AbbVie (ABBV) Management on Evercore ISI 3rd Annual HealthCONx Conference

AbbVie, Inc. (NYSE:ABBV) Evercore ISI 3rd Annual HealthCONx Conference December 2, 2020 2:40 PM ET

Company Participants

Mike Severino – Vice Chairman and President

Rob Michael – Executive Vice President and Chief Financial Officer

Jeff Stewart – President-U.S. Commercial Operations

Conference Call Participants

Josh Schimmer – Evercore ISI

Josh Schimmer

All right. Welcome everyone. It’s Josh Schimmer from the Evercore ISI biotech team and pleased to welcome from AbbVie; we have Mike Severino, Vice Chairman and President; Rob Michael, Executive Vice President and Chief Financial Officer; Jeff Stewart, President of U.S. Commercial Operations. Wonderful to have you gentlemen here. Thanks for the joining us.

Looking at some of the IMS script trajectories for Rinvoq and Skyrizi, it’s hard to tell we’re in a pandemic, really incredible launches. Maybe, we can talk and kick things off, talking a little bit about the pushes and pulls of these launches in a pandemic and where the headwinds are in the talents?

Mike Severino

Sure. I’ll start, and then Rob and Jeff may want to add some color. I think the launches have gone very, very well. They’ve exceeded our expectations and we had high expectations coming into those launches and it all starts with the product profile. Both agents have delivered very, very strong product profiles. And if you look at the levels of response, if you look at the durability of that response, if you look at the response across a wide range of patient types, including heavily pre-treated patients, if you look at the head-to-head data that we’ve generated really across both molecules, we have demonstrated what we believe our category leading profiles that has played through to the labels that we’ve received for both products and you’re seeing that strong product profile in the launch.

And then when you couple that strong data, those strong labels with the experience we have in this area, we’ve been leaders in this area for quite some time with our ability to gain access rapidly. And with other factors like our industry leading patients for programs, it really leads to the kind of commercial performance that you’ve observed. And we had strong momentum coming into the pandemic and we’ve been able to maintain that momentum and I think it’s because of the unmet need that they’re addressing and the profiles that they’ve demonstrated. Jeff, I don’t know if you want to comment or…

Rob Michael

I’ll just add, this is Rob. I’ll just – I think just to highlight it, and Josh, you mentioned, I mean, through COVID, we’ve seen an impact on office visits on new patients starts, particularly in the medical derm segment. And despite that, we’ve raised our financial guidance twice for both Skyrizi and Rinvoq. I mean today, we have a 33% in-place share in psoriasis for Skyrizi, a 16%, which is by far the market leader, almost doubled that the next nearest competitor in terms of Rinvoq, our in-place shares at 16% and RA comparable to Humira. So, we’ve seen very, very strong uptake during what’s – I would say, has been a challenging time. So, it just speaks to the tremendous strength of both products and the field force.

Jeff Stewart

Yes. just to put color on sort of the go-to market, because you look at these how fast they move even through the pandemic. I think the first was, as Mike said, you’ve got very differentiated products with head-to-head data. So, you had basically superiority data for Skyrizi versus the market leader, Humira our own product and you had Stelara, so you had two head-to-head trials, which were really important. And then there were some strategic decisions we made that sort of how we think about this pipeline that’s coming with Skyrizi and Rinvoq. The first is that, we didn’t make the decision to say, hey, how do you go away from the market leader?

And it was actually not as easy as you might think. We’ve gone full bore on the superior product, the best-in-class product on psoriasis. And our sales force, where we get a couple of different sales force is doing this. Humira basically, we pushed into the secondary position for where there’s PSA for skin and joints. That was very, very important, because we had the best product. We needed to commit to what we did.

Obviously, the second dynamic in terms of the push/pull, which was a big, big push was our access. We were able to basically promise to the market. And you have to remember that in many cases, our representatives have been with these customers for a decade or more. They’re actually grown up with the derms. They’re grown up with the rooms and they were able to say, we are going to have extremely strong access, much like you’ve been used to for Humira and we delivered on that promise. And so on the commercial side, we had, you’ve heard 95% access at an unbelievable accelerated pace. So that was a second key, let’s say catalyst.

The third part was again, the doctors know us and they trust us. We know these markets very well, that helps out enormously when you are the leader and then you bring more leadership position. And then finally, the sort of the fourth pillar was we’ve typically been recognized as having the best reimbursement and patient support program across immunology.

