineered CD20s or CD19s, which is a similar target with something attached to it, whether it's a CAR T that uses the CD20 to direct the T cell or whether it's a bispecific that used as a CD20 to engage the cell and then has a CD3 arm that will engage T cells. And those engineered molecules are very active. They also have a lot of toxicity. There's always a balance, right? The more potent you make a compound the more toxicity you bring. And again, just as a side note, on this call today, I thought the quote that we hear all the time, but you said it sort of best was, "We start with the gentle stuff first. And we move towards the more aggressive stuff later." So bispecifics and CAR-Ts. And you also said in referring to follicular margin zone, you said, this is not large sell. We would sacrifice 10, 20 points of overall response for a better tolerated agent. In large cell, with diffused large B cells, the reference, that's where CAR-T and these bispecifics with their more potency, the tolerability is acceptable at a higher -- at a lower level of -- or lower level tolerance or more toxicity is acceptable in that setting because those people are dying much. So I think in terms of the indolent diseases that we are currently targeting primarily, Marginal Zone follicular and CLL, our CD20 stands alone with obinutuzumab, really as the standard -- I mean, to us right now, they're the standard, and we think will be a standard of care. And there's really nothing else coming to replace that product. Again, the more aggressive bispecifics and CAR-Ts will be reserved for future lines of therapy.

Great. Maybe that -- as a good segue into UNITY-CLL. You recently reported top line positive Phase III data for that. So maybe you can share some of the details on why you're excited about the profile you're seeing.

Yes. So somewhat similar to that concept. I mean we designed this study and the combination to be used in first, second, third-line patients. These were studies that weren't designed, and the drugs were never designed to treat salvage patients. Again, that's going to be a great application for CAR-T and CLL. Very rarely will you see it earlier than third, fourth line. But ours are built for frontline and second and third line treatment. So tolerability is key, right? You want to be able to treat the patient, remove the toxicities of the disease without replacing them with drug-induced toxicity, right? These people are not dying tomorrow. They're living somewhat painful existence because the disease is causing side effects that makes it uncomfortable to live. Tons of fatigue, infections, they have a hard time sleeping. Sometimes they have very large nodes, that are very comfortable or painful. So you just want to manage the patient, and you want to give them a good lifestyle. So we studied U2 in frontline and patients with the relapse/refractory CLL in all-in one trial. The primary endpoint is progression-free survival. We announced just a few weeks ago that the study was positive. We also announced that underneath that, when you look at both populations, it showed benefit in both the front line and in the relapsed/refractory patients. And we're looking forward to presenting that data later this year, ideally at ASH. Hopefully, I'd love being an in-person ASH for us to do that, but either way, the goal is to presented it at ASH.

So CLL, there are existing combination strategies there. And so given your Phase III data and you'll share more details later on, hopefully, this year in person where we can all see it. But how does this treatment regimen fits as is in a 2-product combination? And how are you thinking about further developing this unique U2 combination?

