All right, good morning, everyone. Day two at the 37th Annual Piper Sandler Healthcare Conference, and we're delighted to have the team from AbbVie with us. This is David Amsellem from the Piper Sandler Biopharma Team. So we have Roopal Thakkar, Head of R&D. We have Scott Reents, CFO. We have Jeff Stewart, Chief Commercial Officer. Certainly lots to talk about. I wanted to kick things off with a high-level question, and I'll try to ignore the construction. So at a high level, I would say in biotech this year, we've seen the best of times. We've seen the worst of times. What we're also seeing more recently is an uptick in M&A activity. So it kind of leads me to a question about how AbbVie is thinking about capital deployment.
Where does the company stand regarding its motivation to do larger-scale transactions along the lines of, say, ImmunoGen a few years back? Or is the focus going to continue to be a brisk stream of licensings and bolt-ons that continue to bolster the pipeline? So just help us understand philosophically how you're thinking about that. And thanks for attending, and I'll turn it over to you.
Yeah, no, thank you, David. Thank you for having us here. It's a good question. I would say that when we think about our approach to capital deployment, but business development in general, it really is a function of our strategy. We are fortunate to have a clear line of sight of growth with the assets that we have in place well into the next decade. So that means you've seen us do roughly 30 transactions since the beginning of last year. And those transactions were typically smaller size in nature. They were things that we did along the platform. So with Nimble and the oral peptide platform that we took in place, Capstan, B-cell depletion, 8Rx with siRNA. And so we've done platform deals.
We've also done single-asset deals looking for monotherapies across our therapeutic areas, as well as in the obesity space, including potential combination partners across all those areas as well. So it's really been a number of small transactions to drive growth well beyond the next decade or into the back half of the next decade. That's been our primary focus. And that's a strategic decision. Again, with the assets in place today and driving growth well into the next decade, we're able to do that. We're fortunate to have a very strong balance sheet, very strong cash flow generation. So it's not a capacity constraint that we have in place at all. That said, if we were to see something that was compelling in nature that did offer some short-term revenue or near-term revenue, I should say, that's something we would shy away from.
That's just not been our primary focus.
Yeah. Any appetite to venture outside of your core therapeutic pillars? I know obesity, you're venturing into the space, but how are you thinking about other therapeutic pillars more broadly?
Yeah, so I would say that obesity, certainly with the novel asset that we acquired within the Gubra transaction, that's an important one. You'll see us continue to look into that obesity space. We're not finished there, and so we'll continue to look there. I would say when you look at our therapeutic areas with immunology, oncology, neuroscience, and eye care and aesthetics, that's a very broad set of indications, a very broad set of large patient populations that are out there. So we will, though, think about within those areas, are there adjacencies that we can look at? And again, looking more for opportunity and compelling opportunities where we can elevate the standard of care and differentiate the therapies that we bring to market.
Okay, and then switching gears to a cost structure question and op margins, and not just for 2026, but really long term. One of the nice things is you don't have LOE exposure, so that's the good news here. But how should we think about, with all the organic growth here and the absence of LOE exposure, how should we think about the extent of margin expansion in the coming years, and particularly when balanced against continued heavy R&D investment?
Yeah, no, happy to talk about that. So again, assets in place, clear line of sight of growth well into the next decade. We have also given specific long-term guidance of high-single-digit growth from the post-Humira LOE period 2024 through 2029. And what we also talked about when we have given that, we have talked about continued and EPS growing at a faster rate than revenue driven by operating margin expansion. Our philosophy has been, even going into the Humira LOE, to continue to invest in the business. We have increased our R&D investment on an absolute dollar perspective by over $2.5 billion since 2022. We have continued to invest in the business. So if you think about our margin and our expansion over time, you are going to see our gross margin really relatively stable now that our product mix is somewhat stabilized after the Humira LOE.
R&D, as I said, we've increased on absolute dollar. You'll see us continue to increase that on absolute dollar. The current profile is just under 15% of sales with the guidance that we gave on our third quarter call. I would say you should think about that roughly in line with that. So it'll grow on an absolute basis, roughly in line with sales growth. But you'll see the expansion of operating margin coming from the SG&A line. We'll have leverage as sales grows. We've got the ability to capitalize on that. We've historically done that as well. And we'll continue to drive efficiencies. And so you can think about operating margin expanding. It's expanded this year. You think about it continuing to expand at a steady rate over the next several years as we drive greater EPS growth relative to the sales growth through the end of the decade.
