All right. Hello, everyone. Welcome to day one of Cantor Global Healthcare Conference. My name is Prakhar Agrawal. I am a biotech analyst at Cantor, and for the next session, we are very excited to host the team of TG Therapeutics. Representing TG, we have Mike Weiss, Chairman, President, and Chief Executive Officer. Mike, thanks for coming to our conference.
Thanks, Prakhar. Appreciate it.
Maybe we can start off with an overview of the current state of the business, key priorities for the company over the next one to two years.
Sure
A lot is going on in TG right now, so maybe you can level-set expectations before we move on to the specifics.
Yeah, sure. Thank you. Thanks for the opportunity. At TG, we like to keep things relatively simple. We're starting to create a little more noise in some other areas, but it's a relatively simple story. We've got our BRIUMVI approved for relapsing forms of MS. We'll be entering, I think we're just about, I think in February, we'll finish our fourth full year of sales. Currently, we are tracking, as we've said in our last quarter conference call, we're tracking toward a $1 billion run rate before the end of the year. Everything is going quite well there. Then we've got a bunch of clinical programs, which I'm sure we'll touch on, so I'm not going to get into too much depth. Then some critical things over the next few years. Step one for us is always and continuing to build the commercial franchise.
We continue to always add strategically positions when necessary. We're continuing to build our marketing effort, particularly around patient engagement. We do think it's an important part of the process. There's a lot of what is referred to as joint decision-making in MS, and so really making sure that patients are aware of BRIUMVI is important, so we're spending a good amount of effort there. Then we have our two probably most near-term clinical initiatives. One is the acceleration of the onboarding onto BRIUMVI IV. Part of our ENHANCE trial, we studied consolidating doses one and two into one dose to simplify the onboarding for BRIUMVI. That's something we hope to have available in the marketplace sometime in 2027. Then probably the even bigger opportunity is our subQ Phase III data expected late this year or early next year.
That'll open up an entirely new market, which again, I'm sure we'll touch on, so I won't go too deeply into that. Then beyond that, we have a few additional programs. We've got a program in MG, schizophrenia. We've got a CAR T that's looking at MS, MG, CIDP, and a few other indications.
Okay. Maybe you can start with the market right now, especially the IV market. Seems like Roche recently lowered their expectations for OCREVUS IV. They talked about competition. What are you seeing in the field? We're hearing that they might be pulling back some investment from the IV to focus on subQ. What's your take on the IV market right now?
Yeah. I think it's probably not a mystery that Roche is preparing for loss of exclusivity. They launched their current subQ offering, which is an in-office administration with a subQ into the belly. They've definitely pulled back support from what we're hearing in the field, pulled back support for the IV product. I think their goal is to get as many people. I think their goal, actually, I should say pretty definitively. They've publicly stated in an investment forum in, I think it was last November, very definitively stated their goal is to get everyone off of IV onto their current subQ offering, and as quickly as possible, move those people out of the office to an at-home product. I think everything they're doing is pretty consistent with that publicly stated position of theirs.
Okay. Should that not be a tailwind for BRIUMVI because you have so many physicians with infusion-capability centers who probably have financial incentives as well? What are you hearing in terms of feedback from that community and their use of BRIUMVI? Is that increasing?
Yeah. Anytime there's a disruption in the market like that, where people are trying to switch people, there's a new decision that's going to happen, and Roche has been, I think, unabashed about directly making contact with patients and encouraging them to ask their doctors about the subQ option, which then opens up a conversation. There is a lot of brand loyalty for better or for worse, better for us as we grow and continue to build our own brand loyalty. Most patients will, if they do end up switching off of IV, will end up on the subQ product. But to your point, yeah, once that conversation is open, we're going to gain patients from that effort. Yeah, I think we're seeing some of that today.
Okay. And seems like their subQ offering is doing a little bit better this year. Uptake is picking up even in the U.S. Thoughts on that product and implications for your subQ franchise as well as the drug gets approved?
Yeah. To my knowledge, the overall physician-administered product or the overall OCREVUS brand has not grown. Basically, they are transferring from one to the other. I think the overall brand is pretty stagnant.
Okay.
Yeah, they are making a strong effort, is what I am understanding, to get those people to switch over. Yeah, you are going to see an uptick in one and a little more challenge on the other side.
