Apogee Therapeutics, Inc. (APGE) Earnings Call Transcript & Summary

[Audio Gap] Best-in-class formulations, half-life extension and fully optimized antibodies that can be co-formulated together. The upshot is that we have what we feel are potentially best-in-class approaches to the largest markets in I&I. And our lead program we will have data this summer, which could show that it could transform the potentially more than $50 billion atopic derm market from a current every 2- to 4-week treatment paradigm to 3 months or less. Beyond our monotherapies, we're also advancing first-in-class and potentially best-in-class combination approaches, and it will be the first to launch a head-to-head trial with the market leader, DUPIXENT later this year with data coming next year. You can see our pipeline here. Our lead program, APG777, 777 is very appropriate for the venue, is going after IL-13. IL-13 is a safe and effective mechanism as shown by Lilly's EBGLYSS targeting atopic dermatitis. Our data this summer will be in the 16-week endpoint for atopic derm. Here, we aim to show that with roughly half the number of doses during the induction period and then 3 months or less frequent dosing and maintenance, we can again transform this market. Beyond atopic derm, we're also planning a Phase IIb in asthma and that will start later this year and a Phase II in EoE, which would start next year. This will give us kind of Phase II dose optimization studies going in each of the therapeutic areas where DUPIXENT currently plays. Beyond that, APG279 is our co-formulated IL-13 and OX40 ligand combination approach. Here, we are launching this trial later this year, head-to-head against DUPIXENT with data coming next year. Beyond that, in the respiratory space, we feel TSLP is a more exciting and data-backed combination approach. So we're combining that with IL-13 there, and we'll share more plans around that later this year. A little bit more on 777, given that's where the majority of the focus is, given that it's our next big readout. Psoriasis, a market that you know well, just to set the stage, teaches us how these markets develop over time. On the Y-axis is efficacy and on the X-axis dosing frequency. Over time, it's gone from an every 2- to 4-week paradigm to an every 3-month paradigm, right? The market leader, SKYRIZI, has come almost last to this market, but very quickly within a few years, has become the market leader. And importantly, as each new entrant comes, especially if they extend dosing, they don't just take share, they make share. And we see that all these drugs can happily coexist together with the biggest grossing drugs to date being the ones with the most convenient quarterly dosing, which patients describe as a functional cure. Atopic derm by contrast is the definition of white space, right, very similar to where psoriasis was 10, 15, 20 years ago. We've talked about DUPIXENT and EBGLYSS, right, in the every 2- to 4-week paradigm. Nothing else approaches that frontline level of efficacy. And we aim to, similar to what we know wins in psoriasis, improve dosing and with time, also look to improve efficacy. Our first shot comes this summer with the Phase II Part A coming in the middle of this year. And that is aiming to get to every 3 months or better dosing. And we are testing higher exposures of IL-13 inhibition to see if that can lead to better efficacy. That is pure upside. Base case is improved dosing wins a day, and I'll walk through market research with payers, physicians and patients that speak to why the market is set up for that to be the win. And then in the Part B, which is ongoing, which with data coming next year, we're testing additional higher efficacy to make sure that we fully explore that exposure response curve. And finally, second half of next year, that head-to-head trial of our combination versus DUPIXENT will also read out. So 3 shots at improving dosing and efficacy in the largest and least penetrated I&I market for this company over the next 18 months. A bit more around the data that we have shared with 777 to date, just supporting our potential best-in-class PK and overall profile. You can see on the left that in cross-trial comparisons, when we look at the reduction in TARC, a key measure of type 2 inflammation compared to DUPIXENT, right, we get deep and sustained TARC inhibition out to 6 months, which is the available data cutoff. And on a proximal measure of the pathway, pSTAT6, we actually get a very deep and sustained inhibition out to a full year with higher doses. So right, this sets us up to consider not just 3 months, but with time, 6 months and potentially even annual dosing options. The Phase II that's currently ongoing is an integrated design. So this midyear, we will have the Part A readout. This is a 2:1 randomized trial where we're testing dosing at every -- at week 0, week 2, week 4 and at week 12. This compares to 0, 2, 4, 6, 8, 10, 12, 14, 16 for current standard of care and then randomizing to 2 maintenance arms every 3 and 6 months. The week 16 endpoint will be what we read out this midyear, and we are greater than 90% powered for a number of different endpoints, including the primary endpoint, which is change from baseline in EASI as well as EASI-75 and IGA-0/1. The Part B, given the integrated design, started enrolling as soon as the Part A finished enrolling within a few business days. There, we are testing also a higher dose. So an independent safety review committee looked at the unblinded data from the Part A and okayed to go to an even higher exposure level, and we're also testing the lower dose. And this will give us a full proper Phase IIb dose optimization to then inform what we take forward to Phase III. You