Welcome to Miami, to our seventh annual healthcare conference. Right now, I have the pleasure of hosting TG Therapeutics. In attendance with us is Michael Weiss, CEO. Mike, welcome. Thanks so much for making time for us.
Thank you.
Yeah, a lot going on at TGTX. Before we delve into Q&A, we'd love to kind of get your opening comments and the business highlights that you want to emphasize.
Sure. Thanks. And again, thanks for hosting us. Yeah, I mean, look, TG, we started the company in 2012 around the concept of B-cell diseases and B-cell therapy. We're one of the, I think, only companies that's been focused in this area for that amount of time. What we're starting to see, not just in MS and in cancer, but very broadly, that B-cell diseases and B-cells play a critical role in a lot of autoimmune diseases. So I think we're in a really good position from that standpoint. We have our first drug approved for multiple sclerosis. I know we're going to talk a lot about BRIUMVI momentarily.
We've got a nice pipeline coming together, both in what we're doing with BRIUMVI in terms of life cycle management and moving into SubQ, but also with a CAR-T that we have, allogeneic CAR-T, which, again, I know we'll probably touch on at some point. But the business has been going great. The reception to BRIUMVI in the marketplace has been, I believe, overwhelmingly positive and has been better than our expectations. So we've been really pleased with the reception.
Got it. Excellent. Excellent. So yeah, I'd like to just delve into the commercial performance of BRIUMVI, the BRIUMVI launch. So far, you've raised guidance significantly, I think over about $60 million at the midpoint since your initial guidance in February. Hospital prescriptions per your 3Q call now account for the majority of volume, and incremental prescribers have remained pretty steady during the past 12 months. So now, I guess where I'm going with this is now that you've attained significant breadth of adoption, maybe could you comment on the depth of prescribing within these institutions? Is it simply because you've expanded the size of your sales force, or is there something more going on there that's not as obvious?
Yeah, I mean, I'll touch on first, you know, the fact that we raised guidance, you know, over $60 million for the first year. I mean, to be fair, we didn't have a lot of data to go on, and everyone was clamoring for some level of information. So we try to be relatively conservative. And I think we, as a general policy, our guidance, we try to be conservative on the downside with some room on the upside. But always when we do our guidance, we do feel that the midpoint of any range is the most likely outcome if you look at like a normal distribution curve. So, you know, I think we had an excellent year in terms of raising, beating and raising.
And then to your more specific question about where we are, you know, there are plenty more hospitals and community centers that have not adopted BRIUMVI. So there's plenty of breadth to go, and we've seen a nice cadence. That cadence should be slowing to your point. I mean, you know, we've hit probably the major ones that we wanted to hit, and we're continuing to grow. But there's a large world out there, and there's more to come. So I think there's more to go on breadth. And then the depth opportunity is even greater, right? So when you think about, particularly the academic centers, you've got, it could be anywhere from five to 15 or 20 providers at any of these major centers. And we're probably just scratching the surface at each one with maybe one or two really committed prescribers.
So yeah, we've got plenty of room to grow both in breadth, but certainly in depth in a lot of these centers.
Got it. So the key thing is that there still are many more centers to kind of tap into?
Yeah, there's still plenty more centers to go. We're not there yet.
I hear you. Okay. Also, on the 3Q call, you mentioned that, you know, while new start patients still represent the majority of prescription volume versus patients on maintenance therapy, you said that pretty soon you expect this to invert as repeat patient volume can continue to stack. So I'm trying to kind of reconcile that comment with comments you made where you said that new patient starts could continue to accelerate into 2025, and that volume could potentially inflect once a critical mass is reached.
Yeah, so I mean, both can be true, right? So as we keep stacking patients year-over-year, there comes a point where, you know, you've got this accumulation effect so that the new patients in are just the tip of the iceberg, but that group could still be accelerating in market share. It still will be the smaller portion of the overall pool of patients. But yeah, I mean, in terms of acceleration, you know, we've continued to see nice growth in new starts. Our goal has been, continues to be, to be the number one prescribed anti-CD20 by dynamic market share. You know, we've estimated we're around 15% today. Again, it's not a clear number. We don't know the denominator that well, and even the numerator has some flaws to it. But let's assume we're in that range.
You know, we've got a lot more to go to get to our goal. So yeah, I think we're going to continue to grind forward. And yeah, do I think that the growth rate can accelerate? I think it will accelerate. There's some quarters where it won't accelerate. We've seen this with KESIMPTA. I've got the curves. I keep them on my wall, the big picture of the KESIMPTA curve over the first three years of their launch. It was periods of growth, then flat, then growth, then flat, and then they stopped reporting. So I'm not really sure what happened after that. But I think we'll continue to see points where we have greater acceleration than we saw in the last, you know, from Q2 to Q3. As we mentioned on the call, we did see nice acceleration in growth between September to October.
So yeah, I think things are, you know, as we expected, as we're coming into the end of the year. And like I said, we've got lots of room to build breadth, depth, and gain the market share we're looking for.
