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

Hi. My name is Michael Guba. I'm Citi's U.S. Healthcare Sector Specialist, filling in for Andrew Baum, who's our Global Head of Healthcare Research on -- covers major pharmaceuticals here for Citi. I'm lucky enough to be joined by Anat Ashkenazi, Senior Vice President and CFO of Eli Lilly, for a quick little fireside chat here. Taking verbose tact here, I'm here to moderate, not monopolize. So please feel free to send any of your questions to [email protected]. I'll start off with a couple of openers. But obviously, the whole point of the conference is to have a solid investor participation, so I'd appreciate anything you guys have to ask. Anat, thank you for joining us today.

Great. Great to be here.

Yes. Just to kick it off, right, kind of the elephant in the room given the Wall Street Journal headlines today, I just wanted to kind of touch base with you and see if you had any overall thoughts. Obviously, the plan hasn't been officially released yet. But pharma came out and had a press call last night, and there are some sparse details in that plan, which pretty much cover every possible drug pricing legislation that's been thrown out over the past couple of years. So just any kind of commentary there and kind of how should the investor landscape think about this plan.

Sure. Thanks. And obviously, this is a challenging question to answer with any level of precision given that we don't know what will materialize and what will be enacted and not enacted. There have been a lot of things that have been discussed in terms of potential policy changes and legislative changes. Some of the things you may have seen in the article this morning is around the potential for government negotiation, which we don't view as something that's positive for the industry or patients in general. It's really a way for government to engage in price controls, which we wouldn't believe the voters or the American population would want nor is it good for a patient given that it's going to restrict access to patients and likely restrict access to innovation. We've seen some of this transpire in countries outside the U.S. and it has not led to improved health outcomes for patients or reduction in cost for patients. So as we think about proposals and where we would be leaning in, in terms of pharma engaged and helping the system are really areas where we would allow for patients' out-of-pocket costs to be reduced. So proposals that would allow the savings and what pharma will contribute to actually go down to the patient level as opposed to be used as pay-for for other elements of the Infrastructure Bill or anything else and would inhibit or restrict the access to innovation for patients here in the U.S. So things such as reduction in out-of-pocket cost for patients at the pharmacy counter, potential caps on out-of-pocket costs, modernization of Part D, these are some of the things that we would be looking for and advocating for. So obviously, these conversations are ongoing. And as things transpire and legislations go forward, we'll continue to update the investments community on any actions there. It's a little too early to determine what, if any, impact will move forward.

Fair. All right. As I said, details seem sparse at the moment, but I guess, we'll all be looking forward to that plan and kind of seeing what the devil is in the details there. So moving on to another kind of broad-based question here. Throughout the pandemic, Lilly's business has been broadly resilient. So just amidst these kind of rising Delta headlines and everything we're seeing there, I was just curious if there are any kind of individual business lines or therapeutic areas that are seeing more of an impact and then also kind of how it breaks down versus -- from the U.S. versus ex U.S. Obviously, oncology has been an area of concern throughout the industry. So -- but any kind of commentary you have there would be helpful.