And so when that went to what our program, we call it Humira complete that went and became Skyrizi complete or Rinvoq complete and all of those programs that the customers know and trust, we’re still there. And so when you added that into the caldron there, you can see just really explosive growth. And we had big ambitions. We did not think they would move as fast, but it was a good strategy and we’re really pleased with the early results.

Josh Schimmer

I guess, what I kind of find surprising and I’m hoping you can enlighten me on is, with so many treatment options for rheumatoid arthritis and psoriasis, I’m surprised there are this many people out there with unmet need to be mopped up by Rinvoq and Skyrizi. So what – maybe, you can help me understand like that, that burden of disease and why the current armamentarium hasn’t quite been able to get patients on optimal therapy, that there are so many to go on to Rinvoq and Skyrizi.

Mike Severino

Yes. this is Mike, I’ll start. And again, the others may want to join in. I mean, I think if you look at Skyrizi, there was a clear step function in efficacy that one could achieve with Skyrizi compared to options that have been available in the very near past, and even at the time that it was launched.

So, what I mean by that, for example, is if you look at the PASI 90 and PASI 100 numbers, they are very, very high. They’re very, very strong. But a very important part of the data package for Skyrizi is the durability of those numbers. So, there has been a concern with most agents, essentially, all agents before Skyrizi that patients lose efficacy over time. Physicians are concerned about this. Patients are concerned about this. And with Skyrizi, we see those numbers increasing over time.

We had in our one-year data, 60% of patients achieving PASI 100, response to a complete skin clearance. And we have a long-term data beyond that that shows those patients maintain those very, very high levels of response. So, I think that’s the first part of it, that it was a real step function. And then when you couple with the other features that the molecule brings, its safety profile, quarterly dosing, it’s that combination that really drove the adoption amongst physicians and patients.

If you look at Rinvoq, it’s a similar story in that it delivered very strong response, particularly higher levels of response, higher response rates on the ACR scale, 50% improvement, 70% improvement, high rates of patients achieving low disease activity and remission, and very, very strong results. And this is very important in the TNF inadequate responder and bio inadequate responder patients.

So, we had not only TNF inadequate responders, but patients, who had failed multiple prior biologics. We still delivered very, very strong response rates. We had head-to-head studies, not only against Humira, but against Orencia, which is the most commonly used drug in TNF inadequate responders.

And again, it’s that whole package that, that has led to the adoption. And if you think about the RA space, despite the number of therapies that are available, a large proportion of patients still aren’t in remission. And so there is room to go. There is headway on efficacy and Rinvoq has really tapped into that.

Josh Schimmer

As we look into 2025 guidance for these products, Rinvoq, we’ve laid out around $3 billion in rheumatoid arthritis and then $0.5 billion in psoriatic and ankylosis spondylitis. to what extent is that heavy, heavy weighting towards RA, just a reflection of having more time to get there, as opposed to just RA being a fundamentally much bigger addressable market than in some of the other indications we went out and then kind of the same exercise in Skyrizi.

Mike Severino

Yes. Well, RA is the largest individual market, but I think it’s also, as you point out Josh important to think, consider that these are 2025 numbers. And rheumatoid arthritis was the first indication to be launched. So, it is further up that ramp. So, I think it’s a combination of the two. That is the largest individual market, but it’s also the initial indication and the one that has had the longest time to ramp.

So, if you look at psoriatic arthritis and ankylosing spondylitis, for example, as markets, those are about half as large together. They’re about half as large as RA. So, they’re substantial. And they’re indications that we have submitted for approval earlier this year and will be approvals in 2021. So, they’ll start to ramp and they’ll start to contribute to that overall profile for Rinvoq.

And for Skyrizi, it’s a similar story. Psoriasis is the most advanced and it’s a considerable market. IBD is also a very large market. But there, you have the consideration that we were launched much earlier in psoriasis for Skyrizi than we will be for Crohn’s disease. We’re going to have the Crohn’s induction data coming this year from the first study, additional induction data next year, maintenance data next year, as well with the file in 2021, but that’s a launch in 2022 important and ramping in the 2025 timeframe, but hasn’t had the same time to grow that psoriasis has for Skyrizi, because we do view inflammatory bowel diseases as a very significant opportunity for Skyrizi.

Josh Schimmer

And for the IBD indications that decides that market relative to other rheumatoid arthritis or psoriatic arthritis, it was very helpful kind of hearing psoriatic and ank spond versus RA. What is the map on IBD?

Mike Severino

IBD is a considerable market. Rob, you may want to comment on the specific numbers there?