Yes. So before the advent of ibrutinib or BTKs, but ibrutinib was first, and then venetoclax, the only treatment mentions available for patients were chemotherapy. That's not that many years ago, right? We're talking about 7 years ago, 8 years ago, tops? I can't remember exactly when ibrutinib was first approved for CLL. But it's pretty recent. And so if you start to think about ibrutinib as an agent and BTK is generally they're very good drugs, but they're not perfect, right? Not every patient responds, not every patient tolerates the drugs. And in fact, some patients have some really bad reactions to those agents. So is there a need for additional oral small molecules that provide benefit to patients who either don't tolerate or progress on ibrutinib? 100%. And likewise, venetoclax is also a very good drug. Actually, on its own, it's fine. It's not the greatest. It's good, but it's a great combination agent. And when you combine it with, you can do -- you can come up with lots of things. Right now it's combined primarily only with CD20s and the results of in combination with CD20s have been quite good. But again, not everybody tolerates, people will progress. And particularly in the COVID-19 world, delivering venetoclax is a challenge. So even before COVID-19, the community has not bought into venetoclax. So if you divide the world, and this is, again, for us, we ideally will have a label that says you can use U2 in any CLL patient, right? The way the study was designed, it's frontline relapsed. There's no restrictions in the protocol. So in essence, the goal is that we would have a label that says the treatment of CLL. However, within that, we don't expect every people to be treated with it, but it's a tool that you can use in specific situations. And what are the current unmet medical needs for CLL despite BTKs and despite venetoclax, it's patients who are in -- primarily, I would say, in the community setting, which is about 80% of all patients treated with indolent diseases, Marginal Zone follicular and CLL, about 80% of those patients are treated in the community setting, where giving venetoclax is a challenge. It's not 0, but it is challenging, and a lot of new patients maybe even get referred to a hospital to get it, and then they'll come back to their community doctor. Those hospitals in COVID-19 are not taking those patients. So there's been a real challenge -- there's always been a challenge in the community for venetoclax. It's even more challenging today. So now if you just say, you can make it black and white for the moment. 80% of all patients are in the community, and they don't get any venetoclax. Well, there's going to be -- I think that [ Anthony ] made or published a report that about 30% to 40% of all patients that go on to ibrutinib are off within 2 years for a variety of reasons, whether it's toxicity or progression or choice, they're coming off. So there's a huge, huge unmet medical need for patients in the community who want to stay in the community, don't want to get hospitalized to get venetoclax. There's -- it will be U2 or chemotherapy in those patients. And those patients can be identified before they go on to BTK. So if you walk in the door and you already have AFib or any cardiovascular risk, you're probably not a great candidate to want a BTK, whether it's ibrutinib or acala. The risk is still the same on every one of their trials. That may be a site [indiscernible]. It might be every trial. But if you look, you'll see sudden death reported in most trials with a BTK inhibitor. And that's probably a cardiovascular event that was underlying the patient that they didn't realize it and then they end up with a sudden death in their trial. It happens quite frequently in most of their trials, you'll see that. So you can identify patients in advance. Cardiovascular risk is a big one. Bleeding risk, drug-drug interactions is a real big problem for that class of drugs. We don't have that issue. DDI is not a concern when you're using umbralisib. So our estimate -- so that's about 20% of the patients who are -- who want a BTK inhibitor are probably poor candidates for it. And that's where U2 is going to really provide value for those patients. And then of course, on the other side, if you've received a BTK inhibitor, you're in the community, it's U2 or chemotherapy. I think we're providing great value for those patients also.

With the positive Phase III data in hand in CLL, so what's the next step? What's the path from here? And then piggybacking off of that, we are looking at a triple combinations that are currently being explored. So how do you think about triple combination strategies for TG Therapeutics?

Yes. So Step 1, just to go back for a second, we do have umbralisib, the new drug application for single-agent umbralisib for Marginal Zone or follicular is due to be completed. We started the rolling submission earlier this year. It's due to be completed by the end of this month. So Step 1, we should, hopefully, by PDUFA date would be -- if we get in by the end of this month, PDUFA date be the end of February. So single agent umbralisib, Marginal Zone follicular could be commercially available early next year, possibly even earlier, where we have breakthrough designation for the marginal Zone indication. Okay. So now what happens next with CLL because then that's for U2 the combination? So we will start a filing, but we're going to start working on filing shortly. The goal is to get that filing in around year-end. So it could be late this year or into early next year is the target. And again, add 8 months to that, so middle to end of 3Q of next year for a CLL potential approval. So marginal follicular, early next year, middle of next year for the combination for U2. And then beyond that, we do have triple combinations in CLL already ongoing. We have U2 plus venetoclax, where we presented a little bit of data at ASH last year. And at this year's ASH, we plan to present even more data. And we've been enrolling quite well into that trial, both the Phase I that we presented at ASH last year, and we'll provide an updated ASH this year has enrolled, I think, over 50 patients now. And our U2 plus venetoclax study of our Phase II, which may be pivotal, which we call ULTRA-V is probably almost halfway full enrolled as well. So those studies have been going great. And the early data, I think we've talked about this previously, the early data has been quite impressive.

