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

Okay. We're good. Thank you very much everybody, and welcome to this Tuesday session at the Goldman Sachs Healthcare Conference. My name is Chris Shibutani. I'm a member of the pharmaceutical and biotech research team. And we are very honored to have the team from Lilly come join us. The ever-dutiful IR team in the front row has been doing a great job. And our discussion today really is going to focus on the CNS division. We're so pleased to have joining us the head of that group, Anne White, who is a 26-year veteran with Lilly; and Mark Mintun as well. So we appreciate this opportunity to perhaps enable a conversation with folks who maybe we typically don't always get to hear, which I think is a great idea. And also sort of we're kind of on a page between chapters with their business to a certain extent. And I think it's a great time to be perhaps a little bit more reflective rather than reactive so.

But just to start with. Anne, as your time at Lilly, you were part of the Oncology division previously leadership there. You took on this role with CNS neurodegenerative disease, which means the 2 you have some element of something that is perhaps entrepreneurial, clearly, elements of grit, optimism as well. Talk to me a little bit, and I find this interesting because a lot of times, people talk about CNS as being something like, this reminds me of oncology a couple of decades back, the journey where we were at. Where was the science? Where was the regulatory? Where was the business? To a certain extent, we're kind of there, echoes of that, and we'll see how closely that narrative will eventually play out. But tell us a little bit about yourself and perhaps the mindset and ethos that guided your decision to lead this effort.

Thanks for the question, and I'm very glad to be here with you today. Yes, I could not be more excited about what's in front of us in the neuroscience space at Lilly. And yes, so I had led the Lilly Oncology business for a number of years and have a lot of background in the oncology space. But then, when our CEO came to us, came to many of us and said, "We have enough momentum here in the neuroscience business that we want a dedicated business unit to this effort," I was all in, in this space because there's, as you said, the science is breaking. I think we're at the cusp of some incredible medicines that we're able to deliver, first in Alzheimer's, but we're actually also focused on other unmet needs within neurodegeneration as well. And then it's a company that's continued to be focused on pain, and that is actually one of the huge unmet needs, I think, in the world. It's a very underserved population. And not many large companies continue to work on pain. It's a challenging space. So the chance to be a leader in the work that we're doing, Alzheimer's, to make a difference in other neurodegenerative disorders and then continue in pain, I was all in from the beginning and thrilled that he asked. And then just in leading neuroscience, a big part of what I do is drive our efforts in Alzheimer's. And that is a place where the last few years have driven and delivered incredible advances forward. I think you have to remember that Alzheimer's is still the sixth leading cause of death, and the one until only recently had really no answers for people that suffer from the disease. And now in the next year, we're going to get some incredible readouts, I think, including our own donanemab for a Phase III trial in the middle of next year. So the chance to impact this disease, to work with people like Mark, who's been a leader in the diagnostic space for Alzheimer's and then in the clinical programs that have resulted in some of the best successes in the space. So it's an exciting time. And I love to tackle new and challenging things. And this is definitely one of those, and I couldn't be happier to be here.

Terrific. No, it sounds like a phenomenal background. And I actually really appreciate the thoughtfulness that the IR team sort of curated to have Mark up here as well. I think one of the things that a lot of us investors very much focused on the therapeutics world is that we -- it's like the homunculus of the brain. The tongue is everything. It's all about the drug, the drug, the drug. And yet the journey includes patient selection, which diagnostics, not part of every company's business plan or necessarily threaded into the core decision-making processes of designing trials, et cetera. Dr. Mintun, you come in with a radiologic background, innovation. You led an effort that was eventually acquired and folded into Lilly, which I think with some intention, the Avid name has continued to live on within the organization. Talk to us about your goals at this stage of why -- what kind of impact you're having with this effort?

