All right, welcome to the second day of the B of A Healthcare Conference. My name's Geoff Meacham. I'm the Senior Biopharma Analyst, and Charlie Yang is with me on stage too from B of A, from my team. We're thrilled today to have Apogee Therapeutics on stage with us, CEO Michael Henderson. Michael, good to see you.
Great. Thanks so much for having us.
Thanks for joining us. Yeah, we have some questions, but if you want to just kind of give the for those on the webcast and maybe in the audience that are less familiar, kind of give us the high level, and then we'll get right into it.
Yeah, perfect. So at Apogee, we're developing potentially best-in-class antibodies against the largest markets in I&I, so atopic derm, COPD, asthma to start, monotherapies to start, and then combinations over time. So in short, for instance, for atopic derm, which we think could be a $50 billion market, we want to bring an every-three-month Skyrizi-like dosing profile to an area that's currently every two weeks, COPD in an every-six- to eight-week paradigm to what will be an every-three-week drug, and then asthma as well kind of transform the paradigm. So what's unique is we minimize risk by going after validated targets but making much better antibodies. So we finally know which targets work in these spaces, but often they're two- or three-decade-old antibodies.
Antibody technologies have come a long way since then, so we aim to create the best antibody that we can that minimizes that risk but improves on every aspect from backbone to half-life to exposure to formulation to then bring the best that we can to patients because we know historically these markets, they evolve over time to treat more patients, to have longer dosing, and to push efficacy.
Perfect. That sounds great. I mean, the first opportunity we should talk about is atopic dermatitis. But I'd say across the I&I markets, in a lot of cases, kind of the best profile wins share. But there is the element, though, of formulary, of the commercial kind of piece of that. How much of that goes into your consideration, not just will the profile meet the best target, but will it be saleable? Will it be convenient, the non-sort of clinical aspects of the profile?
Yeah, so I think for us, when we think about the eventual profile of our drug, we want to make sure that it's something that patients and physicians want, right? And then it's, OK, will payers cover it? And historically, over time, we've seen that as new agents come on to psoriasis, for instance, everything is at parity, typically. You have to give a rebate. You have to play that game. You can't not, right? You can't come in price at a 20% premium without any efficacy advantage, right? And we don't know yet if we will have it. We're going to test it to see if we can get better efficacy. But if you're similarly efficacious, similarly safe, just to improve dosing, for instance, you give the rebate. You get parity on access. And then in psoriasis, seven different biologics exist.
Psoriasis was launched. Skyrizi is the sixth that was launched there in 2019, a decade after the original incumbents. It's got a third of share is leading the market just a few years in the launch. UCB with BIMZELX, they have rapidly gotten parity on all payer coverage, and they are quickly gaining share. I think that you want to get parity and then let patients and physicians drive decision making.
Right. Makes sense.
So in atopic dermatitis, right, I mean, we have DUPIXENT as the standard of care for first-line biologics, but still, the market penetration is still relatively low. Maybe just tell us kind of why that is the case, and how do you think maybe more biologics coming into the space, or how APG777 can kind of potentially expand this utilization?
Yep, so I think that we all forget that DUPIXENT, it was just launched six years ago, right? It's a $14 billion drug on its way to $25 billion, but it just got launched. And atopic derm, it's following the same, albeit a little bit slightly faster path of penetration that other markets have seen. So psoriasis, five years in after HUMIRA and ENBREL, 5% penetrated. 20 years in where we are now, 25% penetrated. Asthma, right? NUCALA got things started, 5% penetrated a few years in. Now, 35% penetrated. IBD, RA, more mature I&I markets. Single-digit penetration in the early years, now 50%, 60%, 70% penetration as they get to the 30 years in. So DUPIXENT, five years in, it was at 8% faster than where psoriasis was. And I think if you play it forward, atopic derm will become a 20%-30%, if not greater, penetrated market.
A longer-acting agent that can provide potentially better efficacy will further drive that penetration into more patients and also the more mild or moderate patients that increasingly get treated with time.
OK. What would you say is the similarity? You're drawing the parallel here with psoriasis, right, in terms of the journey here. But what's the parallel there in terms of the patients, their disease-related etiology, or they're facing in terms of reimbursement? Or how do you think why are you drawing that parallel, and why do you think that can apply to AD in this instance?
