All right, good morning everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much again for joining TD Cowen's 46th Annual Healthcare Conference. Very excited to be kicking off the company sessions with a fireside chat with Apogee Therapeutics, Best Idea for 2025. You guys made me look smart last year. I needed it. Hopefully you make me look smart again 'cause it's the Best Idea two years in a row. A lot of very exciting readouts coming up, it's my pleasure to introduce Michael Henderson, the CEO, Carl Dambkowski, the Chief Medical Officer, Jeff Hartness, the Chief Commercial Officer, and Jane Pritchett Henderson, the Chief Financial Officer. It's a privilege to have you all here with us. Thank you very much for joining me.
Thank you for having us.
We will go ahead and just go chronologically through the upcoming data updates. You know, obviously you put up really exciting data for zumilokibart or zumi last summer with Part A. Maybe you could just briefly talk about the Part A results with zumi and the upcoming 52-week maintenance data, and what about the Part A results give you confidence in the upcoming maintenance data, and what you believe you need to show with the maintenance data to be successful.
Happy to. I'll get started. Carl, feel free to add on. For four years now, we've been working to prove out that we can transform dosing for atopic dermatitis patients and related Type 2 inflammation, right? The upshot is we know Dupixent is a great drug. It's dosed every two weeks. 50% of patients are off therapy within two years. You know, it's painful, and it just doesn't have great compliance. Same thing happened in psoriasis, right? You had an every two to four-week drug. Now, patients are 90% plus adherent on SKYRIZI. Like, the jingle that it has, nothing is everything. Like, it's true.
If you're a patient, you want something that's quarterly or even less frequent. We've been working to prove that for four years. This is the month where we get to put out our maintenance data and really show can we improve dosing for patients from every two weeks to every three to six months, right? Drastically reducing the burden and improving adherence and compliance. You know, I think that will. It's kind of the final cap in the target product profile for the drug 'cause what did we put out last summer? We put out 16-week induction data showing that we are as good on lesions as Dupixent and Ebglyss. We're also, right, zumilokibart, fast on itch.
We have 48-hour itch relief that's comparable to Nemluvio, better than what you see on Dupixent and Ebglyss, and that is because we give more drug day 1, given an improved formulation, and that drug lasts longer because of the improved half-life. We're seeing rapid itch. We're seeing lesional benefit by week 16 as good as any other biologic. On EASI-75, we're quite proud of that data, and now we're looking to prove out can we get to that every 3 and 6-month dosing for patients. The bar there is quite clear. On Ebglyss and Dupixent, the labels for those drugs has a responder analysis. That is of patients that had reached EASI-75 or IGA 0/1 by week 16, how many of those patients have maintained that response by week 52?
It's about 72% maintain EASI-75 and 53% maintain IGA 0/1. We'll compare our 3 and 6-month regimens against that responder analysis. We also are doing something that docs wanna see, which is whereas they only randomize responders over, we randomize all patients over, right? Docs wanna know, "How does my entire patient population do over 52 weeks?" You know, do non-responders convert? If response is lost, how does that impact the population? We'll be able to have that full picture, you know, something that I think will be just helpful for physicians to see. To set expectations, Dupixent, we know from their label that they do not deepen over time. It is very flat. Ebglyss, We don't have that data for them because they, it's not on their label.
Yeah, it's pretty rare to see non-responders convert on Dupixent by 16 weeks. Is that fair to say?
Yeah, Carl, you can speak to kind of the label data.
I think if you look at Dupixent's label data, it's from their combo study with TCS, which is the only one that they've actually followed people for 52 weeks, their week 16 response rate is around 35%. Their week 52 response rate is around 35%. Almost the same. You're probably getting some amount of patients that lose response and some that gain response, and they're kind of trading off 'cause we also know the maintenance of response for Dupixent is not 100% for IGA 0/1. You're getting some switching in and out, which overall makes it a flat line.
Got it. Okay, I think most people believe that you're gonna show quarterly dosing, right? Obviously, every 6 months would be even better in some situations. How are you guys thinking about quarterly versus every 6 months? What's the significance of that besides the obvious based upon what you've done with your market research, would you move forward into a pivotal with both dosing strategies?
Yeah. We will move forward with both. Right, if you look at kind of what different drugs do in development for atopic dermatitis, you prove out your induction dose, right? In your phase IIb, take a single induction dose forward. Everyone includes multiple maintenance arms, right? Ebglyss, right, Dupixent did Q 2-week, Q 4-week, Q 8-week. Only Q 2-week worked. The others, it fell off. Ebglyss, Q 2-week and Q 4-week, both are on the label. Our intent is to have a Q 3-month and a Q 6-month maintenance arm in the phase III that's launching this year, launching in 2029. Docs want that choice, and what we're gonna learn from the data is do we have the right dose or should we adjust the dose? If 6 months wanes versus 3 months, okay, we can increase the 6-month dose in the phase III.
