Thank you very much for making the trip. I thought it'd be great to just have you start at a high level, just by kicking off with your vision for Anaptys and just touch on the company's three pipeline candidates.
Perfect. Thanks, David. Appreciate being here today. We have a lot going on in the company. Our core focus is to discover and develop antibodies that modulate overexpressed and disease-driving immune cells. Our goal here for patients is to bring them back to a homeostatic state. We're focused on the treatment of these patients in autoimmune and inflammatory diseases. As you just mentioned, we have three development-stage antibodies that are in development. Our lead program is rosnilimab, which is a PD-1 depleter and agonist of PD-1-expressing T effector cells and TPH, PD-1 high-expressing T cells. We have had really impressive data in rheumatoid arthritis of 424 patients, so a robust study, trial that read out the top-line initial results in February. We'll have another catalyst come up in Q2, which will be the full results. We have a second trial ongoing with rosnilimab in ulcerative colitis.
The initial data will read out in the fourth quarter. There's a number of additional opportunities in 2026 and beyond where we can take the drug. Our second program is ANB033, a CD122 antagonist. It's focused on the expression of CD122, which is a receptor that blocks IL-2 and IL-15. It's expressed on NK cells and CD8+ cytotoxic T cells. We're in phase I-A right now, moving through SAD-MAD. It's a really interesting landscape there with the IL-15 pathway that we'll talk more about. Our third program is just entering into phase I-A. It's a BDCA2 modulator, which is found principally on plasmacytoid dendritic cells. These cells really only exist in the setting of disease. There's another competitive program, phase III, in SLE and CLE that's ongoing. That's early stage. We have a differentiation thesis for all of our programs based on what's out in the landscape.
The company is extremely well-capitalized. We had $420 million coming into the year. Our cash runway is out through year-end 2027 plus. We have access, although we do not need to use them today, backstopped by a royalty stream from an immuno-oncology financial relationship with GSK. JEMPERLI is a drug that has been on the market for a few years in a growth stage driven by frontline approval on endometrial cancer. We have a second program in phase III development, cobolimab, a TIM-3 antagonist. Royalties are coming from both of those programs. It is an exciting backstop. There are three different ways to think about the company and the lead asset, the early portfolio, as well as the cash plus royalties.
Excellent. Excellent. Thank you. Congrats on the recent phase II-B top-line results in RA. Could you just summarize those and then highlight what to watch when you present the full details in the second quarter?
Yeah. It's exciting. Five key points on how we're thinking about the data here. It was statistically significant across all three doses, subcutaneous, including two once-monthly doses. The stats sig was at week 12. I think one way to think about the endpoints there, ACR 20, are patients feeling better, 70% plus hit ACR 20 at week 12. At week 14, that number continued to grow to about 80%. Second, translationally, we're seeing the pharmacological impact, immunological impact, right out of the gate with the depletion of the PD-1high T cells that's differentiated. Greater than 90% of them were depleted in the first read. We see downstream from the T cell impact, CRP, which is a biomarker of inflammation, a pretty dramatic impact there at week 12 and week 14, where you're bringing below a level that's generally accepted as being inflammatory or not.
We're seeing it on both sides. There's a consistency there that you do not see on placebo. Third, safety profile was benign, drugs tolerable. About 1% of patients fell off due to AEs in a 424-patient study. Four, and I think this is the most important, is the data is stable over time and potentially improving over time. About 70% of patients hit low disease activity in the first three months, 220 patients across all three doses. At the time of the data cut for what we presented at week 12, over 100 of them were already at week 28, so beyond six months and generally speaking stable. Fifth, this is a very big market. This is a mature market, one sense, in the front line where you're seeing biogenerics on TNF.
We saw a consistency of data both in the naive and the bio-experienced populations where they're impressive results relative to what's commercially available right now. It is a patient population where 500,000 patients move on from TNFs and class switch. There hasn't been a new class of therapy in well over a decade. This is going to be a program that, with a phase II trial that looked like a phase III trial, we believe it could be repeated into the phase III with statistically significant results, but over time, stable long-term outcomes that are differentiated in this space and patients need it. Five core points and why we're excited about the data. You asked about Q2. We will have the full results in Q2, so all patients out to week 28.
In addition to that, the trial design here was pretty unique, driven by the FDA requirements that at week 14, if you did not respond and were on drug, these non-responders were pushed off the trial in terms of treatment. They did get treated at week 14. You will see some activity in their next follow-up visit. Although they are not getting treatment, they did have to come back. You will see patients that did respond out through six months. You will begin to see what happens off drug for up to 12 weeks. You will have 38-week data or about nine months of data. There are a few different things you will have in a full data set. In addition, all the translational data. You have a sampling of what happens with the T cells in the periphery.