Yes, it's a good question and one that we've been answering probably throughout the past year. And it evolves, right, because the pandemic has taken turns that we haven't necessarily anticipated. So what we've seen at the start of the pandemic, while there is impact on most classes in our areas, almost everything has recovered to pre-COVID levels or now above pre-COVID levels. The 2 areas that were impacted the most that are relevant to Lilly are oncology, primarily the infused products. We don't see as much impact to Verzenio or that was -- the oral oncology products have recovered very quickly. And it's logical just given the treatment algorithm here. And the second was the CGRP market for pain. Both of these are recovering. And -- but what we have seen with the emergence of the Delta variant and the increase in the impact of the pandemic globally are 2 things, and it's different in the U.S. versus some other geographies. So I'll walk through what those impacts are. In the U.S., in oncology, what we have seen as of recent is closure of oncology practices, not to patients, but to sales reps. So our reps are not able, in some cases, to go see a physician and talk about [ our products ]. Now the -- it's a different impact than where we were 1.5 years ago at the start of the pandemic and when these practices closed down because what we've done immediately after pulling our sales force out of the field in March is quickly start enhancing our electronic capabilities, virtual capabilities, working with physicians and customers in a different way. So now when we're at that point, these systems are already in place and working well. And even the health care systems are more prepared now to deal with closures, et cetera, and still see patients as needed. So less of an impact in the U.S. Outside the U.S., we saw differences in impact based on just the growth in pandemic as well as the rate of vaccination, where we saw the greatest impact was in Japan. We talked about this on the Q2 call. So they went into the -- I think it was the third lockdown or state of emergency in Japan at the end of spring time, and that lasted for quite a while. It did have an impact on our business. We've shared that in terms of just revenues lower than what we had liked to see. It's now starting to open back up. So hopefully, we'll continue to see the recovery. We have seen some impact on South Asian countries, less of an impact on our business, but more so in terms of pandemic. But again, hopefully, we'll see the recovery as vaccination continues to roll out but also as the entire system is now more accustomed and able to deal with managing patients and working through processes in a different way.

That's helpful. That's helpful. That's helpful background kind of for the broader industry. All right. Now so diving closer towards kind of the Lilly specifics. Obviously, another topic at the center of everyone's mind is dona, right, within Alzheimer's. A lot of chaos throughout the summer there post the Aduhelm approval. So I guess just to kind of start at a high level, I guess, how should investors kind of -- can you give us an update on time line, right, for the filings there? And then we can move into kind of the details on how to think about the broader market as a whole.

So what we've said a few months ago was that we intend to submit donanemab for regulatory approval to the FDA by the end of this year. That hasn't changed. That is still our intent. And we believe the data we have from the first TRAILBLAZER study, coupled with safety data from the TRAILBLAZER-2 study, should be sufficient for that submission. We have extended and added a cohort for additional safety data, but we believe we will have what's needed for submission by the end of the year. So that's progressing as scheduled. As you can imagine, and that may be another question that you have, we're gearing up for launch. So at Lilly, obviously, we've announced the creation of a dedicated business unit for neuroscience with a dedicated leader. But we're now doing everything that we need to do to prepare for a launch potentially in the -- sometime in the second half of next year for marketing, commercialization, sales, thinking about how we shape that environment and prepare for the launch of donanemab.

Yes. So you kind of led it right into my next question. I guess I mean, for that launch, how should investors think about kind of the spend that needs to occur in order to get there just kind of given your role?

Yes, it's a good question. And when we look at spend versus revenue, they don't always align because you spend ahead of a launch and you don't have the full set of revenue, especially if you think about next year, which is a partial year. 2023 is a different story because we'll have a full year of revenue. And I will separate how we -- I'll talk strategically about how we decide on these types of investments because we have 2 major products we're going to be launching next year, both tirzepatide and donanemab. It's different when we have presence in an area like we do with diabetes, obviously, very strong presence. And know-how, skill set, people on the ground, relationship, everything is already there. So that has a different impact in terms of any investments in SG&A because we're able to better look and rebalance and make capital allocation appropriately. When we go into a new space, in a space where there's really no -- I mean, donanemab -- and now that Biogen has just launched their product, but it's really -- it's an open market in terms of -- there isn't any meaningful product on the market just yet that has been there for years with the exception of Aduhelm that just launched. So there is a need to do some patient education, shape the market. Think of how do we launch this product. This is a complex product to launch, and I'll talk about that as well. But we're making sure we're putting the right investments behind it. We'll give additional context and color on that on the December guidance call in terms of where do we see SG&A investments going. Next year, I would expect there will be some increases. But as you know, when we've talked about this in the past, we do make and have significant efforts across our commercial footprint, R&D and manufacturing to drive efficiency and productivity. So that would help offset some of these investments that would have to come through. Some of the things we learned during the last 18 months of the global pandemic is how to run the business in a different way and more efficiently. And some of these things were implemented just because this is the new state for us. So that should help balance these things, but we are doing what we need to be doing right now in terms of making sure we have the right infrastructure in place to launch this effectively. It's an important drug, not just for Lilly. It's an incredibly important drug for patients.