Got it. And over the course of this past year, Mike, a question always comes up in the call, okay, where do these patients come from? What's the breakdown of these patients? Are they in terms of new to CD20, switches from other CD20s, or newly diagnosed? Has that remained or does that continue to remain fairly constant, or have you noticed a shift as of late in those dynamics?
Yeah, it's remained remarkably constant.
Yeah.
Yeah, within a few percentage points of where we started, I think we're still the same general location.
Got it. Got it. Along the same lines, any update on the six-month drop-off rate? Is it still around 15%?
Yeah, we've never given specific guidance on our, that's the number that we've been using. We're still collecting that information, and we think that's a good number. I mean, that's the number that OCREVUS has presented previously. We kind of expected that for ourselves, and we kind of feel like that's a pretty good number.
Okay. Okay. And any foreseeable change? I know you haven't provided any 2025 guidance, but could we expect gross to net to remain reasonably stable?
I mean, it has remained reasonably stable during the course of the year. I think expectation is we'll probably go down a little bit next year, but over the course of the year, it probably will be stable.
Got it. And will you resume providing quarterly guidance? I know you kind of stopped, I think mid-year doing that.
Yeah, because we got to the point where it was only two quarters left, and we gave a year-end number, so we figured being too specific on the quarters didn't really add that much information. Yeah, I think the goal will be if we can develop a pattern maybe early in the year, we'll provide the quarters, and then by the time we get to the second half of the year, we'll just provide what we think is the best year-end number.
Got it. Got it. Okay. Just kind of pivoting to the SubQ formulation, obviously you said there's a phase I bioequivalence study ongoing right now. You said that an update is coming early next year. Begging a lot of questions, like how will it come? Will it come in the form of just a press release or by a general top line and then more detailed data at a medical meeting? How will that come?
Yeah, so the plan, which I probably should have been more clear on the last call, was that we were going to provide an update on whether and how we were moving forward early in the year. And then the idea would be to provide specific data probably later in the year.
Later in the year.
Yeah. So again, I think as we've stated previously, our goal is to create a SubQ formulation that can be given in an auto- injector at least every other month. And, you know, we are still collecting information at this point. We'll be collecting it early next year and beyond, but I think we'll be in a position early in the year to state whether we feel comfortable that we're going to be moving forward and whether we still feel comfortable that we're targeting a pivotal trial in the middle of the year.
Okay, so early next year, it'll be more of kind of a go, no-go call with data later on, probably in the year.
Yeah, exactly.
Got it. And I know you kind of get constantly answered this question. I know the dosing duration, the dosing frequency of this SubQ, you mentioned that at a minimum you want every other month. But if you can get longer than that, that'd be great. And any updates on that front? I mean, it's, you know, just any thoughts there?
No, we haven't provided any more information. Again, like I said, we've got lots of data coming in even as we speak to evaluate that. And yeah, sure, aspirationally, we'd like to do even better than every other month. But we do think every other month would be a fine product, assuming it comes in an auto-injector format that's, you know, easy to maneuver for patients.
Got it. And does TGTX intend to formulate this in-house, or will you partner with a drug delivery company, a third-party type of?
Yeah, so we're doing this all in-house.
All in-house. Okay.
Yeah. So we've done it ourselves, and we feel very good about where we are.
Got it. Hypothetical question. I mean, if partnering meant the ability to dose even longer, like every three to four months, would you reconsider, or?
I mean, we've looked at all the technologies that are out there. There are some that are interesting. Yeah, I think we'd, I think as a next level, if we thought, you know, depending, I guess let's see where we land. Let's step one, let's see where we land, and then we could then assess whether we think a longer duration using someone else's technology would be of benefit. But I guess it's hard for me to say, not knowing exactly where we'll land, and, you know, I think we need to do more research on what duration would make a difference.
Got it. While we're on the topic of SubQ formulations, Novartis, at their recent, I think, investor day, increased their peak sales guidance for KESIMPTA by 50% from $4 billion to $6 billion.
Pretty good.
So in light of this, I mean, what are your thoughts on the peak, number one, the peak potential market share of the SubQ segment and also potential sales of your formulation?
Yeah, so they're carrying probably about 30%, 35% of the dynamic share today. I assume within those numbers, they're expecting to grow their portion of dynamic share. So I'm certainly not going to argue with them. So we'll see how it works out. But yeah, we'll be prepared. The good news is we'll be the only company that really has a true IV and a true at-home auto-injector SubQ. With the proviso that, you know, I'll let you know in January if we're there. But assuming we do that, we'll be able to be on both sides of that market. So if that side of the market's growing, that's fantastic. We do see, look, there is a trend within the academic centers to use more SubQ than previously. So I assume that they have done their research and their expectations are probably accurate.
But again, I don't know for sure.
I see. I see. Before we move on to the other assets, I mean, I want to just touch upon manufacturing real quick. You announced that you'll be proceeding with a new manufacturing plant with Fuji. Will this be dedicated to IV only, or will it also be able to manufacture the SubQ formulation in the future?