We'll also have the cytokine activity in the periphery, what's happening there for responders, non-responders, placebo patients, as well as robust sampling of synovium biopsies, what's happening within the synovium, not just on these TPH cells, peripheral helper T cells, but also the T effector cells that were activated, immunophenotyping, as well as the cytokine activity. It is going to be a rich data set in this robust study that we'll read out in the second quarter.
Excellent. Excellent. We have received questions about the inflection between week 12 and week 14. Could you comment on that?
Yeah. What is pretty clear with this mechanism of action is we have not hit max response at week 12. There is an acceleration of separation from placebo beginning at week 8, accelerating through week 10, accelerating through week 12, and then further accelerating into week 14. We hypothesize that is not the peak response. Again, this trial design, patients at week 14 that were on drug, if you were non-responders, meaning you are not in CI, CDAI, CDAI-LDA at week 14, you were pushed off the study. I think there could have been further acceleration beyond week 14. I think a lot of folks are focused on week 12 to 14. This is a placebo-controlled trial. Patients came to the week 12 visit. They were assessed on the benefit from week 10.
After the assessment, they received either studied drug or placebo in a blinded fashion and went home. Patients then came back at week 14, were assessed on the benefit or not of week 12, received studied drug if you were on rosnilimab, and went home, found out after that if they were in LDA and were notified, you're eligible to stay on treatment or not. Those are the responders and non-responders in LDA. For placebo patients between week 12 and 14, the site was notified that the patient will not be receiving studied drug after week 14. The independent assessor and the patient were not aware of this per protocol. They had their assessments. After their assessments, instead of getting dosed on a blinded form of rosnilimab, they did not receive drug, and they were now terminated from the study outside of follow-up visits.
Per protocol, this is a blinded study through week 14. There could have been a little bit of bias. You know, if you hit LDA, you got to stay on drug. That would be on the margins. We continue to emphasize the stability of the results. You can't, one, fake translational objective data. We know it with the T cells, and we know it with CRP. Those are objective biomarkers that are differentiated in a pretty dramatic way than placebo. Second, again, you also can't fake results out six months. Objectively, subjectively, these measures of high-order response rates, LDA, ACR 70s at six months, that data is stable. We think this is what's important overall.
When we run a phase III program, you could treat 3 to 52 or six months and then out to 52 weeks, I think we'll have the ability to show even higher response rates.
Excellent. Great. In terms of the current data that you've shown in a portion of the patients, could you comment on week 12 to week 28 data relative to peresolimab?
Sure. The data that's in the public domain is from peresolimab's phase II-A trial, which read out at ACR now a few years ago, it seems. The focus when that trial data read out was just the amazing, at the time, absolute efficacy. They had 55% LDA at week 14. This was the same as that trial design that we also had to run in our phase II-B study. What wasn't a focal point, but it's been out there in the supplemental analysis published by New England Journal of Medicine, is what happens to the patients over time. While they hit 55% at their high dose LDA at week 14, that dropped to 37% at week 26 and to 22% off drug at week 36. A pretty significant loss of response from their peak at week 14. Now let's compare that to our data.
I mentioned earlier about 70% of patients, robust 424- patient study, 318 rosnilimab patients. That's 220 rosnilimab patients hit LDA. Big number. What we've seen so far is stable results at month six. A pretty dramatic difference on what you're already comparing to the phase II-A. Now, Lilly did discontinue peresolimab moving forward post their phase II-B trial in RA. What they've said publicly is what we've already seen in the phase II-A results that they lost response over time. There's incremental talks when it wasn't in the placebo-controlled study. However, they are still looking at the program in other diseases to move forward and watching competitive data. I think that's really important for investors to take in.
If there was a class signal here over time, you would not be looking to develop this in other diseases where they do not have the comorbidities that patients in RA do or the black boxes for every other biologic or JAK that is approved in RA. You do not see that in some of these other autoimmune diseases. Lilly is looking at where else they can take their program. That is really important. Again, we have not seen anything on the safety side in our trial to date that would be of concern or a class safety risk. We do have higher efficacy on an absolute basis, and it is stable. Pretty big differences are driven by difference in potency of the antibodies.
Excellent. Maybe you could just add a little bit more, call out it's obviously more than just potency that would drive more durable responses for rosnilimab. Could you just talk about that and help us understand with drugs with the same mechanism in the same disease state, why one would drive durable responses and the other one would have a significant deterioration over time?
