Eli Lilly and Company (LLY) Earnings Call Transcript & Summary

Great. Good morning, everybody. I'm Terence Flynn, the U.S. biopharma analyst at Goldman Sachs, and we're very pleased to be hosting Eli Lilly today at our virtual healthcare conference. Joining us today from the company, we have Anne White, who is President of Lilly Oncology; and Jake Van Naarden, who is CEO of Loxo Oncology at Lilly. Thank you both so much for joining us today. Really appreciate the time.

As I know it's an extremely busy time of the year. You're post the ASCO Conference. Maybe to start, I thought a good place would be just to give us an overview of kind of the company's current strategy here in oncology. What's differentiated about your approach versus other players? And then how are you thinking about the different verticals, targeted oncology versus IO, as obviously there's a lot of ongoing efforts there at the company.

Sure. Thanks, Terence, and thanks for having us today. I can start with that, Anne, and then you can round out my comments. I think from a pipeline strategy perspective, maybe it's worth reminding folks of just the sort of the context of how we got here. I think, as many know, Lilly acquired Loxo in the beginning of 2019. And at the end of 2019, we decided to put together what we're now calling Loxo Oncology at Lilly, which is essentially the sort of rebranded oncology R&D group internally. So we've been at this under these new guys for about 1.5 years, which is actually not a long period of time in R&D life cycles. And as folks know, we initially combined all of the pipeline efforts into one combined pipeline, really anchored on pirtobrutinib LOXO-305, the BTK inhibitor, and a couple of other molecules in clinical development, including the oral SERD, which I'm sure we'll talk more about, with results recently presented at ASCO. We're filing a handful of other INDs, putting more molecules in the clinic this year. We can talk about those, KRAS G12C, a BCL-2 inhibitor, some other things. But I think that the part of the story that remains largely untold publicly actually is all the work that's going on in the discovery organizations, both small molecule and large to, I would say, revitalize, reprioritize and just refocus the kind of drugs we think we can build, the kind of drugs we want to build and get those into clinic. That having been said, some of those are legacy projects that either Lilly or Loxo had been working on for years. And so we sort of had a head start 1.5 years ago when we put this all together. Others are brand new starts. And obviously, 1.5 years in, we're not going to have a candidate that's not really credible. So I expect that over the course of the next 6 to 12 months, the public will start hearing more about these programs because we'd like to start talking about them, and some of them are coming to maturity. I think there -- the kinds of programs that when investors, when clinicians, patient groups, et cetera, hear about them from a profile perspective, I think they'll be sort of obvious in the sense that, wow, like I get why they built that. I think it's probably going to work if it does what they say it can do. The challenge is that these -- some of these product profiles that we've been anchoring on are incredibly difficult to achieve the kind of molecules that meet our standards. And so some of these things have taken years to actually get to where we want them to be. So there's a little bit of this commentary, which is stay tuned, but I think at a very, very high level, the mantra that we say internally all the time is, I'll just repeat it here for public consumption, we want to work on drugs that are going to work and drugs that are going to matter to patients. And that sounds trite, I guess, but when you really sort of double-click on what those 2 ideas mean, the idea of a drug working means that you actually know it's working. And so we do like working on drugs that have a potential to show some single-agent activity in Phase I. They don't need to be accelerated approval drugs. They don't need to be 80-plus-percent response rate drugs, but they do need to be drugs that you can identify a patient population where you really know it's working and can help you dial risk out of the system for whatever the next set of experiments are. And I would just contrast that with sort of true empiric drug development, which I think there's a place for that in our business. I don't know that Lilly is the company to take that on in oncology. So -- and we can talk about then, I think there are some axes of biology that fit more empiricism versus not. And the idea of drugs mattering is again also sound sort of simple, but it's just the idea that we're not going to go through an arduous discovery campaign for -- and spend years of talented scientist time to work on the drug that is undifferentiated. We'll take on modest differentiation stories when there's other hooks. Obviously, you've seen what we've done with Tyvyt. We in-licensed the BCL-2 inhibitor. So they're -- it's not to say we won't ever do me-too type things, but there were -- with different end goals in mind, so to speak. And certainly, I don't think we would do a me-too project that we spent 6 years on in discovery. That's not a good use of resources. Anyway, the last thing I would just say is all this is augmented by business development. We're constantly on the prowl across all stages. Challenging environment right now for BD and oncology, which we can talk more about, but that's another deliberate augment to the overall strategy. And why don't you round out? And then, Terence, if you want to come back to sort of IO versus other things, we can talk about that.

