Good evening, ladies and gentlemen, and thank you for joining the Alpine Immune Sciences 2022 AACR Virtual Investor Event. Currently, all participants are in a listen-only mode. Following management's presentation, we will hold a question-and-answer session with Executive Chairman and Chief Executive Officer, Mitchell Gold, President and Head of Research and Development, Stanford Peng, Chief Business Officer, Rémy Durand, and Chief Financial Officer, Paul Rickey. Analysts will be able to ask questions live. To ask a question at that time, please press star followed by one on your touchtone telephone. If any investors have questions, please send them to ir@alpineimmunesciences.com. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this event is being recorded today, Tuesday, April 12, 2022. Thank you, operator. Good afternoon and good evening. Thank you to all those in attendance, and welcome to Alpine Immune Sciences Virtual AACR 2022 Data Review. I'm Mitch Gold, the Executive Chairman and CEO of Alpine. Today marks an important day in our company's history with the full presentation of the dose escalation data for our lead immuno-oncology program, davoceticept, a first-in-class conditional CD28 costimulator 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 itself in our first lead oncology candidate, davoceticept. The data being shared today reflect over seven years of remarkable effort across our entire organization, and we are proud to present this dose escalation data as we believe this is the first CD28 costimulator to show clinical data demonstrating early evidence of clinical benefit and antitumor activity, as well as a well-tolerated safety profile. As a reminder, our presentation today may contain forward-looking statements, and I encourage you to refer to our most recent SEC filings regarding the risk factors associated with these statements. I now pass the call over to Stanford Peng, Alpine's President and Head of Research and Development, to walk through the data we presented at AACR and put it in perspective. Stanford? Thanks, Mitch. One of the key backgrounds about davoceticept is the recent recognition that immune checkpoints work by binding to and blocking the CD28 signaling pathway. PD-1 does that by either recruiting phosphatases or other inhibitory pathways to the immune synapse, and CTLA-4 may do that and/or also compete for the activating ligands of CD28, B7-1, B7-2 or CD80 and CD86. In this way, when you block PD-1 or CTLA-4 by antibodies against either, you take the brakes off of CD28, but you don't provide the so-called activating or gas signal to CD28. We also know that loss of expression of CD80 and CD86 is a described mechanism of tumor immune escape. This suggests that loss or inadequate CD28 activation in the tumor microenvironment may underlie T-cell hypo-responsiveness and may account for checkpoint inhibitor resistance. Davoceticept is a novel biologic derived from the CD80 extracellular domain designed to address this issue by providing CD28 costimulation in this context. Importantly, it's designed to bind to PD-L1, localize to the tumor microenvironment and isolate transactivation or costimulation of CD28 only in the presence of PD-L1. It also blocks PD-L1, PD-1, and CTLA-4 B7 interactions, and thereby is also a dual checkpoint inhibitor. It's primarily the PD-L1-dependent CD28 costimulatory activity that is the most novel aspect of davoceticept's design. In preclinical studies, davoceticept demonstrated very promising activity, including favorable efficacy against monotherapy treatments with checkpoint inhibition alone. This was recently published in a paper in Nature Communications just last week. With the preclinical data in hand, we initiated a first-in-human dose escalation expansion study of davoceticept in patients with advanced malignancies. We refer to this study as NEON-1. The dose escalation began with a dose that was justified by the MABEL dose calculations of 1 mg per kg. We initiated with single-subject cohorts until 0.1 mg per kg, where pharmacokinetic, pharmacodynamic activity was predicted to be initiated. At that point, we started three plus three dose escalation cohorts. At 0.3 mg per kg, we also looked at a Q3-week schedule. Theoretically, the Q3-week schedule may allow for less risk of T-cell exhaustion, and these two dose schedules were analyzed in parallel. Previously, at ASCO last year, we presented preliminary data through the 1 mg per kg dose levels, primarily of the Q1 week schedule. Now that dose escalation's been completed, we'll primarily focus on the data from the Q3-week schedule, since most of the pharmacodynamic data suggests that there is no significant differences between the Q1 and Q3-week schedules, and the Q3-week schedule is likely to be the regimen taken forward given its greater convenience. As of the data cutoff, which is March 21st, 58 participants had received at least one dose of davoceticept. The median age was 60, a mostly male and Caucasian population. In general, a pretty typical population for a first-in-human solid tumor study. Of note, these were heavily pretreated patients with a median of four prior lines of therapy. Many of the subjects had been previously treated with some type of immuno-oncology therapy, including a PD-1 or PD-L1 inhibitor in 29%. The three most common tumor types were colorectal, pancreatic and esophageal. There were a number of other tumor types, as you can see listed here, but I think the important point is that this is a group of tumor types that are classically not immune responsive. This