can see in blue here on the right, our exposure -- our projected exposure levels from the Phase II with our dosing versus in gray what EBGLYSS has, right, 6 injections compared to 11. You can see that we get to approximately over the course of these first 16 weeks, 30% to 40% higher exposures. There's a number of pieces of evidence that have informed why we are testing higher exposures. One, EBGLYSS has never been tested higher, not due to safety or anything else, just due to commercial considerations, and they don't want to be disadvantaged on dosing to the market leader of DUPIXENT. So we don't know what could happen at those higher exposures for efficacy, but the Phase IIb showed a nice dose response with no dose AE relationship. Additionally, in the EBGLYSS Phase III approval documents, both FDA and EMA noted that there was an exposure response seen and a lower body weight group of not just 5, 10 patients, but 190 patients that had 30% greater exposures showed consistently greater efficacy across different endpoints. Hence, why we're trialing this in the Part A. Again, this is upside base case, and I'll walk through the market research shortly, similar efficacy. I won't kind of walk through each of these, but we've consistently shown what that base case similar efficacy would look like across, of course, safety, but also the primary efficacy endpoint change from baseline in EASI and key secondary endpoints of EASI-75, IGA-0/1 and EASI-90 tracks. Similarly, we'll look to share a robust data set, so data on each of these endpoints with our readout. Following our monotherapy, right, our belief is that the best companies look to continue to innovate and continue to provide better solutions in the spaces that they're going after and to beat themselves, right? The company mantra has refused this topic enough. 279 represents that view for us. Here, 279 is a co-formulated IL-13 and OX40 ligand. We shared data earlier this year, showing that we can co-formulate greater than 180 mg per ml and that our preclinical inhibition profile gets that deep type 2 inhibition associated with EBGLYSS and DUPIXENT, but also that type 1 and type 3 inhibition, which allows JAKs to get to deeper efficacy without the potential safety profile based off of our preclinical data set, whereas right, DUPIXENT lacks that type 1 and type 3 inhibition. This trial schematic is seen here, fairly simple head-to-head trial versus DUPIXENT, safety, PD and efficacy, and we're excited to get this trial going. Just to put kind of the size of this market into context, everyone knows the psoriasis market. And, right, you can see in different shades of gray here, all the different biologics that have launched well in psoriasis, right, 8 different blockbusters. It went from 5% penetration around year 5 up to 24% in year 20 and, right, continues to grow with SKYRIZI setting new records every quarter. SKYRIZI, in particular, despite coming next to last, has gotten to the majority of that share. Atopic derm by contrast has almost 3x as many patients. To date, there's really only been one player in town, DUPIXENT, and it has launched better than all of psoriasis combined and looks to be on track with conservative growth rates to be at least a $50 billion market. When we profile our drug to patients and physicians and payers, right, we get overwhelmingly positive feedback. And when we ask them about a drug which has similar efficacy and safety to DUPIXENT, but on every 3-month dosing profile and maintenance, 80-plus percent come back saying, right, that they would prefer it for their biologic naive. Inadequately controlled patients currently on a biologic, 83%, right, would prefer it, 12% would be neutral and, right, 1/3 and 2/3, respectively, would prefer and be neutral even on controlled patients. Why that's important is when we ask patients, including those who are currently on DUPIXENT, if they would prefer a profile that gives them an injection once a season versus every 2 weeks, they come back overwhelmingly at 96% saying that they would prefer our drug. Payers are looking for more competition in this space and across the board, across multiple surveys have come back and said that parity coverage with DUPIXENT and other frontline agents would be expected with this profile as well. Just to wrap up, over the next 2 years, right, we have a very robust catalyst map. Of course, we have been very proud to over-deliver on our results to date. We put out positive data for our IL-4 receptor alpha program just yesterday, showing that we exceeded the bar there in mild to moderate asthmatic patients. We're looking forward to our middle of this year readout for the Phase II. We're also launching, right, that full portfolio of product initiatives with that -- with our lead program in 777 as well. Phase IIb in asthma starting this year and then Part B and the combo study coming next year, along with EoE getting initiated. 279, our potential first-in-class combo, very excited to be leading the way and doing a head-to-head study here, hoping for -- to approach JAK-like efficacy without the safety issues, which our preclinical data has supported. And then in the respiratory space, right, some initial proof points in IL-13 TSLP. However, for agents that are dosed every 2 to 4 weeks, we hope to maintain that best in category every 3-month dosing for a set of very orthogonally validated mechanisms here. And then remaining this year in our first-in-human study for our TSLP antibody, we look to report that out by the end of the year. And importantly, especially in this environment, we're very fortunate to have a very robust and strong balance sheet, $680-plus million, which gives us runway into Q1 of 2028. Thank you for your time.