Okay.

Well, thanks, Jake, I completely agree with everything you said. It's been exciting, and we have a very strong set of launched products, many of them backbones in cancer care. And then we're looking to continue to grow the portfolio with the next set of exciting assets that come out of Loxo. And I -- just to echo, I couldn't be more pleased with the partnership we have with Loxo Oncology at Lilly and how this is working on. I think it's exceeded all of our expectations, both in the quality of the talent that has joined our team and the quality of the portfolio that I think we're going to be bringing forward. As far as -- you had a question kind of around differentiation, I think one of the things that I think differentiates us in this way that we've designed our organization and the focus that Lilly's had on acceleration over the last several years is that, I believe, we're one of the most -- the fastest and the most agile companies in the business, and that's incredibly important in cancer care, where we need to pivot quickly. And so very excited about that. It's a skill that I think both teams bring to the table. And also how Lilly responded to COVID antibodies and quickly got an answer out to the community in that space just shows you what we're capable of here at Lilly. So that speed and agility, combined with the technical depth that we have, it's going to be an exciting decade for Lilly Oncology. I can't wait to, as Jake said, share more as we move these molecules forward.

Great, great. Well, appreciate all the comments there. The -- I guess, one follow-up is, as you think about the mix of organic versus inorganic, I mean you touched on this a little bit, Jake, but just maybe is there a mix you're solving for? Is it more just kind of you're following the science and kind of you go where it leads you and maybe sometimes it's something internal? Or again, if there's an opportunity externally, that's where you look. Or how do you think about balancing those 2 sides of the coin there?

I don't think about it in a sort of top-down way. I think the only progress you can count on is internal progress because it's the only thing you control. BD is just inherently opportunistic. I would love to be doing more BD if there were more rational BD things to do. The issue is sort of inventory matrix against valuation is tough right now. So -- but we interact with an unbelievable number of companies in the context of BD, probably a similar volume actually to many folks on this call interacting within the context of the buy side. So we look at a lot of things. Not everyone -- there are some things that we see that we actually really, really like and there's no willing seller, willing partner or the price isn't right. I would say more commonly, we just -- we're not finding things that we like that much. I think there's a -- it's interesting. There's a crop of programs out there currently where you can say, okay, that's going to be an approved drug, but maybe it's just not one that really stands the test of time competitively. So you're sort of buying like a stub, so to speak, like, and you're just waiting to get outmoded. That's not our style either. We want to -- if we're going to spend that kind of money and everything costs a lot of money, we want to have some competitive moat that sits around the asset for some period of time. So there's no real rules around it, honestly. But I think, when I wake up every morning, I think mostly about keeping our internal stuff on track on time line because it's just all we can control.

Great. Okay. No, that makes sense. Maybe just the other big picture topic here is obviously the COVID recovery. Anne, would love your perspective on kind of how the commercial teams have been reengaging here post-COVID. What are you seeing kind of in the U.S., outside the U.S.? And then any areas that have been faster to recover versus some others?