is also reflected in the PD-L1 expression level on archived specimen, where you can see the majority were PD-L1 low or undetectable. As of the data cutoff, 55 of the 58 participants had been discontinued from treatment, most of them due to disease progression. Importantly, there were no treatment-related grade five events or deaths. In addition, there were very few adverse events leading to study discontinuation or treatment discontinuation. Davoceticept demonstrates very nice dose-dependent pharmacokinetics and pharmacodynamics. As you can see here, primarily from the Q3-week schedule, there's excellent exposure over the dosing interval. On the right is a target saturation assay where we've looked at the occupancy of the receptors on circulating T cells. You can see particularly by the time we've reached 10 mg per kg, saturation is quite consistent and maintained throughout the dosing period. Overall, davoceticept has been quite well tolerated up through the 10 mg per kg dose level. On the left are summarized the overall adverse events. Treatment-related adverse events of grade 3 or higher were seen in only 12% of subjects. Treatment-related serious events, all of which were grade 3, were seen in only 5% of subjects. To the right is a table that lists all of the grade 3 treatment-related adverse events. There are three that are worth some description or note, which are the immune-related adverse events. The first on the top is a gastritis event, which was also a DLT. It was a grade 3 gastritis which occurred in a participant with colorectal carcinoma, treated at 3 mg per kg every 3 weeks. It occurred on cycle one, day seven, was found to be chronic active gastritis, H. pylori negative by biopsy, and was improved with oral prednisone. The second event in one subject was two events of acute kidney injury and testicular pain, which were thought to be immune-related nephritis as well as orchitis. This occurred at the 0.1 Q1 week cohort. Definitive biopsy was not done, but the patient did respond to corticosteroids as well. Third event is a grade 3 urticaria which occurred at the 10 mg per kg dose level, that was also responded to oral prednisone. Importantly, back on the right, adverse events of interest included these immune-related events, which occurred in about 30%-33% of subjects overall, the majority of which were grade 1 or 2. Infusion-related reactions occurred in about 16% of subjects, all of which were grade 1 or 2. Just as importantly, given the mechanism of action of the drug, no events of cytokine release syndrome have been reported. As you can see from the dose-limiting toxicities with just one reported, a maximum tolerated dose was not reached. A little more description about the immune-related adverse events. We've been particularly interested in these because particularly skin, thyroid, and perhaps even gastrointestinal events have been related to long-term clinical outcome in patients treated with immuno-oncology therapies. These also happen to be the most common events described with davoceticept, primarily skin. As you can see listed here, over to the right are the incidences of these immune-related events in comparison to overall treatment-related adverse events at the different dose levels. Interestingly, the peak or the highest incidence of immune-related adverse events are at the 1 and 3 mg per kg dose levels. This suggested to us that the biological activity of the drug may be best at the one and three mg per kg dose levels. In fact, when we look at immunophenotyping analyses in subjects in these cohorts, the results seem to parallel those of the immune-related adverse events. We had previously described at ASCO last year that davoceticept treatment is associated with a number of favorable changes in T cell markers, including markers of activation, such as ICOS, expansion of central memory T cells, as well as reductions in Tregs. This continues to be the case as we look through the every three-week cohort. When we integrate these changes over time over the first two cycles, the area under the curve of these changes also seems to generally peak at the 1 and 3 mg per kg dose levels, or in the case of Tregs, inversely peak, as that's considered the favorable outcome. This also correlates with our CD28 co-stimulation assay, which some of you may recall is an assay where we assay for CD28 engagement, typically done at the end of infusion samples. Again, we see a sense of a peak or inverse U-shaped curve at the middle dose levels. When looking at overall activity, it's important to just reiterate that this is a population of heavily heterogeneous and heavily pre-treated patients, overall. Nonetheless, there is evidence of antitumor activity. Overall, 11 of 23 subjects had some type of tumor volume reduction, and three remained on treatment for at least six months. Two subjects achieved a partial response. One was an unconfirmed response in colorectal carcinoma, and another was a confirmed response in renal cell carcinoma. This latter subject or participant is illustrated in more detail here. A 68-year-old man who had papillary renal cell carcinoma, diagnosed initially in October 2020, had high-risk characteristics, underwent a nephrectomy in November 2020, but then developed metastatic disease in the middle of last year. Tissue at that time showed undetectable or low levels of PD-L1, but the subject was nonetheless enrolled in our study. In general, he tolerated the drug fairly well. There were a couple of immune-related adverse events, including low-grade arthritis, myalgias, and arthritis, as