Okay. On the BTKs, because it has implications long-term as well. Novartis recently announced BTK data. We haven't seen the data yet, but it is positive in RMS. They have also talked about clean safety profile. What are you hearing in terms of the physician feedback on the BTK class as well, and just general impact of the CD20 drugs?
Yeah, I think the class as a whole, we haven't had any differential conversations with physicians that know anything more than what has been presented. We do not have any inside information on the data that they will present, but I am as excited as anyone to see it. But just in terms of clinician interest in the BTKs, I think there is a little bit of PTSD right now. They were super excited for the Sanofi product. Sanofi had done an amazing job of getting the patients engaged and aware, and they had this really great campaign on the smoldering MS and how BTKs were going to be the solution to that. The doctors talked to the patients, and the patients talked to the doctors. When that all came unraveled, I think that really put a dent on the interest level. Now, I do not think that matters.
If the product really does have a clean safety profile, and the efficacy is as represented, I think it will get used. I think it'll face certain challenges. It's an oral drug. It'll face challenges from what step throughs you have to go through from an oral class before you're allowed to use it. One of the biggest things that I don't know that everyone speaks about, but it is talked about quite significantly within the MS community, is compliance. Oral compliance in the MS community is historically low. You talk about a drug that's now going to be given twice a day to a group that's already pretty bad at taking their meds. I think there's going to be challenges. We'll see how it goes. But hopefully the data will be what they've represented, and it'll look great, and having another option for patients is always a good thing.
Okay. The recently updated guidance for full year for BRIUMVI implies a little bit modest sequential growth in 3Q and then pick up in 4Q. Typically see some seasonal slowdown in the MS market in 3Q. We're in September right now. How did that seasonality impact play out versus your internal expectations and your confidence on the guide?
Yeah. Our quarterly conference call I think is pretty well intact, what we talked about on that call. Again, the exciting part for us is really going to be Q4 and the exit velocity at a billion-dollar run rate. That's really where our focus is. No update from the call at this point.
Okay. You've talked about becoming the leading CD20 drug in the IV market. What's the dynamic share right now, and what gets you to the leading dynamic share over time?
Yeah. You know what? I got to get an update on exactly where we are on dynamic share. I don't have it offhand. The steps it'll take to get to number one, I think we just got to continue to do what we're doing. I think probably more than people realize, I think the simplified onboarding, the ENHANCE study where we're, like I said, taking that day one, day 15, and combining it, I think that's going to have a really positive impact and help us get closer and closer to our goal. The other side of it is, as I mentioned, there is brand loyalty. The more patients that go on BRIUMVI, you've heard me say this multiple times, the more patients will go over on BRIUMVI.
The more people that know about it, so that's part of the DTC campaign, that's part of just adding up the numbers. Once you have this accumulated mass, once we put all these pieces together, I'm pretty confident. The other side of it is, look, the one competitor is trying to pull out of the IV, as far as we could tell. They're trying to get everyone to the subQ and then to an at home. I think the combination of forces put us in a great position to take over the IV class. Just to be very clear, we've said this multiple times. I'll say it here very loud and clear. We are completely committed to the IV business despite our efforts to develop a subQ, which we'll talk about momentarily. We are completely committed long-term to the IV business.
Okay. On the ENHANCE trial and the simplified dosing regimen, seems like you've been a little bit more bullish on the impact from that in 2027 than historically. What's driving that change?
Yeah, I think, one, the data's in hand, which makes it easier to go out and talk to folks, and we've done some additional, both qualitative and quantitative market research. The numbers look pretty compelling.
Okay.
Yeah, I think that's what's been adding to our confidence in-
Okay. The expansion of direct-to-consumer initiatives in the second half of 2026, I know you started a little bit more niche, but what does this expansion entail?
Yeah. We did start with some experiments. We'd go into certain markets. We'd pick basically, I think somewhere between five and 10 markets to what we call heavy up on both linear and direct to TV, both online, and you just sort of do a real full-court press, I might say. The results are quite convincing. We're going to now, and we are in the process of rolling that out nationwide.
Okay.
Has anyone in N.Y. seen the commercial? Come on, not one person? I get calls from every friend telling me they've seen the commercial 100 times. No one watches anything on T.V.? Nothing? All right, we're going to try this again next time, but I can't believe it. Everyone in N.Y. has seen it, except for this group.