So I think that it's very similar to psoriasis because derms treat two drugs with biologics. One is psoriasis or two markets, one is psoriasis. The other is atopic derm. That is kind of psoriasis is where they draw the heavy parallels because they've seen that inflammatory skin condition with biologics introduced and kind of gone through that experience. So when we kind of describe our profile to them in every-three-month drug, they say, oh, like Skyrizi, like psoriasis. Yeah, we get it. This is how these markets evolve. And when you look at psoriasis, it's just very similar. Patients cycle through therapies, and over time, they trend towards the longer-acting therapies that they describe as functional cures, right? A functional cure is not a drug which is a cure, right? That's why the functional is there.
It's a drug that you take a few times a year that you no longer have to think, I have a disease, right? You don't have to think, oh, I'm traveling to the B of A Conference this week. Well, I take my DUPIXENT on Wednesdays. How am I going to keep it cold? How am I going to get up there and inject and not lose efficacy or risk ADAs because I take a few days off? You want to get to something that is livable for this chronic, lifelong condition. And I think that when we look at all aspects, speaking with payers, patients, physicians, a similar and do our market research, 90% share goes to us if we're similar efficacy and safety but longer dosing, and the majority of patients switch over to us, very similar to what we've seen with Skyrizi.
So what would you say is your expectation right now, right? What's your base case scenario in terms of what and then obviously what you're actually hoping to achieve based on what you've seen data so far and what are you doing next to potentially improve on better than dupe?
Our base case is similar efficacy and safety to DUPIXENT and lebrikizumab with longer duration of dosing. That is top-line data of IGA 0/1 in the 35%-40% range and EASI-75 data in the 45%-50% range. With our phase II, which we initiated dosing on today, we are going to test a higher exposure of the drug to see if that can lead to greater efficacy. There is very interesting supportive data from lebrikizumab's approval in Europe showing that 30%-40% higher exposures in those patients that were lower weight led to 10%-15% points better efficacy across IGA 0/1, EASI-75, and EASI-90. It wasn't at that dose. It was at same dose, 180 patients that were in that lower body weight, higher exposure group.
We're going to test that in our phase III or in our phase II, rather, with the data coming next year. We'll see if it translates to better efficacy. I think that is upside. I think that when we speak with investors, analysts, they see that it's just upside. Dosing carries the market, and research clearly shows that it is supportive of a best-in-class profile. But because our PK data earlier this year overdelivered, and we were at 75 days and 50% higher concentration than lebri, we're able to test that higher exposure while still cutting the number of injections in half in the induction phase.
Yeah. Michael, I have a question for you. So when you think about, I know your phase I shows differentiation, and the phase II, you're going after higher doses. Philosophically, I think, would you see Apogee running a head-to-head versus the recent standard of care? I think historically in the I&I fields, a lot of companies will run a head-to-head, but against standard of care from five years back, create a lower bar, right? Because I think it's difficult to show superiority. Non-inferiority sometimes isn't as persuasive, right? But if you have the profile, some companies swing for the fences. So I know you don't have to make a decision on phase III design right now, but is there an idea that you could really go head-to-head versus the most contemporary standard of care?
Yeah, so I think it's a question that we've thought about and have discussed and been pretty open about. I think we need to go over our optimized doses before we make that call. We need to know what that optimized dose delivers. I think then it's a question. Do we run phase IIIs head-to-head, or do we run phase IIIs, power against placebo, get to market as quickly as possible, and then still run those head-to-heads as phase IV post-marketing type studies? Because Skyrizi, to your point, they've done it against lower bars. But those weren't even there, those aren't on the label. Those are just studies that they did contemporaneously to still get to lowest risk approval and then do those studies so that you can promote against them and so that you can also design them to put your best foot forward.
I think we'll look at what others have done, learn from that playbook, and we'll be able to make the right call once we know what we have.
Right. And just given the dosing profile, it does seem like atopic derm and a lot of the other I&I indications you could go after, that maintenance is where a lot of the value is, just given the duration. Switching is also one way to do that as well, right?
Yep, yep. I think switching studies, head-to-head studies, biologic experience studies, milder patients, showing efficacy and giving physicians the reason to believe with data to support that, and payers the comfort to support that is what we'll look to do, right? And I think as part of that, we think each of our programs has pipeline and product potential. So we're launching a phase II in asthma next year for our lead program. That's because there's a 30% overlap between atopic derm and asthma. We're now seeing Lilly launch phase IIIs in overlap populations. They're not doing it in asthma yet.