Yes. Terence, it's a really good question. And it's interesting as you look at it because it is different regionally as we've been examining the dynamics. So a good news story, I think, in the U.S., I would say that we're cautiously optimistic with the pace of recovery and showing year-over-year growth in that market. And prescription data, in particular, over the last several weeks is showing good growth on patient visits and new diagnoses. We're seeing a return to growth in new and total prescriptions across the portfolio versus pre-COVID baselines. Patients are finding a way to seek treatment, and doctor's offices are opening up and getting back to full capacity. One thing we are seeing, and you see it in some of the performance, is that we're seeing a faster recovery in the U.S. on the oral medications in chemo-free regimens versus the infused portfolio. But I even believe that the headwinds in the infused portfolio are manageable, and we're seeing growth there as well. Look, we're expecting to see is sustained growth, particularly in Verzenio and Tyvyt, Retevmo and then as well as Cyramza and Alimta still provides us a nice solid base in '21. Different story, though, in Japan. This is probably a little bit more worrisome. So we are seeing that the recent surges continue to impact the health care system and the pharma market. The extended lockdowns are impacting access and certainly impacting, I think, patients' interaction with the physicians. In fact, in the hospital access, what we're seeing is that hospital access is reduced by about 2/3 right now, which, when you compare that to the GPs in Japan, that's only down about 20%. So obviously, we're a hospital-based team in oncology, and so that is impacting our access. We do, though -- I think there's a reason to hope in the future. I think we're hoping to see good market acceleration towards the second half of '21. So we're forecasting that vaccinations will increase pretty dramatically. Hopefully, over 70% by the end of the year, and that will help us quite a bit. In Europe, I would also say bit of a challenge, although maybe a faster recovery, I think, than Japan. We're seeing that slower vaccination rates and surges are impacting our European countries in various ways. The access to physicians is still, I think, a little bit down, but what we're seeing is we're making that up with face -- with virtual interactions. And so -- and that's something that we've had a capability of in Europe due to limited access in the past already. So we're using those capabilities in a pretty significant way. And I think we expect that vaccinations in Europe will really start to pick up in June, July, August. And so that will then show -- I think, start to look more like the U.S. as far as the recovery dynamic. And then maybe to end with a good news story, I think China is seeing solid growth. So what we're seeing is the pharma market growth is up 8% after shrinking in 2020. So that's a good news story, and I think we're expecting to see solid growth in 2021 already. And customer interactions are only down probably now about 20%. So a good news story in China. So regionally based but, again, I think we're starting to see the light at the end of the tunnel, and I think we'll expect to see the second half of this year really start to recover significantly.

Great. That's good to hear. I guess 2 follow-ups. One on the U.S. side. Would you say it's in line or ahead of your expectations? I know you guys have anchored to kind of the second half recovery broadly. And then maybe just remind us how big Japan is in terms of your total business on the oncology side.

Yes. I would say that in the U.S., it's kind of in line with our expectations. And particularly, I think we had expected kind of a midyear, as we're hearing from physicians is they're kind of going back to full capacity, and that's what we're starting to see. So I'd say it's in line. In Oncology, Japan is a significant part of our business and particularly for medicines like Cyramza, which are very successful actually. So a great deal of Cyramza in Japan even more than the U.S. and one of our largest products in Japan. So Japan is an important part of our business, but U.S. still is leading the way, and so recovery in U.S. is the most important to deliver on our revenue line for this year.

Okay. Great. Maybe just moving on to some of the product questions now. Obviously, at -- we're on the heels of ASCO here. I know we had a chance to talk before ASCO about your oral SERD. Now that we've seen the full data, maybe you could just kind of walk us through the key takeaways, Jake, your profile versus the competition and next steps here for that program.

