AbbVie Inc. (ABBV) Earnings Call Transcript & Summary

Good morning, everyone, and well, happy Friday, the 13th. And on a serious note, thanks for joining us for day 2 of our Piper's Virtual Immunology Symposium. So we're delighted to have AbbVie with us. We have Chief Scientific Officer, Roopal Thakkar. We also have Kori Wallace, who is Vice President, Immunology Development -- sorry, R&D, Immunology. So I want to make sure I didn't mangle that too badly. But thanks so much for doing this. And I know there's a ton to talk about. And so I think a good place to start, quite honestly, would be on data readouts as we -- as the year progresses.

So the 2 drugs that come to mind, Roopal and Kori are lutekizumab and RINVOQ in HS. So with that in mind, with Ludy in HS, how do you see the potential for clinical differentiation given what is a mechanistically distinct approach here, IL-1 alpha, IL-1 beta, particularly relative to HUMIRA and COSENTYX. So particularly interested in how you're framing the potential for differentiation in what is a pretty significant unmet medical need in HS.

Well, thank you, David. Thanks for having us, and thank you to your audience for listening in here today. I think you -- what you mentioned about differentiation is very important. And we've learned some things over the years with HUMIRA and HS. Remember, that was the first -- not just biologic, but first medicine ever approved for hidradenitis suppurativa, and that's something that we started working on almost 20 years ago. And what was important for us was restating standard of care. And I think that's where our targeted development for lutikizumab and RINVOQ play along those themes. Also similar to the rest of our program in immunology, lutikizumab being a bispecific, which we have others in the pipeline that eventually we'll have time to talk about today, may be difficult. But over time, you'll hear about those. We also have other assets that we combine and maybe we can get into some of that today. We're also working on co-formulations for these other potential medicines. And then along with that, remember, we did a deal for orals with Nimble. So you have the co-formulations, combos, bispecifics, orals, more potent, longer half-life. And then we have B cell approaches that we can also chat about that we're excited about. And we've entered into the clinic in APA, which is immune and fibrosis together. So taking all of those aside, we could focus directly on Ludy. And maybe, Kori, as we talk about Ludy, the alpha 1 alpha beta bispecific, why we think that's important and what we've observed in skin and expression over the years we're looking at patients who received HUMIRA or those that didn't.

[indiscernible]. Go ahead, sorry.

No, I would say neutrophils play a really important role in HS and not really targeted right now. So I think lutikizumab targeting the bispecific approach targeting both alpha and beta is really important. IL-1 alpha acts as an alarmin. It's released from keratinocytes and IL-1 beta recruits neutrophils to that, the area of the lesional skin. And so they play really important nonredundant and synergistic roles, and that's why we think targeting both of them is very important in HS. And when you look at the Phase II data that we have, it's really strong, like we have both data in bio-experienced patients, TNF experienced patients in that Phase II as well as we confirm that efficacy in a naive cohort, and it really looks strong and differentiated in that Phase II profile.

Yes. In both of these, and we saw the same for 100% anti-TNF experienced in the Phase II, like Kori said, and that's how we're developing RINVOQ. So we've opened up the Phase II to bioexperienced and naive for Ludy and 100% TNF for RINVOQ. And both of those will have double-blind week 16 data at the end of this year. And hopefully, over time, they'll fit together similarly of how SKYRIZI and RINVOQ are positioned today very successfully in IBD, in Crohn's and UC, where the positioning for SKYRIZI is in treatment naive, where we have extremely strong data and RINVOQ comes in post and with the label enhancement that we've seen with RINVOQ in IBD most recently, we see something similar that could happen in HS.

Okay. So you actually answered a number of my follow-up questions, which is great. So -- but I did want to drill down a little bit more on biologic-naive versus biologic experience. I mean with Ludy, I mean, what's your -- I mean, obviously, you'll be guided by the data, but knowing what we know about the drugs about the agents mechanism, do you have any expectation that Ludy or even risk RINVOQ might fare better in one subgroup versus -- over another? What's generally your thinking there?

Well, the conventional wisdom in immunology has been typically the bio-naive or advanced therapy naive or more recently diagnosed patients tend to have higher levels of efficacy observed with virtually every asset. And HS, it's -- maybe it's a little bit more mixed when you look across the landscape. And some of that could be if you're looking at top line data or the treatment effect, placebo can really bounce around in HS, and I know that's been a challenge for development programs for others. So depending on what you're looking for, if it's a treatment effect where you subtract out placebo versus top line, in general, the conventional wisdom is that your top line high levels of efficacy, naive tend to be a little bit higher, but your placebo could also be a little bit higher. That being said, I think we've seen clinically meaningful effects with Ludy in that 100% TNF failure population that was the original Phase II. Also remember, 70% of those patients were early Stage II and quite a bit of draining fistulas and tunnels there. and showed very strong data. And the team also generated a separate cohort in pure naive and that top line, I think, was even higher than what we saw in the Phase II.