No. Yeah, it will be able to provide material for both the IV and the SubQ at some point if we choose to. Again, I think we'll have our ability to decide how we pull the materials from either place and use it in different settings. But yes, if we choose to, we should, assuming, again, we get it up and running and everything works out, it would be available for SubQ as well.
Okay. Is the plant U.S.-based?
The plant is U.S.-based.
When could we expect it to be operational and up and running?
Yeah, it's going to take a few years.
A few years.
Yeah. Yeah. These things don't happen. You know, first year is all about tech transfer, then the next year, I mean, I think by the following year, we will be doing batches that could be used, right? They'll be used for validating the process, but also could potentially be used. So we could have some of that material coming in relatively or being available into our inventory. But it's a two to three-year process. These things don't happen overnight.
Got it. Okay. Just want to pivot now to azer-cel. Obviously, maybe just remind folks, amidst all of the CD19 assets out there, it's becoming arguably somewhat crowded in the immunology space. Why you chose this one and how could it potentially be best in class?
Yeah, so we have been excited about CAR-Ts in the area for some time. We got to spend a lot of time on the oncology side for those who remember the history of the company. So spent a lot of time. We did get to observe, you know, how the CAR-Ts operated and worked and how they changed the treatment paradigm over and above what you'd get from a CD20 or a CD19. So we think bringing it across to autoimmune clearly makes sense. And of course, there's been early data that's been exciting, not with our compound, but with other compounds. So we think that there's a real opportunity. There's so many different indications. So some of this is going to be which indications you choose. Obviously, we're starting with MS.
Obviously, it's something that we've got a pretty good, strong understanding of, and we've got a nice platform for it. The molecule itself, we got excited about it primarily because it was allogeneic. I think that was the key and CD19 focused, not to differentiate from CD20, but to differentiate from, you know, some other BCMA or whatever. So, but we do like the focus in CD19, CD20. We like the allogeneic aspects of this. You know, what you're sacrificing for allogeneic is potentially durability of response, right? If you look at cancer, the knock on the allogeneics versus the autos is that they don't have the durability, right? They don't stick around long enough, and you may get upfront responses, but you can't hold and maintain those responses. So that's been the knock.
If you think about that profile, that is the precise profile you'd want for a CAR-T in autoimmune diseases. You want a big upfront hit, and then you want it to go away, right? So the difference here, again, for us, we like the allogeneic because if we can get the big upfront hit, this one particularly, we've seen complete responses in cancer, so in patients with diffuse large B-cell. I mean, these are very aggressive, hard-to-treat patients. They've got an oncogenic driver of repopulation of B-cells, which you don't see in healthy or in autoimmune patients, right, who have essentially normal-seeming B-cell populations, certainly in terms of size, not in terms of how they're acting. So yeah, I mean, could it be best in class? We think so.
Off the shelf, big hit upfront, goes away, repopulate your B- cells, hopefully you've reset the immune system, ideal profile.
Got it.
If it works.
No, definitely, and this is something I should have looked into, but I don't know off the top of my head. In terms of the B-cell kinetics, how would you say, if you know, how may compare to OCREVUS or other B-cell MS therapies right now?
Yeah. So presumably, you know, once you remove B- cells and you do it in a deep fashion, each person will repopulate at their own rate, right? The drug is gone, right? So now it's up to you, where are you, where are you to repopulate your B- cells? And everyone does it at their own pace. So I mean, if we look at both OCREVUS and you look at BRIUMVI, I think you're looking at approximately [audio distortion] so a little over a year or so on average to repopulate.
Yeah.
Pretty sure I'm quoting, don't quote me, but anyway, it takes some time. But some people will repopulate much earlier.
Yeah.
So yeah, but the faster you get the drug to go away after you've depleted the B- cells, then the body can start to do its thing in returning the B- cells.
I see. I see. Last question on azer-cel. Beyond MS, I mean, what would be the type of autoimmune indication that you'd like to pursue, assuming MS succeeds?
I bet you'd like to know that. Sorry. We actually haven't said yet, but there's a bunch of areas that are, I mean, we've alluded to areas that are nearby to MS.
Sure.
So things like potentially NMO, MG, CIDP, all, I would say that's more on the neuroinflammatory side. And then, I mean, a little bit further afoot for us would be sort of the lupus, RAs, myositis kind of stuff. So I think there's plenty of options for us, but we haven't actually decided yet.
I see. Jumping to share [audio distortion] share repurchase program early in the year. How should we think about the cadence of share repo going forward now that you're pretty much turning profitable pretty soon?
Yeah. I mean, it's a reasonably quarterly base set in and forget it kind of approach. We're not trying to get one spot price. I did this when I was running my hedge fund. Very rarely do I try to buy everything all at once or in fact sell. I mean, as we, you know, it's kind of the reverse of our ATM. You know, we were really not excited about doing spot deals when we were raising capital, and we feel the same way when we're rebuying shares. So we've got a steady approach that we're working with.
I see. Well, I think we're about time. Mike, thank you so much for spending time with us. Very helpful, and we wish you the best of luck going forward.