Well, it's been -- thank you for the question. It's been an amazing journey. As you point out I left academics, where I was in Alzheimer's research developing imaging agents and then was able to join the company that was then acquired. And as you point out, the company that was acquired, Avid Radiopharmaceuticals, was its goal to develop better ways of diagnosing Alzheimer's disease using PET imaging agents. And one of that, what that meant is that when that was acquired by Lilly, I personally had to sit there and say, "Well, do I stay on? What's going on?" And it was an unbelievably great decision point because I saw, working with Lilly scientists and Lilly management, that they were committed to the concept of understanding this disease and then coming up with the most targeted therapy for the -- in sort of a precision measures and way for the right patient. So as we sort of dug in and said how do we design trials, we realized, and your analogy to oncology a long time ago might be very apt here, is that trying to treat a patient with dementia and assume they have Alzheimer's and assume that you understand what's going on was just -- was slowing down the field, holding us back. And the more that we could tell about what a patient had, more specifically, what level of pathology they have in their brain, the more we were going to have understand our trials and be able to design better trials each step of the way. So I think Lilly was very early in adding these types of measures to the trials. It was actually back in 2012 when we came out and demonstrated that it seemed to us that knowing amyloid positivity was absolutely mandatory to be able to design an Alzheimer's trial. At the moment, people said, "That's just not practical." And yet 2, 3 years later, there wasn't really any trials being started that didn't have that as a core thing. But we continued. Amyloid was only 1 of the 2 pathologies in the brain, and tauopathy being the other one. And so we pushed hard to understand how we could measure that pathology. And so as we came out with that imaging agent and started incorporating, we realized that was telling us a huge amount about what stage of the disease the patient had. And so it's just like you wouldn't start a cancer trial merely on the basis of someone being short of breath. You would say what level of lung cancer do they have? Where is it metastasized? Is it metastasized? How big is the primary? All these things are just fundamental to being able to do a good trial. We feel that doing a good trial means you have to understand the stage of pathology in Alzheimer's disease as well, and that includes both amyloid and tau at the moment.

No, that's fascinating. We'll talk about the P-tau217 assay a little bit later in more detail. I do want to still talk about the context here a little bit. It's interesting. As the investment community, we often sort of feel as if we have to choose an investment vehicle of choice by a company, by a stock, by an effort. And there was this tendency to do comparisons, which is what we're given. So that's what we have to have. You can't have 3 entrees. You got to pick one. And nonetheless, it sets up the sort of notion of this competitive dynamic and opposition to each other. And then I think back on everything that the world has experienced and that we, who are sort of beneficiaries of the efforts of the pharmaceutical industry around COVID, there was kind of this sort of humanitarian understanding of like driving with collaboration, regulators all a sudden, things like Lightspeed, entered the vernacular and the rapidity and the communication and we got vaccines into arms with a rapidity that was just remarkable. You would think that the Alzheimer's objectives aspirationally are equivalent galaxies, quite dark, that's the analogy, but then that we could strive towards. There's probably not a single person in this room, whether you're long or short, an investment vehicle or a company, a stock in this space, who does not endogenously want there to be success. So what I observed in this space, particularly for Alzheimer's, is that there's this degree of kind of artisanal attitude nodes, like we weren't expecting this or this was harsher than that. Is that a fair characterization? Are things going to improve? Particularly coming from oncology, Project Moonshot, we're all going to get there, does it seem that way in outside numbers? What do you think?

