AnaptysBio, Inc. (ANAB) Earnings Call Transcript & Summary

Welcome, everyone, to the JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Priyanka Grover, Malcolm Kuno and [ Rathi Pine ]. Our next presenting company is AnaptysBio. Presenting on behalf of the company, we have CEO, Dan Faga. Dan?

Thanks, Anupam. Good afternoon, everybody. Appreciate the opportunity to be here on behalf of Anaptys. The presentation today will contain statements that are forward-looking. So Anaptys is a clinical stage biotech. We are discovering and developing antibodies that modulate disease-driving and overexpressed immune cells. Our goal is to restore immune homeostasis for patients that have inflammatory and autoimmune disease. We currently have 3 programs in clinical development with many near-term catalysts. My focus today will be on rosnilimab, our lead program, which is a depleter and an agonist targeting the PD-1 receptor, which is specifically found on activated T cells. Rosnilimab is being developed in 2 Phase II trials ongoing right now. The first in rheumatoid arthritis, where we'll have top line week 12 data next month in February, followed by week 28 data as well as translational data sets in Q2 of 2025. Our second trial is currently enrolling in ulcerative colitis. We have initial top line week 12 data in Q1 of 2026. We have 2 additional programs that are moving through into Phase I development at this time, AMB-033, which is a CD122 receptor antagonist. CD122 is expressed on T cell subsets of CD8-positive [ TRM ] cells as well as TRMs, resident memory T cells. This program is moving through a SAD/MAD escalation Phase I in healthy volunteers. We're committed to doing an R&D event. We're going to discuss the differentiation in the IL-15 pathway and other CD122 programs in the landscape, teach in about the mechanism of action further as well as disclose the Phase Ib indication that will be later on in 2025. And our third program, AMB-101, is a BDCA2 modulator targets plasmacytoid dendritic cells. We are just about to initiate the Phase I study later this first quarter. We are well capitalized. We have $420 million of cash coming into this year. We have runway out through year-end 2027. This guidance excludes an important financial asset to the company as well. We do have royalties and milestones via our financial collaboration with GSK, driven principally by the royalties generated from JEMPERLI, an asset, PD-1 antagonist that they've launched over the last few years. And I'll touch on this in a lot more detail later in the presentation. So rosnilimab has the potential to treat a wide range of inflammatory disease. We started the development in moderate to severe RA and UC, which are well-established large U.S. and global markets. In the market subset of biologic experienced patients, there's approximately $17 billion of revenue generated in the U.S. alone. In the case of RA, there has not been a new class of therapeutics launched in the last 10 years. Patients in both of these diseases are accustomed to cycling through biologic classes. And unfortunately, the majority of these patients remain uncontrolled today. The opportunity -- and there's a strong rationale why we believe rosnilimab will differentiate and break through this low efficacy ceiling. So beginning with RA, we have confidence in the near-term likelihood of demonstrating a commercially exciting target product profile in the near term, beginning next month in February. Three core reasons. Number one, PD-1 is a validated target. Activated T cells are a known driver of inflammation in RA. And there's a competing PD-1 targeting program that has shown proof of concept already with this mechanism of action in a small Phase IIa study. Number two, I'm going to walk through data showing why we believe rosnilimab is the best-in-class, a potent depleter and agonist of PD-1 expressing T cells. And to date, we've shown competitive safety and tolerability profile across all the trials that have been run, not just with our own program, but in the class in totality. And three, we are in the middle of running a large, robust, well-controlled 420-patient Phase IIb trial, both in the U.S. and EU. So rosnilimab selectively targets PD-1 positive or activated T cells, which are overexpressed in systemic autoimmune disease. There's 3 mechanisms of action that we focus on. The depletion of PD-1 high TPH cells, which reduce B cells from differentiating into autoantibody-producing plasma cells. The second is the depletion of PD-1 positive T effector cells. And third is agonizing the remaining PD-1 positive intermediary cells. Collectively, the impact on these T effector cells that are PD-1 expressing is to reduce cytokine secretion, T cell migration, T cell proliferation, both in the periphery and in inflamed tissue. So ultimately, we think the immunological effect of rosnilimab treatment will modify disease by returning the immune system back to a homeostatic state. If you look in the bottom left-hand portion of the slide, this represents data from our Phase I trial. You can see at day 15 in the red box, Treatment with rosnilimab has depleted all the PD-1 high T cells that used to exist. If you look in the right-hand side, the stack bar graphs on the right, you see an example of a diseased R synovium. PD-1 high PD-1 intermediary T cells in red and yellow, they represent about 80% of the activated T cells in that synovium. Again, the idea here is to target those cells, [ deplete and agonize ] and return to a homeostatic state that you can see on the right-hand side. Importantly, here, we have a targeted therapy. Rosnilimab does not deplete every activated T cell. And you still see some of the yellow highlighted here on the slide. More importantly, we do not touch or engage with naive T cells, the T cells responsible for immune surveillance. Very few Tregs express PD-1 and the few that do express PD-1E, the PD-1 high expressing Tregs, these are dysfunctional. We hope to reduce them and that will benefit overall. So at the end of the day, we're looking to return back to a homeostatic state in the treatment of disease, both in periphery