Yes. So look, I think at a very high level, the drug is doing everything that we expected it to do. It's firmly on thesis. I would say from the time it was designed preclinically, this is an initial Phase I data set that is just more or less what we thought it would be. I think as we've talked about in other settings, not a class of therapy that's going to have whopping response rates, but you do have the opportunity to see some single-agent activity, and we've seen that. It's worth bearing in mind, as you think about just point estimates of response rate and number of responders and that kind of thing, these responses in hormone-sensitive women with breast cancer happened pretty late in therapy, and that's not just a SERD comment. That's true with other endocrine therapies. And so when you look at our dataset, follow-up is just short because we haven't been at it that long. And so we'll see how the responder population evolves over time, not that, frankly, I think the point estimates even matter, to be honest because this study doesn't do anything for the drug from a registration perspective. So this study, really, I would say, the initial set of questions we asked were around PK. Are we getting oral exposures that -- in line with our predictions? How do they compare to fulvestrant, like box check? I think we're clearly getting greater exposures than fulvestrant, certainly on a protein binding adjusted basis, so free drug. So feel good about that. Number two, safety profile and at the 400-milligram dose we selected, we feel good about that. Number three, some degree of efficacy that makes us feel confident that our PK and target coverage math isn't off. And again, I feel good about that. So I think those were the 3 main things to check with the monotherapy experience. I think that's largely done now. Obviously, patients will continue on. We'll update the data at some future point in time. Okay. Next question is around combinability. And so those experiments are literally running right now in a series of expansion cohorts with a whole variety of mainstay drugs in ER-positive breast cancer, including, of course, abemaciclib. No reason to think those will go badly, but we just need to generate the data and get through the safety experience. I would say the bigger next step, obviously, is the Phase III randomized study that we announced at ASCO in the second-line setting, which we're going to be starting this year. And as we can talk about that, too, obviously, we haven't shared a ton of details around design, but it was important for us to sort of move on with this next chapter. I think it's worth noting, I mean, Anne commented on just speed. We dosed the first patient with this program, and I believe it was December of 2019. And amidst COVID, for a first-in-human drug with not a ton of single-agent activity to get people unbelievably excited, here we are starting a Phase III randomized trial 1.5 years later, it's -- I'm proud of that. That's not easy to pull off. And so I think it's just indicative of like -- of what this organization is capable of and the focus we bring to the effort. I would say just one other comment on just SERD in general, which is just that there are some pretty important fulcrums coming or levers, I should say, for this class of therapy later this year with the Radius and the Sanofi randomized studies reading out. And these drugs are not risk-free programs. In fact, I think they're pretty risky actually to prove their benefit in these randomized trials. And so we're going to be watching those competitive studies closely just to make sure that this whole experiment still makes sense. So yes, maybe I'll pause there. I don't know, Terence, did I cover everything you asked about?

Yes, yes. No, definitely. I had 2, I guess, follow-ups. One is just on the dose response. It looked like -- and again, I know it's always hard with these small studies, but it looked like there wasn't a very strong dose response. I guess, any more details you can give us there? And then on the combinability question, I know one question we got is just on the diarrhea. It looks manageable. But then when you combine it with Verzenio, which is -- that's also on the side effects there, how confident are you that you'll be able to kind of manage through that as you think about the combo side of it?

Yes. So on the dose response, I think, look, you're reacting to the data that we presented. I can't disagree with how those data look. I think the one -- the piece that we've thought a lot about, as we looked at our own data set, is just you're dealing with small numbers in general, and then you're dealing with differences in follow-up, which, as we talked about earlier, matter a lot as you think about just the ability to achieve a response. And then prior therapy, which is an incredibly important variable for this population. And it's just a weird heterogeneous mix as you look across these different dose cohorts. So I don't lose a lot of sleep over where the responses happened from a dose perspective. And for what it's worth, it's not that because the responses happened at 400, we chose 400. That actually wasn't really a part of our rationale at all. So we just -- we like the PK and safety of 400. We -- as we got at the higher dose levels that were going to be like pill burden issues that we didn't -- we thought wouldn't be bad for patients. So there were a bunch of reasons, but the -- we didn't zero in on that dose because of like 2 random responders. That's not -- that's sort of a non-intellectual way to do it. So I'm not that worried about that. On the safety side, look, it's something that we're going to have to pay close attention to. We're running the combination experiment right now on the safety side with abema. I think the -- in a way, the intense focus that the abema team has had over the past couple of years on proactively managing diarrhea for that drug in and of itself, in a way, sort of primes the pump in the event that there's any overlapping toxicity with our SERD. So I'm actually not that worried about it because I don't feel like we're starting from a standing start, ironically, on this particular class of toxicity. But we have to generate the data to improve that. But I'm not that worried about it right now.