If 6 months and 3 months are the same, okay, then we can decrease the dose and have an even friendlier profile for Q3. By having this maintenance data before phase 3, we're able to go into phase 3 not guessing. Like people have done historically, but having a great deal of confidence that we'll have the right dose. From a commercial perspective, Jeff, do you wanna talk about kind of the market research that we've done?
Sure, yeah. I think quarterly in and of itself transforms the market, right? If you talk to physicians and patients, that's sort of pie in the sky for them right now. They can't get their head wrapped around that, the ability to take, you know, an AD biologic 4 times a year. Why do we want both quarterly and semi-annual? Both physicians and patients also want choice, but it does 3 quick things for us. Number one, it allows us to get additional market share on top of becoming the market leader with quarterly alone. When you do market research, physicians say by having the Q6M, it adds another 10% market share in terms of how much they give to zumilokibart.
Secondly, what it does is, it allows us to drive additional volume. Think about what we're solving for. We have a 10% biologic penetration in this space. Quarterly dosing clearly will drive more patients from topicals over. Semi-annual drives even more, so we can deepen the biologic penetration. Then lastly, every 6 months just keeps us out in front of the competition, right? Really we get the trifecta by bringing both Q3 and Q6 month forward.
Got it. Okay. I guess just to confirm, you have room in the formulation to increase the dose for every six months if you need to in phase three?
Yeah, we can also just give, you know, 1.5, 2 injections every 6 months.
Got it.
That's kinda like the outer end of kind of what we would need if six months just was to show rapid remission, which wouldn't be our expectation, but plenty of room.
All right. Yeah, the KOLs feedback on our panels, as most people know here by now, has been quite strong, right? Quarterly dosing with similar efficacy is like, potentially up to 80% market share.
Mm-hmm
... in some cases. Obviously every 6 months would be upside. You know, obviously increased efficacy would be, you know, the dream scenario, on top of the dream. Let's talk about the part B. Actually first, the maintenance data definitely coming by the end of the month, right?
Correct, this month.
Okay.
Mm-hmm.
Part B data coming in Q2. We've seen the Ebglyss EU document right from the phase 3 that looked at difference in exposure and response. You did a very interesting part A analysis with the different quartiles of exposure.
Mm-hmm.
Maybe you could describe the data there and why that could potentially or at least why you're testing that hypothesis in part B.
Yeah. We know that IL-13 has an exposure response and a dose response, right? lebrikizumab Ebglyss, it's an old antibody, so the max that they could formulate was 125 mgs per ml, 250 mgs in a 2 ml injection dosed every 2 weeks, and that's what Lilly took forward into the phase 3. It never went higher than that because they don't wanna be disadvantaged to Dupixent, which is fair, right? They, you know, once people get used to every 2 weeks, people don't wanna go to weekly. Just like once we convert the market to every 3 to 6 months, people aren't gonna wanna go back to every 2 to 4 weeks. Like, you have to kind of keep up and not force a trade-off with dosing and efficacy.
They capped it at that, what we saw from the EMA review is that they said there was an exposure response in induction, not in maintenance, but in induction it was noted. Patients that were low body weight got higher exposures, and they had better outcomes on EASI-75, IGA 0/1, and EASI-90. Like in our part A data, we saw an exposure response as well, and we put out that data. It was post-hoc, right? Very clear about that. That the highest quartile of patients, the highest quartile of exposures did the best. I think we will see in our part B, which is testing a higher dose, which is in line that top dose is in line with that quartile form of exposure, if we can eke out more efficacy or if we've actually...
We're already at the top of it, right? Our EASI-75 was 17 points on an absolute basis better than Dupixent. You know, 14 points better than Ebglyss. 13 points, excuse me. It's like I think that we're seeing signs of that. You know, our itch relief at 48 hours, that's driven by more exposure day 1. It's like, we're gonna see in the part B, does even more exposure beyond what we're giving in the mid dose derive something? If so, great, no one will be happier than us. I think to be clear, like it's a mid-cap investor focus, but not a doc focus, 'cause docs are like, "This is already everything I want and more." Like it's a to your point, it's a dream within a dream.
You don't need to convince me more, but we want to do the best that we can for patients, and if we can get more efficacy, we will be very happy, but we view it as kind of pure upside.