and in tissue. So here, we depict the biology and an inflamed synovium of an RA patient. After becoming differentiated in lymph nodes, there's a twofold increase of PD-1 activated T cells that traffic through the periphery and into the disease synovium. Once migrating there, you have greater than the 80% positive T cells that are activated. Again, it's a targeted therapy, and we're looking to potentially directly impact these overexpressed T cells that are upstream of other validated targets that we've already seen efficacy that are approved on the market today, represented through the various circles on the slide. Here, we look at comparator data sets of rosnilimab, which consistently demonstrates differentiated potency compared to Lilly's parasolimab, a competing PD-1 program. Parasolimab is a moderate depleter and a weak agonist of PD-1 T cells. In contrast, and as shown in our translational data on this slide and directly compared to in-vitro head-to-head, rosnilimab is both a strong depleter and a strong agonist. Across our preclinical, our Phase I healthy volunteer Phase II studies thus far, rosnilimab has been well tolerated with no distinction from placebo. We did not hit dose-limiting toxicity. We see no carcinogenic signals from our blinded surveillance to date in both the Phase II RA and UC trials, there are no safety issues and no concerning AEs. In each trial, we have an independent DSMB that conducts routine safety reviews, and there have been no raise flags from either of those trials to date. As far as we are aware, the same is true in the landscape of PD-1 targeting agents of which there have been a number of trials run over the last few years. Setting some context for RA patients. There is a two to threefold increase in comorbidities versus the general population, ranging from higher infections to a multiplier here on cardiovascular issues. Abatacept is the only immune cell modulator approved in RA with meaningful market share. So immune cell modulators in broader class as rosnilimab that does not have a black box. Looking down the line, HUMIRA, Rinvoq, rituximab, they all have black boxes. There's some very big numbers here tied to the revenues that are still generating today. That has not been encumbrance in terms of the tolerability and really the dramatic need that patients have and the threshold of what's willing to be accepted to drive towards better efficacy. And then these are low bars, and this is what's unfortunate for the patients in this population. So on this slide, we show higher order response rates in the standard of care. So for example, ACR50, the composite in the slide in the top row, this is a 50% improvement in patient-driven response, physician-driven response and the biomarker CRP. So as shown in the top left panel, only 1/3 of patients see an ACR50 response in the first-line biologic therapies. This is typically the anti-TNF treatment, HUMIRA. At this point, patients progress and they cycle through other treatment classes. There's a consistent step-down in efficacy regardless of the class of the bioexperience population. They only achieve about a 20% ACR 50 or mid- to single high-digit ACR 70 rate in this bioexperience population. And while the JAKs have slightly better efficacy, there's still a significant SAE profile that remains a concern. Regardless of this poor response rate, this bioexperience market is greater than $10 billion today in the U.S. alone. And lastly, as mentioned, peresolimab, a less potent PD-1 program has already shown proof of concept in a small Phase IIa study, and those results at week 12 were represented in the horizontal dotted lines on the slide. The way this disease is treated is treat the target. Physicians look to see a response into 12 weeks of treatment. This could be something like an ACR20, a 20% improvement. And then if they're seeing a beginning of a response, you move through to 24 weeks of treatment, looking for higher order response rates. Our goal, our target product profile is represented in the graphic in the top right in the green dotted box. We want to be clearly better than the other biologic classes and approaching JAK-like efficacy. Our Phase IIb RA trial is a placebo-controlled trial out through the first 12 weeks. And for this reason, our Phase II product profile is focused on the achievement of these higher order response rates at that specific point in time, noting that there could be better responses out through week 24 if we were running a study that could show that. Highlighted in the green box on this page, the top 3 rows are the week 12 targets for the bio experienced population. These response rates do represent this bio better and approaching JAK-like efficacy profile, approximately 30% CI low disease activity response, approximately 30% ACR 50, approximately 10% ACR 70. If you look at the 3 rows below, slight step-up in the bio-naive population. I showed you the comps on the prior slide. That should be the expectation of what we're able to deliver here at week 12, that would be an exciting outcome. In this trial, after week 14, any rosnilimab-treated patients that have been in and achieved low disease activity, they can stay on drug out through week 28, and we're looking for sustained response for those patients. Nonresponders are out of the trial at this point in time. So further is the schematic of the Phase IIb study. This is a robust, well-controlled and conservatively powered trial. We have a 12-fold dose range across 3 active arms relative to placebo. It's equally randomized in 420 patients that have been enrolled in the U.S. and the EU. Depending on the treatment arm, patients will receive Q2W or Q4W subcutaneous injections. We stratified by either the bio-naive population, about 60% of the enrolled population or the bio experienced, the remaining 40% of the enrolled population. Our primary endpoint is the DAS28 CRP change from baseline at week 12. We are powered greater than 80% for ACR50, key secondary for the overall population at week 12. As mentioned, rosnilimab treated patients who achieved LDA, low disease activity at week 14. We further assessed out to 