Okay. And out there in clinical trials in terms of the triple combination. There is BTK inhibitor plus venetoclax, and I believe then there's going to be the addition of obinutuzumab. And so with that triple -- I don't know when that day is supposed to read out. But how does that shape, in your perspective, how does that shape, if the data are positive, how might that shape kind of the treatment paradigm? And then with your U2 plus venetoclax, how do these all fit in together?

Yes. So we've been trying to figure out where the puck is going for a while. And so that's why we built this U2 plus venetoclax program. We also have U2 plus our own BTK for another triplet. And so the world of the academics is going to -- not every academic because today was not so enthusiastic about the idea of ibrutinib plus venetoclax. But I'd say, on average, more academics we talked to believe that deeper responses, MRD-negative driven treatment is the future of CLL. And so you can get to an MRD-negative CR in the vast majority of patients, only 2 ways. You can take BTK plus venetoclax, probably with the CD20, and get to a good solid MRD-negative ratio, I mean, with 50% to 75% of the patients, 50% to 80%, depending from relapse to frontline. The other -- the only other way to do that is U2 plus venetoclax. So in a world where -- let's just go to a world where now 100% patients want a triple therapy. We're going to argue that 20% of those patients are going to go on U2 plus venetoclax and the other 80% could go on to BTK plus venetoclax. Now there's another world that we envision that's actually, we believe more likely to occur, which is if you can get to the same outcome by using U2 plus venetoclax and not using ibrutinib, and saving ibrutinib or a BTK for a second line. And that's a better option for the patient because now you've created 2 phenomenal lines versus you put them both upfront, and if it doesn't work out, I mean, it's fine. They'll get U2, and that will be great. But if you truly believe that your 2 best regimens in CLL are going to be a BTK plus something or venetoclax plus something, the something should be, in both cases, U2. So if you start with ibrutinib or BTK, you should put U2 on top of that. And if you start with venetoclax, you should put U2 on top of that, and always reserve yourself a second line. So either way, we're either going to capture 20% because the world has moved completely to that notion, or we're going to capture a much bigger percentage because U2 plus venetoclax is going to get you the same place. If that's your goal to get to an MRD-negative CR, so it's BTK sparing ability to get to the same place. We think that's an attractive opportunity for folks as well. So we feel like we've got a very well positioned program, giving us optionality on every side of this equation.

Okay. Let's -- before moving to the MS side of things, but let's just focus on oncology, still it sounds as if you've got a potential PDUFA sometime in the first half of next year, where you'll be potentially launching a product on your own. And with that said, for a small company that's kind of building out commercial capabilities, how are you going about it? I think investors are always quite nervous about small companies launching products on their own, even larger companies don't get the benefit of the doubt by investors. So maybe can you walk us through as you think about commercialization, how TG Therapeutics is going about it?

Yes. So we've brought together a really strong commercial team. So we've brought in Adam Waldman from Celgene, who is running the heme franchise in the U.S. and by luck or good fortune, Celgene and Bristol decided to merge. And out of that merger from both sides, actually, independently from both sides, we have built most of our team from both the Bristol side and the Celgene side, people who were either cast off, given packages or otherwise wanted to try something different and new. But I think we've put together an A team of folks who have all done it before. A lot of them have done it together before, and there's pockets, right? We have this pocket from Bristol that worked together before. So we've basically taken a dream team from 2 places. There's other folks, of course, but it's coming together quite nicely. And again, I think, I feel confident that they've done it before. They know what they're doing. The group is -- looks and sounds and doing all the right things.

Are there key critical success factors in this particular space that bears paying attention to in terms of success? Again, and when we look at the historical commercial trajectory of the PI3s, granted maybe those assets are different. But can you talk about kind of how you think this launch could be different from other launches in case investors want to kind of bench -- do some benchmarking?

