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

Okay. Good morning. Thanks for joining us for the 40th Annual JPMorgan Healthcare Conference. I'm Eric Joseph, Senior Biotech Analyst with the firm. Our next presenting company is TG Therapeutics, and it's my pleasure to welcome CEO, Mike Weiss, to talk to us a little about the company. There is a Q&A session after the presentation. [Operator Instructions] With that, Mike, thanks for joining us.

Thanks, Eric. Really appreciate it. Thanks for having me. I guess you said the 40th Annual. I guess I'm not as old as I thought. I think I'm on my 20-something JPMorgan conference. But really pleased to be here. Hopefully, next year, we'll get to do this live. Finally, I made it off of Wednesday, Thursday and unfortunately, it's virtual, but we'll get there. So thanks again for having us. Next slide, please. So just on the Slide 2. I will be making some forward-looking statements. So for those of you who are interested in TG, I do recommend that you please take a look at our public disclosure documents and risk factors available on the Internet. Next slide, please. Great. So just by way of background, TG, we're a company committed to developing treatment options for patients with B-cell diseases. On the cancer side, that's diseases like marginal zone lymphoma, follicular lymphoma and on chronic lymphocytic leukemia. And on the autoimmune side, we're currently focused in multiple sclerosis, but there's a number of other autoimmune-related B-cell diseases that we hope to target in the future. Next slide, please. We've put together what I think is a really nice portfolio of complementary compounds. Each of these can be used on their own, and each can also be used in combination with each other and with standard of care treatments. Our lead molecule is UKONIQ. The generic name is umbralisib and the brand name is UKONIQ. This is a very novel PI3K delta CK1 epsilon inhibitor. This compound was approved earlier last year for patients with relapsed/refractory marginal zone and follicular lymphoma. We also have ublituximab, which is our glycoengineered anti-CD20 monoclonal antibody. This compound has completed successfully a Phase III trial as a single agent for patients with relapsing forms of multiple sclerosis. And the BLA for that compound is on file as well. And then you can see the U2 insignia. We have the combination of ublituximab and UKONIQ. We have run a successful Phase III trial in chronic lymphocytic leukemia for that combination, and we'll talk more about that, but that is also on file with the FDA. And then like I mentioned, we have a portfolio of compounds. We'll talk about those just a little bit toward the end of the presentation. So next Slide, 5. So let's begin with a little chat about UKONIQ, our first marketed drug, and this is the first and only targeted kinase inhibitor for PI3K delta and CK1 Epsilon. Next Slide, 6. So it is approved now for adult patients with relapsed/refractory marginal zone lymphoma, who have received at least one prior anti-CD20 base regimen and also for patients who have relapsed/refractory follicular lymphoma were received at least 3 prior lines of systemic therapy. These approvals are accelerated approvals and do require an additional clinical trial to confirm the clinical benefit. Next slide, please. So just working off the approved label. On the right-hand side of this slide, you can see the efficacy of UKONIQ and marginal zone and follicular lymphoma. So about 50% of the patients with marginal zone lymphoma will respond to this compound in a clinical trial sense, but more patients will have benefit. And similarly, for follicular lymphoma, about 43% of the patients will have a true response. Actually, we've now updated that number in the literature, not on the label, in the literature it's about 45%. But what's really nice is that about 80-plus percent in both marginal and follicular will have some clinical benefit in terms of disease control. So in the clinical setting, they won't be counted as responders, but in a commercial setting, most patients, almost all the patients should see some benefit from taking this compound. On the left-hand panel, we talk about some safety for the compounds, some SAEs, about 18% of the patients had SAEs, which again, I think is important to note. On the next slide, Slide 8. So when we typically look at the overall safety profile of UKONIQ, we really kind of resort to the patients who discontinued due to AEs. It's kind of like a catch-all for patients who just don't tolerate the drug. So they have -- you may have AEs and SAEs, but if you can tolerate -- if you can get through and stand the drug, seemingly, we think that that works out, and we have on the other side, you can see dose reductions and interruptions. About 14% of the patients came up drug for tolerability issues, which we think is pretty good and relatively in line with drugs for this class. Well, not drugs in this class, drugs for treatment of these diseases for drugs with the class of PI3K, you're going to see significantly higher rates of discontinuation due to AEs. Next, Slide 9. So we were super excited to be able to launch UKONIQ this year for patients with marginal zone and follicular lymphoma. We fully recognize that marginal zone and fourth-line follicular are not the largest indications. And so in terms of revenue potential, there's some limitations. Although we do think there's an interesting