well as mild transaminase elevations. By the fourth cycle, the subject had entered a PR, which is confirmed at cycle 6. We just heard that the subject just initiated cycle 10 and continues to tolerate the drug well. Over to the right, you can see the scans illustrating some of the general response, comparing the screening scans to the cycle 6 scans. In conclusion, davoceticept is a first-in-class variant CD80 fusion protein, which has been designed to overcome checkpoint inhibitor resistance and uniquely focuses CD28 co-stimulation to the tumor microenvironment. It is also a dual checkpoint inhibitor. In advanced tumors, it's been very well tolerated. We see very nice dose-dependent PK and PD, including relevant immune activation, such as markers of activation such as ICOS expansion of central memory T cells and reductions in Tregs. Overall, the 1 and 3 mg per kg dose levels appear to have optimal biological activity, as evidenced by both these pharmacodynamic markers, as well as the immune-related adverse events. We do see some early clinical benefits suggested, particularly importantly in tumors that are not traditionally responsive to checkpoint inhibitors. We believe that ongoing development is clearly warranted. We're planning expansion cohorts in melanoma, renal cell, and PD-L1 positive tumors at the 1 and 3 mg per kg dose levels. As many of you know, we do have an ongoing combination study with pembrolizumab, NEON-2, and we are considering several other tumor types as well as combination strategies. On the next slide here, which wasn't presented just recently, is a little more detail about our expansion plans. What's listed here are the three primary cohorts that we're planning to initiate expansion on, imminently. Those include melanoma, renal cell, and PD-L1 positive cancers. Part of the rationale for this is depicted in the figure in the lower left, where we're taking a closer look at the waterfall plot. You can see that the four tumors or the four subjects who had the apparently most responsive tumors included subjects with renal cell, melanoma, but then also colorectal cancer. Our interest in melanoma and renal cell are since those are traditionally IO responsive, and we also see preliminary activity there. We are interested in PD-L1 positive tumors, however, since the mechanism of action of the drug is primarily focused to work in the presence of PD-L1, yet we didn't get very many PD-L1 positive cancers during dose escalation. We're still doing some further work. We're thinking around colorectal cancer, but that is a particular area of interest for us as well. Then a word just to reiterate on our dose rationale. It does look like the 1 and 3 mg per kg dose levels have the most biological activity, again, as related to the peripheral immunophenotyping that we showed before. Importantly also the correlation to the clinical activity, at least as evidenced by immune-related adverse events. That all seems to line up, and then supports our interest in those two dose levels. All right. With that, let me turn it back over to Mitch. Thanks, Stanford. I appreciate the overview from the presentation today. The completion of the dose escalation portion of NEON-1 is an important milestone for the company. We are encouraged by the data which included tumor types not considered classically immunoresponsive, and we look forward to starting enrollment in our dose expansion cohorts later this quarter. Davoceticept is also being evaluated in combination with pembrolizumab in our NEON-2 study. As announced in early March, this study is currently on partial clinical hold. Participants already enrolled may continue to receive davoceticept and pembrolizumab, but no additional participants may be enrolled. Similar to NEON-1, we are seeing potential signs of early clinical benefit in the combination study. In summary, we believe the collective data from NEON-1 and early data from NEON-2 support that davoceticept is an active drug. We look forward to further exploring the appropriate patients who might benefit most from this novel first-in-class therapy. Turning briefly to our inflammatory disease programs, we are excited about the continued advancement of Alpine-303, our clinical-stage dual BAFF/APRIL antagonist. Interest in this program is strong based on preclinical data that support a best-in-class profile for Alpine-303. We initiated our phase I healthy volunteer study at the end of last year and are anticipating data around the middle of this year. This study is important because it'll provide not only safety data, but also changes in key pharmacodynamic markers such as serum immunoglobulin levels. While we are still moving through the dose escalation cohorts, what we are seeing thus far is consistent with what we would have predicted from the preclinical studies of Alpine-303. Following completion of the phase I study, we plan to initiate a phase II study in SLE and a parallel plan for at least one basket study in a separate therapeutic area. We look forward to providing more information on the next stage of ALPN-303 in later this year. Acazicolcept, or ALPN-101, continues to enroll patients in our SYNERGY global phase II lupus study. We are pleased with our collaboration with AbbVie, and last year achieved $45 million in milestones with an additional $30 million in pre-option milestones remaining under the collaboration. In addition, our collaboration with Horizon, which we initiated at the end of last year and included a $40 million payment along with $1.5 billion in potential milestones, has been formally kicked off and the teams are working well together on new programs in autoimmune diseases and inflammation. With that, I now open the call for questions. Operator? Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. Our first question comes from the line of Boris Peaker with Cowen. Questions. Operator? Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. First one. Boris, how are you? There's a little bit of an echo there. Hi. Can you hear me? Now we can hear you, yep. Fantastic. I guess my first question is, we've obviously seen strong synergy of checkpoint inhibitors with chemo. I'm just wanting to get some sense of what your thoughts on combining with chemotherapy is or maybe just doing a triple combo altogether because I think that should work the best, checkpoint inhibitor 202 and chemo. Yeah. As you may recall, we presented some data on that in the past preclinically. Stanford, maybe you want to comment on that? Yeah. We have shown at least preclinically that for instance davoceticept combines well with oxaliplatin and that was partly geared toward this concept of maybe looking at colorectal cancer since platinum you know like oxaliplatin is part of standard of care there. One thing we wanna consider though at the same time is that some of these chemotherapy regimens can also be immunosuppressive. That's part of our ongoing thinking and evaluation of the opportunity right now. Give us some time to kinda think through that a little bit more about exactly what setting and what other combinations we wanna look at. Got it. My second question is, you've mentioned that, I mean, you've tested once every three-week dosing and weekly dosing and essentially have the similar result. That's why you're moving forward with every three-week dosing. Do you think that exploring maybe even longer dosing would add value or every three weeks is sufficient enough, that that's not necessary? Yeah. You know, it might be. I think that's something we're gonna look at through some modeling as we get some additional data. You know, part of the limitation that we have with some of the subjects, particularly at the lower doses, was that the time on study was short, so we don't have quite enough data to necessarily make a clear call that, you know, to model that a Q six, for example, might be equivalent. You know, doubling the dose, but Q six might be equivalent to Q three. So, part of our intention with the expansion cohorts is to get some more of that data and look more closely at it. Great. Thank you very much for taking my questions. Thanks, Boris. Thank you. Our next question comes from the line of Mark Breidenbach with Oppenheimer. Hey, guys. Thanks for the presentation and congrats on these data. I'm just wondering if you could break out the doses and the dosing schedules for the three patients who were on study for more than six months. I guess I'm wondering kinda broadly if you're seeing the best clinical activity in this one to three milligram per kilogram dose range. Then I have some follow-ups. Thanks. Stanford, you wanna take that? They vary. Two of those subjects, to my recollection, are at the 3 mg per kg dose level, and one is at the 1 mg per kg dose level. I need to confirm that though, since I don't have that data right in front of me. There is a Oh, okay. In general, there's a correlation with the schedule, or I should say with the dose level. I'd need to double-check the exact number or the exact regimen, whether it was Q 1 or Q 3. Okay. I think the colorectal cancer patient we knew about the response from ASCO last year. I'm assuming that's Q1W, but if I'm wrong, let me know. Can you remind me if the colorectal patient was microsatellite stable or not? To be clear, that colorectal patient was from our first cohort, the one microgram per kilo, and isn't one of the three that were on study for six months. Did achieve- Okay. A PR after some time, but isn't one of those that stayed on treatment for six months. Okay. Understood. Yes, that was a Q1 week regimen. At that subject, being the first subject on study, we didn't require archival tissue or baseline biopsy, so we actually don't have knowledge about their microsatellite status. Okay. Understood. There was a nice presentation at the conference today from Ira Mellman, where he was suggesting that there's some redundancy between CD28 and CD226 or DNAM-1. I'm just wondering if you've looked preclinically at combinations of davo with TIGIT antibodies or anything along those lines. Yeah, we're looking at that. I don't know that we have anything that we're ready to say publicly about it, but that is certainly the TIGIT pathway is something of a lot of interest to our preclinical folks as well. Okay. Makes sense. All right. I'll stop there. Thanks for taking the question. Thanks, Mark. Thank you. Your next question comes from the line of Robert Driscoll with Wedbush Securities. Hey, guys. Thanks for the presentation here. Just wondering if you were able to get data on any biomarkers that might help predict potential sensitivity to ALPN-202, especially in the monotherapy settings going forward, such as CD80/86 expression or lack thereof, since you've done a little bit of preclinical work on that. Jeffrey, you wanna take it? Yeah. I mean, unfortunately, most of the tumors that were enrolled during escalation were pretty cold tumors. As you can see, there's not a lot of PD-L1, and at the same time, there wasn't a lot of CD80, CD86 or CD28. There's just not a lot of diversity there for us to draw conclusions. We didn't put all the data on that slide because it