Okay. I wanted to just pick your brain briefly about the potential competitive landscape. So there's [ AVLOS 009. ] I think that's specific to IL-1 beta. That's in Phase II. You've got the OX40 TNF-directed bispecific, Ravagalimab, that Sanofi is developing. So there's obviously a varied development landscape here. But just general thoughts on those compounds and just what you're seeing in terms of other agents in development for HS.

Maybe I'll make a few comments, and Kori, we can go back and you can comment on the potential importance of the alpha. But one comment is -- maybe I'll start with OX40. I think quite a bit of press recently. One big player kind of jumped out of the OX40 in atopic dermatitis, another one read out. One notable finding, which some of our experts have been talking about is a Kaposi sarcoma, an event of that. So sometimes you never know until you do longer-term data. And that -- if there's more cases of that, then you know that immunosuppression is pretty strong. And I would say in dermatology, atopic dermatitis and any dermatologic indications, that could be a strong consideration when one thinks about prescribing. We see Kaposi -- I mean, we used to see it in HIV AIDS many years ago. And then those individuals that have more intensive immunosuppression post-transplant to avoid rejection, which is very important. But you could see that in those patients. I don't think we've seen cases in atopic dermatitis or even HS. And if you bring an anti-TNF into it, I think there'll just have to be some questions on dual fairly potent immunosuppression, especially over the long term. Other development programs with anti-TNFs as bispecific has led to challenges with immunogenicity. We had our own challenges. Years ago, we had a TNF17 agent, and it actually had a high level of immunogenicity. So making bispecifics with anti-TNFs did become a little more difficult. And as you've seen in IBD, our combinations, even though we have HUMIRA, our combinations were moving away from anti-TNFs to more novel, knowing that many patients have already received anti-TNFs in IBD, in particular, where we're seeing that starting to step down. But in HS, even with 17s, these physicians still like their HUMIRA, their anti-TNFs, they're still using quite a bit of that. So one has to think about what is the strategy that comes next and not the same if you can retreat. And I think on the alpha beta side, yes, I think we like IL-1 alpha...

Yes, right. So as you mentioned, the [ AVLOS 009, ] it blocks just the beta. But I think targeting both alpha and beta is important. So as I mentioned, IL-1 alpha can act sort of as that alarm in release in the epidermis from keratinocytes. And so it covers the damage signaling both from the epidermis and from the immune cells. And IL-1 alpha can also be implicated in increased angiogenesis, so in inflammation. So getting that more blood flow to the lesion, more inflammation. And so blocking both, we think, is really important. And also, it likely blocks some compensatory mechanisms, right? They're nonoverlapping and likely synergistic.

Yes. Okay. All right. Super helpful. So I wanted to switch gears and talk about IBD. Obviously, a ton going on. So just at a high level, we're seeing a lot, and Roopal, you mentioned it earlier in our discussion, co-formulations, bispecifics, and it seems like that's where the next wave of development is focusing on in IBD. So with that in mind, just give us a refresher of what you're looking at, particularly with SKYRIZI in IBD. So you've got combo studies with lutikizumab. You've got a TL1A directed treatment 701. You've got your alpha4beta7 directed treatment 382. So obviously, a lot going on. But maybe the way I'll ask it is -- and I know it's a loaded question, but what are you most -- which combination are you most excited about scientifically?

Yes. Well, it's a great question. I would say I can take it in a couple of different ways. So one comment before the answer is what we also are looking for this year is our SKYRIZI subcutaneous data, which I think will be important also in the market right now where IV. There's competitors that have subcu. Despite that, we still see a very large share in frontline with SKYRIZI, but having a subcu may further support that. So that data will be coming out this year. Now turning back to combos. In terms of what's precedented, how about that versus what we're most excited about. When you talk to the R&D team, we're excited about everything. But in terms of what's precedented, I would say the alpha4beta7 that we have, which is a more potent version, I would say, versus vedolizumab and the TL1A, those are precedented in IBD, where we've seen, I would say, better data in ulcerative colitis, maybe a slight step down in Crohn's, but that's okay when you combine with SKYRIZI, and we feel these are orthogonal approaches. And the alpha4beta7 along with Ludy, we'll get a read this year and then look forward to phase transitions with those assets. Now Ludy looked a little bit better than HUMIRA numerically in ulcerative colitis, probably not as high as we would want, but we'll test it out now in Crohn's, along with the alpha4beta7. The TL1A combinations will start later this year with SKYRIZI. And then our TREM1, which is a very unique mechanism, if you want to hear a little bit about that, Kori discussed that. That one, we'll see actually proof-of concept into later this year, early next year. Maybe TREM1 is an exciting one because I don't think there's much competition in this area.