Well, I think that we're on an incredibly rapidly moving trajectory now. So I'm encouraged by the speed at which we're moving to date. And I think we have to remember that even in cancer, as you think back to a number of years ago, as Mark said, it started with incremental steps, but then each step got larger and larger as you understand the disease. And you have to remember, Lilly, we have been at this now for more than 3 decades. And the fact is every challenge that we faced, successful, unsuccessful trials, what it may have been, we built that learning into the next work that we did. And that -- I think that's culminated in the work that we're doing today. So the fact that we truly understand amyloid clearing, tau, the impact of tau in the brain, thanks to the work that people like Dr. Mintun and Dr. Skovronsky and others have done over the years, has led us to the point that I don't think where -- things that are happening today are just happenstance or a fluke. They're built on the fact that we learned about some of these things in these trials. We learned that you need to clear amyloid, and we believe you need to clear it fast. We believe that you need to be very thoughtful about the patient population that's in your trial because you needed to make sure that you're truly getting the patients that are going to respond to these medicines, not people that don't have Alzheimer's pathology, not people that are either too early or too late in their disease for you to be able to help. And then how do you measure how they're doing in the trials and the effect size and those types of things. And so we didn't just stumble upon some of the things that we think are now leading to the success that we're seeing today. That's decades of iterations. And that's what oncology went through and still goes through today. Every trial builds on the success of the past, but I think we're at the point now where our knowledge of the disease is significant enough that I think we're very intentional about what we're doing today. So I don't know if that answers your question, but I think we're at the point now where I think you're going to see more and more rapidly solutions coming for these patients, greater understanding as we saw in oncology that just continues to keep the momentum going. And I couldn't be more excited about where we're going to be 5 years from now, 10 years from now. But even in the next year, we hope to have answers that are very meaningful for people with Alzheimer's. So that's why I was so excited. But I think this area is just going to expand over the next few years. Every trial gives us such incredible insight about how to study for the next medicine.

Exactly. Right. In the next year, now you're speaking our language, all of which we are measured by. So let's get a little bit more concrete with donanemab. The next year, you're certainly going to have many more cards to fold. The initial chapters of this year have been quite topsy-turvy. And as we think about your programs and your clinical trial development strategies and designs, so we have TRAILBLAZER. TRAILBLAZER II is our Phase III trial. About a year from now, we'll get that readout. Can you talk about how you believe that study and that program differentiates from the work that's come before and from competitors as well?

Yes. Well, it's a really good question. And I think the fact is that as I said, there's been a lot of challenges in this space. I mean really, if you look at it, we haven't had a cleanly successful Phase III study, even a cleanly successful with consistent endpoints Phase II study until the TRAILBLAZER-ALZ study with donanemab that we had. So this has been a lot of challenge in this space. But as I said, I think we've learned from all of those. And so what we're focused on is the fact that some of that learning, we think, could be critical in reaching success in these trials. So a couple of things that are important to us. We think that, particularly in Alzheimer's clearing amyloid, and we very much align with the FDA that that is a robust surrogate for clinical benefit for these medicines, so how fast particularly you can clear that plaque and how early, we think, is important. And we do think that it's too soon to tell, but there may be differences between the medicines as to how quickly they clear plaque, and we believe that donanemab does it the most quickly of what the data is that we've seen to date. But I think, and this is where the work that Avid has done has changed the trajectory here in Alzheimer's disease, is the ability to identify really which patients you can help. So if you think about what we did in TRAILBLAZER-ALZ and what we're doing in ALZ 2, we focused on tau as an area that we think offers a great bit of insight into how you can ensure that you see an effect of these medicines in patients. And so if patients have no tau or very low tau, the challenge with those patients is that they may not progress within the 18 months or, in other cases, 2 years of your trial. The fact is if you don't progress on either arm, then you can't show a difference between the 2 arms. So we're concerned, if you're not screening for tau and screening out those patients, then that may dampen the effect. Now the other end of the spectrum is probably even more interesting, which is patients that have high tau. So we actually added a set of these patients into our TRAILBLAZER-2 study to study how these patients perform in these trials. Because the challenge here is these patients have a lot of tau. They're high tau. Their disease may progress more quickly. And so we may be less able to help them. I think they still may do well on these medicines, but not as well as those that are in more of an intermediate stage. So whether you're staging for this disease may matter. We'll get that answer with TRAILBLAZER-2 because we have both sets in our study. The intermediate tau is the primary endpoint, but we'll also get the data on the high tau and see if that matters. And that's the difference between the trials as well with our competitors. And then the third that many of you asked questions about at this meeting is around the outcome measures. So how do you measure success in these trials? And this is something that Mark and others at Lilly have led for years, is studying all the data, not just our own data, which is significant, but across the field. What are the best endpoints for patients with mild Alzheimer's? And we feel quite strongly that the iADRS, which is our primary endpoint, is the most sensitive, robust measure, the most likely to show an effect when there is an effect of the medicine. But traditional course has been CDR Sum of Boxes. That has been a fraught journey for all of us in this space, even for Lilly. We saw in our own trial, sister trials for solanezumab that we had opposite results. And this also hit the aducanumab trials. So I think those are some of the reasons that we're just making sure that people think about those -- that context as we look to the readouts that are happening later this year and then ours next year that we think we've set donanemab up for the best chance of success based on those years and years of study. We certainly hope for the patient set that all these trials knock it out of the park. That would be a great answer and a great confirmation of the space. But that may be a challenge. It may be a bit unrealistic when you take into account all the challenges we faced to date to think that the next 4 will all be statistically significant and highly positive, might be a bit on the optimistic side. I'm an optimist, but that might be stretching it just a little too far. So we'll certainly look at the data with interest.