Yeah. Let's talk about both the absolute response and the durability of the response. We've said there's three mechanisms of action here at play. Depletion of TPH cells, peripheral helper T cells. I mentioned this in my introductory remarks. These are cells that recruit B cells and mature the B cells into plasma cells which secrete autoantibodies. That's one mechanism of action, the depletion of those cells. You see that in the periphery. You also will see that ultimately in the synovium. The second mechanism of action is the depletion of PD-1 high T effector cells. Third is the agonism of PD-1 expressing the non-PD-1 high, these intermediary expressing T effector cells. We said for years, based on our head-to-head comparisons with peresolimab, that the peresolimab drug is a moderate depleter of the TPH and T effector cells and a weak agonist.
We are a strong depleter and a strong agonist of these different PD-1 expressing T cells. We have shown some evidence of that now in the clinical study where we are reducing 90% of these TPH cells in that first read. In Eli Lilly's phase II-A trial, their published translational data, they were only reducing 60% of the TPH cells in the periphery. The hypothesis here, that is the difference in potency, and that is why you are going to have an absolute difference in efficacy. On the long-term durability, the answer is going to be what is happening in the synovium, as well as the TPH cells that they left on the table that are still driving disease. If you are a weak agonist and a moderate depleter, you are leaving a lot of the activity in the synovium ongoing.
We do believe that over time, the effect of the agonism to keep the proliferation of T cells and the cytokine activity from these T effector cells down will lead to durable outcomes. Again, the whole hypothesis here is a return to homeostasis. A healthy control is about 15% activated T cells at any given time and very few PD-1 high expressing cells. It's very different in disease. Through treatment with rosnilimab, we do believe that you're returning that homeostatic state. With treatment of peresolimab, you're clearly not. They're just not hitting the T cells in the same way. We do think that's going to impact the durability of response.
Got it.
You're seeing it in the clinical data so far.
That's super helpful. Thank you. In terms of pivoting to rosnilimab and UC, that data, I think this winter you shifted up from early 2026 readout to a readout later this year. Could you remind us about that trial, how you're setting expectations for the UC results?
Yeah. This is exciting. I've been saying for a couple of years that if Lilly didn't have interesting phase II-A results, which we just beat in RA, UC was the trial we were going to go start and run on our own. The disease biology is pretty clear here. There's actually interesting correlative data that if you deplete TPH cells or we just reduce them in the periphery, that's highly correlated to clinical remissions in disease. ENTYVIO, all that drug does is block those TPH cells from moving from the periphery into the site of inflammation in ulcerative colitis, which is the lamina propria. That's the way the drug works. That's not the highest efficacy, but the way they get efficacy is just that peripheral T cell depletion, which we just showed you 90% of those cells were depleted in RA studies.
We have a lot of confidence that we should have a result here in UC just based on the read-through of how other drugs and mechanisms work. We've been talking about this for some time, and we just now were able to show the data. Our clinical trial is a 132 patient, three arms, two active versus placebo, of subcutaneous rosnilimab. There's a once-monthly dose and every other week dose. This is a more standard design. The GI division looked at this slightly differently than the rheum division on what we were able to do, but it's a treat-through design through six months. At three months, there is an assessment. Placebo patients that stay in response in MMS, they continue on placebo through month six. If not, you cross over to a dose of rosnilimab. It's a treat-through design.
The importance here is that while the non-responders came out of the RA trial at week 14, in UC, we're not going to have that feature. We should be able to see max response through six months. In addition, responders at month six get to stay on drug through month 12. It will generate long-term stability data beyond six months, as well as longer-term safety data. We're going to have a lot of, I think, interesting attributes here answered, not just in the clinical efficacy over time, but also through further translational data. When I said in my opening remarks, what I think is exciting here is we've already hit proof of concept in one rheumatological disease. This is now in IBD, or one form of IBD.
There's a lot of other places I think we could develop rosnilimab, which is a very differentiated way to treat these diseases that read through from all these trials. We believe there's a pretty reasonable chance of success in UC that just further de-risked with the translational data in RA. To your point, the initial data, so all patients out through week 12, which is the primary endpoint, we'll have that data in Q4 plus additional data for longer-term results wherever we are in the trial.
With respect to alternatives for patients today with UC, what are some of the efficacy ranges that you would characterize?
