Good evening, ladies and gentlemen, and thank you for joining the Alpine Immune Sciences 2021 ASCO Virtual Annual Meeting Investor Event. Currently, all participants are in a listen-only mode. Following management's presentation, we will hold a Q&A session with Executive Chairman and Chief Executive Officer, Mitchell Gold, President and Head of Research and Development, Stanford Peng, and Chief Business Officer, Remy Durand. Analysts will be able to ask questions. To ask questions at that time, please press star followed by one on your touchtone phone. If any investor have questions, please send them to ir@alpineimmunesciences.com. If anyone has a difficulty hearing the conference, please press star then zero for operator assistance. As a reminder, this event is being recorded today, Friday, June 4th, 2021. Thank you, operator. Good afternoon and good evening. Thank you to all those in attendance, and welcome to Alpine Immune Sciences Virtual ASCO 2021 Data Reveal. I'm Mitch Gold, the Executive Chairman and CEO of Alpine. Today marks an important day in our company's history with the first public presentation of clinical data for our lead immuno-oncology program, Alpine-202, the first-in-class conditional CD28 co-stimulator and dual checkpoint inhibitor. As many of you know, one of the founding intents of Alpine was to harness the power of the CD28 costimulatory pathway for the treatment of cancer, and that vision has manifested first in our lead oncology candidate, Alpine-202. Data being shared today reflect over six years of remarkable effort across our entire organization, and we are proud to have the opportunity to present this initial clinical experience. I would like to remind you that we'll be making, or the team will be making, forward-looking statements during the course of today's presentation, and I encourage you to refer to our most recent SEC filings regarding the risk factors associated with these statements. I'll now pass the call over to Stanford Peng, Alpine's President and Head of R&D, to walk through the data we presented at ASCO to put it in perspective. Stanford? Thank you, Mitch. As Mitch mentioned, today we are very pleased to share with you background and a clinical update on ALPN-202. We will begin with a video that illustrates the rationale and mechanisms of action of ALPN-202, followed by a reprised presentation of the ASCO poster, which was presented by Dr. Justin Moser, one of the study investigators. We'll then finish with some additional remarks before opening the line up to questions. First, the video. In a variety of malignancies, immune checkpoint blockade has proven to be an effective strategy for enhancing the effector activity and clinical impact of anti-tumor T cells, resulting in significant clinical benefit in multiple cancers. However, the majority of patients treated with approved checkpoint inhibitors fail to respond or develop resistance. Recent work has demonstrated that immune checkpoints like PD-1 and CTLA-4 primarily work by interfering with the activation of the CD28 costimulatory pathway. Additionally, the immunosuppressive tumor microenvironment often lacks the CD28 ligands, CD80 and CD86. Next-generation immunotherapeutic strategies may therefore improve anti-tumor responses by providing T-cell co-stimulation through CD28, while also inhibiting one or more checkpoint pathways. Preferably, such activity might be focused primarily within the tumor microenvironment to limit potential systemic immune activation and toxicity. ALPN-202 is a CD80 variant immunoglobulin domain Fc fusion that functions as a conditional CD28 co-stimulator and dual checkpoint inhibitor. In the tumor microenvironment, ALPN-202 binds PD-L1. This blocks PD-L1/PD-1 interactions, thereby preventing PD-1-mediated T-cell suppression. PD-L1-localized ALPN-202 also drives T-cell activation by binding CD28. This provides PD-L1-dependent CD28 co-stimulation to T cells, and in effect, transforms the PD-L1 suppressive signal into an activating signal. Additionally, ALPN-202 binds to and antagonizes CTLA-4 expressed on T cells. This blocks interaction of CTLA-4 with its ligands, further potentiating T-cell activity. These three mechanisms of action of ALPN-202 are intended to address deficiencies of checkpoint-only inhibitor strategies by directly co-stimulating T cells in the context of dual checkpoint blockade. At the same time, these activities are designed to be preferentially limited to the PD-L1+ tumor microenvironment, reducing the potential for systemic toxicity. ALPN-202 is therefore being developed as a novel anti-tumor immunotherapeutic agent and may hold promise as a monotherapy or in combination with other anticancer agents. Now the ASCO poster. The video does a nice job summarizing the mechanisms of action, but there are several points worth re-emphasizing and elaborating on. First, as depicted in the upper right, recent work has demonstrated that immune checkpoints work primarily by inhibiting CD28, a critical costimulatory receptor