No, exactly. So TREM1 -- go ahead. Go ahead.

No, no, no. Go ahead. That was...

I was going to dive into TREM1 a little bit. Yes. No, I think the combination is too, the unmet need in IBD really is improved efficacy, deep durable remission, really modifying the disease. And so when you look across that sort of landscape with competitors, really, right, it's a differentiation, which is why we're going with that combination approach. And then I'll pivot to TREM1, so triggering receptor expressed on myeloid cells. So it kind of tells you at least where it's working, right? It's upstream. It's really involved with the sort of amplification of inflammation, a lot of preclinical data supporting the mechanism and even some reverse translation work that demonstrates is upregulated in patients who fail TNF. And so I think this is -- it could be a really nice new novel mechanism.

Is that potentially a monotherapy approach? Or could that be another novel combination with, say, SKYRIZI or another mechanism?

Yes. I think so right now, we're evaluating it as monotherapy because it hasn't been evaluated in the clinic before. And so what we want to do is -- I think there is a potential there for monotherapy. And what's nice is we get -- we'll have some samples, we can do reverse translation, and we can figure out the appropriate combination partner based on orthogonal mechanisms. And we have a nice portfolio of assets that we could potentially combine with it if the monotherapy alone isn't sufficient.

So I wanted to switch gears a little bit and drill down on the TL1A. And I know you're focusing a lot on combination usage. I believe it's an ultra-long-acting profile. So I think that is a point of differentiation that you've called out previously. But I wanted to take a step back because we are getting Phase III data for Merck's Tulisokibart later this year in UC. So I wanted to get your thoughts on just how to think about the data, what's your general view of where this class could fit within the broader IBD armamentarium, what you're kind of looking for from the Merck data and ultimately, where you see your TL1A...

So when we saw the Phase II data sets of not just 1 TL1A, but 2, I think that's a convincing mechanism and it showed efficacy, I would say, stronger in ulcerative colitis than in Crohn's to date. However, at that time, we didn't see differentiated efficacy versus SKYRIZI or RINVOQ. So in order to break that efficacy ceiling, our position and strategy was, look, we like the mechanism. It looks like it's driving some efficacy here. It could be orthogonal to IL-23. And we thought the combination is the best approach as a next-generational therapy, given that they don't -- whether it's TL1A or an oral or anything else that we have seen to date in Phase II, none of them differentiated from Phase III RINVOQ and SKYRIZI data. And it's a rare circumstance that the Phase III data look better than Phase II. It can happen. I think it happened with RINVOQ, and it has surprised us a few times. But other than RINVOQ, there's not many examples where efficacy tends to rise. What ends up happening, you bring in -- you have to enroll these studies, so you're bringing in patients that could be failed multiple lines of therapy, so then efficacy settles down. So that's why the combination approach, if we can give higher levels of efficacy, maintain safety and give a convenience of co-formulation, that would be the approach of the future. I would say the present really SKYRIZI, RINVOQ really serve the needs today, especially in that frontline setting. And then physicians have the flexibility to use RINVOQ second line and don't have to step through an anti-TNF anymore.

What about the role of biomarkers in the future? I mean one thing we hear from KOLs is that, well, if we can have more biomarker enriched populations in IBD that perhaps we won't necessarily migrate on mask to these novel combinations, I mean, which is kind of an interesting thought. I've heard it mentioned by a few KOLs. What do you think about that?

I think we would agree. We would love to demonstrate convincing data with a biomarker. That was one approach that we had, in fact, with lutikizumab with IL-1 alpha beta. Kori and her team will be getting tissue from all of our studies. We work with our precision medicine team internally. And if there is biomarkers that are robustly predictive, we would absolutely want to bring that individualized care to the community as quickly as we could. Immunology has been difficult, I would say. It's not as targeted as we have had success in oncology, but it hasn't dissuaded us from at least taking a deep dive into tissue and biomarkers to do our best to see if we can see segregation of populations that we can detect and then give a therapy that's more fitting for an individualized patient. And TL1A, I think, showed glimpses of that. And we'll have to see if the companies that are bringing in the monotherapies if they have some thoughts on a biomarker approach, but we continue to investigate.