Yes. I mean, look, we're starting off in second line Marginal Zone and third-line follicular. These are not huge markets, they're good markets. I think if you -- I can't think of the analog. I mean, the early venetoclax launch in 17p, CLL might have a similar number of patients in that category. So I think 30% of relapsed patients are 17p. So I think there -- certainly, I don't think we should expect that by year 2, we'll be doing $1 billion in sales and Margin Zone and follicular, I think that would be quite an -- pretty aggressive expectation. I think if everyone has reasonable expectations, these are not small markets either. We're talking about in the settings in which we would be labeled, we assume that there's somewhere in the order of, was it, 7,000 to 8,000 folliculars and about half that number. So I think it's like 8,000 to 10,000 total for the group of patients. So it's not tiny, but it's also not large. I think the key is -- our team is to get out there. They need to educate the physicians and the nurses. I think people are -- the research that we've done thus far, people are excited for the compound. They're excited for new drugs in this area. And I think part of, again, back to your original point, education, it's like -- remember, [ SideSims ] an educated consumer, is our best customer. For us that's what we're looking for. We want to make sure we educate everyone and we think people are going to have a great experience.

Okay. We've got, I believe, less than -- about 10 minutes left. And so with that said, maybe we'll say a few words about the MS opportunities as we touched upon before. So maybe there, I think you've got Phase III data upcoming soon -- or not soon, but it's upcoming. So how should we be thinking about that opportunity? And then we'll ask questions about how does that fit in the competitive landscape? And then what your TG Therapeutics' plan around what to do with that asset afterwards?

Yes. So I'd say in biotech terms, it's very soon. We're 3 or 4 months away. I don't know, we've been doing this for a long time. This is where -- we're at the edge, as far as I could tell. So that's coming up very soon. We're expecting data end of 3Q into 4Q this year on the Phase III trials. So MS, obviously, it's a large market. I think worldwide sales are in the $20-plus billion today, and we expect it to grow $25 billion to $30 billion over the next 5 to 10 years. The CD20 market, though, is really our competitive space. So while there might be 10, 15 drugs available for MS, the nice part is it's really -- the CD20 market is being created today. By the way, it's raining cats and dogs. I don't know if you could hear that out there. It's pouring here. But -- so they -- so the CD20 market is creating its own little submarket within MS. The projections are for the CD20 market alone, it could exceed $10 billion. Roche with ocrelizumab, I think, is on track this year, close to a $6 billion run rate. So it's already -- and then once ofatumumab enters the market, which is -- will be the second CD20. My expectation is they'll continue to expand in the market, and then we'll come into the market. And so we'll have these 2 big pharmaceutical companies that are doing everything they can to expand the market. I've seen OCREVUS commercials. I'm assuming there'll be some ofatumumab commercials. But no matter what they do, and we hope they do a lot of it, the same conversation is going to occur with the doctor and the patient. Right? Even they walk in with a picture of the screen of an OCREVUS or ofa commercial, the physician is going to have the same conversations. He's going to probably start off by identifying which of the 3 drugs is on their plan and available to them, right? And so Step 1 for us is to make sure that we price, and this is now ubli for the people, that we price MS in a way that grants as much access as possible and the best access of any CD20s, if it's possible, right? The insurance companies are interesting, the payers are interesting. It's not always the lowest price that gets the best access. So we want to be cautious. We're obviously not going to do it if it doesn't work for the patients, it's only giving them better access. There's no reason for us to drive such a low price. So we'll be working closely with our teams, our pricing team to figure out what is the right level that provides access to the patients. And then once they do bring in access, and let's assume that everyone in this example have access to the 3 drugs. So then the conversation is going to be -- okay, so there's 3 of them. They're all -- we believe, virtually the same. As far as we could tell, I mean, we do have -- there's a chance that ours will have a potentially better activity profile because it's more potent. But putting that aside because that's a high hurdle to get past. And so base case assumption is that the physicians are going to look at all 3 of these drugs and say, they're essentially the same. So we have 3 drugs. Here's the difference in profile. One, you can basically inject yourself. It's a monthly injection. You're going to come into my office 3 times in the first month, and I'm going to inject you, and then you're going to take it home and you're going to inject yourself every month. And for those of you who have been on other injectable products before, they may choose that going from 3 times a week of COPAXONE to once a month ofa might be very attractive. But for patients who have come into the system over the last 5 years or so, they may not be so attractive. They've been on oral therapies, probably. And so coming into the office every 6 months for an infusion may be much more attractive to them. And so -- and then if they decide that they want to come in every 6 months, your choice is you can have one that takes 1 hour, or you could have one that takes anywhere from 2 to 4 hours, depending on when they get their approval to go to a 2-hour infusion. But either way, you've got one that's 1 hour and one that's at least double the time. And by the way, that 1 hour infusion will probably cost you personally less, but you pick. So we think we're going to do pretty well in that marketplace. Again, we didn't do this to be -- with the expectation that we were going to be the #1, CD20 in the market. We could be -- again, if price matters enough, then we could be the #1. If it doesn't matter enough, we're still going to be helping a lot of patients who want a better experience at a shorter infusion time and a better price.