Rob Michael

I think, it’s around $20 billion in total market. So, it’s a significant market for us. I mean, it’s not as large as room, but it’s significant. And I think we’re going to see in this case, both agents play a role. I think having treatment options in gastro is very important. So, we believe there’ll be space for both Rinvoq and Skyrizi. And so they will be significant. They won’t be as significant if you think about it, stack ranking of the indications clearly, the room indications for Rinvoq and then psoriasis for Skyrizi will be the largest indications, but each of them will play an important role in the overall brand.

Jeff Stewart

I’ll give a little color on how we attack the IBD space, which is important. It’s substantial right now in the other therapeutic areas like derm and obviously, room; you already have the early entrance. So right now basically, all of IBD is covered by the Humira reps and the Humira promotion. And so we have two sleeves. It’s important how we think about going at these basically 8,000 or 9,000 gastroenterologists that treat IBD. So, we have one sleeve called 150 reps that basically, they focus first on Crohn’s and then another sleeve focus on UC they’re cousins, but they’re very different. So, and we’re the market leader in both of those.

What’s interesting around how this will come, as we start to see the data for both Skyrizi Crohn’s, and UC for Rinvoq, they start to stack up very, very close in terms of a coordinated launch in 2022. And that means that we can bring, if we look at our Phase 2 data, we’ll see the Phase 3 at some point here sort of best-in-class agents in both disease states at roughly the same time by your AbbVie representation. So when – again, when we see the timing of all these things, we think that’s going to allow us to really have an impact pretty quickly into the market.

Josh Schimmer

So, as we think about these two products and some key events ahead, we’ve got hopefully clearing the pandemic. I’m not sure. I mean, just given how successful they’ve been in so far, if you think that alleviates a headwind the next major event, in addition to kind of generating data and expanding labels, I’m kind of thinking more of that RA and psoriasis indications will be the alternatives biosimilars to Humira. So maybe, talk like for those two particular events, how you think they may impact the trajectory of these launches?

Rob Michael

Well, I think it’s important to keep in mind that from Skyrizi and Rinvoq, I mean, we’re going to cover all the major indications of Humira plus one, which Humira doesn’t have today in atopic dermatitis. So we do believe, and if you think about the peak revenue for Humira was around $20 billion. We think over the long-term that Skyrizi and Rinvoq can completely offset the erosion that would come from the U.S. Humira LOE. So, just within immunology itself, we see a path to growth. So that’s, that’s very important. As it relates to your question on biosimilars, there’s no perfect analog in the U.S. to – from Europe, but I think that Europe experiences informative and we think about the competitive intensity we saw with four biosimilars coming in at the same time. And we saw in that first year, if you just look at those markets about 43% erosion in those particular markets, and then cumulatively through 2020, we’ve seen about it’s now 51%.

So, as we’ve been saying steep erosion in year one more moderate in year two and beyond. And so I think the best way to think through the dynamics for U.S. Humira in 2023 would be similar. We’d see with the fact that we’ve got, seven to nine biosimilars coming in at 2023 with Amgen coming in at the end of January and the rest coming in, mid-year, we’ve assumed also there’ll be two interchangeables, at least in our planning assumptions. So, I think it’s reasonable as to for modeling purposes, I think through a 45% plus or minus 10% erosion in 2023 with a more moderate erosion beyond that, based on the experience we’ve had with Humira to help overseas.

Mike Severino

But I think one thing that Rob mentioned that’s worth amplifying on is, these two molecules together, Rinvoq and Skyrizi will cover essentially the full footprint for Humira all of the major indications, plus an additional indication atopic dermatitis, which has been underdeveloped as a market up to this point is another very important market. So, they have broad potential and an important part of our strategy was not just to cover that footprint, but to cover it with agents that are better than Humira, that then raise the bar on efficacy and we’ve shown that through our head-to-head studies for both molecules.

And so one of the key things to consider is these are out in the marketplace now, and they’re raising the bar on the standard of care now ahead of biosimilar launch and they will have had a substantial period of time to establish themselves. By the time, we come into the biosimilar era in the middle of this decade. So that’s an important thing to consider when one thinks about the combination of headwinds and tailwinds that we will be looking at in 2023 and beyond.

Rob Michael

And if you think about clinician experience, I have four years now with Skyrizi and Rinvoq before the U.S. Humira LOE and so – and they’re highly differentiated. So, I think that those are very important points to make.

Josh Schimmer

To the introduction of Humira biosimilars in Europe, alter the trajectory of some of the other branded biologics, other mechanisms in Europe that might be an interesting area?

Rob Michael

No. We studied that and we have not seen an impact across mechanisms.

Josh Schimmer

So, if that’s the case, then is there a chance that the introduction of Humira biosimilar somehow erodes AbbVie’s power when it comes to formulary and access, because that would be kind of the other variable at play for the U.S.?

