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

All right. Good afternoon. I'm Eric Joseph, Senior Biotech Analyst with JPMorgan. Our next presenting company is TG Therapeutics and -- to present on behalf of the company is CEO Mike Weiss. There's a Q&A session after the presentation. [Operator Instructions] Okay, with that, Mike?

Thanks, Eric, and thanks everyone for joining us. We have the honor to close out day 2 of the Biotech JPM, I think, or at least Eric's team. All right. So I'm going to get started here first, I got to say a big shout out to Blue, Michigan Wolverines, National Champions, I promised everyone when I put this on. My daughter is going to be very pleased about this. All right. So let's get going here. So I will be making some forward-looking statements. I usually say, I may be making forward-looking. I will be making some forward-looking statements. For those of you who aren't sure I do encourage you to review our public disclosure documents. Okay. Just a quick background before we get into some details. Our company was founded in 2012 with a focus on B cell-mediated diseases. Today, we're primarily focused on the commercialization of BRIUMVI. There's our anti-CD20 monoclonal antibody approved for relapsing forms of MS. I'm going to spend most of the presentation today discussing BRIUMVI and our launch and all about BRIUMVI. But at the end of the presentation, we're going to talk about the pipeline, how we're broadening the uses of potential uses and indication of BRIUMVI and also a new product that we brought in today. There was an announcement out this morning, we brought in a really nice, very complementary product called Azer-cel. It's a CD19 allogeneic CAR-T, which we're very excited about. Okay. Just a quick background. Again, BRIUMVI, first and only anti-CD20 monoclonal antibody approved for relapsing forms of MS that can be dosed twice yearly as a 1-hour infusion after the starting dose. We received approval late in 2022 and about a month later, early in '23 we launched. So in the U.S. we're commercializing ourselves. In ex-U.S., we have a nice partner called Neuraxpharm. They're based in Europe and they're set to launch shortly within the next few months this quarter. All right. So we got some nice updates coming up for you here. So this is new information, everyone get ready. Very exciting. By the way, I was up really late last night and I got up at 5 a.m. to get here after the game. So if I'm pushing a little bit just let me know. All right. So 400 centers have adopted BRIUMVI since launch, over 625 prescribers within those centers. So off to a great start. That has led to 3,200 prescriptions into our hub. So we don't get every prescription, we don't know [ about it ] with prescription. We believe that 80% to 90% of the prescriptions are making it into the hub, which would translate to this number actually being somewhere over 3,500 prescriptions written in the first 11 months of sales. One caveat to that, we -- we don't have a good -- we don't have a perfect accounting of the infusions so -- but not every prescription will lead to an infusion. But obviously, on the front end you got to get a prescription before you can even try to get an infusion. All right. So that's where we are in terms of some metrics. I'm pleased to report unaudited preliminary fourth quarter revenues. So we came in at a really nice $40 million. I think the actual number was $39.9 million for those who are very particular. We guided to $32 million to $37 million for the quarter. I think, obviously, we were a little bit outside of that on the high end. What I can say also is when we did our calculations we really didn't have any basis to understand what might be some year-end purchases from distributors. There probably was a few million of that at the end of the quarter, but certainly high end to just above the high end of the range, a really nice quarter for us. And that led to a really, I mean, I think, a fantastic first year or partial first year, just under $90 million for the year, exceeded all of our expectations and certainly exceeded 2023 consensus at the time of launch, which was $67 million. So a great first year. shout-out to the TG team for doing an amazing job. We put together what I thought was an amazing launch strategy and the team executed it, I think, close to perfection. So a nice job team. All right. What I'm going to do is I'm going to start with some background on MS. Then I'm going to talk about some of the nice attributes of BRIUMVI and then I'm going to go back to the market again. So as you can see, this is a somewhat dated slide. This is a 2019 picture of the treatment landscape. So it's not as relevant today, and I'll show you some things that have changed. But what I think is really nice to see in this picture is, one, across multiple interventions for MS. You can see a number of multibillion dollar brands. So I think the take-home message is, there's plenty of room within the CD20 class for multiple brands to be blockbusters. And I anticipate personally, we know 2 of them are already blockbusters only one wants to get there. That's us. And obviously, I think we're well on our way. The other thing about this is interesting, if you look at Ocrevus was the only anti-CD20 approved at the time, and my calculation this is about 20% of the market. When we move forward to today, the CD20s have really captured a big presence in the space. And now of the total market share CD20 is up around about 40% of the market. And on an annual basis, the dynamic share, we're seeing about 50-plus percent of new patients going on to BRIUMVI. So again, a shifting landscape. While on the left-hand panel when we were early on getting into this, it has simplified quite a bit there people always say, oh, it's a very crowded space, there are so many treatment options. There's 3 treatments now for about 50% of market share on new patient starts every year. So it's us plus 2, and we'll talk about why now we think we can capture market share and a lot of it has to do with some of the key attributes of BRIUMVI. So just some -- I'll give you some quick bullets here and then we'll go through some detail glycoengineered for efficient B-cell