Good afternoon, everyone, and thank you for coming to the H.C. Wainwright 28th Annual Global Investment Conference. My name is Emily Bodnar, and I'm an Equity Research Analyst at H.C. Wainwright. I'll be doing a fireside chat with Mike Weiss, Chairman, President, and Chief Executive Officer of TG Therapeutics. Maybe to start, can you set up for us the current landscape in relapsing multiple sclerosis and where your commercial asset, BRIUMVI, fits into that landscape compared to other anti-CD20 antibodies?
Yeah, sure. Thanks, Emily. Good to see you. For relapsing MS, we estimate that there's approximately 40,000 new patients per year. Actually, let me double-check. That's for all MS, so RMS and PPMS?
PPMS.
RMS. RMS confirmed about 40,000 a year will go on to a CD20. That's any given year. About 65% will choose an IV option and about 35%, maybe it's 60%-65%, 30%-35%, so it's like 30%- 35% for a sub-Q option, and 65%- 70% for an IV option. Today, there's just one sub-Q option, so it's a market that we don't currently participate in. We participate and compete in the IV market, which includes both our IV product, another IV product, and I guess a sub-Q physician administered sub-Q, which we consider to be, since it's a physician and office based, we view that as part of that competition.
Right now, I don't have the exact numbers, but we've been tracking over 1/3 and growing of the IV portion of the market. So things have been going quite well. We will complete our fourth year of on market as of, I guess, February 1. So, I think we've done an incredible job of breaking into a very competitive marketplace. I think that's probably the RMS market, just generally speaking. That's probably a good start there.
Yeah. BRIUMVI obviously has done very well. You've kind of beat your guidance pretty consistently. In 2Q, you updated your guidance to $890 million to $905 million. What metrics are you kind of estimating to go in that, and is there a bit of conservatism in that guidance?
In terms of the metrics that go into our projections, probably the two biggest will be new patient starts and persistence. What's interesting over time, persistence becomes probably the biggest variable, because we estimate from a competitor product that the median on CD20 is about five years. Right? So after a number of years, what you notice is that the repeat business becomes a bigger portion of every quarter. Right? So only a smaller portion is going to be based on those new starts. So persistence and new starts, those are the two biggest variables that we look at. Gross to net changes, so mix of business will have an impact.
Remember, again, as that GTN goes across a bigger installed base, and repeat business changes, GTN can have some material impacts. They are, just to be very clear, GTN does fluctuate quarter- to- quarter. That will have some impact, and there's just natural variables that change that GTN on a quarter-by-quarter basis. Those are probably the biggest three. There's a few other variables that will go into it, but I'd say those are the biggest three.
Okay. Maybe walk us through the second half of the year, how we should be thinking about revenues, any seasonality or gross net expectations for the remainder of the year?
Yeah. The nice part, the second half of the year does benefit from improving gross to net. The first quarter, if you talk about seasonality, there's seasonality in both gross to net. There's seasonality in terms of those 40,000 dynamic share patients. One is the first quarter of the year is usually the lowest GTN. Then it typically will sort of slowly climb during the course of the year. You get a little bit of a tailwind from GTN changes. Whereas you also have in the summer, you probably have the lowest portion of that 40,000, right? It's not linear, it's not 10,000, 10,000, 10,000, 10,000. Every quarter's slightly different, and certainly the third quarter is going to be the one that has the smallest dynamic market available.
But again, you get some benefit from the GTN, so t hose things sort of hopefully balance each other out in some proportion, some way. As we've said, based on the call, we're looking for ending the fourth quarter with over a billion-dollar run rate, which is what we've really been focused on and targeting. We're pretty excited about that. That'll be a big milestone for the company.
Awesome. Maybe walk us through the dynamics of new patients going on BRIUMVI. Is it all newly diagnosed patients, or do you have patients who are switching from OCREVUS or KESIMPTA, and has that dynamic changed over the years?
Yeah. That's really interesting, and I do have some fresh information on that. It's not like it's not MNPI, but information. But we've recently did a new look and I had an original look that was six months into launch, and the pretty interesting part, two pieces that are interesting, one of which may be obvious, one of them may not be as obvious. The one that may be obvious is that the proportion of truly naive patients has grown over time. Right. You can imagine you launch a new drug, maybe the newly diagnosed patients are the ones you're not going to put it on immediately, and you'll put on sort of later stage patients. That proportion has grown over the last two and a half, three years since our first data.
The one that might be surprising is that the proportion of patients coming on from other CD20s has basically not changed. It has been very consistent, and in fact, at this point, almost these three groups are almost equivalent. I say three groups, and we only talked about two. One group is truly naive. The second group is coming from something other than a CD20, and then patients who come to us from another CD20. Those groups are essentially equivalent now. I think in the past, I've described them as a little bit imbalanced, pretty equal, but they're really much tighter today than they were. But like I said, the distribution has been more naive, which has outpaced from transfers from other treatments. But the CD20 switches have really maintained rock solid since we started, which is pretty amazing quarter- over- quarter.