6 months. We will report top line data for week 12 next month in February, week 28 data as well as the translational data sets in Q2 of this year. Now I'm going to transition to the second trial that is ongoing for rosnilimab, the Phase II trial in ulcerative colitis for moderate to severe patients. UC is also a T cell-driven systemic autoimmune disease. Similar to RA, there's a twofold increase of PD-1 positive T cells in the periphery those migrate through the laminpropria. This is the inflamed tissue in the colon in this disease, where about approximately 40% of the T cells of the inflamed LP express PD-1. Rosnilimab's MOA, again, hits on the key immunological drivers of efficacy across multiple currently approved therapies in UC. There's an interesting data set in literature as well as data that we have produced with rosnilimab in a murine T cell transfer model, supporting our rationale and excitement for developing in this specific indication. I'm going to highlight the data on the left-hand side panels. There's a reduction of elevated TPH cells via treatment that strongly correlates with clinical remission. TPH cells are de facto PD-1 high expressing T cells. We should be largely depleting those T cells in the periphery, and that should drive response. And this will be a fundamental derisking event for us when we see translational data that could see the same thing in the arthritis patients next quarter. Additionally, in vitro experiments using PBMCs from UC patients across each of the 4 readouts on this page, rosnilimab makes an impact at clinically relevant concentrations in reducing PD-1 positive T cells. On top, we've isolated depletion in the agonism mechanism of action. On the bottom, you're seeing reductions in chemokines and cytokines that are relevant in this specific disease. Here, we're looking at a current picture of the UC treatment landscape. On the left-hand side of the page, the biologics and orals that are driving the most response, REMICADE, Rinvoq, the ones with the biggest black boxes and the worst SA and AE profiles. In the middle, the emerging classes and TL1As. What you're looking at here is consistency on a placebo-controlled basis, somewhere in the 20% range, plus or minus, for induction of clinical remission at week 12. This is generally speaking, what we're looking for in the UC trial coming out. There's not a lot of differentiation. There's 3 TL1As that were all tucked in over the last year. There's one PD-1 agonist looking at UC. This is more or less the emerging target product profile, and we'll come in and give more specifics over the next number of months. This is a schematic in rosnilimab's Phase II trial in UC. What we're looking at here is different from the RA trial. We're targeting enrollment of approximately 132 patients that will be stratified and experienced and bio-naive. But we have a placebo crossover at week 12. All patients remain on treatment through month 6. At that point, if you are in clinical response, we'll be generating data and the opportunity for patients to stay on drug out through month 12. The primary endpoint is at week 12, and we're on track to report out those results in Q1 of 2026. I want to spend a couple of minutes in summary here on the GSK Immuno-oncology financial collaboration. JEMPERLI is a PD-1 antagonist discovered at Anaptys, launched a few years ago. Cabolimab, a TIM-3 antagonist and currently in Phase III development. Both these programs form the financially oriented collaboration we have with GSK. A portion of our JEMPERLI royalties have been collateralized in the cap transaction with a group called Sagard. These royalties range from 8% for the first $1 billion of JEMPERLI revenues in a given calendar year, quickly up to 25% at $2.5 billion of JEMPERLI revenues. Outside of this transaction that's been collateralized, we have a $75 million payment that could come due as quickly as this year once $1 billion in the calendar year is achieved in the first time. So again, outside of that arrangement. Second, outside of that arrangement are all the royalties and milestones that are tied to cabolumab. So why am I walking you all through this? There remains a significant financial upside for Anaptys post the paydown of the Sagard relationship. To put this in perspective, GSK is currently guiding at $2.5 billion of revenue at peak. Wall Street consensus is sitting at $1.2 billion at peak. There's a big gap in there. If you just look at the consensus curve, which is really driven on currently approved indications, we will pay down the staggered royalty in the next few years, where all those royalties will then revert back to the company in addition to the $75 million payment that should come in the next year. When we look at this further, JEMPERLI IP is out through 2038. Over the next 6 months, there is a number of catalysts that can drive upside to where Wall Street is currently valuing towards where GSK is guiding. Frontline endometrial approval in Europe is guided to the next couple of months. They just hit on ovarian cancer and PFS in December. That's going to the regulators. And I think importantly, the biggest upside driver just in the next few months, there's an ongoing Phase III second-line non-small cell lung cancer trial comparing chemo to chemo plus JEMPERLI to chemo plus JEMPERLI in combination with civolumab. 800-patient trial have been ongoing for 2.5 years, and they've guided to that reading out in the first half of this year. Tremendous upside still in the residual value of this royalty on top of the $420 million of cash we have at year-end. So in summary, this is our calendar -- catalyst calendar. We have 3 immune cell modulators in development. We have near-term catalysts in the RA trial next month with 12-week data with 28-week data in Q2. translational data in Q2, read-through to the UC trial that's enrolling will complete later this year, and we'll have the readout there in the first quarter of 2026 at week 12, in addition to the other 2 programs that we're excited about have just moved into clinical development. So on that point, Anupam, I'll turn it back over to you for Q&A.