depletion. This is different than some of the other molecules. It's the only CD20 to achieve an annualized relapse rate of less than 0.1 in Phase III trials. Again, I'll give you a little more color on what that means. The safety is in line basically with the CD20 class, but we do not carry a breast cancer warning in our label like the other IV CD20. And from a tolerability and convenience standpoint, the 1-hour infusion provides patients, centers, confidence in the scheduling and obviously the convenience of being able to come in for just 1 hour. All right. So I'm going to do a little biology, which is rough since I failed high school biology but I'm going to give my best effort here. So just a basic -- hopefully, you can see and I can't really point to it so easily. Which is my pointer? Whatever. You guys will see. So there's 2 business ends to an antibody. One side of it, you got to bind to your target. Everyone is aware of that. And on the other side, on the Fc side, you actually have to bind to the immune effector cells. So when you put the 2 pieces together, the immune effector cells, in this case, NK cells actually do the killing. So you basically land on the cell, you got to stick tight and then you got to bring in the immune system and you get a stick tight on that side and that unleashes the cascade of the immune system. So we talked about binding. This was published data presented at the conference. You can see compared to other CD20s again, this is all a test tube kind of stuff. But a binding affinity to CD20 of the ones that are used in approved or used in MS lower is better here just to give people perspective, higher binding affinity is represented by the lower bar. So you see a really nice tight bind to CD20 for BRIUMVI, which is generically referred to as [ ublituximab ]. And then probably the key to the BRIUMVI story is, and we'd like to say, differentiated by design, so by intent, but also by the design of the molecule. So what we've done with this molecule is what we call glycoengineered. When antibodies are produced, naturally, you get sugar side chains attached to the Fc region, the sugar side chains can interfere with the binding, the effective binding of the Fc region of the antibody to the Fc receptor on the immune effector cells. So if you've got something blocking, you doesn't have that tight bind, we've reduced dramatically the fucose, which is the sugar that's involved here, and that helps to free up the receptor to bind. And you can see a pretty dramatic difference, again, lower being better in this picture, a pretty dramatic effect on inducing antibody-dependent cellular cytotoxicity, which is, again, the effect of those NK cells going in and killing the target cell. And then there's another twist to the story here. The actual Fc receptor, depending on your own -- on each individual, you can have 1 of 2 varieties. Again, non-scientifically I'll say there's the easier one and the harder one to bind to. The F is the harder one. And what you could see again, in each of one of these bars here, the blue and the red, you can see the relative binding to that receptor given the different polymorphism. What I like to look at, for me personally is I look at the red for ublituximab versus the blue for the others to get a sense of no matter what the polymorphism, you're going to get a really nice high affinity bind while using BRIUMVI. So -- and the real question is, does it matter? I don't know. I mean it's all pretty -- it looks pretty cool. The science is very strong but it doesn't matter. In MS, we don't know yet, actually. The jury is still out and I can't say it's definitively proven in other areas but we do have information in NMO where you have a greater risk of relapse from CD20 therapy if you have the more challenging polymorphism and RA and lupus, you have lower response rates to Rituxan if you have the poorer or the tougher polymorphism. So again, these are not in MS but interesting to think about, and we're going to do some research in this area in MS. Which leads us to the clinical data, remember, I mentioned it's the first and only anti-CD20 to achieve an annualized relapse rate of less than 0.1 in Phase III clinical trials. Again, we have no head-to-head trials with the other CD20s. The trials were designed similarly, but again, different patients, different studies. But it was a milestone mark to get below that 0.1 and I know that clinicians were very excited about that. Again, putting that into a clinical perspective, that translates in the first study to one relapse every 13 treatment years. And in the other, on relapsed every 11 treatment years, which is about half the relapse rates you would see with the active control in this study of teriflunomide, which is a pretty good drug. I think recently, the BTKs tried to beat teriflunomide and didn't have success at this point. This is supported by our MRI data. So classic signs of MS, you get these lesions in the brain. In this particular case, [ gad 1 – gad-enhancing ] T1 lesions and T2 lesions. And you can see just dramatic effects in the reduction of these lesions. On the safety side, this is anti-CD20. You're depleting B-cells. As we mentioned, we are efficiently depleting B-cells. If you remove a portion of the immune system, you should worry about infections. Doctors are well aware, patients are all aware that, that is a risk with CD20s and we can see that here. If you look at the infection rates, numerically slightly higher than teriflunomide, which is itself an immunosuppressant drug, but none of the numbers are statistically different. We can also -- I mentioned again, no breast cancer warning in our label, which is different than the other IV CD20. And then the other part is infusion reactions. We have a CD20, you worry about infusion reactions, mostly, you worry about them around the first dose, digging a little deeper in here, yes, you've got to think about it associated. We talk to clinicians and we make them very well aware that on the first dose that you're more likely to see it. Again, most of these are mild to moderate. What's really interesting is it is highly associated with B-cell count at the time of the infusion. And what you can see