In the Phase III data, which is 3 to 4 months away, what's going to look good? Is it going to be just about hitting stat sig? Is there some other -- some other way to think about that data?

So yes, I mean, look, hitting stat sig is going to be the answer. I mean that'll be perfect. There's nothing else that's going to matter unless the annualized relapse rate is so dramatically low that it will appear to be obviously related to the enhanced potency, right? So that you can't put a number, but I'd say that anything south of 0.10 annualized relapse rate will certainly give people pause to say, huh, is there a potency advantage here? And anything that -- in every 0.01 below that, they're going to be -- their eyes will start to light up. And I'm sure 0.07, 0.06, people really start to think, huh, it probably is because it is more potent. And then you also have to look at the comparator arm. Let's just say the comparator arm locks in with the comparator arm for the other 2 drugs. But yet, again, our annualized relapse rate is dropping into the lower mid-single digits, right? So that's -- so that could happen. But again, I just think stat sig, which probably puts us with an ARR between 0.10 and 0.15 versus a comparator arm, which is probably 0.20 to 0.25 or even a little bit higher, now is going to put us exactly where the base case puts us. And again, like I said, we have to drive pretty low for people to get more excited about it -- to believe that it's more efficacious. It's a high hurdle for sure.

And it sounds like it's an asset that's really more of a partnership opportunity. So is there any -- what can you say about how you might think about commercializing this?

Yes. So look, we are -- we're not rushing to partner in this. We definitely have opportunities to do so. But the more research we do, and again, we brought in some Celgene folks who have worked on the team there to do MS. It's kind of shocking to think that on the sales side of this, the MS where there could be 300,000 or 400,000 patients treated a year with MS. The same number of doctors, about 5,000, treat 80% of those patients as they do with cancer. So you're talking about the same size sales force. You need about -- it's 100 give or take. It's plus 25, minus 25. You're going to be in the range of well suited to sell an MS drug. And I can tell you from the largest pharmaceutical companies out there, they have sales force between 100 and 125 to the smallest company that probably recently had an MS drug, Acorda, also, I think, had a similar-sized sales force. So the sales side is not the challenge here. The challenge is, if we're super successful and we have 50,000, 100,000 patients on, it's making sure those patients are taken care of, right? So the patient services side that becomes more expensive. And -- but that's a good problem to have. Because if you really are getting that many patients, you're driving a significant revenue, and you can pay to make sure those patients are being provided for and serviced properly. So we're not running away from doing this on our own. We think there's a real opportunity for us here.

Okay. Great. We've spent most of our time kind of on the later-stage side of things. Maybe if you can touch upon maybe one of your earlier-stage programs that you think are most exciting for investors to pay attention to.