We need more streaming ads.
Okay. I progress.
I guess you've not provided peak sales guidance, but flagged it like BRIUMVI IV will be a multi-blockbuster product. It will be annualizing at $1 billion. Street estimates are sitting at $2 billion in peak sales for the IV franchise. Where does this fall in terms of your range of expectations for BRIUMVI IV peak sales?
Sounds pretty low. I do not know about you, but I think your model might be a little bit higher. I do not know where you are exactly, but that sounds low to me.
Okay. What about next year? You will be annualizing at $1 billion exiting in Q4, so street estimates are $1.2 billion for 2027. BRIUMVI is a pretty easy product to model now, given the number of patients who are on therapy and the long persistence, high persistence. How are you thinking about next year and your comfort level around 2027 estimates?
Yeah, so that is something that the modeling team refines on a pretty regular basis. Honestly, I am not privy to their refinements in a real-time, so I do not have any comments. I know that we are going to have, early next year, we will put out our number for 2027. I cannot give too much guidance there.
Okay. SubQ formulation. After the phase I data was-
I'm going to have to ask you for a favor. You have to call it subQ.
All right, subQ. subQ-
It's a big internal debate, subQ versus subcut.
What do you like?
I can't handle subQ. It just makes me a little bit subQ.
All right. subQ.
Just for this conversation, if you could.
Let's stick with subQ. The subQ BRIUMVI, after the phase I data was released, I thought street has become a lot more comfortable around the quarterly dosing, and your ability to get there. KESIMPTA is a monthly, but there are differences between the products as well, which I think is sort of underappreciated. So maybe just taking a step back and remind us about the differences between BRIUMVI and KESIMPTA at a molecular level, and obviously, you'll have the dosing convenience advantage, but what does it mean between the differences on the product profile?
Yeah. So one thing we haven't had to do, we spend a lot of time comparing ourselves to ocrelizumab, because that's in our marketplace today, our direct competitor has been ocrelizumab. We have not done any work publicly on the differentiation with ofatumumab, a molecule we know quite well from our days in oncology. It's not a molecule that's foreign to us at all. The one thing I'd say is, it makes for a really great setup for us particularly, but even just for people to think about, ofatumumab was specifically designed to enhance complement-dependent cytotoxicity. Ublituximab, BRIUMVI, was specifically designed to amplify ADCC. So you really have this concept of ADCC versus CDC almost in its purest form. We do have some CDC, and they do have some ADCC, but really, these molecules were designed for two different ways to amplify cell killing.
Biologically, there are differences. Now, one difference that, credit to the developers of subQ KESIMPTA, ofatumumab, as an IV agent in cancer, took a really long time to give, because ofatumumab will engage CDC, all these complement-dependent triggers for infusion-related reactions. You can ameliorate that by putting subQ. So kudos to the folks who figured that out. But that's just one example. The other is, when we think about deep tissue killing of B cells, CDC doesn't operate in deep tissue spaces. So again, you're talking about just two biologically different ways of killing B cells. So you think about it, you got the same target, but these agents may be as different of a CD20 competition as you could think about.
Our team is out working on all the different studies, both preclinically and clinically, that will help to magnify the differences between these two molecules, of course, over and above what we believe will be a convenience advantage.
Okay. Once we have the phase III data in hand, what steps could you take up to speed up the launch? Something like a priority review voucher in play to make sure that you get to the market fast, and especially with the OCREVUS LOE as well down the line.
Yeah, I think you've probably hit on probably one of the few ways in which you can accelerate the review timeline. I wouldn't rule it out. I think it's probably too early for us to say that we'd go out and spend the money on a PRV. But certainly, it's something that's certainly crossed my mind. But I think we'd get a little closer to try to figure that out.
Okay. subQ products typically do really well in ex-U.S. as well. Does your ex-U.S. partner, Neuraxpharm, they have the opt-in rights for this product as well? Are you able to disclose what are the opt-in rights?
Yeah. They do have an opt-in right. Once we present to them the opportunity, they have 90 days to opt into the program. It's probably somewhere in the order of a $40 million- $50 million upfront payment associated with that, plus share in cost of development on a proportional basis to the global opportunity.