Got it. That's really comprehensive in terms of the key issues. Let's dive quickly into each of them specifically, speed of clearance. So we have TRAILBLAZER-4 head-to-head against Aduhelm, which like having a foot race with someone that's been put out back to a certain extent. What can we still learn from this study?

Yes, I think your comment is fair that from a commercial lens, probably showing superiority to aducanumab may not be as impactful as it was some time ago. But I do think that there's a lot that we learned from this trial. And as I said, one of the things we're really excited about is how quickly and how deeply donanemab clears plaque. And so what we do in these trials is once patients have cleared plaque, and the first time we measure that at 6 months, we continue to follow them. And we think that there's going to be really valuable biomarker data, particularly now we can look at it head to head, which is very helpful to aducanumab. We believe that the faster and quicker that you can clear plaque, the better that these patients will do, and biomarkers that are important to the space that we think, again, lead to indications of clinical benefit. So still a lot -- everything, there's something to be learned from every Alzheimer's trial that we do, and there's still a lot of value here. So just to give you an update, we will present that data in a meeting later this year. And just a shout out to the sites that were involved in this study. We have such a great set of sites that we've used on multiple trials. And this study actually enrolled in less than 12 weeks. So if anyone is worried that there's not an appetite for these medicines, I think that tells you that there is an appetite because this was active on both arms, physicians desperately wanted to get their patients into these trials.

Got it. The second point you made, I think, was on patient selection. So Mark, let's thread you into the discussion here. Certainly from the work that you're doing under the diagnostics tied with Lilly, in particular, with the P-tau217 assay, talk to us about next steps from a development and a regulatory standpoint.

So the P-tau217 is a measure of the phosphorylated tau that leaks out of the brain into the blood, and it's really specific for Alzheimer's disease pathology in the brain. And so you can detect it in the blood. And one of the ways that you can use it is a longitudinal measurement of what's going on in the brain during therapy trials. And so one of the things that we were able to show is in another indication that our pivotal Phase II trial was successful. The donanemab arm had a dramatic drop in P-tau217 in the blood that was sustained, even when they went off the drug because of reaching amyloid negativity. But they've also -- different academic groups have shown in a research setting, it's also really has huge potential as a diagnostic. And we believe diagnostics is going to be a really big challenge for patients in the current situation. Patients are typically, with Alzheimer's disease, actually diagnosed late, often later than when they would be suitable for early symptomatic Alzheimer's disease. The vast majority are diagnosed late. How do we increase the sort of diagnostic ecosystem to make sure patients can get diagnosed and then have therapy options? We already have 2 PET tracers, one for amyloid, which is well-known, that's been approved. It was the first approval back in 2012. The second one, not as well known, is our tau tracer, Tauvid, very limited distribution. So we're going to be planning to greatly expand those -- the distribution of those tracers as a package, so that people can actually have access to them in the United States. But we all realize, of course, a blood test would greatly lower the barriers to getting diagnosed and getting diagnostic journey. And so we are working very, very hard to take the P-tau217 assay and turn that into a commercially available test that will be done. We plan to do that through an LDT, laboratory-developed test, and make that available sometime early next year. And so we hope that that allows an ability to start that diagnostic process early. It doesn't mean that there's no reason for PET scanning or for other types of diagnostic tests. There may be patients that are in an in between intermediate level that need to have additional testing. But we hope that that will make a huge difference in being able to lower those barriers.