market opportunity there, we do think in times of COVID, that that is even more challenging. I'll discuss that briefly. But I think in terms of the goals for the year, we really had 3 primary goals for the UKONIQ launch. One was building awareness of UKONIQ's differentiated profile. So again, we try to compare UKONIQ to other treatments for the disease is not necessarily for drugs that fit in the class of PI3K. When you look at other PI3Ks, we think that UKONIQ has really changed the profile of this class with a much better safety and tolerability overall profile. So we wanted to get that profile out to the physicians because there is some negative perception of PI3Ks. And we were pleased with the effort. And based on our market research, about 80% of our target customers are aware of UKONIQ. And again, that's nice because our target customers for UKONIQ as a single agent in marginal zone and follicular has about an 80% overlap with potential customers for chronic lymphocytic leukemia and the potential for U2 in that area. So again, all the efforts that we're putting in to get people to understand UKONIQ in that marketplace, we expect would pay dividends for us going forward. So step one is building awareness of the differentiated profile, just making sure people understand that this is a different PI3K compound. Next is, of course, to drive adoption. So this is the part, again, we just want people to try the product, right? Step one is to try the product, hopefully have a really good experience. Again, with 14% patients dropping out for AEs, you don't expect everybody to have a good experience, but the vast majority of folks are going to have a good experience. So we wanted to get as many people to try the drug as possible. And I think the team did a nice job again under the circumstances. COVID, everyone has talked about, every company has talked about it. I think particularly in chronic diseases, what we've seen is the access to talk to the doctors about these patients, and this disease has been challenging, and the patients have been challenged to come in and get treated. And what we've seen, I think most research has shown that many of the patients have not been going in as frequently to get treated or diagnosed. So the number of newly treated patients is down and treated patients is down. So that's obviously for everybody, and we're seeing, I think, some consequence of that. But net-net, I think we will be able to get out there and get lots of folks to try the drug. I think in terms of revenues for the year. I think we came in at about $6.5 million in revenues, which is not so bad, again, under the circumstances. And again, we've talked about this quite a bit over the course of the year. But I think we're giving away almost 40% of the drug for free for patients who can't afford their co-pays. So in the next segment, I'll talk about access, but we've had really good access. The team did a really phenomenal job in getting coverage. 90-plus says here, I think we're at 95% of Medicare commercial labs are covered, but that doesn't always equal that they're going to get the drug on their plan because they still are required to pay a pretty significant portion of the cost of the drug as a copay. So patients who can't afford the co-pay, even though they have coverage, we provide the drug to them for free. So if you think about $6.5 million in sales, you can almost gross that up by almost double to see what the actual demand was for the drug. So not terrible, nice year for getting started. But again, all of it has really been designed to help build toward the launch of U2 and CLL. So let's talk about that on Slide 10. So U2 was the subject of a successful Phase III trial, CLL Phase III trial. The trial enrolled patients with both frontline and relapsed/refractory CLL. And we were able to show a really nice improvement in progression-free survival. The efficacy was so good that the study was stopped early. We had a p-value of less than 0.001, and the study was conducted under a special protocol assessment. We took that positive study. We filed it for approval with the FDA as a BLA as a supplemental NDA for UKONIQ. The PDUFA goal date was set for March 25 of this year, so a little over 2 months from now. And then a few weeks ago, we did announce that the FDA came to us and said they'd like to review the overall risk benefit of this compound at an ODAC meeting to be scheduled. The initial guidance was sometime perhaps in March or April. We're still waiting for confirmation of the precise time frame. But I think we can probably, at this point, project that the target goal date will not be met in late March. And so we don't know exactly when that will occur. So all of our focus for this program right now is really on the ODAC meeting at preparing for that meeting. We did have a pretty lengthy call covering the subject a few weeks ago, so I'm not going to go too far into it. But again, I think the FDA is concerned about the overall risk-benefit profile of this compound in patients with CLL. Their concern surrounds the overall safety profile, whether it's in some way having an adverse effect on overall survival. That overall survival analysis was done as part of an information request from the FDA during the review process. It is a prespecified secondary endpoint, but was not part of the primary analysis. And when we ran under the physical analysis, when we ran the first look at this