Okay, that's helpful. So I wanted to dive into the commercial portfolio. Maybe a question for Jeff and also Roopal. So thinking about Skyrizi and the IL-23 market, so you've got a competitor in Tremfya, and one thing that J&J has touted is its sub-Q induction option. So I guess my question here is, how are you thinking about potential impact here on Skyrizi? And also, can you talk to your own sub-Q induction option for Skyrizi that's in the works?
Yeah, thanks for the question. So Skyrizi is a really exceptional product, and in the third quarter, grew 46% year over year with very balanced growth, I would say, across IBD and the psoriatic disease, where we launched the original indication back in late 2018, I think. And so if I think about why is Skyrizi such an exceptional product in IBD, it's first, we really started to restate the efficacy dynamic. So we hit all endpoints on the classical ones, a clinical remission, how much do you feel better? But then really what we did is based on the designs that Roopal came up with and his team is we could really see totally distinctive endoscopic remission. And so physicians really like the profile, and they love the convenience of it for two reasons. First, it's really the only product that has true eight-week dosing.
And also, we have a unique on-body device. Basically, patients can't feel the needle. They can't see it, and they love it. Now, to your point, Tremfya, how do you think about what's happening with the market as that comes in? Now, we knew that there would be some share pressure within the IL-23 category. You plan for that because Tremfya is a good drug. We don't think it stacks completely with Skyrizi based on the pure efficacy and convenience. But nonetheless, what we've seen is a rapid, rapid increase in that segment size. So I think I highlighted on the third call, if you look at the IL-23, I'll use Ulcerative Colitis as an example. 18 months ago, the IL-23 subcategory was about 4%. Now it's approaching 40%. So this is really a big lift in sort of the preference around the market.
You'll see basically Skyrizi and Tremfya both growing over that time period. The other perspective I give is basically how the markets develop is we look at Psoriasis or Psoriatic Disease. When the IL-23s really first launched six years ago, you had about single-digit IL-23 total patients in the category. Now it's 60%. 60% of all patients in psoriasis are on there. So we see basically some share movement from new to brand share, but certainly offset by huge market expansion. So that's kind of how we look at it. Now, you mentioned the sub-Q induction. And there's clearly a segment of physicians, for example, maybe they don't have access to an infusion center right in their IBD center or suite. They have to go to a hospital. They have to make an appointment. Those are the physicians that have adopted on the early days the sub-Q induction.
But we also have one that's coming. And so we'll quickly, sort of relatively quickly, close that gap. And Roopal can highlight where we are with that program, with that OBI or that on-body device.
Maybe a couple of comments. Our sub-Q data in Crohn's will be available the first half of next year, and we'll begin the submission process, and another perspective to add on how we address IBD. I think at AbbVie, we can do something quite unique, and we consider this as lines of therapy and different approaches and how clinicians are trying to come up with that best innovation for an individualized patient, so when we're out there talking about Skyrizi in Crohn's or ulcerative colitis, the main focus and the best data is in that treatment naive group, and that's where we also see fantastic safety and this terrific profile that Jeff was describing, and when you're able to do that across UC and Crohn's, you're also able to now talk about Rinvoq, which we've had a recent update in our label that gives physicians more flexibility.
So they don't, in all patients, have to wait to go through an anti-TNF. They can go prior to that if they feel that an anti-TNF is not appropriate. So what we're able to bring in Jeff's team and the sales force and our medical affairs teams is to be able to talk about Skyrizi in that treatment naive population and then say, "Look, if you need another therapy, we can come in with a very convenient oral, which has best in category efficacy across Crohn's and UC." So in fact, when AbbVie is talking about IBD, we can cover multiple patient types, multiple patient lines, and you really don't need to consider any other therapy other than what we're offering until we start bringing novel therapies in the future.
I wanted to take a step back and talk about novel therapies because there is a lot of development right now in IBD. This is a longer-term question about Skyrizi and the IL-23s and IBD in particular. Looking at the broader IBD development pipeline in the industry, I'm looking in particular at the TL1As, for instance, a lot of excitement there. How do you envision the impact of the TL1As on, say, a frontline option like Skyrizi and IL-23s more broadly? And what about the potential impact of a novel mechanism like the TL1As on a second line option like Rinvoq?
So whether it's TL1A or maybe upcoming oral therapies, I think there's been data released over the last year or so. I'll focus on ulcerative colitis because I think that's where most of the data are. That's about a third of the IBD market. Remember, Crohn's is about two-thirds. So when you look at Skyrizi and Rinvoq, we cover very robustly UC and Crohn's. But specifically to some of these emerging assets, we see the efficacy. We don't see it differentiating against a Skyrizi or Rinvoq in its monotherapy form. And that's why we would be interested in novel mechanisms like a TL1A, which we have our own, but more as a combination agent given the orthogonal nature of the mechanisms with something like a Skyrizi and the safety profiles that we're seeing with these assets.