For sure, for sure. Kind of in just -- in that, right, moving on to kind of how to frame the overall opportunity there, I guess how should -- how large is the overall patient population for donanemab and kind of how should investors think about that? And are there any kind of points of differentiation that you'd like to highlight relative to Aduhelm?

So the global opportunity in terms of prevalence of Alzheimer's disease, our current estimate is, across the U.S., Japan, Europe, it's about 13 million to 14 million patients. As you look more narrow at the populations that we target through our clinical trials, that number is lower, and it's about 4 million to 5 million globally, about 1 million to 2 million patients in the U.S. So a sizable patient population obviously.

Very helpful. Very helpful. And then from there, I guess, like how should we think about pricing, right, especially on the heels of kind of all the controversy there? I guess how -- at a high level, is Lilly kind of approaching that topic? Obviously, it's early, right? You still have to submit. But I would love kind of just a general framework on how to think about that.

Yes, you're right. We haven't submitted so we can't discuss or even negotiate pricing just yet. It's too early for that, but it doesn't mean we're not thinking about it in terms of, as you said, what's the framework, what's the strategic framework to think about how we price this drug. And it's the general framework we have for any product we launch, and it's that the price should be commensurate with the value that we bring to the health care system. And here, there are a few elements. Obviously, there's a product now on the market, and that product was priced. So we -- and we often get asked about pricing versus a competitor. But outside of that, we look at where do we differentiate and what value, unique value we bring to the health care system. The cost to the health care system of an Alzheimer's patient is obviously significant given just the rate of deterioration. But as we think about donanemab more specifically, we have the opportunity here to bring a product to market that could have a more limited dosing schedule. So as opposed to a chronic treatment or something where a patient gets dosed for years to come, what we've seen in our study and you've seen the data is that we're able to achieve plaque clearance in 40% of the population within 6 months, and that number increases in a year and 18 months significantly. So as we think about that, we have the ability to actually treat the target. So dose the patients for, let's say, 6 months or 12 months until they cleared plaque as opposed to dosing for a longer duration. Obviously, as a payer looks at this, as health care systems look at this, this has implication in terms of the overall cost burden to those health care systems. So we look at that as well. And we believe, given that we have a differentiated product, we have the ability to do something unique here. We know that CMS looks at this as a class, and we're looking forward to seeing their draft conclusions in early next year. But at this point, we provided data into that process that highlights the unique elements of donanemab, both in terms of dosing, but also the rapid clearance of plaque, which we know links to outcomes. So these are -- this is to some extent how we're thinking about pricing for donanemab. The other element that we might be looking at, we've not started engaging on this yet, is linking price to value. And we've talked about the fact that we are very much supportive of value-based agreements with payers in the U.S. primarily, where we link price, or I should say, net price -- it's not the list price, but net price, which means rebates and discounts -- to the outcome our drug provides in the real world setting, which means we may align on a specific outcome, and then we would measure that after some period of time that we agreed on. And our net price will then be linked to that outcome, whether it was achieved or not. We've had good success with that to date. And we believe that when we engage in these types of conversations, it shows that we, as Lilly, we stand behind our drugs and what is expected to deliver for patients. So that could play a role here as well.

Got it. Just very helpful. And then, I mean, you mentioned CMS and then also kind of earlier talking about potential launch. I guess how would like a national coverage decision impact patient adoption? And then kind of more broadly speaking, how should investors think about the anticipated launch there?

So anticipated launch from a timing perspective is that if we submit at the end of this year, the launch could proceed...

Yes, exactly, if keeping the time line as stated and assuming everything goes to plan.