Okay. So there's a lot of chatter about TL1As in fibrotic diseases and the role TL1A plays in fibrotic processes, and that certainly can be highly relevant in IBD, but certainly other conditions. I know Roche is running a MASH study with theirs. But how are you thinking about the potential for wider development of 701 in -- particularly in fibrotic diseases?

We like the molecule. Kori, you can talk about maybe some of the indications we could be interested in and why we like the molecule mechanistically.

Sure. So yes, TL1A, as you mentioned, there's lots of preclinical data out there supporting its role as an antifibrotic agent. And so right now, we're focusing on IBD, but all autoimmune disease, unchecked inflammation leads to fibrosis scarring that you can't reverse. And I think importantly, too, fibroblasts play a role early on in disease. And so TL1A targeting sort of that inflammatory profibrotic component is really attractive. So as we think about future development, diseases like RA, PSA, HS, systemic sclerosis, I think, are all on our radar.

And remember, we have an LPAR program internally that may be even more specific to fibrosis, and that has entered the clinic as well. So we'll have a biologic in that space and an oral looking at IPF and sclerosis.

Okay. And then we've got a couple of minutes. I want to -- I'm going to bounce around on a couple of topics. So you mentioned you have an oral IL-23. J&J obviously is pretty well along with theirs. But I wanted to get your thoughts on how you think just conceptually, an oral IL-23 directed treatment could be impactful in the indications where we see a lot of IL-23 usage, psoriatic diseases, inflammatory bowel disease. And so just talk to how you think about the potential impact of a movement to an oral and how you're thinking about your molecule?

Similar to what I described in the TLA space, we think there's a next-generation opportunity, hence, the deal for Nimble. And what we're trying to accomplish there is higher potency and then probably even more importantly is a longer half-life. Even with RINVOQ in the oral space, it's very difficult for patients to be 100% adherent over time. The greatest adherence we see is with something like a SKYRIZI, where you're taking it quarterly. And in between, you're not worrying about food or water intake, when can I eat, when can I not eat. So that can also impact adherence. So people could miss some doses. And what we've seen with blocking 23, you want to try to block that to the maximum level. That way, you can deliver results like SKYRIZI, whether it's in psoriasis, PSA, Crohn's or UC. And the existing oral that we've seen data from are, I would say, not like a SKYRIZI biologic. It could be like older biologics, but the efficacy just doesn't match -- and part of that could be a half-life disadvantage and potency and how much drug you can actually deliver. So that's why we're working on a potential next-generational approach. But in the meantime, like I said previously, SKYRIZI and RINVOQ are very well serving needs today at levels of efficacy that still are not matched by either novel orals or novel biologics.

And then just real quick, I wanted to -- if you can, give us 30 seconds on 319, pretty unique here, ADC targeting CD19, steroid payload. You're looking at it potentially in SLE, maybe Sj�gren's. Just very quick thoughts on your excitement about that compound.

I think in general, on going after B cells is stepping back is very exciting, and that's what got us excited about borrowing this asset 319 that kori can talk a little bit about with the steroid warhead. We borrowed that from our heme colleagues in the oncology space. And recall, we also did the deal for CASA, which gives us an in situ lipid nanoparticle CAR-T that doesn't require lymphodepletion, no DNA integration. It's tunable. You can redose it. It's transiently expressed. So you could imagine hopefully having long-term safety and from a CMC standpoint, scalable. So that's something maybe we can do a deeper dive over time. But 319, maybe, Kori, this one is exciting...

Yes. 319 with the GRM ADC payload. So it has really 3 mechanisms, right, delivering that steroid to the B cell. It's actually inhibiting CD19 activation. And also, you have like that antibody-dependent killing of the cell as well based on the antibody. And so with that steroid payload, it's really unique in that when you look at B cell depletion and what has been shown in the literature so far, it's that rapid deep depletion and that prolonged deep durable drug-free remission. So when we're looking at how to dose 319, it's really sort of this upfront dosing and it's self- tapering then of that steroid. And as we get more data from 319, we actually have an asset ABBV-519, same antibody without the payload. So if patients would need a boost or anything like that, we can come in with the steroid-free version in 519 and looking at that as a maintenance opportunity.

Okay. Well, that's...

And also we have data from -- we have data from our 319 in oncology. It's given every 3 weeks for a year, and we haven't seen any movement in any steroid-related markers. And those are at much higher doses than we would likely use in immunology.

Okay. Terrific. Well, thanks, Kori. And thanks, Roopal. I wish we had more time. But yes, this will be some food for thought for another discussion down the road. But yes, great stuff. And thanks again, and thanks to everyone listening in, and I'll wrap it up there.

Thank you, David.

Thanks.

All right. Bye-bye.