Okay. How are you internally thinking about the peak sales for the subQ formulation? I know Street estimates are anywhere from $1 billion- $2 billion.
Sounds light also.
Sounds light.
Yeah. We haven't given any numbers out, but I think what I said on the conference call not that long ago, whether it was the last one or the one before that, I said we're approaching $1 billion in sales for BRIUMVI, and I thought we were multiples away from peak. I thought that the subQ opportunity was potentially more than double that. I think that sounds pretty light. I don't think people are appreciating the subQ opportunity just yet.
Right. When you were launching BRIUMVI, you had to build a brand, but now there is some brand awareness, so why shouldn't the subQ uptake be much faster given people are familiar with the brand so much?
I have no reason to believe it won't be faster.
Okay. The one key debate amongst investors is also on the impact of Ocrevus LOE. How does it change the market, and how do the biosimilars impact the IV market longer term? There's a volume piece to that, and there's a pricing piece to that.
How are you thinking about both attributes?
Yeah. The worry about ocrelizumab LOE has been something that I have to believe it's a small group of people have been worried about since launch. I think they thought it was a problem at $8. I guess they assume it's a problem at $55. I'm not sure what their aim is other than trying to lose money for themselves and their investors. But in terms of the opportunity after LOE, again, in MS particularly, maybe in other categories as well, there is a distrust for generics and biosimilars. There's been certain studies where they've looked at generics and found that they do not meet the same specifications despite the fact that they're supposed to. So I think there's a general mistrust within the community of biosimilars as well as generics. We talked earlier about when we're going to be number one.
We'll certainly be number one after LOE, right? Because I think any opportunity someone has to put them onto BRIUMVI at that point, they're going to take that opportunity. In terms of pricing and volume, again, I see volume increasing following loss of exclusivity. I know that one of the potential risks is pricing pressure. I think it's important for people to realize that a typical biosimilar will price in the 20%- 25% discount range from the innovator drug. BRIUMVI is already 20%- 25% discount to ocrelizumab. So if you want to get the interest of the payers, you're going to have to go another 20%- 25% below us. That's implying that a biosimilar is going to go in at a 50% discount to the brand. Still very unlikely they're going to get the insurers to step patients through biosimilar ocrelizumab to BRIUMVI.
All they'll be doing is destroying their own market. Their goal should be and will be to get every patient that's left on IV ocrelizumab, which may be very few. If Versus is successful, there'll be very few patients left on IV ocrelizumab. But their goal is to get every patient who's on IV ocrelizumab to go to the biosimilar and to get anyone who would normally go on to IV ocrelizumab to go onto the biosimilar. I think they're going to be hard pressed to get payers to cross-brand step through.
Okay. Got it. I did have questions on the pipeline, but one thing that is still very underappreciated is the IP for BRIUMVI. I think Street doesn't seem to be giving the IP any credit, I think a 2045 for patent expiration. But if you can elaborate on that patent and what are some of the strengths of that patent?
Yeah. So there's two patents. One is a 2042 that was issued, I think, last year, and one is a 2045, which is not yet issued.
Okay.
The 2042 is a composition of matter patent. One thing that needs to be fully understood is when you have an antibody, the process is the product. Remember that. The process is the product. That process evolves over the course of development. We were changing that process through the end of development, and we were able to bridge back through all those process changes to basically incorporate all of the data that came before it for the approval. That process changes over time. The final process and the final embodiment of that process was filed at the completion of our clinical program. That is what has been granted a patent to 2042. The protein sequence patent will expire in 2035.
The BRIUMVI patent, if you want a BRIUMVI biosimilar, you got to run through the 2042 patent, which includes not only the sequence but also the glycosylation pattern, which in this case is extremely important because it is a glycoengineered product, and the potency of this product is dependent, so the biological activity of this product is dependent on that glycosylation pattern. That pattern is part of the patent. You can't make BRIUMVI unless you go through the 2042 patent. I think it's pretty darn strong.
Okay, great. Maybe moving to the other pipeline indications for BRIUMVI. Very interesting indication of treatment resistant schizophrenia that you are testing. Maybe just talk about the rationale of why you decided to choose this indication. What evidence do we have?