Then, obviously, this is a unique launch in the sense that if you look at the patient journey to date for Alzheimer's disease, it's a lengthy and complex process, and we'll look to simplify this for patients. It can take 8 to 9 months for patients to actually receive Alzheimer's diagnosis. Their first stop is a primary care physician. Actually, 100% of the cases, the first stop is a primary care physician. With some symptoms, they go through some -- not physical testing, but oftentimes surveys, questionnaires, et cetera, to assess where they are. And then it can take months for them to be referred to a specialist and then from there, months for them to get a scan if they get a scan. Right -- I believe right now, patients are eligible to be covered for one PET scan in their lifetime. You can correct that if I'm wrong, but I think that's one PET scan for a lifetime. So we will be looking to introduce something that will allow them to go through that process fairly quickly. We think of our launch as an infused product. So we would be looking to make sure that patients have quick access and easy access to these infusion centers. Given the experience we've had with our COVID antibody and obviously different -- completely different class and product, but we were engaged early on in rapidly establishing these infusion centers and allowing patients to get access. So we have -- we already have some of these relationships established. We know those centers well, and we'll leverage on that to make sure that we have those. There's also -- if you think about the incentive structure in the system, there are incentives for these infusion centers to be set up and how reimbursement works, et cetera. So I think that the good thing is from that perspective, I think that will be set up quickly and will allow patients to flow through that process more easily. But obviously, early on, we'll have to make sure patients and physicians understand the product, how to diagnose patients and help to get them through treatment quickly. If there's no incident, what we'll see in January in terms of the recommendation will be important for what we see later on in terms of reimbursement. We'll continue to advocate for that. It's obviously important throughout the process.

Helpful. Helpful. And then kind of one just question from the field here. Are you able this time to give any sort of update on the TRAILBLAZER-2 trial enrollment?

Yes. So TRAILBLAZER-2 concluded screening of patients already, and we are expecting to have the last patients' dose -- first dose by the end of this month, so by the end of Q3. So it's progressing very well and on schedule. We're pleased to see where it is. I know there were some -- I had previously on whether or not the fact that there is -- that Aduhelm is on the market will impact that. And we're not seeing that. It's possible, but we're not seeing that at this point.

Got you. All right. So anything I missed there on donanemab? In terms of a [ flow ] of questions, I think I covered them, but kind of any other questions that you get frequently, would love to kind of check.

No, good questions. We were -- we announced the start of the TRAILBLAZER-3, which is in earlier patients. So these are asymptomatic patients who have a positive amyloid plaque. So we're starting with that. We've not dosed patients yet. We expect this to initiate by end of the year. But I think that will be another exciting area for the field in general. It's to look earlier in disease and see what the impact could be of an Alzheimer's agent, of plaque lowering when patients don't even have symptoms and could potentially change the course of the disease. Obviously, much to see there. It will be a longer trial because it will be event-driven, so we'll have to see the event [ come forward ], could take several years for us to complete the trial. But it's -- that's an important investment in this field. Lilly has been engaged in Alzheimer's disease for many, many years with billions of dollars of investments, and we've always been a believer in this field. And given the huge unmet need, this is -- I think this is an important step in terms of innovation for patients and just knowledge of how early would we be able to treat. Important product [indiscernible].

Awesome. Very helpful. So moving over to tirzepatide, which you kind of mentioned earlier ahead of that anticipated launch. I guess kind of some -- I would appreciate some high-level commentary on how to think about that launch. Obviously, the GLP-1 class has performed very well throughout COVID. And kind of how should investors think about that growth going forward and anything to add there?