got a little bit busy. As you can see from the PD-L1 data, there wasn't such a range, plus we didn't have a lot of so many responses to allow us to draw a correlation. That'll be a focus of the expansion cohort since we will be requiring baseline biopsies as well as studying at least those four markers. Got it. How might you compare kind of the safety and tolerability profile here to that seen for checkpoint inhibitors such as anti-PD-1 ones, and how are you thinking about the potential overlapping events for the NEON-2 study where you are combining 202 with a PD-1? Yeah. I mean, I think the overall level of tolerability with davoceticept monotherapy is quite good. You know, it's hard to speculate, but it seems like the incidence and grade of some of these events are lower than what you might expect, for example, with nivo plus ipi. Perhaps our hypothesis is panning out or that, you know, the design of the drug is panning out, at least in the monotherapy setting. I would say for the combination, that safety profile is still emerging. Would rather not make definitive comments yet until we have a little bit further, more clinical experience in escalation with that regimen. Fair enough. Just maybe if you could expand a little bit more on the phase I-B expansion plans, assuming patients will be, and you know, the renal cell and cutaneous melanoma landscapes have evolved recently. I'm afraid I missed part of that. At least you cut out a little bit for me. Yeah. Could you repeat that? Yeah. I was just wondering if you could expand on, you know, the kind of the patients you might enroll in the phase I-Bs, assuming they will be IO experienced? Yes. We expect them to be PD-1, well, probably failures, although at least experienced with PD-1, if not multiple checkpoints before coming into this study. I think there was actually some comment about that at Dr. DeVore's presentation today that that is in fact our primary interest, and that would also help confirm that the mechanism of davoceticept is adding something to what's already out there. Got it. Thanks a lot, guys. Appreciate the presentation. Thanks, Robert. Thank you. Your next question comes from the line of Joseph Pantginis with H.C. Wainwright. Hey, everybody. Good afternoon. Thanks for taking the question. Looking at the waterfall plot and then, considering your expansion cohorts in melanoma, renal, and PD-L1 positive, I just see obviously that those three responders did not see prior PD-1s. Will your expansion cohorts also be PD-1 naive? Well, they need to fail at least. We haven't finalized the exact criteria, but they will have had to fail at least one or two prior lines of therapy. For most of those, they will already be experienced with a PD-1 since that'll be standard of care. I think we would expect to get the majority of patients to be PD-1 experienced. Got it. With regard to your earlier comments, I'm hoping that I don't know if it's a little bit of a thought question, but obviously you said your, you know, your Q3 week schedule was, you know, geared towards reducing the potential for T-cell exhaustion, and I'm wondering how much that plays into the curves that you showed earlier on regarding the reduction of activity for the 10-mg dose or if you have any other thoughts on why that may be the case. Yes, it might have to do with the degree of target occupancy. It may be that as you get to a higher dose, you have higher or longer persistence or longer occupancy of CD28, and that may result in it having some slight antagonistic activity. That may be where some of the potential for, I guess, attenuation of activity. We weren't necessarily thinking of that when we first designed the study. The idea was that if you overstimulate a T-cell too often, that may lead to exhaustion, as opposed to giving it a break. Whether or not that necessarily meant drug on board or not, it just meant giving the CD28 mechanism a break. As it turns out, what we've seen how the drug behaves is that, a lot of the target occupancy is probably also reflective of CD28 occupancy. That seems to be going hand in hand. Got it. Thanks a lot, guys, for the update and nice data. Thanks, Joe. Thank you. Your next question comes from the line of Joel Beatty with Baird. Hi. Thanks for the presentation and for taking the question. In looking at the patients that have had the best responses and longest survival, are you able to, you know, pick out any things that could help with reproducing their good responses in future studies? Well, we certainly have some speculation. I hesitate to say anything publicly since we're basing it on N of one or N of two. I would say certainly thinking about whether or not they've seen checkpoint inhibitors and what their response was, perhaps also if they've had toxicities before from checkpoint inhibitors certainly also played a role. One thing we're also paying close attention to, we're starting analyzing more closely is the most recent line of therapy, what mechanism was that and what was their response. Great. Thank you. Thanks, Joel. Thank you. I'm showing no further questions. With that, I'll turn the call back over to CEO, Dr. Mitchell Gold, for any closing remarks. Well, thank you all for taking the time to hear the update on our three clinical programs today. Given our strong balance sheet, highly experienced team, and the breadth of our clinical programs, we believe the company is in a unique position to transform the treatment of serious and debilitating diseases. Thanks again for taking the time. Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.