Rob Michael

I think I’ll let Jeff chime in here too. I think Josh, what’s really important here is that with both of these agents having to differentiate profiles, they have, they both demonstrated superiority to Humira. When payers look at that and they understand the demand pull through and we will have had four years of experience now with these agents. I think those are very important to highlight that the profiles of Skyrizi and Rinvoq, given their elevating standards of care put them in a position, where there shouldn’t have that same pressure as you’ve articulated as it relates to the Humira biosimilars.

Jeff Stewart

Just the macro dynamic that we’re seeing in the U.S. over the last few years has been the expansion of the formularies. I think that’s an important concept, right. So in other words, a few years ago, when you looked at like an express scripts or CVS, you might have five drugs on the preferred formulary. Now, you have 10 or more and you see the – basically, the advanced therapies being placed onto the formularies.

And so you’ve got this macro trend that says that the market is rewarding this innovation, because of the still really low penetration is shocking that only 12% of anyone with moderate-to-severe psoriasis in the U.S. is actually on one of these medications. So, it’s still a substantial runway in terms of the potential penetration of both older and newer high-end products, so the goals towards the expansion of choice.

and the other thing that we see is as that expansion has taken place, we see the clear development of markets through multiple lines of therapy, where you’d see sort of a big frontline therapy and a smaller second line plus therapy. Now, you see second and third line therapies expanding even faster than the frontline therapy.

So, the markets are super dynamic. And if we look to Europe, we also see that there should be even with the availability of biosimilars, lots of choice in the marketplace, at least that’s how we see it playing out right now when we look across the major dynamics in it, how the payers are thinking about it. They’re still thinking, I mean, they’re still several years away. So, it’s not like they have definitive strategies in place, but we watch very carefully these macro trends that are taking place.

Josh Schimmer

Are there additional indications we should be looking for between Rinvoq and Skyrizi?

Mike Severino

We have a broad program underway, and a number of them are already submitted, or we’ll be delivering data in the near-term. And so just to go through them systematically, if you look at Rinvoq, obviously, RA is the lead indication in the first approved and doing very well as we described, psoriatic arthritis and ankylosing spondylitis were submitted earlier this year, and we’ve recently submitted atopic dermatitis.

Then coming this year in terms of data will be the induction study on ulcerative colitis with the additional data, second induction and maintenance next year. So, we’d be in a position to file UC in that timeframe. And then the Crohn’s disease program for UPA is not advanced, but will come in the following years. And so that really rounds out a very strong profile for the indications for Rinvoq.

Josh Schimmer

Yes. Are there more to come?

Mike Severino

Those are the principle ones. There may be some smaller ones, but those are the principle ones. And then for Skyrizi, it’s principally psoriasis, we’ll have psoriatic arthritis data later this year. So before the end of the year, we’ll have Crohn’s induction before the end of the year and second induction studies and maintenance midyear, and submission then as well. So, those are the principle indications for Skyrizi.

But if you look at that full footprint, the full rheumatology footprint, not just RA, but psoriatic arthritis and ankylosing spondylitis, if you look at plaque psoriasis, obviously both components of inflammatory bowel disease and atopic dermatitis, that covers, as we said, the full revenue footprint of Humira of all the major indications, plus the addition of atopic derm. So, those are the principle indications.

Josh Schimmer

And remind me, how you define the China’s strategy for these programs?

Mike Severino

China is not a large market for us. So historically, we’ve had a relatively small presence. we’ve recently gotten on the NDRL for Humira, but it’s not been a large presence for us in the room space or overall.

Josh Schimmer

Got it. Maybe, finishing off my questions in the interim space, the ADC-TNF antibody was steroid. What is it that you’re ultimately going to look to show, are you going to need to have some head-to-head data versus Humira to differentiate, or is there another way for that product?

Mike Severino

Well, head-to-head data will be important in Phase 3. So, the goal with that program is to bring forward differentiated efficacy, so greater efficacy than what can be achieved, not only with Humira, but with other agents that would be out at the time when it would be launched in the middle of this decade. So that would include Rinvoq for example.

So, we recently top-lined or earlier this year, we top-lined proof-of-concept data, that was a relatively small, early phase trial, but it met all of our expectations for efficacy. We’ve advanced the platform. we’ve selected 154, which is a closely related molecule, but has some advantages in Linker Technology that relate to manufacturability and the ability to concentrate. So, it had high concentration formulations as the molecule that we will advance to a larger scale development.