If you, I guess, speak with the KOLs that are maybe a bit more challenging in terms of TPP and future uptake, and want to see greater efficacy, what do you think is like the minimum threshold or delta on EASI-75, 90, IGA? Is it like 5 points? Is it a few points? Obviously, these different measures have different absolute rates. How are you thinking about... I mean, I'm assuming 1 to 2 point separation is not enough. How are you thinking about the kind of minimum separation that would-
Yeah
... claim superiority?
Yeah. Carl, you wanna speak to kinda how we think about go forward phase 3 dose?
Yeah. I think the simplest but maybe most unsatisfying way to say it is we'll know it when we see it, and I think we'll all in this room, everyone, will look at it and say that's what they should go forward with versus not. I think data-wise, that probably means pretty consistent 5 percentage points or better. I think less than 5 percentage points, and you're talking kind of noise, you know, between a couple patients here and there. Probably not gonna be compelling to us. 5 percentage points or more is probably gonna be much more compelling.
Yep.
Can I ask, can you, as you go up this higher doses, you're not concerned about any sort of impact on safety?
The question was, as we go up on dose, do we have any concern about safety? No. I think the only adverse event known to the class is a largely aesthetic one called conjunctivitis. It's transient redness of the eyes. It often resolves without any meds, if you need anything, it's Visine. If anybody needs Visine, I have some. Happy to share. It's over the counter. You know, what we see with Dupixent's data is as you go up in exposure, we actually have a decreased rate of conjunctivitis. It's counterintuitive because it's an inflammatory kind of bounce back mechanism that's happening. The more anti-inflammatory antibody that you have on board with Dupixent, then the less... Like, you're actually kind of blocking the adverse event in and of itself.
I think importantly our view is conjunctivitis, and this is I think docs are very clear, like they're very comfortable with it. It doesn't kind of cause discontinuations. If we see in our own data that we're seeing a discontinuation rate that's higher than what others see, others see kind of a 1%, 2%, 3% rate, then okay. Like, we should think about that, and that should inform our decision-making. Otherwise, nothing to be concerned about. The other adverse events that are seen on Dupixent, you know, head and neck erythema, certain arthralgias, eosinophilia, we have not seen that in our data. IL-13 seems to cause less of that in general.
Even in the minority of patients that get conjunctivitis or red eyes, it typically goes down quite rapidly after the initial incidents, right?
Yeah. You see a decrease over time. You know, I think the big bear thesis was it's a long antibody, it's gonna cause long cases of red eyes. We saw our rate was less than 30 days. Dupixent's reported rate was 170 days on average. I don't think that we're causing minor cases. It's just people now look for it, minor stuff now gets coded. You know, like we had 1 patient that should really get rid of their cat 'cause they're allergic, they, you know, have less than 7 days of conjunctivitis. That's now recorded as a case.
Great.
For Dupi, what causes discontinuation is the ISR, right?
Mm-hmm.
It hurts. Like, it's not the conjunctivitis that causes the discontinuation.
Yeah. People didn't really hear about the ISR till they started having alternatives.
Agreed. Now docs talk about it a lot.
Yeah.
Yeah. Some out there in the audience might like to do placebo-adjusted analyses when the Part B data come out. You guys did a really good job with the placebo rate in Part A. Historically high placebo rate. Can you talk about what's different with Part B and why that placebo rate might somehow come down into the more normal end of the range potentially?
Yeah, yeah. Carl, what have you done?
Yeah. You know, I think we're fighting. One trend that we're fighting here is this placebo rates are going up in AD overall. You know, use the most recent data we have from an AD study, which is tralokinumab's very large phase 3 study. They obviously have quite a lot of experience in AD over decades, and still kind of in the EASI-75 of 25%-30%. We're fighting something that just exists in the world overall too. Like to frame it that way as well, because there are some trends that probably are gonna be difficult to overcome. I would also say that KOLs, we know people in this room will do placebo-adjusted.
KOLs, I know you have a panel tomorrow, just don't really care about placebo-adjusted numbers, right? They're really looking at top-line numbers too, they're thinking about other aspects of the study as well, really focused on top-line numbers overall, 'cause they're saying, "When a patient comes into my clinic, what will happen to them over time?" That's what they care about. That said, we're still trying to control placebo rates as much as possible in Part B. We implemented a lot of stuff in Part A and Part B. We're also doing some additional pieces, largely focused on our site footprint, which is increasing in Europe. We added 45 new sites in Europe across 7 or 8 countries, so larger European footprint. We think that's important because historically Europe has had the lowest placebo rates.