We haven't set TPP guidance. I think the difference between UC and RA is when we retested the RA guidance, which we hit and beat on our TPP, it was consistent over the years. That's defined by a mature market. What's interesting with UC is there has been evolution. A couple of insights here. Where is this market going? Before setting guidance on outcomes like clinical remission, endoscopic remission at different time points, this market is evolving in a very favorable way for biologics. That's going to look ultimately a lot like RA, which is a mature market in that you're switching between four-plus classes of biologics plus JAKs. You're going to see this happen in UC. You're starting to see that already with surgeries.
Prior years, if you fail one to two classes of drugs in UC, you're going to get surgery, which is high cost. There's a lot of incentive to keep patients on therapeutics if you could see responses. What's the issue here, going back to stability of results. A third to half of patients, if you're the minority that actually get clinical remission, they lose response at one year. There's a lot of opportunity to play here with another class in a growth biologics market that will ultimately see class switching over time. That's where that's going. It's a really exciting dynamic. For a company like us, upon positive phase II results, this is a place where we could commercialize independently in the United States. We can go run the phase III program here. Slightly different dynamics than in RA.
A lot of strategic optionality for us moving forward, given the growth dynamics in ulcerative colitis.
Excellent. Excellent. Why don't we pivot to your other pipeline candidates? Obviously, they're not an investor focus today. You are going to start to generate data and draw more attention as those pipeline candidates progress. Maybe we could start with CD122 and if you could add a little bit more color beyond what you touched on in your initial response to my first question, then we'll go from there.
Sure. This is an exciting pathway with IL-15 amplified inflammation. We've seen various levels of potency in drugs. Amgen had a program that was a weaker potency. You're seeing Teva and Calypso was acquired by Novartis generate positive initial phase I-B data. They started in Celiac and EoE. That's interesting, exciting, and differentiated with IL-15 as a driver in these types of diseases. CD122 targeting is we're targeting the immune cell directly, not just the cytokine. Again, specific to our thesis of immune cell modulation, CD122 is preferentially found on a subtype of NK cells, about 80% NK cells in humans, as well as CD8+ cytotoxic T cells and TEMRA cells. The advantage of targeting the dimeric receptor CD122, as I was saying earlier, is it blocks both IL-15 and IL-2 on these cells, which are dependent.
Without interaction with these cytokines, you starve out these different cell types. Not only are we blocking IL-15 and IL-2 from these specific cells that are prolific in disease, you're freeing up IL-2 as well for availability for things like Tregs, which are dependent on IL-2, which we are not going to block based on the affinity and the PD dynamics of our specific asset. Inherently, that's where the differentiations can become from other CD122 programs. Incyte has a program of first-generation CD122. They've talked about having results from their phase I-B data set in vitiligo later this year. There's another smaller cap company that's in an initial phase I-B in celiac disease, and they've talked about having initial results in Q2. There's more data coming in these pathways. We believe we're differentiated, and we've committed to having an R&D event later this year.
We'll talk about this landscape in a lot more detail, the disease biology, and how it's applicable to the disease stated and others, and then where we're going to go with our first phase I-B. We're moving through the phase I-A right now. We started in October of this past year. We're well through it. We're on track to start the phase I-B later this year. We'll pull it all together in an R&D event for investors.
Excellent. Great. If you could just sort of run through similar commentary on the BDCA2 as well.
Sure. This is the first program we licensed in about a year and a half ago. We're an R&D innovative research discovery engine. We did complement with another program that we saw was differentiated from a first-generation BDCA2 modulator that's out there. As I mentioned earlier, there are various receptors that are expressed on plasmacytoid dendritic cells. These dendritic cells secrete type 1 interferon in a thousandfold more than you would see in a healthy control in the settings of diseases like lupus. They cut off the PDCs right at the head. We also believe that by targeting BDCA2, these are non-depleting antibody approach. You will internalize the antibodies. We do believe that the plasmacytoid dendritic cells will become more tolerogenic. There's some benefit there.
We've already seen differentiation from internalizing BDCA2, which in the results from Biogen, which has the phase III program ongoing right now. They had the most robust, highest response rates on the SLE and primary endpoint, the CLASI score in their phase II results that have been published to date in a robust trial. That's different than the ILT7 receptor, which is in high density. We have seen depletion there where they do not get the same type of response. We do believe that's because you're keeping the PDCs around in a tolerogenic fashion than depleting them. There is a benefit to that. We're seeing that in the data. We have different affinity and different PKPD dynamics in the Biogen asset. We haven't put the data out there in the public domain specifically. Ultimately, we're watching the space. We started the phase I-A.