We’ll be doing definitive dose ranging studies, a definitive dose ranging study in RA in the first half of this year and you can expect us to do other Phase 2 studies, and other immune indications beginning in 2021 as well. And so that would all lead to Phase 3. And in Phase 3, we absolutely think that a head-to-head component would be important. And while we haven’t designed the full Phase 3 program yet, I would say, we would go against the highest efficacy agents that are out there. So, it wouldn’t necessarily just be Humira. It could also be Rinvoq. But the goal is to bring higher levels of response to patients that can be achieved with other agents. And that needs to be demonstrated head-to-head in Phase 3.

Josh Schimmer

Maybe, have pivoting to the hem/onc portfolio, in Imbruvica and Venclexta of 2025 guidance, I think Imbruvica is a little over $11.5 billion Venclexta is around $6 billion. How should we be thinking about here to there? What are the key drivers that that’ll get you to those that type of performance, which indications in the markets?

Rob Michael

So Josh, I think you’re – for Imbruvica, you’re referencing the $11.5 billion as the nominal sales guidance that was provided back in 2017, that did include solid tumor indications like breast cancer and pancreatic. It’s probably better to anchor on the peak risk adjusted sales of greater than $7 billion, in which CLL will continue to be the largest component of Imbruvica. Think of it being in the $5 billion of that $7 billion range coming from CLL. We also have – we’ll have indications in NHL disease areas, things like MCL, Waldenström’s, NGL and follicular, which will make up the remaining $2 billion.

As you think about growth going forward, it’s really going to come from new patient capture. We’re currently capturing about 30% of frontline CLL patients, about 37% of second line CLL patients. And it’s important to keep in mind that really treats progression results in that base growing each year. So, it’s really important also to highlight the share of treated patients that Imbruvica has in frontline CLL, is about 55% and it’s 75% in second line CLL. So, as we think about that growth, what gets us from, or today to that greater than $7 billion, it’s largely that new patient share capture that builds through treat depression.

Josh Schimmer

Got it.

Mike Severino

And for Venclexta, there are a number of sources of growth going forward. It is performing very well in CLL and has established itself based on the MURANO data as the gold standard in relapse refractory, so second line or greater CLL from an efficacy and a overall benefit risk perspective. And it’s also performing very well in frontline in the segment of patients, who prefer a finite duration of therapy and very strong results have been demonstrated there as well, but there are additional sources of growth beyond progress in CLL. And those would include AML, where we’re performing very, very well. We’ve recently received full approval based on principally, the VIALE-A data, although there were other data like VIALE-C that contributed to that approval as well. VIALE-A demonstrated an overall survival benefit in the azacitidine combination. That launch is going very, very well. And we have a program in place in Phase 3 to extend beyond those initial patient definitions.

So, moving into the frontline eligible patient population, both for treatment intensification, maintenance therapy, and also have opportunities in related diseases like myelodysplastic syndrome, where we are advancing to late stage studies as well to large scale Phase 3 studies as well. And then of course, we should also consider the multiple myeloma opportunity in the t(11;14) populations. The CANOVA study is well underway. We’ve demonstrated strong data in mid-stage trials and in subset analysis of our Phase 3 trials in that t(11;14) population. And there’s good reason for that, that population has a B-cell like phenotype and the B-cell too high. And so we have the CANOVA study, which is well underway, which if positive could be a very meaningful opportunity in multiple myeloma. The t(11;14) population is about 20% of overall myeloma and the overall myeloma market is very substantial. So, 20% of that is a meaningful opportunity.

Josh Schimmer

Excellent. And maybe, you can – you’ve talked a lot about Navitoclax and maybe, kind of help focus us on the two or three leading liquid tumor pipeline programs we should be looking at for an eye?

Mike Severino

Well, beyond the on-market products that we considered Navitoclax is an important one. Navitoclax has been advanced to Phase 3 studies on the strength of its Phase 2 results, Phase 1b/2 studies have shown very good response rates in a heavily pre-treated population that’s resistant to JAK2 inhibition, principally the Jakafi. Navitoclax is a BCL-XL inhibitor that also has some BCL2 activity in both may be important, but we think that XL is one of the primary drivers of myelofibrosis. And we’ve shown both preclinically and have evidence from early clinical studies that we are not only driving good response in terms of spleen reduction, which is the regulatory endpoint, and is clinically meaningful to these patients, because spleen enlargement, spleen ruptures responsible for much of the morbidity and even the mortality in that disease.