Perfect. Now the real world integration of what's involved to take this from a whiteboard exercise into the actual real world, you did discuss about what it's going to take to implement here. Recognizing time, I want to make sure that we continue to touch on things. The metric, iADRS, here. Talk about what kind of an effect size you seek to demonstrate in TRAILBLAZER-ALZ 2. And particularly, I think the company has commented previously that the 3-point difference that was seen from the original -- from other studies is a clinically meaningful level of achievement, and that perhaps that the regulators would concur, and therefore, that this provides you with sufficient confidence to believe that regulatory filing should that level be achieved? Fair? How do you say?

Well, I think what we're looking at is our TRAILBLAZER-ALZ demonstrated a 32% slowing of this metric. And it demonstrated a little more and a little less than the other types of clinical measures. But the iADRS, which is, we believe, is the most robust and most powerful for being able to show the effect of an Alzheimer's drug, showed the 32% slowing. We believe that's clinically significant. In fact, when you actually sort of -- if you just sort of draw a line, you realize that the patients that were on donanemab are -- at 18 months are equal to the amount of clinical decline that the patients that were on placebo at 12 months, which is implying sort of like a 6 months sort of benefit. We've ratcheted back the disease for 6 months. I see that is actually really important. And if that can continue, and of course, that's a big if, but if it can continue, what that means is that the ability to be able to slow this disease by about 1/3 means that over a 3-year period, you could potentially be giving people back a whole year. So 6 months is, I think, really important and meaningful. If it only lengthens over time, I think it will just continue to become even a stronger and stronger benefit. We hope that TRAILBLAZER-2, in the way we've described it and sort of walked through the details, will be able to very powerfully replicate the data that we have in our TRAILBLAZER-ALZ 1 trial. And so we see that as being very suitable for submission and, we hope, approval.

And then lastly, you both made reference to kind of the scaling of the benefit, the 6-month perhaps in terms of delay in the progression for patients there and 6 to 12 months. To echo back to an earlier analogy I made about oncology, this kind of has resemblance to things like PFS. And so if we were to go from 6 to 12 months, can you comment a little bit about what your modeling has shown? Because you have discussed, if the trial had extended for longer periods, you could show that. What does your modeling show in terms of potential to go beyond that 6 months? And do you feel that this could be reflected perhaps in a commercial realm in terms of how you could possibly price this drug? Certainly, we admire and reward drugs on the oncology side that have a longer PFS, et cetera.

If you want to take [ amyloid ], and I'll take the commercial.

Yes, I'll take the first question. We -- I don't think we have already disclosed the sort of exact modeling. But one thing I should point to is that the patients on donanemab, ending in our Phase II trial, had less progression of tau on their tau PET scans, which is a really big deal because almost every group that has been using tau PET has shown that the more tau PET a person -- the more signal on a tau PET scan, the faster they decline. So we've already -- those patients already are going into the next 18 months, if you want to look at that way, less sick with less pathology in their brain than the patients who were on placebo. The other thing is that the P-tau217, which a lot of research centers sort of feel is the sort of leading edge of the tau pathology, is actually lower. So in the blood samples, the P-tau217 that's coming from their brain is actually considerably low or significantly lower, which means that we think that the formation of the tau pathology is actually now proceeding at a slower rate. And the neat thing about our Phase II trial is that there was a fair percentage of patients that went off drug at 6 months because they had amyloid cleared. At that point, we had a year of following them, and that P-tau217 continued to stay down. It did not bounce up. Now their amyloid also continued to stay down but seeing that the P-tau pathology. So we believe we have good reason to be able to predict that those patients will not continue to progress like the placebo patients. Now that said, Anne has to -- maybe can make a few comments about what that means.