in T cells. PD-1 recruits phosphatases to the immune synapse, inhibiting intracellular phosphorylation of CD28, while CTLA-4 competes extracellularly for binding of the CD28 by the CD80/CD86, in turn inhibiting CD28 activity. Anti-PD-1 and anti-CTLA-4 treatments therefore inhibit these brakes of CD28 but do not provide activating gas signals to CD28. Inadequate synthetic CD28 activation may therefore underlie T cell hyperresponsiveness during checkpoint inhibition, accounting for therapeutic resistance. As depicted in the lower right, ALPN-202 is a novel biologic designed to address these issues. It consists of a variant CD80 extracellular domain engineered by directed evolution to bind PD-L1, as well as CD28 and CTLA-4 fused to an Effectorless Fc domain. This design results in localization of ALPN-202 to the tumor microenvironment by high affinity binding to PD-L1, resulting in cross-linking and agonism of CD28 only in the presence of PD-L1. ALPN-202 also blocks PD-L1, PD-1, and CTLA-4 CD80/CD86 interaction, and as such, is a dual checkpoint inhibitor in addition to a traditional CD28 co-stimulator. In preclinical tumor models, ALPN-202 was demonstrated to be superior to checkpoint inhibitor therapies alone, yet demonstrated favorable safety in toxicology studies. NEON-1 is a first-in-human dose escalation and expansion study of ALPN-202 monotherapy in advanced solid disease. Participants must have tumors that have failed all or have no available standard of care therapies, including checkpoint inhibitors when indicated. Dose escalation began with an accelerated titration design using single-subject cohorts before utilizing a standard 3+3 scheme, exploring two dose regimens in parallel, weekly and every three weeks. The data presented here reflects available data through the completed 1 mg/kg weekly and ongoing every 3 mg/kg weekly cohorts. As of the data cutoff, 32 participants have received ALPN-202. The mean age was 63 years, the majority being male and Caucasian. These participants had generally received many prior lines of therapy, with a significant minority having received prior IO therapy. The majority had one of three tumor types, pancreatic, colorectal, or mesothelioma, although multiple advanced solid tumors are also represented as one or two each. It's important to note that the majority of these tumor types were not considered classically immune responsive. As shown on the top left side of this slide, ALPN-202 had exhibited dose-dependent PK as well as pharmacodynamics, as assessed by target saturation on circulating T cells. These findings are largely consistent with the preclinical PK/PD models generated during non-clinical development of ALPN-202. On the lower left, agonistic engagement of CD28 was confirmed by a pharmacological costimulation assay based on ex vivo CTLA-4 engagement of peripheral blood using IL-2, a key target cytokine of CD28 signaling as the principal endpoint. As assessed in end of infusion samples, maximal CD28 engagement of peripheral blood T cells was observed as early as the second dose cohort, 10 mg/kg. Interestingly, these activities were correlated with a dose-dependent expansion of CTLA-4 cells, as shown in the middle lower graph. As shown, these effects were less apparent in CD8 cells, consistent with the known preferential importance of CD28 signaling CTLA-4 over CD8 T cells. On the right, the emerging adverse event profile shows that ALPN-202 has been well tolerated, with only one patient as of the data cutoff having been reported to experience a grade three or higher related adverse event. This was an SAE of testicular pain and acute kidney injury in a subject with renal cell carcinoma, who improved after treatment with a combination of ciprofloxacin and corticosteroids based on a working diagnosis of infection versus immune-related orchitis and epididymitis. The most common events of note include immune-related adverse events, particularly of the cutaneous system, which have generally been grade one or two and managed with topical therapies. Some infusion-related reactions have been noted, again, generally grade one or two, and treated with conservative interventions such as antihistamines, acetaminophen, and warm saline. Importantly, no events of cytokine release syndrome have been noted. Preliminary efficacy analyses suggest clinical benefit among most treated participants, even though this is a heavily pretreated, advanced population with tumor types traditionally considered unresponsive to immune therapies. This is emphasized in the waterfall plot in the lower left. Of the evaluable patients at the time of analysis, 13 out of 23 or 57% of subjects had an event outcome of stable disease, and one subject had achieved a partial response. For a clinical benefit rate that defined as stable disease or better at any post-treatment initiation tumor assessment of 61% based on investigators' assessments. This latter participant is noted at the top of the swimmer's plot at the right, where the PR was obtained