So, it’s shown good response in spleen reduction, but it’s also shown improvement in fibrosis, which is essentially unheard of in this disease. The fibrosis relentlessly progressives, we’ve seen patients, who’ve had not only one grade, but two grade improvements in their fibrosis. So, that’s quite meaningful. And also have early evidenced showing reduction in a low burden. So based on that, we think there’s strong potential in myelofibrosis. We think there is the potential for disease modification, which could be game changing in that condition, because nothing has convincingly demonstrated disease modification.

And there’s also potential for combination use with Jakafi and to re-sensitize patients, who have failed Jakafi or other JAK2 inhibitors. So, it really will be a useful, we believe across the spectrum of frontline and a relapse refractory setting. So, Navitoclax would be one of those programs that would highlight in liquid tumors.

I would also point to our BCMAxCD3 bispecifics. So, T-cell redirecting programs aimed at BCMA and multiple myeloma. The more advanced in those is one that we have in partnership with TeneoBio, which should be in a strong position to give proof-of-concept data in the coming year, in 2021. And we also have an additional opportunity there that really brackets a range of affinities, because it needs to be experimentally determined what the optimal affinity is for the binding epitopes. It’s not always higher is better. Sometimes there’s a sweet spot and we’ve bracketed lower to higher range affinities of our binding constructs and also different binding geometries to try to come up with something that will have an optimized benefit risks.

We have a couple of opportunities there. And so that would be important in liquid tumors. We have advanced an MCL1 inhibitor into the clinic. That’s been a very, very difficult target to drug, but so is BCL2. And we’ve been the only people to successfully drug that target. And so we will be pursuing that program as well. So, those are some of the highlights and there’s more beyond that in late pre-clinical development preparing to enter the clinic.

Josh Schimmer

So, you had mentioned the bispecific on BCMA, you’ve also partnered with Genmab with the CD3, CD20. AbbVie always brings strategy to the table, especially when you’re in a competitive dynamic area, certainly not the only bispecific BCMA or CD20. How do you leverage AbbVie’s core competencies to gain market share and what does seem to be a little bit of a competitive space for similar modalities?

Mike Severino

Well, the Genmab partnership is an important one, and that also brings important additions to the liquid tumor armamentarium that you’re asking about. The most advanced molecule there is epcoritamab, which is the CD3xCD20 that has completed early stage trials and is moving now in rapidly progressing towards startup in Phase 3 in relapsed refractory diffuse large B-cell lymphoma and other indications.

So, when we looked at that molecule, we saw a couple of things. One we saw what we believe was an optimized benefit risk based on the profile that it had demonstrated in early phase trials. So, if you look at the CD3xCD20 space, there are agents that show very, very strong efficacy. Those agents have also typically been associated with high rates of high-grade CRS, including fatal CRS, cytokine release syndrome. And there are other agents that have seemed to navigate high-grade CRS and other AEs like the neuro AEs that can go with this class of molecules, but to do so they’ve also given up on efficacy.

And epcoritamab seems to have hit that sweet spot, which as with BCMA has to be experimentally determined in most cases that it high efficacy, very good response rates in heavily pretreated diffuse large B cell lymphoma patients and in other indications like follicular lymphoma, but does so with a favorable benefit risk. So, no high grade CRS observed in the early phase clinical trials. So, no grade three or grade four observed in the early trials, good rates to overall AEs. It has a convenient dosing administration, fits well into maintenance regimens. And these are all important features, because as you say, we have to think strategically about how to develop these agents, and a number of these features become very, very important when you think about how to move to earlier lines of therapy.

So, we’re designing with Genmab, a very broad program aimed at a number of indications, diffuse large B cell lymphoma and follicular lymphoma, the most advanced across a range of patient types and across lines of therapy. And that really leverages a number of things that we’re quite good at. We know this space well. We have shown the ability to develop these drugs effectively to expand into new markets effectively and we think it’s a very strong partnership that’ll utilize the best parts of both companies.

Josh Schimmer

On the solid tumor portfolio, you’ve got a number of ADCs now in the pipeline. And as we think about the experience with Rova-T not getting across the goal. And was that an issue with the Rova-T target, the Rova-T, ADC chemistry, and how do we kind of look at some of these new ADCs with that lens, we get confident that these will be able to generate the term profiles we’re looking for.

Mike Severino

Well, it’s important to consider that Rova-T was in the clinic at the time that we did the Stemcentrx acquisition. So, the Rova-T platform in terms of the Linker chemistry and other features of it from a platform perspective is different than the platform of the ADCs that we currently have in the clinic and the ADCs that we are continuing to prosecute. But to answer your question about whether it was a principally, a target failure or a platform failure in the platform that it was on, I would say principally, it was an issue with target in that the fundamental thesis for Rova-T was that one could go very specifically after the tumor initiating cell compartment or the cancer stem cell compartment, those are related, but they’re not exactly the same and used that to control bulk tumor.