Yes. Okay. Sounds good. And then maybe one last one before I go to Anne for some Verzenio questions. It's just how do you think about the implications of the Sanofi AMEERA-3 study in terms of your development program? Just again, is that something that would cause you to kind of reassess the design of your Phase III program? Or is there just no read across at all?

I can take that, sure. Yes, I mean, I think there's a lot of read across there. It's -- the study that we're starting this year is not identical to that one, but it's pretty close. I mean, put it this way, it's close enough that if that study is a flat failure, and we can't justify a rationale that our study design compensates for, I do think, we and, frankly, the field is going to need to sort of look in the mirror and say, "Oh, boy. Like what's going on with these drugs?" It's sort of a similar -- I think it's -- it could be -- again, I'm not predicting the study will fall. I hope it doesn't. But we think we need to be prepared for either outcome. It reminds me a little bit of when the PARSIFAL data came out last year, many of our competitors' development programs were sort of already baked, and so like they almost didn't have a chance to then react to those data. In a way, because we were a little bit behind, we had an opportunity to look at those data in the clear light of day and say like, "Uh-oh. What does this mean about, like, this class of therapy?" So I view AMEERA-3 coming out at sort of a similar moment in time. We're going to be pretty clear eyed about it.

Yes. Okay. Makes sense. And obviously, Verzenio is an important franchise for you guys. You've had a lot of momentum on the metastatic side. Maybe just help us think about that momentum going into '22, why you feel confident that will continue. And then we can go on to some of the adjuvant questions, which is the other important growth driver, obviously, for the franchise.

Well, thanks, Terence. We love to talk about Verzenio. I couldn't be more excited about the data readouts we've had or the momentum that we've seen on the revenue side. And so I would say that I'd characterize that we're really pleased with Verzenio growth this year. We've continued with the positive momentum in U.S. share of market. As you looked at the April month end, we had TRx of over 18%, NBRx of over 30. And globally, what we saw was Verzenio sales grew 43%. It's now approved in 74 countries, and we have an NBRx of over 50% in Japan. So all of that great momentum. And what we're really seeing is more and more adopters of Verzenio. So as physicians trial it, they have a great experience. As Jake said, they really learned to manage things, like the minor inconvenience of the diarrhea through very simple solutions. And then what's really powerful is just the overall survival data, which is the gold standard that we have from MONARCH 2, and I think that's really bolstering it. And then importantly, I think that leads into your next questions, is just the differentiation I think people are starting to appreciate in this class, and that was just reinforced by the remarkable results that we had in really breast cancer, along with overall survival and other attributes of Verzenio. So it is, as you said, we've got great momentum. I really look forward to what we'll see this year and then what we're going to see next year.

Great, great. I guess any more color on that breadth of prescribing that you can give us? I mean, how much broader is that base now than maybe where you start -- where you ended in 2020?

Yes. Well, I think that what we're continuing to see -- we look at the deciles of prescribers. There's very few physicians who have not trialed Verzenio now. And as I said, what we track very closely is once they've trialed, do they become adopters, and that rate of adoption is just increases month by month. So we couldn't be more pleased. And it's not just in combination with fulvestrant, but in combination with AI as well. All of those markets are growing in our Verzenio revenue lines. So it is, I think, really a sign that people are, as I said, starting to realize that continuous dosing, we think, makes the difference, that the strength of the overall survival. And I would also say one message that really resonates is the performance of Verzenio in endocrine-resistant population. So some of the competitors have data in, obviously, the endocrine sensitive population, but Verzenio performs well in both resistant and sensitive populations, and I think that's really reassuring to the physicians that for their hard-to-treat patients, they're giving them the right medicine to be as aggressive as possible for cancer. So that's a message that really resonates with the physician, and I think we're seeing good adoption based on that message.