is with BRIUMVI, you get a very rapid depletion of B-cells. So you've got a lot going on, you're going to see the reactions. The predominant reaction with BRIUMVI is flu-like symptoms during the course of the infusion. So it's going to be headache, fever, chills, we do encourage folks that if they're seeing any of those reactions, slow down if the patient is having a problem, you should slow it down. Despite -- given that kind of guidance, it just didn't really need to happen, 95% of all infusions were conducted on time. So whether it was the 4-hour infusion where we saw more reactions and then over time, you can see that the reactions minimize. When we do our 1-hour fusions, again, 95% of them go off on time. That's really reassuring to both doctors and patients that they can schedule their lives around that 1-hour infusion. All right. So back to the market. As I mentioned earlier, about 40% of all patients on DMT, a disease-modifying therapy today are now on a CD20. That equals approximately 140,000 patients on a CD20 today and we believe, certainly growing. The other thing that's important to remember about these drugs, it's not one treatment, and maybe you get it for a year. The median time on therapy is over 4 years and probably growing. Ocrevus has only been on the market for 5 or 6 years, so we're still seeing what that looks like. But remember, every patient that comes on today you might expect over the next few years to still be on, and that becomes what we call a stacking effect or pancake effect, whatever we want to call it, and that will enhance long-term revenues for any of the companies who are treating patients with MS. In terms of the overall market, remember, I said about 50% of all new patients to a therapy are getting CD20s. So our estimate is that about 80,000 patients are either switching or getting their first therapy every year. And like I said, about half of those are going on to CD20. And the breakout of the market, it's been creeping up originally the subcutaneous portion of -- well, originally the subcutaneous market was 0 because [indiscernible] launch. They've been creeping up from about 30%. Newest information says they're actually closer to 35% will go on a subcutaneous form and then 65% will go on one of the IV forms, whether it's BRIUMVI or the other IV. And then just this is very back of the envelope, as we ended the year in the final quarter we had about 1,000 BRIUMVI prescriptions into the hub. If we assume an equal distribution of the 40,000 patients coming in per year to a CD20, 10,000 per quarter, and we have 1,000, that will be about 10% new patient prescriptions as we ended the quarter. Again, with the caveat that those are prescriptions that not necessarily infusions, so it's not apples-to-apples exactly. But again, I just think it shows a really nice what is the demand for BRIUMVI and where is it tracking today? And then I'll just finish this section with the size of the market. I think the estimate for 2023 is about $10 billion in CD20 sales, growing potentially as high as $14 billion over the next several years. So this is a large and growing market, and there's only, as we mentioned, 3 players in it. In terms of commercial launch, again, TG is launching -- has launched here in the U.S. and we will continue to our launch. Our long-term goal is to have BRIUMVI to be the #1 prescribed CD20 dynamic share. So I don't think that's going to happen in '24, probably not going to happen in '25, but that is our goal, and that's what we're working toward. We spent the first year, we had a really, like I said, I thought it was a very focused and targeted strategy. We wanted to make sure we educated the healthcare providers, we wanted to make sure that they knew about BRIUMVI, knew the differentiated profile. Our goal is to get folks to try BRIUMVI, hopefully get them to use it some more and hopefully fall in love with BRIUMVI and I think certainly some have for sure. And then to make that work, you really need to have a good patient support program and access to insurance. And so those were the 2 main pushes for the first year. And now as we move into year 2, we're going to be expanding our target list of healthcare providers that we're going to be talking to and engaging with. And then the bigger piece probably for the year is we did not do a lot on -- by design with respect to direct-to-patient initiatives. Our goal was to make sure the healthcare providers were aware of BRIUMVI before, the patients came to them asking about it. This year is all about now and I think awareness in healthcare providers is extremely high today for BRIUMVI. And now the next step is -- our goal is to get the awareness extremely high on the patient side. So that's a goal for '24. As I said, outside the U.S., we have a nice partnership with Neuraxpharm, a really nice company, midsize, really similar in culture to TG. They're dedicated to neurology, they've got a great European presence. We didn't -- like I said, financially, it was a very nice deal and they'll be launching soon. So keep an eye out for that, we'll give a little guidance later on what we think is going to happen in Europe this year. So I'm going to talk a lot about where we are at the BRIUMVI in MS. Now let's talk about where we can go with BRIUMVI and where we can go with other things that have recently come into the portfolio as of this morning and potentially others. So first thing is we want to continue to maintain our leadership position in the convenience of CD20s and BRIUMVI particularly. So I'll talk about that. We think there's room to broaden the indications for BRIUMVI, and of course, like I said, we expanded our portfolio this morning. We're really excited about our new opportunity with Azer-cel and we'll talk a bit about that. So the 1-hour infusion for BRIUMVI is really the standard of care today in terms of convenience or short infusions. We have -- but we do still have that first starting dose that takes 4 hours. It's particularly, I say, I won't say problematic, but definitely has some drawbacks for patients who are already well maintained on another CD20, so they have low B-cell counts. Remember, I said that big drop in B-cell accounts and then you