Biogen's SLE and CLE phase III programs will read out, it looks like in the first half of 2026 is their guidance. We'll read through from there. We'll also be able to compare and contrast our drug relative to Biogen's that's moving forward. Our vision here is not just to be in the same place as Biogen is. There are a number of other diseases that you can also pursue with this mechanism of action. We're excited about it. We have a lot more things coming. It sets up, I think, from an investor perspective, not just the rosnilimab data this year and where we're going next year with rosnilimab, but also readouts in these other drugs.
Excellent. Any other competitors to watch with BDCA2s?
The only other one in the clinic is Biogen.
Very interesting.
Yep.
You said phase I-A. When should we expect to get data?
It'll be more of a 2026 discussion.
Got it. Okay.
Back half of this year, we'll talk through more of CD122, which is ANB033. ANB101 is our BDCA2 inhibitor. And that'll be more into next year.
Excellent. Great. Maybe we could pivot to the financials. If you could just remind us current cash position, sort of burn rate, and how durable your cash is.
Yeah. We have a lot of flexibility in how we think about this. Our cash runway guidance is through year end 2027. That includes the enablement of phase III. I mentioned earlier, ulcerative colitis is an attractive place for us to go on our own with rosnilimab. Also moving into phase II for the next two programs that we just discussed. That's $420 million coming into the year. On top of that, like I mentioned earlier, is the financial collaboration with GSK. I'll get in a little bit more detail with JEMPERLI. JEMPERLI has been on the commercial market for three years. It was discovered by Anaptys. It is a best-in-class PD-1 antagonist. There's head-to-head data in lung cancer with JEMPERLI versus KEYTRUDA, where it wasn't powered this way, but it showed superiority. This is a really good drug.
They got approved in frontline endometrial cancer last summer. That has really changed the inflection of the growth curve for JEMPERLI at GSK. They have taken a unique approach. They are playing in spaces where they are first to market or only to market. The data was impressive overall survival in frontline endometrial. That was in the U.S. last summer. They just got approval a month and a half ago in Europe. In a 40-patient smaller study that had a 100% response rate in rectal cancer, they are now in a registrational study that reads out next year in rectal cancer. There are other ways to sit here and find growth. GSK's guidance is $2.5 billion in peak revenue. Wall Street consensus is $1.3 billion. This is not the biggest program at GSK and probably not where most analysts are focused in detail. There is a pretty big gap between the two.
As soon as JEMPERLI hits $1 billion, we will get a $75 million payment. If you look at Q4 revenues at a consistent growth rate, they'll do that this year. If it's not this year, it seems like it's more or less a guarantee for 2026. We will have more capital coming in just from that milestone. We did monetize some of these royalties. To put this in context, there's an 8% royalty up to $1 billion and a 25% royalty at $2.5 billion. A pretty dramatic escalation on tiers in between the two. There's a huge value stream for us coming from this program over time. Importantly, there's a big catalyst that GSK is guided to in the first half of this year. There's a second line non-small cell lung cancer trial that's going to read out. It's a 750-plus patient study.
Last patient in was November 2023. Fifteen months ago plus. They need to hit a number of events to actually read this out. It is a chemo versus JEMPERLI plus chemo versus chemo, JEMPERLI, and cobolimab triplet. Three active arms there. That reads out this year. Their guidance does not include that $2.5 billion, not include hitting in the combination studies. Those are the first ones. A big deal. It is becoming pretty long in terms of where this trial is ongoing to hit these events to actually have a readout. We are getting pretty excited that whether it is JEMPERLI or the combination of JEMPERLI and Cobolimab after KEYTRUDA fails, that there is extended survival here. This could be a very, very big deal in terms of the royalty value. Now, I am saying this. We do not need to monetize our royalty anytime soon.
There's a lot of ways to create value here between Wall Street guidance or Wall Street expectations and GSK's guidance. There is a lot more to come to this. We do not need the capital today. We have cash for another few years. We are going to watch this grow in the background. I think it is just going to be a great backstop asset value that if it makes sense, we could look at this in 2026 on different ways to monetize or beyond. Or we never have to monetize this. Lots of choice on what we do to here. The excitement has nothing to do with a lack of excitement in the rest of the portfolio. We are really excited with what we have going on in Anaptys. This is found value, I think, where there is just dramatic growth in the last year that we expect to continue on.
Really strong financial position.
That's great. It is a great way to wrap us up here. Thanks so much for joining us. Appreciate you being here.
Thank you. Appreciate it.
That was great. Thank you.