around 120 days into treatment after two prior findings of stable disease. Another participant of note is second from the top on the swimmer's plot. This participant had a history of metastatic melanoma which had previously relapsed after receiving combination nivolumab and ipilimumab, and was removed from treatment with ALPN-202 after three weekly doses due to clinical progression. During treatment follow-up, however, apparent stabilization of disease was observed without subsequent systemic anti-cancer therapies. In the waterfall plot, this participant is second from the right with the best change in SLD, just approaching -3. This slide shows peripheral blood immunophenotyping of T cells during the first cycle of therapy, which on the left demonstrates dose-related upregulation of the activation marker ICOS, as well as the proliferation marker Ki-67 on T cells, particularly CTLA-4s more than CD8s, again consistent with the known preferential role of CD28 in CTLA-4 versus CD8 T cells. Similarly, on the right, naive T cells appear to be somewhat reduced during treatment, while central memory T cells appear to increase, again more prominently in the CTLA-4 over CD8 population. Interestingly, regulatory T cells in the upper right appeared to decrease during therapy. To our knowledge, these changes in the peripheral blood at a population level have not been observed with blockade of the PD-1 and CTLA-4 pathways alone. Instead, they're consistent with the additional CD28 mechanism of ALPN-202 and known biology of CD28 in T cells. In conclusion, ALPN-202 is a first-in-class variant CD80 Fc fusion protein. It has been designed to overcome checkpoint inhibitor resistance by focusing CD28 co-stimulation in the tumor microenvironment while inhibiting both the PD-L1 and CTLA-4 checkpoints. In this advanced tumor population, ALPN-202 appears to be well-tolerated with manageable immune-related toxicities such as cutaneous adverse events. Dose-dependent PK/PD has been observed. Most of the participants enrolled in this study had tumors traditionally considered unresponsive to immunotherapy. Nonetheless, evidence of clinical benefit appears to be present at this early stage. Peripheral immune cell analyses demonstrate evidence of T cell activation and proliferation consistent with CD28 agonism, including upregulation of ICOS, Ki-67, and central memory T cells, as well as downregulation of Tregs. Further development of ALPN-202 in advanced malignancies is clearly warranted. After completion of dose escalation, a biologically optimal dose or doses will be chosen for expanding cohorts. Further development in combination with other treatment modalities may be of significant interest. To our knowledge, this is the first demonstration that endogenous CD28 may be safely agonized in the clinic, successfully eliciting immunological activity, as well as demonstrating an early potential for clinical benefit. It's now poised for more broad applications in cancer immunotherapy. There are a couple of additional points we'd like to make that could not fit in the space of the ASCO presentation. One, the immunological effects seen here seem particularly remarkable. For comparison, data from a recent study with combination nivolumab and ipilimumab are shown to the right. Note that compared to screening levels, on-treatment circulating central memory T cells and Tregs do not change, in contrast to the observations seen here with ALPN-202. At the same time, although the immunological changes seem compelling, we would like to identify a dose regimen that results in an optimal degree and duration of favorable immunological changes before opening expansion cohorts. This will require analysis into further cycles of therapy as we continue dose escalation to ensure selection of a dose regimen that preserves immune activation and avoids immune exhaustion with repeat dosing. As such, we see a high-level development plan for ALPN-202 as shown here. The NEON-1 monotherapy trial will continue through dose escalation through most of this year, and we plan to open expansion cohorts as soon as possible after analysis of that data. In the meantime, we are in the process of opening the NEON-2 PD-1 inhibitor combination study. It will include a dose escalation portion that's shorter than NEON-1 and then plan to proceed to expansion cohorts informed by the combined experience in NEON-1 and the PD-1 combination dose escalation. At this point, we thought it'd be of interest to reflect on the history of therapeutic efforts on the CD28 pathway and the place of ALPN-202 within it. CD28 was identified over 40 years ago as a monoclonal antibody specificity on T cells. It was quickly recognized as a principal regulator of T cell activation. In fact, much work has successfully developed antagonists of this pathway for inflammatory diseases, including the approved drugs abatacept and belatacept. These drugs block both the CD28 ligands CD80 and CD86, but not CD28 itself. On the oncology side, though, it has taken