Yes. obviously, as you know, we can't comment on pricing strategy prior to approval. But because of the attributes that, I think, Mark just mentioned, I think we're excited about the value that donanemab could bring to the health care system, because the fact is that many patients are able to stop dosing even after 6 months. And that's not just in the fact that then they would save drug costs and infusion costs, but also monitoring, scanning, those types of things that you have to do to make sure that you're following these patients carefully. So we bring that -- we think that that's a pretty strong value proposition. And the other thing that I'd like to believe that we're known for at Lilly, I think we've been a leader in things like value-based partnerships and agreements. And we've shown that in diabetes, oncology, immunology and that same thinking and approach, we'll take care in Alzheimer's because our goal is always to make sure that these medicines are accessible to patients. But I don't think we can lose sight of the fact that Alzheimer's cost the world, I think the number I last saw was $1 trillion a year across the globe to care for these patients and look after them. And so we've got to believe that treatment modifiers like donanemab and others, if successful, are going to help address that number. That number is just spiraling out of control. And the way to do that is to have medicines that modify the disease. So we're definitely trying to be part of the solution here with bringing a medicine forward that helps slow the progression of the disease, hopefully, keep people out of care longer if we can, help the caregivers retain some ability to function in their normal lives. So we're very committed to finding answers to help make sure we can address that number because it's daunting. It could double by the end of the decade.

Certainly makes sense. And to get to that destination, actualization to be able to address that trillions in health care cost, there's kind of the passage involves getting past 2 gatekeepers, won't call them [ controls ] under the bridge, just call them gatekeepers, the FDA and the CMS. So let me ask you a couple of questions here. Your perception of their take on a couple of stuff, TRAILBLAZER-ALZ, a Phase II study. Your level of confidence says the FDA will find the results from this study as validated, pivotal study supportive for potential approval?

Yes. We did that prospectively as a pivotal registration level study.

Okay. Have you whispered into the ear or had conversations with CMS about that? Any feedback there?

So we have -- I have to say CMS has been open to having dialogue with us. We've had dialogue with them throughout both the national coverage determination, and then they've shown openness to continue to meet. In particular, what I've been impressed by is they've been very interested in understanding the TRAILBLAZER-2 Phase III program. What endpoints are in the trial? What's the design of the trial? What patient population we've enrolled? Many of the concerns that they've had around representative of kind of the Medicare population, I think many of those are built into our trial. We've been passionate of being very inclusive in our trials and who we enrolled. So I've been impressed that they've been open and willing to have dialogue and continue to understand that program, such that when we have the TB-2 data, we'll bring that to them and I think have a robust conversation. But we're in unprecedented times here with CMS. This is not something they've ever done before. I think we remain hopeful that a robust Phase III study, particularly one that then brings potentially FDA approval, should provide coverage for the American people. And there's no other therapeutic area where that's not been the case, where with that kind of data, you don't have coverage. So it's our goal to make sure they understand that data and then we have it to provide that as quickly as possible and request they reconsider this.

Yes. Well, robust Phase III data would certainly be the pillar of our dreams. But in the investment community, we're gluttons for torture, so let me propose a hypothetical to you. So Lilly has stated that you expect results from TRAILBLAZER-2 to provide the basis for approval. If only, let's say, the -- and that the interest needs to be statistically significant. But in a scenario where perhaps it is not, but then secondary endpoints or vice versa, the primary is and the secondary endpoints. And I know iADRS is actually a mathematical kind of composite of things like CDR Sum of Boxes anyway, but you get kind of like an imperfect report card to a certain extent. Is it your belief that the drug is still approval in the eyes of the FDA?

Would you like to hop that one?