maintain the patient. So you have these patients that are well maintained, they prefer not to spend 4 hours an extra day. So we started a study to see if we can eliminate that for our dose safely and move them straight into 1 hour BRIUMVI. So we're going to present some data from that during the course of the year. And then we also have strategies to otherwise minimize that 4-hour dose and potentially even minimize the 60-minute dose of BRIUMVI. And then that's been on top of mind for a lot of folks, and I'm sure -- maybe I was telegraphing a little bit when I was talking about the subcu market that's been growing. But we are now in a position to say that we're going to move forward with subcu development of BRIUMVI. We're preparing to enter human studies this year, probably by midyear and like I said, we think the subcu market is attractive, and it really represents a new market for us. The IV markets and the subcu markets are quite distinct. And then in terms of broadening BRIUMVI, I know it's a bit of a cliche, but we do see BRIUMVI as a pipeline in a product. We've only scratched the surface. And we did have a lot of programs in cancer that would have been a nice opportunity for us. It didn't quite work out, but there's over 20 other disease indications where CD20s have proven to have utility, lots of options for us. We're getting excited to get going on our first autoimmune disease study outside of MS also this year. And then expanding the portfolio, super excited to report, the announcement came out this morning, we signed a really nice deal with the kind folks at Precision [ BioSciences ], global licensing deal, allogeneic CAR-T, CD19, right up our alley, fits -- scientifically fits in the disease [ errors ] we want, CD19 and CD20 are cut from the same cloth in a lot of ways, T cells and [ of course ] antibodies. So we're -- we couldn't be more excited about this product opportunity. We think the allogeneic, obviously, allogeneic off the shelf, that's pretty clear, the advantages and the convenience associated with that. But what has been somewhat of a challenge across the board for allogeneic therapies in cancer is the ability to maintain those products for extended periods of time. We don't think we need to even think about or worry about that on the autoimmune side. We actually think that what may be a drawback on the oncology side is a distinct advantage on the autoimmune side. So one, permitting faster -- potentially [ permitting ] faster immune reconstitution is a real benefit of not having CAR-Ts on board for a very long time. And also, of course, recently, there's been some genetic alterations that have led to secondary malignancies, which, again, with a shorter residency time in the body, you would have -- seemingly have a less likelihood of that occurring. So again, really excited. I think this really fits well into what we're doing, and we're excited to get going on it. Also, financially a really nice deal upfront and near-term milestones. I think the whole deal is almost $300 million, $17.5 million upfront divided up over the next 12 -- good portion upfront and divide over the next 12 to 18 months and nice royalties. We're going to pick up equity in Precision, can't be happier about that. Our success, we can share it from our own and we can have it in their stock, and they have a really cool gene editing program that we'll get to participate in as well. So win-win all around from where I sit. So I'm going to go through some nonfinancial goals, which is really just ties into what I was talking about. We're going to push forward with our subcu BRIUMVI development, BRIUMVI and autoimmune disease outside of MS. We're going to get aggressive on Azer-cel in autoimmune disease, hopefully file one or more INDs, hopefully, more than one by midyear. And we're going to continue to present data from this enhance study that I referred to, showing that we can, hopefully, we'll show the data if it exists, safely move patients across from other CD20s without the need for the 4-hour infusion. We safely do that. Okay. So we got a little financial guidance up as well today, get your pencils out. You're going to need them. All right. So in terms of the first quarter, we're going to provide guidance of our target range of $41 million to $46 million. As I mentioned earlier, we think there may have been some late December purchasing that could rightfully have occurred in January. So we think $41 million to $46 million is a good starting point. We're going to have an opportunity to take another look at this as we move along in the quarter, we'll have our quarterly conference call at the end of February, give or take. But we think it's probably a decent place to start. The current consensus is about $43 million, so not a bad place to begin with guidance on that front. And for the year, again, we're pretty new to this, so we're giving our best shot. It's a pretty good range at this point we'll try to tighten that up over the course of the year. But again, I think we're well within where consensus sits today so I think it's a good starting point for the year. And again, we'll have multiple opportunities to potentially update that. From operating expenses and cash guidance, we're targeting about $250 million in operating expense. Could it be $10 million higher or $10 million lower or whatever, yes, for sure, give or take. But I think the net take home is we [ should ] be utilizing a whole lot of cash this year based on the potential revenues coming in and the target expenses. And those expenses include all of these clinical activities that we're referring to, also includes a modest expansion of our commercial teams. So it's a pretty fully big number. And then just -- because people will always ask, we got to give a Neuraxpharm a little time to get going. They're launching here in this quarter, we're going to get a milestone payment this year, probably early in the year, like I said, probably in the first quarter. But we're not expecting material, I mean, single-digit royalties during the course of this year, as we get into '25 we'll provide a little bit better guidance. But that's where we stand and thank everyone for joining us at this late hour.