We think there's a better way to improve standard of care is through combination approaches. So one thing that we're working on is exactly that. We have Skyrizi as a backbone. We're combining it with our own internal alpha-4 beta-7. We have IL-1 alpha-beta. These are in phase two right now.
That's what's the Lutikizumab?
Lutikizumab, where we've seen strong data on Hidradenitis Suppurativa, and it's in phase three for that. And we'll see that data end of next year. Those combination data will start to read out next year. The TL1A that we have has an extended half-life, so we would anticipate the dosing paradigm that Jeff was speaking about, the only one to be able to go to every eight weeks, which would combine nicely with Skyrizi. We also have a TREM-1. These will begin combinations next year. So we see the advancement isn't bringing forward a new monotherapy that is still within the efficacy paradigm that we've established with Skyrizi and Rinvoq or even below. To exceed that, we think the combination approach is the best way, and that's what we're really working on.
And then one more question about novel mechanisms. You mentioned some other agents. There's Obefazimod, the Abivax product that's mechanistically distinct. So I mean, again, a question here is, as you think about beyond TL1As, I mean, how do you think about an agent like that, another oral? And obviously, this is a very data-driven market, so oral convenience is great, but the data matters, of course. But how do you think about an agent like that and its potential role?
Yeah, it's not a category of mechanism that we know well or we frankly don't really understand it very well. But that being said, there is some efficacy in induction. When you step back, as you stated, efficacy is important. Long-term data maintenance is important, but in particular, safety. And with Skyrizi and Rinvoq, we have very well-characterized safety. I guess the questions that would remain on this type of agent is, what does that mean, long-term safety, and where could something like that eventually fit in? We don't see the efficacy differentiating as of yet with induction data. We'll have to wait for maintenance. But when you look at the safety profile, Skyrizi and Rinvoq don't lead to headaches. So even if they're transient or can be addressed by another therapy to deal with the headache, we don't have that. So you can all clear that off the table.
We also, excuse me, haven't seen pancreatic enzyme elevations with Skyrizi or Rinvoq, whereas in induction data, I think with this agent, there has been elevations. Now, the question will be in maintenance, does that result in events of pancreatitis? And that's not something that you would want to see. Again, we'll have to wait for the data. Also with Rinvoq and Skyrizi, we did not have this aggressiveness in contraception, whether it's for females and males is what we've observed in their clinical trials where even males are told to continue contraception for six months after they've finished the study and to maybe even avoid the study if they have a partner that's of childbearing potential that is considering having children. So that, along with what's publicly available in their own protocols that suggests that this is a teratogenic.
So that'll be something else that will come out over time. And then this miR-124 elevated levels, there's quite a bit of literature that is associated with cardiac dysfunction, particularly heart failure risk. And I believe they're based on their endpoints that they've published and protocols. They're looking at echocardiograms and, I guess, careful assessments of EKGs. So all of that taken together, one will have to see. But right now, today, what we have in front of us with phase three tested and induction and maintenance with Skyrizi and Rinvoq, we don't have those issues, and we have very strong efficacy. And then the combos that we would bring wouldn't have these potential cardiovascular or teratogenic issues.
Sure. Let's switch gears. Rinvoq, a number of label expansion opportunities. So you had a nice win on Vitiligo. And this is a more severe population with more body surface area affected. So maybe talk to the opportunity for Rinvoq and Vitiligo. I know there's a number of other label expansion opportunities as well. And you've got SLE data, for instance, next year. But just interested in how you're thinking about the Vitiligo opportunity just as I think about it, given the dearth of options for these patients.
Yeah. I mean, I'll maybe touch on the size of the opportunity. We've highlighted in this third wave of Rinvoq indications of which vitiligo is quite unique and will be the first systemic agent, more than $2 billion of incremental sales at peak. So it's substantial. And we are seeing some nice momentum from the smaller GCA indication in Rheumatoid Arthritis. But vitiligo is unique because you only have topical approaches or very old oral approaches. And maybe I'll let Roopal highlight why this is so impressive and what we see as we move forward.