Time will tell, b ut they're doing it in asthma-adjacent diseases. So they're doing it in allergic rhinitis, chronic rhinitis with nasal polyps. So I think we'll look to those are billion-dollar indications in their own right. Makes a lot of sense, a nd they're going straight to phase III. We'll look to kind of prove out the full value and story over time with the appropriate studies.
For sure, I think you have the core indications. You're seeing the bigger companies going after sort of one click away, more niche kind of orphan indications as well. That's probably not in wave one for you guys, though, right?
Yeah, and I think wave one for us is the biggest markets. It's the biggest markets with our monotherapies and then combinations in those same markets with our OX40L-IL-13 combos, for instance. And then over time, it's expanding even further.
Maybe just on the safety side, since you want to dose higher, what's your thought about potential safety profile? Will we be able to achieve essentially the same safety as dupe even at higher doses?
Yep. So when we look at DUPIXENT, lebrikizumab, other IL-13s, there has never been any safety AE relationship observed across any of the agents or for any of the studies. DUPIXENT did; they doubled the dose in their phase IIIs, and they saw no safety at that higher dose. Lebrikizumab, there are 200 patients that were at the exposures that we're going to be testing that had no safety issues. IL-13, there's no healthy function for it. It only exists to kick up your inflammatory state and to catalyze that type 2 inflammatory cascade, right? And I think in all the targets that we've gone after, you don't want to half-life extend and push exposures for something that has a therapeutic index issue. Otherwise, it's just not the best idea. So we've focused on safe targets for where we could push exposure and prolonged dosing.
So just to hit home how safe we've seen this target be, in our non-human primate studies, we wanted to push it. So we did YTE in a non-human primate dose weekly. It got to 50x higher exposures than we're going to be testing even at this elevated exposure in the phase II. There was no adverse event seen at six months, and that was the highest that we could ethically give to non-human primates.
Great. You mentioned about the OX40 mechanism by obviously Amgen, Sanofi. They each have OX40. And I believe there's other companies with IL-13 or even IL-31 that could potentially come into the market in the next coming years. How are you thinking about them as competition-wise? Again, differentiating perspective, where does 777 can potentially be better than them?
Yeah, so when you look at IL-31, I'll just kind of hit on that one first, nemolizumab. It's a really interesting disease for itchy patients. When you ask dermatologists, OK, what do you think about a drug that can help improve on itch but is much lower on lesion appearance? They say, oh, yeah, I'm excited for that new mechanism. Great. You have 300, 400 patients on your panel. How many will you use it for?
Oh, I've got two or three, which is great. It'll still be a blockbuster. It'll be a billion-dollar drug. But it's not going to become the market leader. It's going to be for that prurigo type patient that might have atopic derm and for some atopic derm patients that are incessantly itchy. But it gets to not near the lesion clearance of the other agents, a nd patients want to see their lesions cleared up.
They don't want to have that red, scaly, patchy skin that's visible and causes them psychosocial distress. Then for OX40L, it's a super interesting second-line agent as a monotherapy. It hits type 2 inflammation, which is the IL-13-IL-4 pathway. But it also hits type 1, TH17, TH22. We know that as patients are younger or more severe or different ethnicities, especially more Asian patients have more TH17, TH22, there is less response to monotherapy lebrikizumab or DUPIXENT. However, there's better response from OX40 ligand. So our approach there is interesting monotherapy, combine them, co-formulate two long-acting, best-in-class monotherapy agents into a single injection that can still reach that best-in-category dosing and fully tamp down type 2 inflammation, which is the primary driver, but also capture the TH17 and TH22 type 1 inflammation so that you can get broader and deeper efficacy across the full atopic derm population.
Then if OX40 ligand data from Sanofi in asthma and all-comer asthma looks interesting later this year, great. Another expansion. If it looks interesting in alopecia or celiac disease next year, more expansions.
Got it. So I guess obviously, you have the dual mechanism, why the APG990. You made an announcement earlier this week on that. Maybe just tell us about the timing of this molecule in terms of how this will potentially follow on the 777.
Yep. So we're really excited earlier this week to announce that we nominated our dev candidate for our 990 program, which is our OX40L ligand, similar binding, overlapping epitope, as amlitelimab, similar potency, longer half-life. So we'll now be in the clinic ahead of schedule with this program by the end of this year. That will enable us to actually do initial healthy volunteer combo studies with our lead program as early as next year. So I think next year, when we take a step back and look at our pipeline, we're going to have the phase II atopic derm data, definitive 16-week data, part A greater than 90% powered for the primary endpoint delivering data.