data, we preset the primary endpoint, of course, which was always PFS. And then a series of secondary endpoints that we were going to test sequentially. Overall survival was not part of the primary analysis in secondaries that we originally done, mostly because it was not powered to be tested, and it was pretty early in terms of information available. Nevertheless, we did run that analysis for the FDA, the best that we could at the time. There was clearly missing information, but we gave them everything that we had. And as it turns out, there was an imbalance in favor of the control arm in overall survival. Important to note that if you remove or censor the COVID deaths, that imbalance is almost completely eliminated. So there's a lot to think about here. Again, our goal is 100% to make sure that we are putting a safe and effective treatment out there for patients. And I know that's what the FDA is targeting as well. Unfortunately, we don't have perfect information. The overall survival are going to be underpowered and at an early time point is subject to lots of variability and noise. So we're -- I think the FDA and TG are doing our best. The one thing I can say, again, because we are so concerned about this, I mean, we literally have gone patient-by-patient every death on the trial in the U2 arm, we've gone patient-by-patient to determine whether there's reason to believe that the drug contributed to the death. And when we come out to the other side, it just doesn't appear to be a problem. I mean we've looked at and I encourage everyone to take a look at the labels and publications around ibrutinib, acalabrutinib, venetoclax, every drug is associated with some level of treatment-related deaths. And we think that what we've seen so far with U2 is not out of the ordinary. So again, we're continuing to do our work. We continue to push through. We're looking forward to tell you more with the FDA about this and of course, sharing our findings with ODAC. But again, our goal is the same as the FDA's goal and making sure that we bring a drug combination to market that is safe and effective for the population. Next, Slide 11. So let's start to now switch gears a little bit. That's the, I guess, core part of our oncology franchise. Later, I'm going to talk a little bit about the next gen of the oncology franchise. But let's spend some time on RMS and autoimmune because this is probably the biggest opportunity that the company has is ublituximab in multiple sclerosis. So just a quick primer on ublituximab. This is a glycoengineered anti-CD20 monoclonal antibody. The glycoengineering provides an enhanced potency in our hands. And our annual analysis, this is the most potent CD20 available. When you look at preclinical assays, it's about 50x to 100x more potent than rituximab, the comparisons on ADCC rituximab to OCREVUS, the approved IV CD20 would suggest that we would have about a 25x to 50x potency advantage over ocrelizumab. The other unique and exciting part about this compound, we're able to deliver it in shorter infusion times. In MS, we use a 1-hour infusion. We'll talk more about that. What's not talked about frequently is that we use a 90-minute infusion in CLL, and that's also significantly shorter than other CD20s. This drug has been in a lot of patients through our varied clinical trials, both in oncology and MS. And following the successful Phase III trial, we submitted a BLA for patients with relapsing forms of MS and we have a PDUFA goal date, target PDUFA goal date of September 28, 2022. So we'll be able to share some exciting times for our MS franchise. And next, Slide 12, please. So I'd like to take some time to go through some of the data from our Ultimate I & and II Phase III trials. So as I mentioned, very successful Phase III trials. These are the first studies in which the annualized relapse rate was below 0.10. So TG and ublituximab broke a very important barrier with a very high level of activity. And as I mentioned, we've now filed this data. So let's go through the next several slides, starting on Slide 13. Some of the data from the study. So the first is the primary endpoint, annualized relapse rate. And what you can see on this slide is that in Ultimate I, it was about a 60% relative reduction in relapse rates by using ublituximab versus the active control arm of Teriflunomide. And similarly, in Ultimate II, it was about 50% reduction using ublituximab over Teriflunomide. And like I said, getting below that 0.01 mark for ublituximab, which was 0.076 in Ultimate 1 and 0.091 in Ultimate II, was a barrier that has never been reached in any other Phase III clinical trial. So super excited about that. Next slide, please. Slide 14. What's really remarkable about this compound is its ability to shut down what appears to be the disease process when you look at sort of a biomarker endpoint such as T1 gad-enhancing lesions. So these are lesions that you pick up on MRI and same thing with T2 lesions. And what you can see on the left side and the right side are the T1 and the T2s and 96%, 96%, 92%, 90% reductions in these lesions across the board in each of the studies. So really, the drug does an amazing job of shutting down that part of the disease process. Slide 15. And the other interesting part is on disability. So we saw some interesting results on the disability progression as well as disability improvement. Disability progression, although that secondary end point was