these nearly 40 years for the industry to reach a state where there is significant scientific activity in therapeutically activating native CD28 for cancer. As I'm sure you're aware, progress here was hindered significantly by the TeGenero drug TGN1412, which resulted in nearly lethal cytokine storm after its first dose in its first-in-human healthy volunteer study in 2006. This resulted in what seemed like a moratorium on CD28 binding therapeutics, even despite TheraMAB's apparent attempts to advance the compound. Only recently have there been advancements in the clinical compounds, often bispecifics, that are designed to agonize endogenous CD28. ALPN-202 is therefore significant in this context by demonstrating successful CD28 agonism in cancer patients, doing so with a structure with a single ectodomain. Seemingly the first to disclose this data. With that, we'll now open the call for questions. Operator? Yes, sir. For the participants who would like to ask questions, press star one on your telephone. For our first question, we have Joseph Pantginis from H.C. Wainwright. Joe, your line's open. Hey, guys. Good evening. Thanks for taking the question, very nice first look, thanks for the details. I guess my first question, you touched upon this a little bit during your prepared remarks, is really a little more detail on what your open questions are for dosing. I'm glad you brought up about looking to balance T cell exhaustion with repeated dosing. Obviously, you're going to continue dosing as you put in the initial slides. I guess, what other options might you have? Amend the protocol for different types of dosing structures, looking at potential metronomic dosing. I guess I would link that question to when you look at the swimmer's plots, all the stable diseases appear to appear around day 40. I'm wondering how that might impact any impacts on dosing strategies going forward. Yeah, thanks for the question. There's a few points. Maybe first, toward the end of your comments about stable doses appearing around day 40, that's just also the protocol-defined first assessment, the first tumor follow-up assessment, that's more likely an artifact of or reflective of how the protocol is designed to follow up tumor size. I think I might just point back to, the data so far are preliminary in that we've analyzed only through the first cycle of these subjects. As we get additional data in subsequent cycles, we'd like to make sure that these changes persist at all the dose levels. There's a theoretical possibility that frequent dosing may overstimulate T cells, and with subsequent cycles of therapy, you may actually see the effects not hold up as long. I don't think that we necessarily consider different dose regimens. We think one of these dose regimens will be what we choose, rather, we just want to confirm before moving forward that we're not prematurely choosing in terms of mistakenly choosing the highest dose that's tolerated just because it's the highest dose. That may turn out to be a dose that leads to exhaustion. That's actually really helpful. Thank you for that. You touched upon this on your call, and it certainly makes sense, that you're really going after very late-stage tumors and not necessarily IO responsive. When you look at, and I'll say this sort of broadly, the investor community liking to see waterfall plots that have a lot more drop-offs versus understanding the true perspective here, if you can add a little more color, the real perspective of having patients that have such high level of pretreatments and have exhausted these options and really what the true clinical impact is, from a meaningful standpoint, even to achieve stable disease? Yeah, we're actually pretty enthusiastic about this data because, for the reasons you mentioned. This is a heavily pretreated population with tumor types that you really wouldn't expect responses in. It reminds us of, with a timely set of data, it might be the LAG-3 data. As you may recall, when the phase I data first came out, particularly with the therapies that were in populations similar to us, with pancreatic or colorectal, there was a very low response rate there, it was primarily stable disease that we're looking at. I think for us, seeing a similar type of elite early durability, if you will, particularly in association with these particularly compelling immunological changes that seem to be unprecedented, that's really exciting to us. Thank you very much. Thanks, Joe. For our next question, we have Boris Peaker from Cowen. Boris, your line's open. Great. Maybe I'll just initially follow up the questions regarding dosing. I'm just curious, theoretically, when you have a dual checkpoint inhibitor and a CD28 co-stimulator, what is the desire to the optimum PK/PD profile for a drug with that kind of a profile? Well, Boris, I think it would be primarily the immunological endpoint, so maybe not necessarily exposure per se, but of course, the physiological consequences of the drug. That is why we have mainly