Yes. So another exciting product for Lilly, obviously, and I think one of the highest value products in the industry today. We are marching forward with submitting tirzepatide for approval yet this year. So very exciting progress and launch sometime in the second half of next year. You're right about the GLP market. What we've seen, not just throughout COVID, but even before that, rapid growth in the class in total. It's a class that physicians have learned to prescribe and see the benefits to patients. Obviously, Trulicity drove much of that growth in recent years. And with tirzepatide coming in, we see an opportunity for market expansion. The GLP market is already growing double digits. But we -- but it's -- I would say it's -- the penetration of the GLP market is still low relative to every -- all treatments in diabetes. So there's huge opportunity for continued growth in that class. And that's when we think of tirzepatide launch and how it will grow. And oftentimes, I get the question of cannibalization of Trulicity, but that's not where it's -- there will be some cannibalization of Trulicity. But for the most part, I expect to see market expansion with this product significantly expanding the GLP/GIP market. It was interesting what we saw with Trulicity after the launch in 2014 being the fifth GLP to market, and one could have thought this -- with GLP, you may not have a space there. We sold over $5 billion last year and we're marching towards continued growth for that product, as you've seen in the first half results. And it has grown the market substantially. And we saw the need there and the benefit of having a simple, easy-to-use once a weekly injection for patients. Tirzepatide is launching on the same platform. So from -- even from a manufacturing footprint perspective, we have the advantage of already having that in-house and that we're obviously prepared there for launch, but we'll be launching with the same easy-to-use auto injectors that we saw patients really liking that product. What we saw with Trulicity, which I expect we'll see with tirzepatide, is the fact that the adherence for patients on Trulicity is the highest we've ever seen even when you compare it to oral treatments. And oftentimes, people think that an oral medication is the easiest for patients to make as opposed to an injection. But when you think about the diabetes market and it's a market where patients progress -- it's a progressive disease that starts with prescribing diet and exercise and patients don't necessarily adhere to that regimen, and then they advance and they don't always adhere to the other regimens that are prescribed, that adherence is incredibly critical. We have the longest duration of treatment of Trulicity again when we compare it to other therapies. And I think much of that is -- it's the outcome that the product provides, but it's also the convenience. And that's what we're going to be bringing forward with tirzepatide with even greater efficacy in terms of getting patients to even normal levels of A1C, something that physicians -- never been aspired to achieve in years past. And now it's a reality where patients can actually get to normal A1C levels and see weight loss that is 14% on our highest dose, on the [ 4.5 milligrams ], which is impressive. And we know that when patients lose weight, there is benefit beyond just the number in the scale dropping. There are significant health benefits associated with that. We see it in liver. We see it in cardiac impact and other areas of the body that are impacted by higher weight. We saw it with COVID patients who are obese, have a higher risk of death in complications associated with COVID. So there are broader set of implications that patients would benefit from. So it's exciting for us. We're -- as I said earlier on, this is an area we know very well. And we execute exceptionally well in this space in diabetes. We have strong relationships. We have strong sales forces globally in this space. We have great relationships, credibility as well, which is important with health care physicians in the U.S. and outside the U.S. So that should -- all these elements should help us move forward with a very strong launch with tirzepatide.

Very helpful. Okay. Kind of going further down, now moving over towards your bread and butter. Obviously, the ProQR collaboration was announced last night. So I guess like I'd love to kind of hear your high-level commentary there on the rationale and then kind of move over from there over to kind of the broader BD strategy and kind of any changes notably within CMS given the Aduhelm approval.