And what we’ve found prosecuting, not only that, but a number of targets that came off of that target discovery engine is that it is very challenging to control tumors in that manner. And essentially, one can’t do that. The programs that have been most successful are programs, where you have broad expression of the target across tumor. So, you can get both control of bulk tumor and hit those key cells that are driving progression. And so we today, are not pursuing targets that don’t have that broad expression. And so from that perspective, you can view it as a target failure.

With respect to the platform, I wouldn’t say there was anything particular about the Linker chemistry, but we are learning that PBD toxins and other ultra potent toxins may not be the way to go. Because there are just too many ways for a construct to get into bystander cells, other than CDR-mediated interactions. So, there’s non-specific uptake, there’s uptakes through managed receptors. There are many ways that these constructs can get into cells, bystander cells or other cells. And when you have a toxin that’s – that is as potent as a PBD, for example, or some other DNA damaging toxin, that limits your ability to deliver that agent.

If you look at the field, agents that have intrinsic therapeutic indices that you’re trying to expand have shown greater promise. And if you look at our ADCs in the clinic, they mirror those learnings. So, we’re looking at molecularly targeted warheads and other novel warheads that in and of themselves may have a therapeutic index that we’re trying to expand and trying to enhance by targeted delivery. So, there are components of both, the target selection and the nature of the construct with Rova-T. But I would say the learnings from both have been incorporated into the ADCs that we have in the clinic.

Josh Schimmer

Which one or two, when you focus on in the solid tumors are assigned to watch what?

Mike Severino

Well, we have a number in the solid tumor side. We have a program that’s aimed at CMAT, which is a target that people have been trying to prosecute for quite some time, but has not been prosecuted in an – with an ADC in the past. that’s in a substantial phase 2 study that we’ll read out right around the end of this year. We’ll have the data at the end of this year when we are able to get into a meeting cycle. We’ll probably carry into 2021. That’s an interesting program. We have programs aimed at delivering molecularly targeted warheads and we have a number of those. We have one that is an XL targeted warhead, but we have others in development as well.

So, they’re really a wide range that we’re focusing on. We’re also focusing on additional targeting agents other than just monoclonal antibodies. So for example, we’re using T-cell receptor based targeting proteins to allow us to go after intracellular targets as well. And we have some of those that’ll be either in the clinic now or in the clinic in the coming year that will allow us to explore those possibilities as well.

Josh Schimmer

Maybe, we can add, take a few minutes and talk a little bit about Allergan, which – where Allergan brought a lot of new products and therapeutic categories to AbbVie. What would you say AbbVie is bringing to Allergan, that’s going to get more mileage out of those products? How has that kind of playing out now that you’ve had a few quarters to integrate?

Rob Michael

Yes, Josh. So, I mean, recall that Allergan was really trying to build out as therapeutics discovery engine, which restricted investment to a certain degree. And so what we’ve been able to do is really add more investment, a fuel growth for several products. We’ve already seen that for Botox, Juvederm, Vraylar, and Ubrelvy through DTC. One of the things that aesthetics before the combination, I was not able to do; I was to run DTC concurrently for Botox and Juvederm. Now, we’re able to do that. We think that’s actually a better way to get a return on your DTC investment.

And the other area I would point to is our strong international footprint. We inherited that strong infrastructure coming out of Abbott. We’ve been able to leverage that we think with our integrated brand team approach, our approach to the market access that there’s a number of things that we can do to drive those brands even further internationally. And we’ve been very pleased if you look at just early days, even through the COVID pandemic, we’re still beating the expectations in terms of accretion. We said, year one on an annualized basis, 10% accretion, we’ve delivered 12%. So, we’re already seeing very nice performance.

I’d point to neuroscience in particular Vraylar and the migraine franchise, as we look at that and gotten more comfortable with it post-close. we think there’s tremendous potential upside versus what we expected the deal model. And then as I mentioned on the aesthetics front with more investment and we’ve stood it up now with a dedicated R&D organization supporting it, dedicated BD, we’ve done the Lumenera deal as an example there in dermal fillers. So, we think there’s opportunity with the right investment, the right structure in place to continue to drive that business beyond what we had expected when we initially did the deal model.

Josh Schimmer

So, you had talked about the Ubrelvy and migraine, a couple of the aesthetic indicated programs. So, are there any other gems in here that you’re finding that you think we should be paying attention to, or that could become relevant growth drivers for AbbVie?