We're going to have our second program, IL-4 receptor alpha, with that FeNO data in asthma, then dovetailing into a COPD trial, and then 990 half-life data and combo initiation to really bring the full story together. Not to mention, we will have a new agent, which we disclose later this year. As part of the recent raise and follow-on, we announced that we added a target, but we haven't disclosed it yet, that will further feed into this broader and deeper combo approach that we're going to be pushing.
Yeah, just a question on that. I mean, you don't see that many combinations across the I&I space, presumably because you have maybe overlapping toxicities or maybe you don't get a lot of bump in the efficacy. Is that sort of an Apogee strategy going forward for a lot of these big indications to go after two drug or more combinations? You see that in many other therapeutic categories, obviously.
Yeah, so I think we haven't seen it so far just because it hasn't been tried and because of the toxicity piece. We've seen one example of someone that's actually tried it. J&J's done it in IBD with the VEGA and DUET studies. They get purely additive efficacy. It's pretty wild, actually. You just 24, 24 equals 50. I don't know if we can expect that level of additive efficacy. But with our approach, to your point, you look at obesity, you look at CV, you look at oncology. If you don't have overlapping tox and you have orthogonal pathways, combine them. See what happens. So our strategy is, yeah, we want to be the first to do it for our programs because they don't have overlapping tox and they're orthogonal pathways. So let's be the first to see if we can push the bar even more.
Part of our mantra is refuse to stop at good enough. It's like, why would we? Let's combine these best-in-class agents.
Your platform allows for pretty easy target selection, right?
Yep, easy target selection, validated targets where we know about the tox profile going in. And additionally, just the ability to maintain that best-in-category dosing so that we're not taking a step backwards.
So actually, just on that, the platform in terms of the YTE, can you just tell us about how does that fit into the Paragon agreement? Is that you developed internally, or is that coming from them?
Yep. So to date, we've had a great collaboration with Paragon. They have been the engineers and developers of our programs. We get full commercial rights. They had early equity in the company. And in exchange, we got low single-digit royalties, very unencumbered assets. Over time, we have the flexibility to go broader than that. However, it's also like, if anything broke, don't fix it. And with the most recent raise and thinking about another target, we went to them and quickly decided that there was a new target that we should work on together and expanded that collaboration. So they've been great partners, a nd we have the ability to move quickly with them. And because they're so incentivized with equity as well, it helps us to align interests and move quickly. But we have the flexibility, if we ever wanted to, to go externally.
Got it. Is there a limitation in terms of what indication that you can do versus that you cannot? Because obviously, they have other companies that they spin off as well, right?
Yeah, so there's no limitation. I think that they would be limited by what they've agreed to with other companies. And we would, of course, be respectful of that. I think for us, as we've thought about where to expand, we don't want to do too much. You can't be good at everything. You really need to focus on a call point and some diseases of interest. So we're really kind of focused on the largest I&I markets. That's where we decided to focus, so atopic derm/derm and asthma/COPD/respiratory. So you'll see as kind of the targets that we had feed well into that call point and strengthen the combination approach of our existing agents to go broader and deeper into those diseases specifically to start.
For a lot of these I&I markets, obviously, you have HUMIRA and REMICADE that are post-LOE. Does that worry you when you look at sort of long-term modeling? I know there's a lot of next-gen drugs. But I fully expect payers to throw up all kinds of step edits, right, and that may change some of the assumptions that you'd have to make for share or for value, really.
So it doesn't scare me long-term because I think that we will bring more than dosing long-term. I don't know if it'll be via higher exposures with our lead drug or if it will require combinations. But I think long-term, prior to biosimilars coming onto these markets, we will and need to and will have that sort of higher efficacy play to protect against biosimilar competition. I think with our monotherapies, we will not be launching in a biosimilar world. We will launch prior to them existing. And then it'll be about getting parity, getting patients and physicians to us. So then later on, if we have not brought additional efficacy in some way and biosimilars start to enter, then we'll see what happens. I think so far in psoriasis, you're seeing step edits, b ut Skyrizi's continuing to launch great.
It does have a bit better efficacy against a HUMIRA biosimilar. But in wet AMD, you're seeing same efficacy for longer-acting agents. They're continuing to launch really well. I think it really does come down to you don't want to launch in a biosimilar world. You want to get your foothold. Then we want to keep bringing innovation so that we don't then settle for 20% of the market. We're looking at still maintaining market leadership and evolving the care for patients.