Okay. Great. Obviously, the other big driver is the adjuvant setting, as you said, a point of differentiation here. You guys have filed for a supplemental NDA, waiting to hear back from the FDA, I believe, later this year on the PDUFA date in the fall. They have asked for an updated cut of the overall survival data because, again, you had, I think, only about 70 events or so here from the monarchE study. So maybe just help us think about your confidence level that will continue -- the survival will continue to trend in the right direction, and you'll see separation. When you look at the current data set, where does that confidence level come from?

Yes. Thanks for that question. I can tell you, as the data mature, given the strength of what we've already seen with the DRFS hazard ratio, we are highly confident that the OS will trend in favor of Verzenio. So it's just a matter of when that will occur and not if. Now as you know, everyone in this call knows with adjuvant breast cancer, thankfully, overall survival results -- that result takes a number of years to deliver. And so I think, as you said, that was reinforced as we share that data in the JCO article, 39 deaths in abema and 37 in the control arm, so extremely immature even though we're several years into the study. And there's 5,000 patients -- over 5,000 patients in the study. So we will provide this early data cut to the FDA. We won't delay our standard review time, and we'll provide it within that time frame. And just as I said, we firmly believe that Verzenio is a really strong medicine in the adjuvant setting. There's already strong data to support this. And what we saw, and you saw this from the interim, even to the primary outcome, the data strengthened over that time, so we have no concerns. Of course, coming together, any of the other things that could happen here, we think the data will strengthen over time and that the survival benefit will produce itself.

Okay. Great. One other question we get is just how frequently can you provide the FDA with updated cuts? Is there some standard periodicity to this? Or is it something where you guys are looking every month or something and giving that data to FDA? Like how does that interaction happen over the course of the back half of this year?

Yes. These are -- obviously, we always want to do this according to statistical rules and applications. So this is not something that we look at frequently. We did this exploratory data cut at the request of the FDA. And so -- and again, this is an exploratory data cut, not a robust statistical analysis. So we'll just continue to work with the FDA. As I said, they announced for this data cut during the review cycle, and we'll provide that during that review cycle. And then we'll go from there. I can't hypothesize what they will do with it, but what I can say is we, as you can probably tell, remain very confident on the robustness of this data. You can -- it's well studied, that DRFS. Our endpoint translates into overall survival. And so again, we're very confident that this is a medicine that women and men with breast cancer should receive and should have access to. And so the goal here is just to work with FDA, get it as quickly as possible available to them and move forward from there. So we'll keep you posted as this progresses, but progressing well at this point.

Great, great. We'll stay tuned. Okay. I guess just moving on, I think, in the last few minutes here. Obviously, one of the other very exciting pipeline assets is LOXO-305, and we saw very compelling data back at ASH last year in CLL. And you guys are obviously moving forward into pivotal studies now. But again, I think as we've talked about before, Jake, there are some questions on how this market evolves on the forward because of fixed duration versus continuous dosing and then also the IMBRUVICA LOE kind of end of the decade. And so as you thought about designing that pivotal program, how did you kind of navigate those considerations as you thought about it? And maybe just remind us in terms of that design and those 2 inputs.