Mike Severino

Yes. So, what I would say one of the things that has shown to be a real gem in the portfolio is Vraylar, and obviously, its performance in its approved indications has been very, very strong and you’ve seen a real inflection point in its growth as it added additional indications, syndications are in schizophrenia, mixed bipolar and bipolar depression. I think there is real potential for adjunctive major depressive disorder that has one study that is readout positive already. That’s a phase 2b study, but it’s pivotal. So, we just need one additional study to file. There are two Phase 3 studies that are ongoing and we didn’t build into our deal model success, because of some of the challenges that are inherent to working in depression. But as we’ve dug into the program, as we’ve looked at the prior study results and also, done a deep dive into the ongoing studies, we feel like they’re well-designed, we think we’re enrolling the right patient population.

And so there is potential there that would represent a very substantial upside, that’s one area that I would say would be a gem and another area also in the neuroscience franchise is the migraine portfolio. you talked about Ubrelvy and that certainly has performed very well. The approval came after certainly, we announced the deal and after all of the diligence that we did, but what I would say is the label is very consistent with our expectations into the upper end of what we would have expected from the efficacy profile. We dug into that molecule very carefully. We were very comfortable with the safety without our head a strong shot at having good efficacy. But if you look at how it ultimately performed, how the phase 3 data read out what the label looks like, it’s a very strong profile and it really adds to a strong portfolio.

And ubrogepant has been a similar story, obviously, not as far along, but the ubrogepant Phase 3 data in episodic migraine were reported top lines probably a month or two ago fairly recently. And those were also very, very strong and met the upper end of our expectations there. at the upper end of the results that one is seeing across the range of CGRP agents, all of the others, obviously being antibodies in terms of those that are used preventative at this time point. And you did it with a very, very favorable safety profile as well. And so we think that there’s real opportunity there.

So, those would be the principal gems. I would also say that in eye care, it’s a business that’s very attractive. There’s not an individual gem, but it’s a business that I think, has a lot of potential and one that we can continue to build on over time. And of course, aesthetics, I think was widely recognized to be a very important part and a real gem in that portfolio. So, those would be, I think, our impressions up to this point.

Josh Schimmer

And there are – there’s a lot in this pipeline that we haven’t talked about. Are there like one or two programs in here that you think we’re going to be talking a lot about next year or the year after that we haven’t touched on today?

Mike Severino

Well, we’ve touched on the TNF steroid lead, but I think, it’s not fully appreciated that that can represent a platform. So, we can not only target TNF mediated diseases with a steroid warhead, but we can change the targeting antibody and we have a number of programs that are still preclinical, but they’re poised to enter the clinic, where we’ve changed the targeting antibody to antigens that might be more relevant to lupus or to scleroderma. We can also change the warhead to other warheads beyond the steroid.

Now, these wouldn’t be cancer type set of toxic warheads, but there would be warheads that would be aimed towards immunologically-mediated diseases. If you look at oncology, we touched on a lot of the more advanced agents in our hem-onc portfolio, but we didn’t touch on lemzoparlimab, the CD47, which is a very strong fit for our portfolio, very strong fit for the hem-onc franchise. CD47 is a very attractive IO mechanism. And it is in areas again that we know very well like AML and MDS.

It should complement Venclexta very, very well. Venclexta has shown a very strong survival benefit in combination with azacitidine in AML. but it’s still a very, very significant illness that has short survival times overall when compared to something like CLL, for example. So, the ability to combine with an IO mechanism like CD47 and drive deeper response, longer survival, and subsequently a longer time on therapy would be very important. And it would be a very important addition to the therapeutic armamentarium and it can be very commercially important as well. So that’s another molecule that I think you’ll hear a lot about.

And we’re making strong progress with our early neuroscience portfolio as well in disease modification and neuroprotection. So, I think people think of our tow program when they think of that, but they don’t think of the neuroinflammation programs, which are just about a year to two years, depending on which program behind tow, in terms of providing proof-of-concept readouts programs like RGMa, neuroprotective agent in MS, spinal cord injury and stroke, which is of course, high risk, high reward. When you think about those areas, but it does have the potential, if those studies readout positively to be game changing. So, there’s a lot in the pipeline that people will be hearing about over the next year and beyond.

Josh Schimmer

Awesome. We’ve covered a huge amount of territory in a short period of time. So, Mike, Rob and Jeff, thank you so much for taking the time.

Mike Severino

Thank you, Josh.

Rob Michael

Welcome, Josh.

Jeff Stewart

pleasure.

Josh Schimmer

Take care.

Question-and-Answer Session

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