not just a significant, the rates of progression were extremely low for ublituximab but 5% for a 12-week and 3% for 24 weeks. And Teriflunomide definitely performed better than expected. So it wasn't a statistical answer. But certainly, by using ublituximab, we saw very low rates of disability progression. And likewise, even maybe more interesting is confirmed disability improvement where there was a statistical difference between the 2, almost doubling of that effect using ublituximab. So a really nice interesting results also on disability. Next, Slide 16. And then one of the endpoints that's really coming to focus over the last few years is something that's called NEDA, which is no evidence of disease activity. And it's kind of a compilation endpoint where they take each one of the MRI and disability and ARR and they kind of merge it together to say, okay, if you had no evidence of disease activity on any of these measures? And what we showed was that ublituximab in both studies have a significant doubling or almost tripling effect of patients who had no evidence of disease activity. So I think unequivocally, we're looking at an extremely active agent for patients with relapsing forms of MS. Next, Slide 17, please. And then just going through the safety profile. Of course, safety is going to be an important measure. The top line there, you see infusion-related reactions. Teriflunomide is an oral drug. It's given in this particular study with a mock IV, so a dummy IV. So you can see that even about 12% of the patients getting a placebo IV will have some form of reaction. But the Ubli side is certainly aligned with expectations. And then as you go down the line, for the most part, all things are relatively equal. Lymphopenia in the target of this drug is depleting B-cells. So that's no surprise. And then, I guess, at the bottom, you could see that Teriflunomide causes some hair loss, which you don't see with ublituximab. Next, Slide 18, please. Serious adverse events, pretty well balanced across the board, Things you worry about most are infections and infestations with the CD20 relatively in line with what you saw with Teriflunomide. And then some reports of malignancies is pretty well balanced, some deaths on the study, very minimal. And one pneumonia was deemed potentially related. And then you've got post-measles and the postsurgical deaths, which are both in Eastern European countries. It was nice to see that there were no cases of PML on this trial on either the Ultimate I and Ultimate II trial, although we know that all CD20s carry a risk of PML. Next slide, please, 19. So in terms of market opportunity, I think this is a very -- in a way, a very generic side. We've got lots of numbers here. But I think the overriding point is that we will be the third CD20 to market. There's a number of other classes, whether they're T-cell targeted orals, interferons. There are multiple classes with multiple drugs and each drug seems to find a really nice market opportunity. We think that the profile of ublituximab will support a really nice position in the marketplace. Some estimates are that CD20s could represent anywhere from 40%, 50-plus percent of all new patients started in MS. It's tracking pretty close to that already and potentially can grow beyond that. So our goal is to get in there, really focus in on why folks should be using ublituximab in MS. And on the next slide, 20, we'll talk a little bit about that. So what do we see as the potential opportunity for ublituximab? I mean we do think it is potentially best-in-class profile. The clinical activity is obviously in a noncomparative way, the best ARR that's been produced. So we're very excited about that. The one-hour infusion every 6 months provides a convenience advantage, and that has really resonated with potential physicians, prescribing physicians. And lastly, the -- one of the most important aspects of being successful in RMS is making sure the patients have easy access to the drugs. We hear it all the time that patients have difficulty getting on OCREVUS. And despite the fact that OCREVUS has billions and billions in sales, they still have issues. So one of our goals is to make sure that we create the best possible access for patients. And to do that, we are prepared to strategically price ublituximab in a way that ensures that access. Now again, that's not an easy -- I can say that we can just lower the price and everyone will be running too, but the payer landscape is such that we have to work within it in some ways, but we are prepared to strategically price ublituximab in a way to ensure the best possible access and that we'd like to do. So between the clinical profile, the convenience and hopefully, very good access, we see such ublituximab playing an important role in the overall MS landscape, and particularly in the CD20 segment, which could be the largest segment of treatment options for MS patients. And lastly, I'll just remind everyone, PDUFA date, September 28, 2022, put it on your calendars. It's online in big bright letters. Slide 21, please. So I'm going to take just a few minutes to pivot back to the hem/onc franchise and talk about what's potentially next for U2, why we see so much value in U2 and why we believe so much in U12. So U2 as a stand-alone combination has, we think, a lot of value in CLL. The market is not huge. It's actually -- it's a lot bigger than what we're doing today, but it's got a focused