So what you saw yesterday in the announcement -- and it wasn't the first announcement we've made in this space. And we may have -- I think we've shared this in the past, but we're building a capability around new modalities, RNA included, that would allow us to implement some of these technologies and approaches through drug development. So this is one of them. We've done others in the past. I expect we'll do more in the future. And it's linked to your second question around business development. This is core to our strategy. So as we think about where do we invest, and this is one good example, is we invest in 2 things. One is innovative products, where it's an actual molecule and we invest in it maybe in early-stage development or a Phase II. I will say, my preference is typically to go earlier because that's where we can add real value from an R&D perspective. We're able to invest more, obviously, because these are lower costs as you go to a Phase I asset, for example. But even if it's a [ Phase II ], there are areas that are -- products that are in our wheelhouse, in our core therapeutic areas, where we believe we can enrich the pipeline with their molecules. The second category and what we saw yesterday is around technologies and platforms where we view certain areas as some that could be breakthrough moving forward, and we're able to place a number of bets across multiple of these technologies and platforms and bring them in-house as another driver for drug development. So this is the collaboration we've announced yesterday. We've announced other collaborations. And those -- you should continue to see this from us. These type of investments tend to be in the range of $1 billion, maybe $2 billion. They're kind of lower numbers. It doesn't mean we're not going to do another Loxo-like acquisition. It's the same size. We haven't done these often. In the 20 years that I've been with Lilly, we did 2 kind of larger scale for Lilly. First was ImClone and the second was Loxo. These are more rare opportunities to find. It's not that we don't want to do them, but it's harder to find. And when we pay for these products, we want to make sure we pay appropriately and we don't overpay, obviously. But it would be -- it would have to be companies that have unique innovative platforms typically coupled with strong talent and capabilities we'll bring together. They wouldn't be -- you shouldn't expect us to see do mergers of equals. That's outside our strategy. But if there was something that was higher than $1 billion to $2 billion and came through, we look at this very closely. And if we feel that it kind of passes or have very high thresholds for these types of investments, we'll proceed. But I will say it's hard to find these type of opportunities. The more likely in years to come is these small type of business development acquisitions in our core areas.

Makes sense. Makes sense. And kind of on that point, FTC has obviously kind of come out a little bit more aggressively, we'll say, against the pharmaceutical industry. So I mean, I guess, how are you thinking about that? Does that play into this development strategy? And to your point, you just said the focus will likely be on those 1 to 2 areas without completely excluding anything higher. But I would imagine there's an impact there, right, in terms of deal size, right, and overlapping modalities. And I guess like broadly, how are you thinking about business development with the backdrop of a little bit more of a stringent FTC?

Yes. So you're right in your observation. We've noticed this as well, right, a greater focus from the FTC on these types of transactions. Likely going to continue. So that's already kind of ongoing assumption at this point. When we engage in the smaller acquisitions and their breakthrough products in early preclinical stages or early stage clinical, the risk for any competitive situation concerns from an FTC perspective should be lower. There should be less of that. It doesn't mean it goes away. So I expect that the FTC scrutiny as it continues to have lower -- less of an impact on us just given our strategy. But obviously, anything that comes through, we'll look at that through that lens as well. What we've seen so far from some of the companies that went through, it didn't stop them from proceeding with these transactions. But these transactions now are scrutinized after the announcements. But we've always looked at this, so we'll continue to look at these very, very closely. I will say the interesting piece is on the flip side. So what are these transactions going to -- if the FTC does increase the level of scrutiny significantly, does it result in more required divestitures of assets? And how does that translate with -- to other business development [ opportunity ] on the receiving side as opposed to the acquiring side? So we'll continue to look at that and evaluate. No, I don't envision any major impact because again, we're going -- earlier and typically smaller opportunities.

Makes sense. Makes sense. And then kind of just taking another one that I just got from the field, how should investors think about the potential of lebrikizumab given kind of the recent FDA communication around JAKs? And then on the back of that, I guess, is there anything else by way of Lilly's strategy given the rebate on Taltz or how you guys can secure formulary access for lebri?