We saw that in our own data for Part A. Europe, which was only about 25% of the study, had the lowest placebo rates. Again, historically, across just about every trial you can look at, that has been true overall, and we expect about 50% of the population or more to be from Europe in Part B, so we think that's an important measure. The second thing we think is important is just size of the placebo arm. In Part A, it was 41 patients in the placebo arm. In Part B, it'll be more than 80 patients in the placebo arm. That low, small N, lots of variability. One patient in Part A counted for 2.5%.
The swing factor we're talking about here between normal and maybe a little high placebo rates in Part A was really two patients. We didn't see anything that accounted for that in a systematic way, so we think just bigger N leads to lower variability. We think that's another important aspect of Part B.
Great. We need to get to 279, the OX40 combo data the second half. Quickly, you guys are starting a phase 3 in the second half with Zumi. Anything brief to add on that study design beyond what we've already discussed with the 3 and 6 months?
Yeah. Jane?
We'll start the phase III by the end of this year. We're gonna follow the path that has been set out before us, which is two replicate trials of Zumi versus placebo. Of course, for the label, we'll look at doing a third trial, which will include TCS, so we can have that on the label. That will enable us to stay on track to launch in 2029.
Great. Jane, you're fully funded for the phase three, or what's the runway look like?
We are funded into the second half of 2028, which provides runway through the phase 3 top-line data.
Perfect. Let's move to APG279 head-to-head versus Dupixent study reading out in the second half. Very bold of you guys to do a head-to-head versus Dupixent, a standard care. Maybe you could just elaborate on what gave you confidence to run this head-to-head study, what you saw pre-clinically, and what the expectations are for success there, at least from an efficacy standpoint.
Yeah. Our view is, right, the future will be frontline will be ZUMI, right? Patients go on IL-13, safe, effective, right, great dosing. If you need something more, right, people talk about AD as being crowded, but it's really not that crowded in our view because all the readouts that have been happening, they've been for drugs which either have, you know, worse efficacy and/or worse safety than DUPI. What do docs reach for if patients don't respond to a frontline drug, which is DUPI now or in the future ZUMI? They reach for a JAK. You know, JAKs, I think they are a, you know, they're a sledgehammer. You hit Type 1, 2, and 3 inflammation, you do get deeper responses, right, across a number of endpoints and itch.
They are effective, and they do beat DUPI head-to-head. Our view is if we wanna have the second-line drug of choice instead of a JAK, then we need something that beats DUPI head-to-head to give docs that confidence. Otherwise, right, it's a big market, but we don't wanna play for third, fourth, fifth line. We wanna have the frontline drug and the second-line drug of choice. When we think about this, you know, the equipoise that a doc will have for 279 layering on OX40L provides that Type 1, 2, and 3 inflammation. It is broader. It has that immunomodulatory effect like a JAK, and it has a cleaner safety profile than a JAK, right? JAKs have multiple black box warnings. They cause a number of things, Kaposi, lymphoma.
You require labs, DVTs across the full population, whereas, right, OX40L, it does have this Kaposi signal in high-risk individuals. Still, when we talk to docs, we ask, "What are you most excited about for second-line?" It's, "Well, 279," because it could be still quarterly dosed or better, and it'll require less monitoring and be safer than a JAK if you beat DUPI head-to-head. Then it becomes, okay, what is that metric? How much do we need to beat DUPI by? That kind of comes to 8-10 points of efficacy. Right, I think it can't just be on a single endpoint. It's gotta be, right, trends across endpoints and that 8-10 points that gives us confidence we can, you know, go on to effectively power it.
Okay. You mentioned the Kaposi sarcoma cases that have been disclosed. Can you talk about, you know, the incidents in those programs, your level of concern? I think in both disclosures, they said the patient had risk factors. Just again, your overall level of concern with that.
Yeah. Carl, please.
Yeah. I think that it's, our level of concern is, I guess, low to medium, I would say, in this too. I say that because low because for our mechanism overall, for what we're trying to do here, prove head-to-head versus DUPI, I think that it's low in that case, that we're gonna have a positive benefit risk profile to move forward. A lot of what we're hearing with Sanofi, KHK and Amgen is they're talking about the benefit risk profile, but the benefit is really low for amlitelimab and rocatinlimab because they're seeing EASI-75 rates at week 16 that are 40% or less versus what we're trying to do here, which is be head-to-head better than DUPI. I say medium because we're not trying to take this lightly.