All right. Okay, great. Thanks, Mike. [Operator Instructions] But just to start out, lots of numbers, lots of math to do and all the update. We appreciate that. Certainly, that was my #1 set of questions that I was getting heading into this conference. What's TG going to say in terms of preannouncements and forward guidance. So I'm sure the Street is really appreciative with all the detail provided here. Just on the 4Q print, Mike, a couple of things to unpack there. You are highlighting, I guess, the breakdown in demand between those [ new ] brands and those that are sort of repeat infusions, repeat biannual infusions. Of those that are new to brand, where you think is trending sort of around 10% of uptake in the CD20 class, what do you -- what's your sense of the factors of driving preference for BRIUMVI over the alternatives? And sort of where does that decision kind of taking place? Is it top down from payers and providers or is it perhaps from motivating patients?

Yes. So I can answer the second question probably better than the first. But I mean, we haven't done a whole lot of patient awareness campaign, so we do have some reasonable awareness that's happened just naturally, social media kind of stuff so we are really pushing forward with this year. So most of it is provider driven. It's not payer-driven either. So it is provider-driven. We spent a lot of time with the providers going through those differentiating factors. I think when they talk to the patients about it, I'd say what we hear most is if the patient is receptive to the attributes of BRIUMVI, they're going to go on it, but some patients still will say, well, I know the other one better, I've seen their TV commercials. But yes, I think all the factors, the 1-hour infusion, the clinical data, safety data, the label, I think everything comes together to help with that decision.