Yeah. Walk us through how it's decided what therapy patients will go on within the anti-CD20 class. Is it more patient-driven, formulary-driven, physician-driven?
Yeah. It's definitely an area where shared decision-making is quite popular. Once the clinician decides that the CD20 class is right for the patient, pretty much the threshold question they will ask is, would you like to self-inject, or would you like to come in and get an infusion? Like I said earlier, about 30%, 35% are taking them up on the offer to self-inject, and the remainder will choose an IV. Once they choose an IV, then the clinicians will usually give them information about both of the IV products, and will typically send them home, give them some time to think about it, and when they come back, they have another conversation about which CD20 they'd like to go on.
Sure. As you're approaching that $1 billion sales mark likely next year, how are you thinking about peak revenues for BRIUMVI in the IV market? How do various dynamics like OCREVUS's patent expiring in 2028 and other factors play into that?
Yeah. I've said both on a conference call, not the last one, but the immediately prior one, I think I said it last week again. The way we're viewing, we haven't given a peak number out yet, and I think the team is probably reserving at least until we have all the pieces of the sub-Q put together. But for the moment, what we've said publicly is that we feel that the IV market is still at the early phases, that we believe it could be multiples of where it is today, and that the opportunity in sub-Q is at least as large, potentially even larger, than the IV opportunity. I think that sort of gives at least a little bit of a framework of what we're thinking about. True guidance is yet to be given. And then there was a second half of that question.
I think you answered it.
Okay. I'll go with that.
Okay. Maybe on the flip side, talk about the ex-U.S. commercialization, how that's been growing recently, and you have your partnership with Neuraxpharm. How has that been growing?
Yeah. They seem to be doing quite well. I think they're doing as well as we would've expected, if not better. Again, it's probably a more challenging market than we sit in here. I think we give them a little credit in terms of how well they've done in that marketplace. Sub-Q there is, I think, by category is the largest contributor. Whereas here it's 30%, 35%, there I believe it's above 50% of dynamic share. Again, given those kinds of dynamics, I think they're doing a nice job.
Mm-hmm. You recently had data from your enhanced trial, which was looking to combine the first two doses into a single dose. How are you thinking about practical benefits with that shift in administration, and how do you think that that could play into growth in the IV market?
Yeah. That's interesting. When we started that program, we definitely wanted to, obviously, make it a little easier to get onto BRIUMVI. I don't think there's any surprise what we were thinking. I think what's different than what we originally had thought was the impact. We've done both what I describe as qualitative research, so discussions with clinicians, but also quantitative research. Both of those have surprised us in the potential impact that this change could have. I think people are really much more enthusiastic than we originally had anticipated.
Both from the patient side, the clinicians believe, obviously, that bringing them back twice in the first two weeks is fine, but if you don't have to, it's much better. Then from the practice, we've always heard this comment from the practices that they're playing Tetris, trying to schedule the two visits and fitting them both in. When they heard that we were consolidating the dose, they just seemed to get really excited about that's going to just simplify everything. Yeah, we're pretty excited about it. We think it's going to have a nice impact on our growth in 2027.
Mm-hmm. Maybe just touch on where you are with getting that supplemental BLA update for that trial and timing.
Yeah. I think we're working very hard. It should be imminent.
Okay. You're also, as you mentioned, developing a subcutaneous formulation of BRIUMVI, which you recently shared phase I data for. Maybe talk to us about what you saw in the phase I with exposure and bioavailability, and how that gets you confident with the phase III coming up.
Yeah. So obviously we're very excited about that sub-Q. I think we've been pretty vocal about it more recently, especially since we put out that information. So just circling back, so threshold question is do you want to self-inject or not self-inject? And about 30%, 35% of the market were not participating in, so we do see this as a material increase in market potential for BRIUMVI. The data that we presented was phase I, but it's not a small data set. This is bioavailability information. I think we had approximately 90 subjects that were in that study. They're all MS patients. Actually, some were MG patients as well. And we basically demonstrated that it's a little over 60% bioavailability. The confidence interval is relatively tight with 90 patients. So, we're feeling good about that. So again, it should be reasonably straightforward from here.
We've talked about our sub-Q injection, which is basically a concentration of 200 mg per mL. We're delivering basically in 400 mg mL, so 2 mLs, 400 mg. We're dosing two schedules. When we first started, admittedly, the bioavailability looked a little bit lower in the earlier patients, and we designed the phase III with the utmost caution. So we have a group that's getting dosed every other month and a group that's getting dosed every three months. Based on the bioavailability information that we have from the phase I, the modeled result for the phase III would be about, I think, a 1.23. Which, just to give you a sense, if you have a one, it means that the concentration measured by area under the curve is exactly the same for the two. The FDA standard is 0.8- 1.25.