We know that there's some immunomodulatory risk with the mechanism, but we think that is all able to be properly monitored in a study overall too. What we're talking about here is cutaneous Kaposi sarcoma. This isn't... If you go Google pictures of it's gonna look terrible if you put Kaposi in ChatGPT. That's not what we're talking about here too, that epidemic or AIDS-related Kaposi sarcoma. We're talking about cutaneous skin lesions here. Not trying to underplay that, but there's a treatment for it. There's tens of thousands of cases every year in the US of cutaneous Kaposi sarcoma. Docs that actually treat it are dermatologists, so this is, like, in their profile of what they know to do.
The surveillance for it is skin checks, also something that dermatologists, whether they like it or not, are really good at doing it, and it's a localized treatment overall too. You know, I frame that all because we're not taking this lightly, but there's plenty of monitoring mechanisms to put in there, and the thing that docs don't like about the current profile of rocatinlimab and amlitelimab is the benefit part of it, and then this just adds to that negative downside. Our whole play here is much different in terms of the benefit part of it, so this risk part of it should really be compared to a JAK, which Michael said, sometimes you forget. Go look at that label again.
It's a laundry list of things that can happen that you can't just do a skin check for too.
We need to get to the other indications in the last three, four minutes, but just very quickly, what's your best guess as to the incidence of Kaposi sarcoma based upon the number of patients that have been treated. Are you guys testing a lower exposure of OX40 Ligand in the combination, therefore lower liability?
Yeah, I think that our best estimate is somewhere between 1 in 2,000 to 1 in 4,000 is somewhere where they're hitting. It also seems like that the cases are happening in higher risk individuals. The causative agent of Kaposi sarcoma is HHV-8. But we know certain populations, like HIV negative, gay men, have a higher underlying seroprevalence rate of HHV-8, something like 25%, therefore making it more likely that this is uncovered with an immunomodulatory rate too. We think that it all being in a high-risk population also is better for surveillance as well.
Great. All right. We already talked about the AD market. It's huge, $50 billion. Dupi, Nemluvio, Ebglyss are all growing magnificently. Let's go to asthma and respiratory. Maybe just briefly talk about why you guys are so excited about the Zumi data in asthma that we've seen, and then also the status of the Zumi TSLP combination and future plans for that combination.
Earlier this year, we disclosed our 1B for Zumi in asthma, where we showed both magnitude of phenotypic suppression, as well as durability of that suppression out to 32 weeks. That positive data is going to enable us to design a trial to take that forward, and we'll come out later this year with those designs of that trial, as well as EoE. With a pipeline and a product opportunity here, that will be an important indication for us as well. As we look at the combo, so IL-13 and TSLP, our 273 program, we will also announce design of that trial later this year. All of those are gonna be with the benefit of our Part B dosing.
For the combo, we'll also have the benefit of the lunsekimig data, which is Sanofi's IL-13 TSLP nanobody, and that will enable that design as well. We continue to be very excited, not just about AD, to your point, but this pipeline and the product opportunity.
Great. You mentioned EoE, your entrée into kind of the GI indication. Can you elaborate on the status of the program in EoE, when we could get data there, and maybe even any other indications you guys are focused on, as if you don't have enough to execute on?
Entrée to GI.
Yeah.
I like what you did there. We'll share plans for the EoE trial later this year, and then that will include timing. I think, you know, to Regeneron and Sanofi's credit, they optimized their dose via phase 2B in derm, then in respiratory with asthma, and then in GI with EoE. That enabled them to then skip dose range finding and go for their other indications among those TAs, and go straight to phase 3. I think that's a clever playbook that we'll look to also utilize.
Perfect. Since we're up on time, we will close out with one of my favorite questions. What do you believe is the most underappreciated aspect of the Apogee story by investors? Of course, less underappreciated today than it was a year ago.
Yeah
I'm curious to get your latest thoughts on that.
I think, you know, investors are busy. I get it. I think that you can look at us and think, "Okay, this is a, you know, it's a phase 2 company, and it is, you know, it's not, it's not cheap." Like, maybe it's valued well. If you take a step back and you think about what are we gonna be by the end of this year? We're gonna be a phase 3 company with the frontline drug of choice set to launch in the largest and fastest-growing I&I market with a clear path, even with conservative assumptions, to mega blockbuster potential and a full pipeline and a product set of expansion indications going, and combo optionality on top. That profile is very different than where we are today and has a very different value than where we are today.
I think people kind of, taking a step back and being, you know, 6 months patient, which I know is hard in this market, could be quite valuable, and people miss that sometimes.
Wonderful. With that, thank you to the Apogee management team.