Yes. So for -- we -- obviously, we saw the same announcements that came from the FDA around the JAK and the safety profile. We'll wait and see what the label impacts would be, obviously. So hard to speculate at this point. As we think about lebrikizumab, obviously, in IL-13, different class. And specifically to that therapeutic area and disease states in atopic dermatitis, the patient population is large and fairly heterogeneous. So we believe that as patients -- as physicians look for ways to treat patients and the drug that will work best for the patient, having a diverse set of options across multiple classes is the right thing and one that is still needed in this space. So coming in with another mechanism of action should help and provide opportunities for patients and a good opportunity for lebri. Just as a reminder, from a data perspective, we saw the -- we had the top line data release in terms of skin clearance, which was very robust and positions us to have a differentiated product in terms of providing that skin clearance, itch relief as well as any impact to sleep disturbance. So we're excited to have that product come through and offer meaningful value to patients. You asked about the contracting in Taltz, and maybe the question is on the heels of what we announced with the ESI agreement. And that specific agreement does not -- will not impact, shouldn't impact the access for lebrikizumab. For Taltz specifically, that allowed us to materially expand access. The Taltz commercial access now is very broad, which is good. It allows us to drive adoption of the product. And what we're seeing, which not unexpected, is that physicians know that they have access and patients can get reimbursed on that product. They're prescribing it to all patients, right -- not all, but they're prescribing to more patients, patients that may be part of the ESI program or maybe in a different program. But they're seeing the benefit that patients are getting the very rapid clearance that Taltz offers, allows them to feel more comfortable with the drug and just increase the volume of prescribing. So as we think about lebrikizumab, we'll do what we always do, which is negotiate with payers based on the value the drug is providing and the level of differentiation and innovation it's bringing to the marketplace, which we believe, again, we have. There's a maintenance study that's still ongoing so that -- we need to wait for that to read out and then we'll have the full data package and be able to move forward with submission. And later on, once we have approval and negotiate access and pricing, it wouldn't necessarily be linked to Taltz. It might be, but it's -- that's not how we necessarily look at it today, but rather on the merit of the product itself and what it can provide. Another exciting -- if you think about immunology and what Lilly has done in immunology, and if you go 10 years ago, we weren't present in immunology, right? We've built that capability over years, investing in different assets and bringing this asset in. We're really broadening our presence in that space and building the relationship and credibility that we have with physicians.

For sure. For sure. Another one from the field. You have 2 really exciting and potentially very significant launches outside of tirzepatide and Aduhelm coming up next year with Verzenio in the adjuvant space and Jardiance in HF. Can you talk about how Lilly expects the ramp for those -- what Lilly expects the ramp for those to look like and what investment needs to be made kind of to support those potential launches?

Yes. So both of these -- in terms of how we support these launches, both are sitting on existing infrastructure. So that helps from that perspective. We already have the field force for Verzenio. Same thing for Jardiance. Different for Jardiance given that we are not targeting cardiologists today, so it's a different way of thinking about how we commercialize that product. For Verzenio, we shared some of the discussion on data around the high Ki67 cohort. And hopefully, that will move forward, potential approval yet this year within the current approval time line. And then beyond that, we have a second or an interim readout for the broader population sometime middle next year. So we're ready for that launch and gearing up for that. I think it's -- the Ki67 is one measurement that's well known and understood by oncologists. So it's not something where we have to go out and educate on testing for Ki67. It's very prevalent from a testing perspective. So that's easier from that perspective in terms of diagnosing the right patients to get on Verzenio. And we -- one of the reasons we saw this -- the OS benefit for this cohort of patients early on is that this marker is correlated with forced prognosis of disease. So it's logical, unfortunately, that we would see more events in the survival data for this cohort of patients. We're confident we'll see that overall survival trends for the rest of the population. It just takes longer for these patients to progress lower, which is good. The fewer events, the better it is for patients, but we should see that next year. So from an uptake perspective, the way to think about it is the product is already on the market. It's a well-known measure that's available. We already have the resources needed. So once it's approved -- we obviously are not promoting on this right now until it's approved. Once it's approved, we can start communicating that and should see an impact next year. For Jardiance on the cardio side, so right now, we're targeting the diabetes, obviously, indications. And we just announced this morning the breakthrough designation. So we're excited to see those benefits for Jardiance. I would say it just -- it cements the Jardiance value of patients. This product is already best in class in terms of diabetes and cardiac impact as we saw several years ago. And it just provides another layer of comfort for physicians to continue to prescribe that. We'll now have to look at how we get cardiologists to feel more comfortable. This is a group that doesn't move with early adoption fast. So that's work we will have to do with our partners, BI. And obviously, we'll engage in that moving forward.

Helpful. Helpful. Kind of coming up towards the end here, but just 1 or 2 more from the client base. So Lilly has invested a significant amount of R&D in COVID therapeutics over the last year. Could you help quantify the level of spend that needs to come out of the business as we look forward to next year? Given Lilly will also be increasing promotional spend as things return to normal, how should we think about the net change in OpEx? Do these wash out? Or should we still expect some sort of impact there next year?