I know we spent like 25 minutes on AD, but you have asthma and COPD. But maybe we can switch gears just to talk about your 777 opportunity in there and why the IL-13 targets versus, and obviously, you have the 808, IL-4 for that. So what's the thinking about choosing one versus the other and why doing both?
Yeah, so we wanted to develop and prove out that our IL-13 could work in asthma because there's a 30% overlap between atopic derm and moderate to severe asthmatic patients. I think this is a headwind that lebrikizumab's launch might face because if you're a dermatologist, you want to write the script for someone and know that it'll cover their comorbidity. So for us, it was very important to show that. And we're going to launch the phase II next year. When we thought about IL-4 receptor alpha right there, we can get to every six to eight weeks. We can't get to three to six months with that drug because it is a receptor-bound target. But in COPD, dupi is going to be every two weeks.
We'll see about the TSLP. Maybe out to every four weeks. But an every six to eight week drug could still be meaningfully differentiated. As a monotherapy, by focusing that one on COPD, that's the only Medicare IRA-exposed indication that dupi has. Then we keep our IL-13 777 drug free and clear from IRA exposure, only going after commercial markets. We concentrate any potential exposure to our COPD drug with that secondary mechanism.
Got it. So I guess maybe just on the if you just could give us a high-level overview about the asthma and we'll talk about the asthma market first. There are a lot of biologics there. What's the positioning in terms of efficacy? Or is it just more of a longer-interval play?
Yep. So two really interesting things about asthma. One, there's six different biologics that are all doing a few billion. So that's just a reminder. These aren't winner-take-all markets. If you hang around the hoop in these markets, you do really well. You just price it parity. Physician preference drives a lot. In asthma, DUPIXENT is the number one market leader because it has that comorbid overlap. So I think there, the next market leader projected is probably FASENRA, which actually has worse top-line data than anything else but has every eight-week dosing. So I think that pulmonologists, allergists, market data supports that they should be well predisposed to a long-acting agent that covers multiple comorbidities. So I think that sets itself up very well for asthma. And for COPD, we'll see how that market develops.
But an every eight-week drug versus an every two-week drug, when we ask pulmonologists if that excites them, it's pretty clear. And in COPD, those aren't the most reliable patients always with all the medications that they have to take. So having a drug on board that they know will provide lasting coverage in between visits is critical for them.
A question on when you look at asthma versus COPD and Regeneron's recent data looked at eosinophil testing, which is not as common in COPD, to what degree do you guys want to look at maybe more predictive biomarkers that you could put into studies that may have some element of differentiation or competitive moat?
Yeah, so I think what's been really exciting recently in both asthma and COPD is FeNO. So FeNO, you and I are both, Charlie, too, so all three of us, we're all throwing off FeNO right now. We can't control how much we're throwing off. There's no placebo effect for FeNO. So both in asthma and COPD, we've seen recently that a 10-15-point improvement in your FeNO, so reduction in how much FeNO you're exhaling, leads to very reliable outcomes and predictive outcomes, 52-week data in phase IIIs for both FEV1 and exacerbation data. It's like arguably more predictive than FEV1 is for exacerbation because of the placebo effect. So in our initial study for 808 next year and for our asthma study for 777, we're going to use FeNO for early predictive data. And then for 808, why run two asthma studies next year?
It's because 777, we want to take fully in asthma over time. 808, we'll see how the data is. But it'll, at the very least, validate the efficacy and help refine the doses that we're taking into COPD to enable us to move a little bit faster.
Yeah, makes sense.
So then competitive escape, I think Sanofi is making a lot of inroads in that. They could actually come to market relatively in a few years as well. Just how do you think about their data set about what they have shown so far and versus what you're looking to differentiate?
Yeah, so with amlitelimab, for instance?
Yes, and TSLP.
Oh, their IL-13 TSLP, yeah. So on amlitelimab, we're excited to see how the data looks later this year. Whatever they can do, we hope to have a half-life extended version, combine it, and drive deeper efficacy and go deeper and broader across all patients, not just the greater than 150 subset of asthma. With their IL-13 TSLP, it's really interesting. It's just going backwards in dosing. So it's an every two-week drug a nd it's unclear what the true contribution of effects are. So we're excited to see how that data looks. And if it looks really interesting as a combination approach, I think that's interesting for us to consider longer-term in terms of potential. There's a lot of TSLPs out there now. So it's an interesting combo that we could always access to.
Perfect. All right. Thank you, Michael.
Perfect. All right. Thank you.
Thank you.