utility, right? There are several really good agents already available in CLL, although those agents are not perfect. They're not perfect from an activity standpoint and they're not perfect from a tolerability standpoint. So patients still can have tolerability issues on BTKs and venetoclax and patients are still failing BTKs and venetoclax. So U2 alone, we see as an important treatment option for patients who may not be good candidates in the first place for BTKs or venetoclax, or have come off of either or both of those treatments for some tolerability issue. So that's step 1 for U2. And that's where we're working with our current application. But the future is really seeing what else can we do with U2? How can we make other drugs that are good, even better. So the next series of slides, I'm going to talk about are U2 in combination with venetoclax and U2 in combination with BTK inhibitors. So I'll start here with venetoclax' study. This program has been talked about quite a bit. We're obviously very enthusiastic about it. Venetoclax is a very good molecule but really needs to partner with other molecules to get the best out of it. It's also a molecule that has challenges in being delivered in the community setting and still has a significant uptake -- has been challenged with its uptake in the community setting and particularly, I'm assuming during COVID as well. But academics love venetoclax. And so how can we help to make venetoclax a better treatment option for patients? I will focus your attention into the box on the left, where you can see cycle 12, and it says 91% peripheral blood undetectable MRD and 72% of bone marrow undetectable MRD. So that's the goal, right? We want to get people the deepest possible response, get as many of them to that response and then get them off therapy. So here, with 72% and 90% of the peripheral and 72% of bone marrow, we're giving patients a really deep response combination with venetoclax. And hopefully, that's going to translate into a very long period, perhaps for some of these that will translate to cure. And for others, hopefully translate to a very long period of off-treatment benefit. Because anytime you can be off a drug, it's better than being on a drug, because all drugs carry some side effect liability. So that's venetoclax. This is from our Phase I trial. We also, in the right-hand panel, have conducted a Phase II trial with about 165 patients, and we should be able to report data from that study in the middle of the year. So if timing goes well, it will be just post-ODAC, fingers crossed if we're successful at the ODAC, and we'll come out with this data, again, starting to show why it really matters to get drugs like U2 approved even in the setting where U2 may not be the most active treatment in CLL as a stand-alone, it still provides for patients who don't fit with the current therapies and then can be used to further enhance and better all therapies. Let's go to the next slide, Slide 22, because I'm going to continue to make that same point. So on Slide 22, we start to look at -- all right, we looked at U2 in combination with venetoclax, which again is a very important part for CLL. But the most important drug today in CLL is Ibrutinib. BTK inhibitors as a class are the most important. And within that class ibrutinib, the granddaddy of them all is still the most important. And in fact, there could be nearing 100,000 patients in the U.S. alone that are on ibrutinib. So like I said, every drug carries some level of side effect liability. So patients who have to stand a drug for a long period of time, some people have no challenges, but most people have some challenges. So the goal, if you can, is to figure out a way to treat them with the drug and get them off the drug. BTKs today are designed to be taken forever. This is an experiment. There's a clinical trial where we said, "Hey, can we take U2, give it to patients who are on a BTK inhibitor, on a Ibrutinib, and get them to a deep response, an undetectable MRD and then take them off therapy?" And what we showed was that within a very short amount of time, you can look at the time on the right-hand side of the slide, the blue and gray bars, the blue bars are the patients who got to undetectable MRD that was 77% of the patients got to an undetectable MRD. And you can see how long it took them to get there. Some people got there with U2 on top in as short as 2 months, some it took 12 months of therapy. But once we get them to that, we can get them off all treatments. So again, remove this lifetime issue. And then we're going to follow these patients and see how long can we keep them off therapy, and then can we retreat them sort of in a pulse manner given the holiday, then pulse or boost. People are now familiar with boosters, thanks to COVID. So can we basically treat them, get them off drug and then have a booster, maybe annually 2 or 3 months of therapy, something to that effect. So that's something that we're really excited about and working on, and this is a really exciting start to that kind of program. Let's go further on Slide 23 and talk about our own BTK, 1701 in combination with U2. First and foremost, let's look at the BTK alone. Everyone knows Ibrutinib's profile and everyone knows some of the other BTK, 1701 is a little unknown. So just to give you a little flavor for the activity, this is a 200-milligram doses in green and a 300-milligram dose in blue. And what