Yes. So probably the most boring of our pipeline is probably the most interesting for the moment. So I can talk about we have CD47, CD19 bispecific, which I think is very cool in various uses. It's a little bit -- it's still early, we're still in dose escalation. And that has a real opportunity to be a very nice component in our immunotherapy platform. So we have CD20, which we know pairs very nicely with CD47, and we have PD-L1, which has never really been paired with those others. But if you think about combining T cells, NK cells and macrophages. The only way to do it is to combine PD-L1, CD20s and CD47s. So that's coming, and that's probably the most -- the sizzle. But the stake is clear, right? U2 plus BTK across CLL, Marginal Zone and probably even follicular, is a very potent and also very well-tolerated treatment option. And particularly, we have the luxury to design our BTK as a combination with U2 to ideally lower the toxicity profile of that compound. So we don't have to push it for acala and for ibrutinib. And again, despite their -- they appear to be very well tolerated. They still have issues. And so because we're doing it in combination, we feel like we have a bit of latitude to create even a better tolerated triple therapy, which, again, when you think about CLL, follicular, Marginal Zone, it's all about tolerability. It's like real estate is location, location, location. In indolent diseases, it's all about tolerability, tolerability, tolerability. So I think that's an exciting program. That's something we can have in Phase III early next year, mid next year. And so dovetail very nicely. By the time we are into the launch of the U2 combination, we could be on the other side of a triple combination data from our own portfolio and also probably from venetoclax too. So 2 triples, again, to make sure that we've blanketed the opportunities. If you want to use a BTK, we're going to give you U2-plus. And again, there, we'll come up with a very good price for the BTK when you use it in combination with U2, and U2 plus venetoclax, where we can't control the price, but if we get more patients to MRD-negative CRs and off drug, we'll save the system money at the same time.

Okay. Great. Maybe 3 last quick -- well, 2 last quick questions and then one final question. But where are you on cash? I know you were successful in an equity raise very recently. So where are you on cash? Where does that take you to? And then if you can remind us, given everything we've said today, what the catalysts are, I know we've got a readout in MS in 3 to 4 months, but maybe over the next 12 months, how should we be thinking about value creation for TGTX?

Yes. Absolutely. So from a cash perspective, I think we had over $300 million after the raise, and the projection is well over 2 years of cash. So I don't -- refined it further for the moment. But financially, we're in very good shape. We're in the best shape in the company's history. So that's quite nice. We feel good about that. And it's a good time to have cash because the catalyst, as you described, I mean, it lines up. So Step 1, Margin Zone and follicular, NDA submission complete before the end of this month. Then, call it, end of September into October, we've got the Phase III readouts for MS. Then, if we get a little bit lucky, a little bit lucky, perhaps we can get an approval before the end of the year. But if not, I -- by -- should have a PDUFA date by the end of February for the Marginal Zone follicular. Within that same time frame, end of year to, I guess, February-ish, we should have our CLL filing in. And not too far after that, we should have our MS filing in, which then lines up for a CLL approval, call it, 8 months later in the third quarter, mid-year, third quarter, depending on how fast we get the filing in and how long it takes for the actual approval. And then a very late year approval for MS. So that's '21. So between here and the end of '21, we should have those 5 indications for the 2 drugs.

Yes. That's remarkable. Thanks for that. And maybe just with the last question, and it is -- it will be my last question to ask of you and as well of my 3 days of moderating fireside chats. But you've been in the industry for 20-plus years now. You wear multiple hats. You're CEO of a company or Vice Chairman of another. You've been an investor. As you look out over the next, call it, maybe 3, 5, 10 years, what do you think are the one or 2 biggest trends that investors should be looking for that may be important in terms of being transformational or highly disruptive in health care or biotech. I mean we're at an incredible place with great innovation, but there's also policy changes, potential policy changes, there's pricing discussions, and how does that play out? It's an open question. So any which way do you want to go, but I thought we'd just do this for fun.