Particularly in these cases, it's the bottom, it's a non-inferiority, so you can't go below 0.8. I think ours comes in about a 1.23, so we're in a very good position. That's with the quarterly. I could say with the every other month, it's higher than that. Many drugs, particularly antibodies, they will go well over, because there's typically not a dose response for toxicity, or for activity for that matter. Pretty much you hit a threshold for both, and the more antibody you add, you don't really see much additional benefit or safety concerns, so most people do go over the top. But we should be pretty darn tight in that range, so we're feeling really good about it, and that data should be available end of this year or early next year.
Based on what you just said with the every three month dosing, how do you think that stacks up competitively versus KESIMPTA and also OCREVUS, which is also developing a similar kind of on-body administration, which they spoke about?
It's hard for you to say without laughing, so I get that. Anyway, how do I think we compete? I think an auto-injector pen that delivers in approximately 10 seconds every three months is a highly attractive proposition for patients. I think that KESIMPTA's currently at once a month. I know they're trying to improve that to every other month, so we'll see how successful they are with that program. But I think every three months auto-injector is a very attractive profile.
Yes, we are aware that the competitive IV product, which is now also given as a sub-Q in the office, has plans to try to convert every single one of those patients from the office sub-Q to an on-body injector at home. All we know is it should be every six months is what their plan, and we've heard that the volume will be lower, but right now their volume is, I think, 23 mLs. It's unclear how much lower they're going to go, but that's a pretty hefty sub-Q compartment.
Okay. I'm going to ask this only because we get a ton of questions about it, but do you feel like the oral BTK inhibitors will have any impact on the anti-CD20 market? Or is that going to be a separate segment of the market?Rituxan
Yeah. I think the answer is minimal. I think it's primarily a separate market. There's always going to be some bleed over, but I think generally speaking, about 35%. When we talk about the dynamic share, which I didn't give the percentage, but right now CD20s I think represent about 50%, 55% of the dynamic share. So a new patient, a patient starting a new therapy, whether they're naive or coming from something else, about 35% of those will go onto an oral, right? 50%, 55% will go onto CD20, 35% onto an oral, and then the remainder, most of those go onto TYSABRI, but there are still a portion of patients that go onto platform drugs, which I find pretty insane, but it happens apparently out there.
Anyway, so in that 35%, I think, there is an opportunity for a novel oral therapy that can provide good control of the disease. So I think, it has its own set of challenges, right? It's twice a day. It's in a highly genericized marketplace, so how it breaks in is yet to be determined. But I do think there's room for a novel therapy there.
Yep. Makes sense. Maybe for our last couple minutes, you also have trials ongoing for other indications like myasthenia gravis, and you recently announced the treatment-resistant schizophrenia trial. Maybe just touch a bit on those and how CD20 plays a role in those diseases.
Yeah. So with one of the diseases, CD20/CD19 is a pretty well-validated treatment option. I think what we're trying to contribute to that area is potentially a new paradigm of how you treat those patients. Today, one of the major treatments is using anti-FcRn therapy, and they're basically pulsed treatment. You get a weekly injection for four weeks, or one of them I think is six weeks, and then you stop, you wait for the symptoms to return, and you retreat. So they have very rapid symptom relief, but then you wait for them to relapse, and we think that a more interesting way to approach the disease would be not to put people through those continuous cycles of also weekly treatment, or every other week, and potentially I think they're working on, but this would be you'd give them four weeks of FcRn therapy.
You'd get them into a symptomatic remission, let's call it, and then you'd hold it there using BRIUMVI probably quarterly with sub-Q. So that is something we think is really interesting, and not only if it works here, there's other diseases where you could import that too, and so we think that's a treatment modality that can be used in other areas. Then schizophrenia is one that's no real proof. There's a small group of patients that were treated with Rituxan with good results. But the biology is, I don't want to say screaming, but certainly pointing in the direction of a neuroinflammatory component to schizophrenia and a number of other mental health disorders. Again, we think that if we can prove that you can dampen that neuroinflammation and improve symptoms for patients with schizophrenia, that could be translated to other mental health diseases as well.
We think both of those have really both direct impacts on the current diseases, but also broader implications.
Great. Maybe to close out, if you can kind of give us a summary of upcoming catalysts that we should be looking out for the next 12, 18 months.
Yeah. I think we've got a pretty catalyst-rich next 12- 18 months. First up will be, you asked about the supplemental BLA, so for our enhanced, our simplified dosing, probably before we have the phase III data for sub-Q, we should have some azer-cel data at ECTRIMS, then the pivotal phase III data for sub-Q, and then into 2027, hopefully launching of the enhance protocol. Along the way, I'm assuming we'll have some schizophrenia information, hopefully sometime in 2027. Then that'll lead us into the 2028 approval of sub-Q.
Great. Thank you, Mike. Thanks everyone who's been listening in. Hope everyone has a great rest of their day.
Thank you.