focused on the immunological endpoint, and we want to make sure that we are seeing persistent expansion and activation of T cells or B cells in general, and that persists over time. It would be sort of the optimal biological effect, if you will, short of necessarily going after an PK/PD. Do you think it makes sense to maybe do some kind of dosing based on a test, on a patient test, to assess their immunological state and then adjust the dose to that, not just necessarily to their body weight? That's something that we're looking at and exploring. Maybe stay tuned about that. That's the concept that we have around tailor dosing. We're not sure that's absolutely necessary because it's hard to necessarily get a good index from, for example, a simple blood test about the overall immunological burden of target. That's something we're looking at now. Gotcha. My last question, can you just summarize the next milestones for ALPN-202 in terms of monotherapy as well as NEON-2? When are we going to get more updates from this study as well as the PD-1 combo? I'd say the major thing to look out for is our completion of the dose escalation or rather initiation of the expansion cohorts. We expect that to take most of the rest of this year. Of course, a lot of it will be data dependent with regard to once we have enough data to confirm the type of immunologic changes that we see and confidence in the specific dose regimen to proceed with expansion cohorts. Boris Peaker, thanks for your question, and we'll continue with that. As we get additional data, we'll hopefully be in a position to present it at additional scientific conferences either later on this year or next year. That's all right. Thank you very much for taking my questions. Of course. For the next one, we have Mark Breidenbach from Oppenheimer. Mark, your line's open. Hey, guys. Thanks for taking the question, and Stanford, thanks for the presentation. Not to belabor the dosing questions that have come up just recently. Since you're maxing out some of the pharmacodynamic effects at 10 mg/ kg or 100 mg/ kg in terms of IL-2 production, maybe you can help me understand what can be gained with continued dose escalation. Why haven't we already sort of reached an optimal dose? What more can be achieved? I'm also wondering to what extent the expansion of CTLA-4 positive T cells was predictive of the disease stabilization achieved so far, and if you see a need to expand the CD8 T cell population as a means for tumor shrinking, is CD8 positive T cell expansion a prerequisite for tumor shrinkage, or is it irrelevant in this case? Yeah. Maybe to clarify, you were talking about the assay that uses IL-2 as a readout. What's being shown there are only the samples at the end of infusion of the first dose. What it's telling us is that at 10 mg/kg, at the end of infusion, there is engagement of CD28. Because at such a low dose, what we didn't show is that the exposure drops off quite quickly, and as a result, you don't get a very long persistent CD28 engagement. As we continue to increase the dose, there is more persistent CD28 engagement, and I think that also correlates with the dose-dependent increases we see, for example, in CTLA-4 cells or some of the activation markers. You may have noted the 10 mg/kg dose level, for example, didn't really show much persistent CTLA-4 expansion in contrast to doses that were higher than that. You're right, we do see engagement at 10 mg/kg, but it's probably not long enough engagement. The question is, well, what's long enough? That's where we're looking at the resulting immunophenotyping data to give us a sense of what the sum total of the activity is over time. Okay. To the CTLA-4 versus CD8 question. Yeah. Thank you. Yeah. No, we agree CD8 cells are important. I think it's also kind of underneath what I'm commenting as well, as we've shown, there are changes in CD8. They're not as prominent as in CTLA-4, but we'd like to look at the sum total of this data before we choose the final dose. It may be that, as you know, probably what's happening based on the CD28 mechanism is that CTLA-4 cells are the first to kind of respond. CD8 cells may be second to respond because they're less dependent on CD28, and so we may not get to see the depth activity on CD8 until we look at either subsequent cycles or even further dosing. I think Stanford's review, Mark, of kind of the historical challenges around targeting CD28 hopefully was helpful. We went in dosing very cautiously at the beginning of this trial, and I think we've dose escalated now to the level where we're starting to see activity. We're going to continue to move along our dose escalation protocol as we've designed it, and then we'll report data on it as we get it. Okay. That's super helpful. Maybe one last sort of related question. I'm just wondering how relevant it is to profile peripheral T cell populations for a therapy that's intended to act locally in the presence of PD-L1. Isn't the real picture only going to be revealed sort of