Okay. Question here. Hold for one second.

I was going to ask anecdotally, do the patients and the doctors have they seen cases where it really does seem to work better than Ocrevus just with the additional Fc mechanism?

The answer anecdotally is yes. We have reports, yes, from clinicians. That's -- they talk about how they weren't getting the B-cells depleted with Ocrevus they were able to get it with BRIUMVI, they were seeing crap gap, they came on to BRIUMVI, they didn't have it. But again, that is anecdotal so it's hard to make too much of it. But it is nice -- I mean, I know we were at a conference and a number of clinicians were sharing stories and they got together and they said they wanted to put together a paper to talk about their real-world experiences with patients going from Ocrevus to BRIUMVI, so we'll see if that comes out. But I mean, yes, if you ask me, we've heard people say that, yes, we've heard people say that.

And can I just ask a really quick follow-up. -- do you get the majority of Ocrevus failures at this point? Or is it still too early in the awareness and everything?

Yes, I think it's too early for me to know the answer to that question. I'm sure we're not getting all Ocrevus. I'm sure we're not getting all the Ocrevus failures and I'm pretty confident that not all of our patients that switch from Ocrevus switch because they failed Ocrevus because -- I mean, it's hard to technically fail Ocrevus. It's quite an effective drug, but folks that will have crap gap wearing-off effect or are not depleting B-cells well are more likely to try something different.

Congrats on the [ bit ] and a great quarter. Just on the guidance going forward. Curious if you could give a little bit more color on the December, you mentioned like potentially pull forward from January. And then just because the $41 million to $46 million range, I think, is not too much incremental growth on what you reported this quarter. So curious how much you think might be pull forward and why?

Yes. I think -- so there's a few reasons why we're being cautious on January. One, we've heard that January generally is a tough -- well, for the quarter, but January, particularly is a tough time with insurance policies, people changing their insurance. So we have that factor. We have heard, but again, I don't know if it's anecdotal that some patients accelerated their infusions at the end of the year so that they could get it under the -- their deductible that they will get reset in January. So you have that factor. And yes, it did appear, although we don't -- it's hard for us to really tell, but it did appear that the distributors went to a few more days of inventory, it's not like we're talking about a ton of extra inventory, but maybe they've added a few days of inventory at the end, but it's hard to really know for sure. So again, I think being cautious, I think with those several factors coming together, I think that's probably where we came out with the guidance.

Sticking with first quarter guidance. Any anticipated fluctuation in gross to net. And just sort of how do you think about where gross -- I guess the range in which gross to net should trend over the course of '24?

Yes. Again, I think also the gross to net is usually lower in the first quarter. Again, higher copay obligations that we support also add into that. So I think there's probably some of that going into the projection as well of lower co-pay. I mean a lower gross to net, which probably rebounds somewhat after that and then -- but the trend over the long term is going to be a lower gross to net over time. But yes, the first quarter seems to be also a place where you see a lower gross to net that you expect the rest of the year.