Yes. Let me take the second part first about IMBRUVICA LOE. I think that's a little bit more straightforward. I think if you believe the core proposition of pirtobrutinib is in BTK experience patients, which I think for the foreseeable future is a true statement and a reasonably large opportunity, by the way, the IMBRUVICA LOE, in a way, you could argue might actually help expand that opportunity because it will lower access barriers to patients getting IMBRUVICA in the first-line setting, which will then generate more patients ultimately who are PTK experience and then candidates for pirtobrutinib. So that's a long ways away, obviously, but I don't think the LOE has really impact on the core proposition of the drug. Obviously, we are going to run a head-to-head study against IMBRUVICA and the time lines associated with that study start to bump up actually in all likelihood against the IMBRUVICA LOE. And in that case, I think it matters, and it matters because it just increases the bar for what kind of difference you'd need to see with pirtobrutinib. But I think as we think about it internally, that's all sort of upside on the overall plan for the program. I think the overall plan for the program is really more focused on the experienced population because that's just -- we have to be -- we have to admit the fact that we are coming into a somewhat mature market landscape now. And totally reinventing it with this new drug, I think, is really challenging. So we're going to run the study because we think it's an important study to run, and the LOE makes the bar higher. But I think the core proposition of the drug is in the experience population. Now that ties in actually to your first part of your question around fixed duration. Continuous BTK monotherapy versus some kind of BCL2-based fixed duration regimen, I think we're going to see and we're sort of already seeing just different flavors for different patients depending on the treatment setting, community versus hospital, depending on their risk factors for tumor lysis, depending on their age, financial issues, geography. So I don't think either one of these is going to sort of be dominant. I just think you're going to see different consideration sets. As you know, we think it's important actually to enable pirtobrutinib prescribing under both regimens because of the fact that patients and doctors may want to do things different for different people. So In the experienced population, we're running a monotherapy study. We're running a -- that's dosed continuously. And we're running a combination study on top of the MURANO regimen, which is venetoclax, Rituxan, in the experience population, and that's a 2-year regimen. I think the other important thing to pay attention to here that is a trend that we've observed, and I'm sure others have, but it's not really one that's being talked about is that In the world of fixed duration therapy, just because of the nature of how this has all evolved, the second-line setting is actually more valuable than the first-line setting. First-line fix-duration therapy with venetoclax, obinutuzumab or venetoclax, ibrutinib, let's say, for CAPTIVATE or GLOW, that's a 1-year regimen. In the relapse setting, it's 2 years. So if you're a believer in fixed-duration therapy in general, the relapse setting is actually a more valuable place to be. Now it just so happens that we think it's the place that's more well suited for pirto anyway, which is why we're running that study, but it's just a trend that I think is important to pay attention to. Last thing I'll say on this is just as it relates to our own in-house BCL-2 inhibitor, which is a life cycle play for this exact idea that we're putting into the clinic this year, to the extent that our BCL-2 inhibitor looks clinically on par with venetoclax, I think we have some interesting optionality for owning both parts of that doublet that really no one else out there has. But we've got some -- we got to prove our BCL-2 inhibitors worth its salt before we can get there.

Okay. That's great. Is there an earlier path to market on like the C481S population or something here? Or when will you guys have visibility on that question? I guess, that's one we get oftentimes too for this program.

Yes. So I wouldn't focus on C481. That's turned out to be, I think, a bit of a nothing actually. In other words, If you look at a BTK experience CLL population, C481 status just has really no impact on the degree of pirtobrutinib's efficacy. So I think we all got a little misled there, including us. So that was just -- it's sort of a fascinoma at this point. Now that's not what -- that's different than, I think, the core of your question, which is, is there an accelerated approval path for the drug in general, whether it's in CLL or mantle cell. I think the answer remains maybe. And the truth of matter is we just don't know because we haven't gotten a clear answer from the agency on it, and in part because our data continue to evolve and develop. I mean, even the data that were published in Lancet earlier this year are a moment in time, and we need more follow-up. And so we'll see. We're not going to give up engaging with the agency, but at the same time, don't yet have the confidence that we can pull it off. I do think, by the way, if that door opens up for us, which would be great, obviously, if it did, I think the physician community, particularly the academics that have been involved with this drug, are pretty darn excited about it. So I think, to the extent that door opens up, it would be great for patients, it would be great for the program. And I think the sort of market would be ready for it, so to speak. But again, we don't know, and we're standing up the RCTs to be ready in the event that, that's our base case.

Great. Well, really appreciate the time today. And Jake, congrats on all the progress, and looking forward to more ahead here back half of the year. And thanks so much for the time. Stay safe.

Thanks, Terence. It's great to see you.

Thank you. You, too.

Thanks, Terence. Thanks for having us. Bye.

Thanks.

Bye.