Thanks, Dan. [Operator Instructions] I guess there's an intermediate strategy where you can just e-mail me. But I will -- I'll kick off here. Not to get a little bit more granular on time lines. You've already gotten February. So maybe pre or post Valentine's...

February is already a shortened month.

I gave me 3 days. right? So I guess I'd be interested in hearing a little bit more about the spectrum of the RA patients that you're enrolling. You talked about the trial design, talked about how it's stratified. But given the competitive landscape, which population should we be focused on and why?

Yes. And I'll try to flip back to the TPP slide here. We're highlighting both the experience in the naive population. It's the enrolled population. Any go-forward Phase III program, you're going to be treating all-comer patients across both. From a commercial perspective, practically speaking, we're looking at a TNF advanced market. I'm not going to be off on the slide quickly. Here we are. We're guiding very specifically here across a number of these high-order outcomes, LDA, 50% response, 70% response. These are the commercially relevant metrics. These numbers represent a bio better profile, clearly distinct from the other classes and emerging on the JAKs. It's not one answer. It's not that simple, but I think investors, what they need to realize is this is not the peak efficacy we should see with this drug. This is where we're at week 12. We need to see quick enough responses to be competitive. And then from there in future development, there should be a reason to believe to see accelerated outcomes. But higher order responses are going to drive the differentiation, and it's not just efficacy. It has to be a tolerable profile in the context of how not tolerable the standard of care already exists with the black boxes.