To talk about vitiligo is to talk about dermatology. We have a tremendous amount of experience with Rinvoq in derm. The dermatologists know Rinvoq already with atopic dermatitis. When you look at that category, you have best-in-class efficacy and oral convenience. Even before vitiligo, two phase 3 trials are positive for alopecia areata. We are not the first to come, as Jeff stated, in vitiligo. However, we have best-in-class efficacy. Honestly, that data were surprising to us, even to us. We had very high expectations. Then comes, excuse me, vitiligo, which also shows very strong efficacy. We have not seen a plateau yet. As we put out more data, we anticipate that the repigmentation will continue. It takes a little bit of time to address the inflammation than it takes time for the melanocytes to essentially come back and repigment.
Over time, as we continue to publish, we think that would be a great benefit across the total body and even facial repigmentation. There's topicals available, but you can't do the coverage of the patients that we studied in that level of severity. Jeff's team and our medical team has already been in front of the dermatologists with Rinvoq for many, many years. When this data comes out, we'll also have the best characterized safety profile of many of these JAK inhibitors. We'll have more than a decade of safety with that agent. I think all taken together, it will be a very important category for us.
Yeah. It seems like you occupy a pretty unique place in the vitiligo armamentarium.
Yep.
Yep. Okay. I wanted to spend a few minutes that we have left on neuroscience, which, frankly, I think kind of flies under the radar relative to your other businesses. But one product that I think has been particularly strong is Vyalev, pretty brisk uptake here. So what I'm interested in here is your thoughts on how you're gaining traction, not just in advanced Parkinson's patients, but what we're hearing from key opinion leaders is also usage of these pumps in more moderate disease as well. So how are you seeing that play out? And how does this all play into your thoughts on peak sales expectations for Vyalev?
Yeah. It's very impressive. And I would say thanks for bringing up neuroscience. I mean, it's our second biggest TA area. It's our fastest growing. And the portfolio is progressing very, very nicely. So in terms of Parkinson's, we've got a really incredible position there with both Vyalev, as you mentioned, and then we basically have filed tavapadon. You, Roopal, can get into that. But regarding your question around Vyalev, what we see basically is the fact that the 24-hour coverage where you get it throughout the night and you can wake up basically in a very on state without being either frozen or dyskinetic with the movement disorders with that continuous infusion is really capturing the spirit of the movement disorder experts and the neurologists. So this is quite significant. Now, in terms of your point on moderate, there's a lot of nomenclature.
I mean, we're approved for advanced Parkinson's, but there's a big dose range. So in some cases, basically, physicians are like, "I can use this pump for people that maybe are having trouble even with 400 mg of oral levodopa/carbidopa." And we can go up all the way up to 3 or 4 g. So the spectrum of dosing to get to control is quite flexible. So that's very distinctive relative to other offerings. And certainly, it's way better than having a surgery because we're carving out this sub-Q space in this advanced Parkinson's market. And what's also unique about Vyalev is many patients can get off all supplemental orals, which is very unique. So the ability for that 24-hour pump to give the control is quite striking. So when we look at the peak sales, we've really surprised how fast it's moved around the world.
We've guided towards greater than $400 million this year. We don't really have full coverage yet in the U.S. We've said more than $1 billion. We're going to get there pretty quickly. When you add tavapadon on top of it, as we sort of see that data, we believe we have a multi-billion-dollar potential with this Parkinson's franchise.
Yep. Yep. Wanted to switch gears. We have about 90 seconds left. So I wanted to make sure we turn to psychiatry. So you acquired Brotosilicin from Gilgamesh this summer. A lot of excitement about all things neuroplastogens. So the question here is, I know you're running an MDD study, but just taking a step back, what are the potential points of differentiation versus the other neuroplastogens that are in development for MDD or GAD or other psychiatric conditions?
Yeah. Well, you do get the psychedelic effect. And I think one differentiation of brotosilicin is that that experience lasts about 2 hours rather than 4, 6, 8. So that means someone can go into a clinic, get their dose, not have to stay there all day, then be able to leave after the experience. So that short duration of experience is one benefit and one differentiating factor. And also is what we've seen in that first proof of concept study was very strong efficacy. Now, we'll get two more phase two readouts next year as well before we transition to phase three. The other benefit that we saw was on the 5-HT2B receptor, meaning ours is an antagonist. The other products or assets out there are more agonist. And if you recall, many years ago, there were these challenges with an agent called Fen-Phen.
And part of that was because of the agonism at the 5-HT2B receptor leading to cardiac valvular issues. So that's always a concern over the long term. So we see the short-term benefit of rapid psychedelic experience and then offset strong efficacy and then the potential for a nice safety profile over chronic dosing. So that's what got us really excited.
Terrific. Well, we're out of time. Thanks, Roopal. Thanks, Jeff. Thanks, Scott. And thanks to everyone in the audience.
Thank you.
Thank you.
Thank you.