The hypothetical is interesting. I mean, obviously, anytime you fail on your primary, you -- everything depends on exactly what those other things are and how powerful and convincing they are and how much will look like post hoc. But the iADRS is so much more powerful than all the others. And I will take a tiny bit of issue with the idea they've added together because actually, all of the measures are actually just individual smaller things added together. So the CDR Sum of Boxes is a bunch of sum of boxes. It's a bunch of individual things added together. So is CD -- ADAS-cog and so is the functional measurement IADLs. And so the concept of adding them together and getting a combined cognitive and functional, it turns out mathematically that -- and then in reality, it's just incredibly robust. So it has a very, very high chance. So I think the -- I think it's a very low likelihood if that actually fails given how powerful it is that there is a path forward. But obviously, the data is going to be important. But it's really important is also understanding, we continue to learn about subgroups. And remember, the conversation perhaps is going to happen already when things like [ lecanemab ] and gantenerumab report out their results. And so there's a -- we're not -- as Anne said, we're not optimistic that all of these trials will hit. And then it will become really important exactly what's actually happening. Are they removing amyloid at a high amount like we are hoping to do in our trials? Is there a subgroup issue? Is ApoE4 carriers responding differently than noncarriers? A very important question to ask. Is there evidence that the drug worked, but it was just not that powerful? It was at a matter of degrees and that all the underlying, the ADAS-Cog, maybe they've been put together an iADRS composite because you can create that. They were all going in the right direction, but they didn't quite hit significance. There's just more heterogeneity under the surface in their trial. Exactly what some of the things we're worried about, is that heterogeneity does sort of hurt you in your power of your trial. So if those things are in evidence, then that will actually -- we still have a chance to sort of look carefully at reporting and have conversations with the FDA about that.

No, those are really helpful comments. I think people are recognizing that competitive trials [indiscernible] we'd be looking to see what is really focused on, how can we read across to how that influences your level of confidence and whatnot. So sticking to the FDA, during the last earnings call, [ Louise ] stated, and Lauren has been helpful to make sure I'm fairly accurate on this, that the plan is to complete the rolling submission for DMAB for accelerated approval by the end of Q2. We're at, what's today, June 14. We're almost there. How are we doing? We on track?

Yes. I can confirm that that is still the plan.

Okay. Awesome. Let's go to the other side, CMS and the NCD. The final NCD seemed to sort of leave, what was the phrase like every time a door closes, a window opens, a window seems to be open, right? There seems to be the ability to retain some flexibility. And I remember talking to Dave about this a little bit. There were some specifics with the vocabulary that looked as if, well, that was a broadly used term, and yet the final NCD also seemed to have that to enable individual drugs, perhaps based upon their clinical profile, to have a different kind of outlook. Fair? And then what's your take?

Yes. I think that's the correct take on the NCD. We were encouraged to see that CMS commented that they may see differences between the medicines. We all may see difference within these medicines, both based on maybe their MOA, it may be the benefit risk profile, the results that we may see from the trials, even how the trials are designed. And we've mentioned some of those differences here. So I was also encouraged to see that. And we do believe, you can hear probably the confidence in our voices, that we believe that TRAILBLAZER-ALZ 2 sets donanemab up for the best chance of success in this space. So we look forward to taking that data to them once we have it, and they have expressed interest in seeing that quickly. So we'll certainly partner with them to get that data to them and then establish next steps.

Got it. And then finally, just in terms of the dance that you do with the CMS, the interactions. Have you had interactions since the final NCD was issued and, therefore, have you gained any further clarity on the types of post-approval requirements that they may have in mind? Or if you have not, are you waiting to see once you have TRAILBLAZER-2 data in hand before engaging further?

No. They've been really quite open to meeting with us. So yes, we have met with them since the NCD, and we'll continue to meet with them over time. So they've been willing and welcome to do that. And again, it's been very focused on just education about the program, the space and those types of things. Really on the question you're asking around their position and understanding that, I don't believe we'll have any more clarity on where they'll go next until we have the TB-2 data. I commend that they're interested in learning such that when we have that data, then they have a look at that and then move forward from that point. But I don't know that we'll get any more clarity on what their response will be until we have that data in hand.

Okay. I've probably been unfair to everything else in the CNS realm, but Lauren's just going to have to let me bring people over to Indianapolis so we can have more extended conversation.

You'd be very welcome.

Thank you both for really insightful commentary. We really appreciate it.

Welcome.

Thank you.

Thanks.

Thank you.