So you're right. We've made significant investments in COVID antibodies last year. I'm incredibly proud of what we did there because we're able to deliver our product in under a year and under incredibly critical circumstances. Our data shows that as of early this year, we have -- we estimate about 10,000 lives were saved because of the use of antibodies. So very impressive. We've invested $450 million in R&D, in the COVID R&D, last year. This year, we said our estimate was that we will be investing $400 million to $500 million. Right now, given where things are, we expect that to be on the lower end of that range for total. So combine these 2, just short of $1 billion of R&D investments. There wasn't much from an SG&A perspective given that it's an EUA. Obviously, the ability to promote is more limited. So as you think about the pushes and pulls, the $450 million last year were out. This year, closer to $400 million in total. That would -- should not repeat itself next year. Obviously, we're a science-based company. If we need to invest anything differently, we'll provide that guidance in December, but that's for this year. But if you think about this year and the pushes and pulls, kind of the pluses and minuses, we did put in TRAILBLAZER-2 and increased our R&D guidance associated with those investments. We had a high level of conviction in the molecule, so we put the investments behind it. Those investments should continue going into next year. And then obviously, the tirzepatide obesity studies, there is -- there are 3 studies that started this year, so you should continue to see those investments going to next year.

Very helpful. And then kind of one last one from the field. Can you give us any update on the potential LOXO-305 filing?

Yes. So I would say at this point, no change in what we previously communicated. We're obviously incredibly excited to see the data that we saw that's earlier stage, but the overall response rate was very impressive. And it seemed durable for the 18 months that we've tracked patients, both in CLL and MCL. So exciting data. Sometimes in solid tumors and oncology, you can get approval based on more limited data. Hematology was a bit more challenging. So at this point, there's no change to our estimate in terms of potential review time approval, et cetera. We're focused right now on our Phase III and initiating that work moving forward. If there are any changes there as we're having discussions with the FDA, obviously, we'll provide updates on that. Another exciting project.

Yes, absolutely. Absolutely. We look forward to it. So with that, I mean, we're right up on the edge there. I just want to -- is there anything like a chance for last comments or anything I missed here? Any kind of broad message you'd like to give to the investor base? Or did we cover it?

You covered a lot. I will say -- and this is the conversation I've had in recent days. We allocate 45 minutes for Q&A, but there's so much that's going on at Lilly that it's almost insufficient, right? There's -- we can probably spend another 45 minutes and talk about other earlier stage molecule that we have in the pipeline and other progressions that we've missed. What we've done in the last couple of years in terms of pipeline progression is incredibly impressive. And I think it's evidence of the strategy. We've had a consistent strategy for years, and we haven't changed it, right? It was very focused in our core therapeutic areas, organic growth supplemented with bolt-on add-on acquisitions in our area of specialty, enhancing our presence on the commercial side, building skill set on the virtual side, and you're seeing all this come through with really unique innovations we're bringing to market and coupled with stellar execution. So it's kind of a win-win right now. I always say in [ comments ], when we win, patients win. So it's exciting to be here today. It's an exciting company, tremendous potential ahead of us long term. We have a couple of, as you said, very exciting launches. We also have to invest in these launches. So for the investors sitting on the call today, as you think about this, we do have an investment year next year. And it's in our kind of long-term interest to do these well. We can't miss on these opportunities. We have to invest and invest to win in these spaces. So you'll see us make those decisions, and then we should see the long-term growth come right behind it as these products grow rapidly and then the second cohort of products [ growing ] right behind them. So thank you for all those on the call. Thank you for the really good questions and for those who are investors, being an investor in Lilly or having an interest in the company.

Awesome. Thank you very much for joining us. Again, I'm Michael Guba filling in for Andrew Baum, Citi's pharmaceutical analyst. [ Pleasure to have you ] today.

Thanks, Michael.