Yeah. There is emerging evidence. I'm not going to be able to quote you the papers. There is probably someone in this room who can quote the papers. I'm not going to quote those papers. There's emerging evidence of an immune-mediated inflammation that is potentially a trigger for, and also compounding factor to, schizophrenia. Potentially also major depressive disorder. Epilepsy is possibly tied into this as well. There's a few interesting indications, but there appears to be this auto-inflammatory response. There is one disease that is particularly interesting, the Anti-NMDA receptor encephalitis, which again, is a completely different disease, but it shows you what the immune system can do to the brain. Part of that process is a psychosis similar to what you see with schizophrenia. We know that the immune system can create symptoms that look like schizophrenia.
There is a bunch of emerging evidence showing that there is this autoinflammation that is occurring at the time. There is also some very early, small numbers of patients with rituximab showing some pretty interesting results. We just thought it was an opportunity to take the lead in an area that is pretty cutting edge, but supported by some really intriguing science. Relatively small investment, but we think it could have a big impact and could bring us into an area that is definitely in need of much better treatment options.
Right. You have the phase II ongoing, that is open label. What are you hoping to see in terms of the efficacy there and what patient types will be included?
Yeah. So that study is set up almost like an oncology trial, right? We were looking for a particular symptomatic response. We have a sense of what potentially placebo response could look like in a treatment-resistant patient, fully medicated. It is relatively low, but it does happen. We know what that is. Then using basically a Fleming's two-stage design, we are able to basically look at what we believe a good drug would look like versus what a placebo would look like. If you stack up those two, you do it in two tranches, and if you meet the hurdles, the response rate hurdles, you can argue that you have an active agent. That is the design of that. It is a really good way to do an exploratory study. Any placebo design study would have to be large.
Again, it is just really challenging to do, and unless you are going to run, you might as well just run the phase III. This was the best study design we could come up with to get an early signal.
Got it. The myasthenia gravis indication is also interesting because you have a unique value proposition here in terms of BRIUMVI maintenance after VYVGART induction. Explain to us why wouldn't just patients go through a VYVGART induction and maintenance, which is happening a lot in the real world right now, versus going on BRIUMVI maintenance, and how are you convinced that BRIUMVI is having the similar efficacy as VYVGART in the maintenance setting?
Yeah. The thesis around the study, for those of you guys who aren't aware, is using FcRn therapy in patients with myasthenia gravis to induce a rapid response. Anyone who has looked at or anyone who will look at the data will see that the responses to those agents are really rapid. It's really quite amazing how quickly they can get to a response. But to keep the response, you have to keep them on the agents, or the way they're currently dosed in MG is cycling. So you give them a dose for four weeks, you see the symptoms go way down, and then you release, you stop treating, and then over the next eight weeks or so, you see symptoms return.
The idea of our program is by removing the B cells, which are ultimately the source of the antibodies, you can basically cut it off at the source, but you want to get rid of the offending antibodies first, right? So it's really an elegant way to sweep those antibodies and then cut off the source. Then you can do something which is not a weekly treatment or maybe every other week is coming, but you can do this either quarterly subQ or semi-annually with an IV product. So we think there's a real opportunity to decrease the patient treatment burden, but also simplify the treatment to make sure that they don't have to have symptomatic return and then have these cycles. They feel good, they feel like crap, they feel good, they feel like crap.
This is a way to hopefully smooth that out, get them down quickly, and keep them down for a period of time. I don't think it's something that should be too challenging for patients who are going through this cycle of feeling great, feeling crappy, feeling great, feeling crappy, to get them to try something that will give them some duration response. Again, there is an approved CD19 product that when you look at the data too, it takes a while to get it flat, but then you see a nice symptomatic relief. So you put those two pieces together is what we're trying to do. But with that approved product, I think that should be also comforting to patients that they're not taking something that's completely experimental.
This drug is, but the concept of using CD19, CD20 is not completely experimental in MG, and of course, rituximab has been used for years.
That readout is in 2027?
Say that again?
That readout will happen in 2027?
That I cannot promise. I don't have the timelines yet there.
All right. Great. Seems like a lot of interesting pipeline readouts to look forward to with the subQ readout later this year or early next year. Thanks, Mike. Really appreciate your time. Thanks everyone for listening in.
Thank you. Appreciate it. Thanks everybody.