you can see is pretty much everyone responds to the BTK inhibitor 1701 at either dose in CLL. So really nice activity. And then on to Slide 24. You can see in combination. And these are not all CLL patients. There's a series of marginal zone patients in here, all of whom responded. And there's a series of follicular patients in here also who did quite well. There are some mantle cell patients that did well. So you're not getting the exact same apples to apples as the prior slide with CLL only. But with CLL, we think that the combination of U2 plus 1701, we can use the same concept to create a treatment regimen that has -- gets to a deep response and then provides off drug holiday. And we think that's really an important new concept of how these patients ought to be treated in the future. So again, moving forward, understanding the combination, toxicity and tolerability is key. Some of it will be shown on the next slide. So let's go to Slide 25, please. So here, you can see again the left side in the -- I guess, the blue and the green and the dark blue is the 200 milligram and the 300-milligram groups. And you can see Grade 3s are at least in some of these higher numbers are relative to nonexistent. They're not nonexistent. You could see below with the lab testing, there's some Grade 3 lab abnormalities, neutropenia being one. But overall, tolerability profile looks pretty solid. And then when you sort of shift gears to the right side, you get the black box and the light blue box, these are combinations of different doses of U2 with different doses of 1701. And then all the way on the right-hand side, you've got 1701. This is actually a low-dose strategy that we're working off of low-dose U2, low-dose 1701, and you can see the toxicity profile looks quite good. So we're working on creating the right mixture here to get the desired outcome. But I think the overall enthusiasm is that U2 has a lot of flexibility and utility to be used both alone, which is what we're targeting right now with our application for approval, but later on to improve care for -- in combination with standard of care agents. Next, Slide 26. And similarly, again, with AEs of interest for BTKs, very low on some of these measures as well. Next, Slide 27. So I'll finish off here to try to save some time for some Q&A. So in terms of regulatory goals, look, we've got to get through a favorable ODAC to make the CLL application work of course. So we're focused on that. Our team is engaged fully in making sure that one, again, step one is we want to know the truth, we want to understand is there an issue here that we should be concerned about. We have no interest in putting anything forward that's not safe and effective for patients. Like I said, everything we've done thus far gives us a high level of confidence that the drug is not unduly unsafe. And so we're working toward that. So that hopefully would follow a favorable outcome, no doubt it would get us to a U2 approval. And then, again, probably the biggest of all the events of the year still is the approval of ublituximab and RMS and the target PDUFA date again, September 28. I gave a little bit of a discussion here on some of the pipeline activity we have ongoing. So middle of the year, I think we can get some data out on the venetoclax Phase II. And during the course of the year, again, continue to present updates on our combination efforts of U2 with BTKs. On the financial front, we have -- we ended the year with $350 million in cash. It was very nice to be able to re-up with our collaborators at Hercules. With that, we added $70 million of nondilutive cash to the balance sheet. We also, I will say, have taken some pretty nice and important efforts to streamline our operations and cut our burn rate. So we both looked at operating expenses. We've looked at personnel, and we've taken some cuts on both. I'd say the cuts that we've taken are equally across R&D on the one hand and SG&A on the other. And we think that those streamlining efforts in combination with the additional cash brought in nondilutive will carry us well into '23. I think we're focusing on a burn rate for the first 2 quarters of this year of about $55 million to $65 million. I think the expectation is that we'll be a little bit on the high end of that range for the first quarter and hopefully closer to the lower end of that range for the second quarter. So I think we've set ourselves up for a nice financial position moving forward. I will also note, some of you may have seen a Form 4 that I filed. There's a lot of stuff in there that most of it is transferred to -- that were required for end-of-year trusts and some shares were sold for my kids. But probably the more interesting part of that entire Form 4 was that the vast majority of my cash compensation for 2021 to save the company money and also align myself with the shareholders, of course, is I took my cash compensation for '21 and converted it into equity. And I plan to do that if I get a bonus, I will do the same thing with my bonus. So I won't be taking any cash out of the company for bonuses, for my bonus. So look, we're all -- TG is really excited and pushing hard. And I think streamlining is an unfortunate part of biotech, but I think it gives us a lot of flexibility to really push forward and make sure that we're successful at ODAC and we're successful with our RMS filing. So with that, I'll pause there and open up for the Q&A session.