Yes. Well, the first thing, I'll thank you for reminding everyone how old I am. That was nice. But sure, so yes, I actually started in the industry in '93. And I'd say, when I got into the industry, we were just ending Biotech 1.0, right? So all the low-hanging biological manufacturing fruit, the NEUPOGENs, the EPOGENs, [ BORDAN ]. And then we started to get into what I'd call the heavy lifting phase. '93 to even -- I mean you could really take it almost to 2008 was a really hard -- developing drugs was hard, much harder, honestly, than it is today. The targets were tough, the FDA was tough. Everything was just tougher. Things loosened up. And I think a big part of it was the genomic revolution, right? So all of a sudden we had abundance of targets and not only do we have abundance of targets, but we also had great tools to attack those targets. Just as a background, you probably don't know this, but I had the first antisense drug. So RNA interference drug for Bcl-2. So venetoclax, a Bcl-2 inhibitor, I was on that target in the '90s with an RNA interference technology. And I was also involved in the first AEV gene therapy company, also back in the '90s. So what was wrong back then? The technologies just weren't ready for prime. These delivery systems, the gene therapy, the RNA interference, they just weren't refined enough, right? And the targets there were not as many targets, but the ones we did have were actually pretty good targets. Bcl-2 was a good target, but we didn't even understand Bcl-2 because we cover both Bcl-2 and Bcl-XL. And today, we know better that you don't want to cover both you want to cover just the Bcl-2. So again, the sciences wasn't all there. So we made very good attempts and we have we're on to very good places with therapy and the targets, but the size wasn't there. Anyway, fast forward into the, past 2008 into the, I'd say, the last 10 years has been -- or 12 years has been kind of a golden period of drug development. The tools are great, and the targets are great. And the FDA is accommodating. I don't think that they're making things easy, but I think they're accommodating. And part of it is that, look, I showed up with a Bcl-2 antisense to the FDA, and we had a 10% improvement. And today, people come in with a 150% improvement. So it doesn't make it easier for the FDA to be accommodating. They don't have -- there's not a -- it's not a -- there's no margin of error at 10%. At 150%, it's -- it makes it easier. So anyway, so where does that take us going forward, right? So what are -- so I think that innovation continues, right? I think we're in a really nice place in terms of innovation. I think the tools will continue to get better, whether it's gene therapy, RNA drugs, DNA interference drugs, whatever -- that stuff is going well. I think the other thing that's actually interesting from COVID is that the tools for making vaccines will get so much attention right now and so much research and so much money. I mean that while billions and billions, and maybe who knows how many will be spent over the next 10, 20 years, waiting for the next pandemic, but we will be much better positioned to create better, more specific vaccines going forward. So that will be a nice outgrowth of what's happening. But to me, probably the most interesting and disruptive area is something that we've been championing, right? And I said ubli for the people. And I think that concept and next we'll have BTK for the people. And after that, we'll have PD-L1 for the people. We think that time has long come for drug categories that have multiple players to have someone in that category come in with a better price, right? It really hasn't been done. And in part, it hasn't been has been done, and you said it in the answer to the question, is because the payer system has some interesting incentives. And so the lowest price has not been as attractive in the past. We think that there's going to be a convergence of the payer and the government piece of this saying, you know what, we do want a better price. This whole charge me a lot and give me a big discount isn't quite the fairest system. And look, it may work in certain settings, but I think there's going to be a rotation over the next several years toward a system where a lower price can get market share. And I think we're going to be an innovator and be disruptive in that. And I think that's a place where that could happen, not just with us. I assume other people will see us doing it, and they'll jump in at some point. And so there's multiple classes of drugs where there's 2 or 3 or 4 participants, and they all charge the exact same price, and they're fighting for market share by trying to differentiate on this AE or that AE or 2% better response rate. But in the end, the doctors know that they're about the same, and it's hard to really differentiate. But price can change it. And then that creates real opportunities for patients and the overall cost of the system. So I think that's a disruptive area that I think is going to be extremely important over the next 3, 5 and 10 years.

Well, I applaud you on that vision. I think that's what's needed as a consumer. I think it would be nice to see more companies adopt that philosophy. So best of luck on that journey. With that, I know we've run a little over, but I thank everyone for joining. Mike, thank you very much for representing TG Therapeutics, and I want to thank the audience for those who have stayed with us through this late hour. Thanks, again, for joining us at the Goldman Sachs Healthcare Conference. Have a great day, and best of luck, everyone.

Thanks.