within the tumor? How useful are the peripheral T cell characterizations? Well, I think it's a fair question. I'd say we are interested to look at on-study tumor biopsies for similar types of readout. We haven't required those during the dose escalation primarily since it is a first human study at an early-stage therapy. That is something we intend to do as we move into expansion and with subsequent studies. Okay. Got it. We'll look forward to that with next data from expansion and then perhaps from escalation as well. Thanks for taking the questions and congrats on the progress. Thanks. For our next question, we have Wangzhi Li from Baird. Wangzhi, your line's open. Hi. Thanks for taking my question. I have a question about the patient prior therapy histories. In addition to this one partial response you mentioned we had prior PD-1, CTLA-4. How about the other rest of the patients? How many of them had prior PD-1 or CTLA-4 therapy? Any count on that? Yeah. Can we move the slide? Can you go back to the Demographic slide. I think it was 28% is the number. Sorry, specifically more on the stable disease patients. Do you want to go to this one? I want to make sure I'm answering your question. Do you mean on the waterfall plots, which ones were prior PD-1 therapy? Yeah, the partial response had a prior PD-1, the CTLA-4. How about the stable disease patient? They also had a prior PD-1, CTLA-4 therapy or kind of naive or any color on those? Yeah. Some of them had prior PD-1 therapy before. I can't recall off the top of my head which ones, so we'd have to go back and look at that specifically, but about a third of patients overall had prior PD-1 therapy, and so far, that doesn't seem to have predicted necessarily the duration of stable disease. Those are preliminary assessments. Okay. At least those levels, do you have PD evidence that the PD-L1 blockade sufficiently or the CTLA-4 blockade leads to PD effect or contributing to clinical activity? Well, we know we get some blockade just based on some of our pharmacology data. Based on the target saturation we're seeing in our preclinical pharmacology data, you would expect to have some antagonism, although it's probably not until the higher doses and perhaps the dose levels that we're exploring now, where you would expect to see over 90% target occupancy of PD-L1 and CTLA-4 during the entire dosing interval. I think one of the key points I wanted to bring home is, and Stanford presented this in his concluding remarks, was that the changes in the T cell phenotypes that we're seeing, particularly central memory T cells and a decrease in Tregs, has not been seen with checkpoint inhibitor therapy alone, and is very unique to this particular program. I think Stanford used the word unprecedented, the data that we're seeing. We think it's something unique with ALPN-202 that's much different than what you see with checkpoint inhibitor therapy alone, that's like the CD28 axis. Yeah, that's helpful. I'm trying to get a better sense of, is this currently the PD effect mostly driven by CD28 agonism, or is it synergy between CD28 with the PD-L1, PD-1 blockade or PD-L1 blockade? It looks like this dosage may be the more CD28 stimulation driven. Related to that, if you look at the area of interest, the skin and thyroid, do you think that's more related to CD28 agonism or maybe they're seeing with the PD-1 blockade, too. Any thought on those? We think most of the biology here is being driven by CD28, but to be fair or clear, these are all related issues, right? If you block PD-1 and it's working well, it's because there are sufficient endogenous B7 ligands that agonize the CD28 activating T cells. While we may agonize CD28 and then relieve the blockade from PD-L1 or CTLA-4 and achieve the same thing that you would otherwise get by blocking PD-L1 and CTLA-4 at a lower dose. I think the issue is it's kind of intertwined because these three targets have intertwined biology. I think it would be unfair or it would be oversimplification to try to make it all attributable to CD28 or PD-L1. As Mitch said, we're quite encouraged even at these doses to see differentiating pharmacodynamic data that suggests that this is CD28. Whether it's how much more we can get with actually getting full occupancy of PD-L1 and CTLA-4, that's part of what we want to see as we continue with this escalation, if that makes a difference or not. Got it. That's very helpful. Thanks a lot for taking my questions. Thanks, Wangzhi Li. For our next question, we have Robert Driscoll from Wedbush Securities. Robert, your line's open. Thanks. Thanks for taking my question, guys, and congrats on all the progress. You talked a little bit in the past about potential patient selection, biomarker development. Just wondering if you could give us an update on those efforts. Yeah. We're still analyzing some of that data, some of the samples we're still doing preliminary analyses on. I also am not sure we have enough clinical outcome data to draw any firm conclusions anyway. I