You talked a little bit about kind of what you already know about the molecule from a safety perspective. Can you just remind us like how the RA doses compared to maybe the alopecia doses?

Yes. So we ran an alopecia trial a couple of years ago, we were looking at 400 milligrams monthly out over 6 months, those are subcutaneous injections. The disease in alopecia is not a systemic autoimmune disease. There wasn't an engagement there with PD-1 positive T cells at the hair follicle. So we're never going to see the efficacy. What we did learn from that trial is that at 400 milligrams monthly, we're penetrating through to the skin, and we had 6 months of safe placebo-like AE profile. The 400 milligrams sits somewhere in the span of a 12-fold dose change from low dose to high dose in the RA trial. In addition to standard modeling that you have with the Phase I that gave us more confidence that we're going to get enough drug into the synovium.

Question from the audience? So I mean, I think the Street seems to be focused on ACR50 really. Where would you put -- then you talked about your target profile, but would you anchor the Street around ACR50? Or would it be the totality of kind of the data on the efficacy side? I guess this is at week 12, right?

Yes. Yes. So at week 12, patients coming in this trial have high disease activity. That's defined as CI greater than 22. The threshold you're looking for to stay in the trial over time is low disease activity, CI less than 10. That's more than a 50% improvement. It's a high bar. So it's really a collective of all these outcomes. If you -- if I sat here and said we had ACR50 at 25%, but we had ACR70 at 24%, that's going to look pretty good. So you can't just look at one of these. It's really the collective of how this all works together that these are composites of physician and patient assessments. They're complex. There's a lot of rigor over decades as well as biomarkers like CRP. So really looking at a collective disease modification over time. It's more than ACR50, but ACR50 is a very simplistic way to look at, are you having a meaningful effect or not quick.

Questions from the audience? Maybe just from a mechanism standpoint, while you haven't -- what would you be looking for on the safety side?

Yes. I tried to just walk through this a little bit. On target is depleting activated T cells that are well overexpressed. What we don't anticipate happening is shutting down the immune system. Now these patients in this trial, like all trials in RA are on background conventional DMARDs like methotrexate. Many of these patients are on steroid, and you're going to have events. I think that's the reality. When you look at placebo rates, and we're highlighting a few on the sides, pull up Slide 11 here. Just look in the bottom in some of these placebo-driven infections, 30%, 45%, that's placebo. You're going to see all grade infections, you're going to see events. The question here is, is the drug tolerable and can patients stay on this for a longer period of time? And like I just said, you asked about alopecia, we have 6 months of data. The Eli Lilly trial, while we don't know the results from the Phase IIb, that trial went on for 60 weeks. Their Phase IIa study looked benign in terms of AE. So I think the class is starting to build a set here of tolerability overall. I think that's what we're looking for. Do we have dropouts? Can patients to the drug and they're getting the benefit in the context of how this is not a disease like atopic dermatitis in terms of what would be acceptable or vitiligo or alopecia. It's a very different type of patient population. And the bar is so low on efficacy that patients are driving towards and cycling through all these anyway for any way to achieve that disease-modifying LDA.

Okay. And you guys -- Dan, you outlined timelines for the longer duration update. Talk to us why that in particular is that portion of the study is important in terms of durability and what you could learn from that.

Yes. We're looking for stability results. So if you responded by week 14 you state in the study, we're looking for a consistency of those patients that they sustain that response for the additional 3 months while on drug. This is not a disease where we're looking for 8 weeks or 12-week holidays on drug. Physicians are okay with these every other week or monthly injections while on drug and having stable outcomes. We do have a 10-week off-drug period for a safety evaluation at the end. Contrary to what we're doing in RA, and this is driven a bit by the FDA and how they push to run the trials, the GI division did allow that placebo crossover, we will be generating durability and safety data up to 1 year in that trial. So that's all moving in the background. And we think about moving forward with this program into Phase III or Phase IIIs, it's the collective safety database and overall tolerability and duration of effect that we're looking for. So the 2 trials will work off each other in that sense.

We've got a couple of e-mail questions here. The first one is, are you seeing any sort of blinded blended data for the study?