think continue to collect that data and do the analyses, we'll of course disclose it at the right time. Got it. Maybe just one more. I think looking ahead, the combination with PD-1 obviously makes a lot of sense. Any speculation about any other kind of novel I/O pathways you might look to combine with? As of right now, our focus is going to be on starting the NEON-2 combination checkpoint inhibitor study. Then we're going to look at other opportunities after that. We're pretty enthusiastic about starting that study for a variety of different reasons, hopefully that'll be starting here pretty shortly. Great. Thanks a lot, guys. Thank you. We don't have any further questions. Remy Durand, Chief Business Officer, with online submitted questions. Please go ahead. Thank you, operator. One question came in. Stanford, can you talk about the mix of tumors that you've seen in NEON-1 and maybe what you might expect to see just based on their profile and prior history? When you say expect to see, do you mean in terms of outcomes? Right. Yeah. Well, these are tumor types that historically have been poorly responsive to many therapies, including immuno-oncology therapies. In many cases, we didn't necessarily expect them to be on study for very long. Of course, the objective of dose escalation is primarily safety. We of course accepted these subjects because they may derive some clinical benefit, but also will help assess the safety of the drug. We've been pretty pleased so far to see that even the number that we've seen with stable disease now a handful of months. That's quite encouraging to us in contrast to what you'd otherwise expect historically for patients in those lines and types of therapy. Lines of therapy and types of tumors. Great. Next question. What data can you point to specifically that suggests CD28 engagement might be added into the combined checkpoint inhibition of the drug? For me, the main difference is that we've not seen these types of immunological changes before at a population level. What's been described with PD-1 inhibitors or CTLA-4 or even combination of PD-1 and CTLA-4 inhibition is that sometimes you'll see some subjects increase their central memory T cells or sometimes decrease their T-regs, but the overall treated population doesn't seem to do that. At least we showed one of the figures in one of the publications that reflects that. In contrast, we're seeing at a population level mean changes in these populations, which to me suggests that can't be explained by just PD-1 and CTLA-4 alone. Of course, there's the actual biochemical engagement that we're able to demonstrate, like with the IL-2, which is a key cytokine readout. Of course, it's been well established as a key cytokine readout of CD28 signaling and so on. That gives us confidence in the engagement of target and then also the importance of the physiological engagement of that additional target. One more came in. You mentioned this earlier, but how can we place this data in context to recent data from maybe other costimulatory bispecifics or specifically the LAG-3 antigen molecules you mentioned? Of course, it's hard to compare across studies per se. I think trying to draw parallels, one of the key things to think about, I guess, that for many IO drugs, responses per se may not be the best way to evaluate them early in development. Like with the LAG-3 data, original phase I data, particularly in the non-melanoma populations that were studied early on, you don't necessarily see a lot of objective responses, yet there does seem to be valuable clinical benefit with further study. For us, we place our drug along the same veins, where we're actually seeing some evidence of clinical benefit even at this early stage. Of course, we'll be quite enthusiastic to continue studying it in further studies. Thank you. I think the last question here, is ALPN-202 a molecule you want to keep in-house or do you think there's value in potentially bringing on a partner? We partnered our lead program, ALPN-101 with AbbVie last year. We think we're very early on in the development of ALPN-202. We're just now moving through dose escalation. As we highlighted today, we think we have a molecule that's creating a very unique profile. There's a lot of value to be created in ALPN-202. With that being said, there's been a lot of inbound calls of interest for partnering for ALPN-202. We'll entertain those, and if there's something appealing, we'll consider it. Our goal is to continue to develop it on our own and continue to create value. I think that concludes today's presentation. I'd like to thank everyone for making time on a Friday afternoon, evening, where as you can tell, we're pretty excited about our early experience with ALPN-202, and we look forward to continuing to give you updates as we make progress through completing the dose escalation portion of this study. Thanks, everyone. Ladies and gentlemen, this concludes today's conference call. Thank you all for participating. You may now disconnect.