All right. Good afternoon, everyone. I'm Stephen Willey, one of the senior biotech analysts here at Stifel. Glad to have with us, from Pyxis Oncology, Interim CEO, Thomas Civik. Tom, thanks for joining us here this afternoon. Really appreciate it. Maybe before we jump into Q&A, you can give us just a quick overview of the company. Sure. Yeah. Stephen Willey, first off, thanks for the invite, and appreciate everyone who's joining us today. I'm really excited to be here representing the extraordinary work that's going on in Boston here for the Pyxis Oncology team. We've got a lead program that we've had in the clinic that we're excited on the progress that we're making, and I'm quite thrilled to be having this opportunity to share that work with you. All right. Very good. MICVO is the centerpiece of this story. I think a very unique approach to antibody-drug conjugate design and payload delivery. Maybe you can just briefly talk about what differentiates this ADC from a design and mechanistic perspective. Sure. Yeah. Scientifically, it's a really interesting both target and construct. We're focused on a target that's in the extracellular matrix, and the target is EDB-FN. The extracellular matrix is this matrix that sits around the tumor, and our aim is to, by targeting that with EDB-FN, we find that in those tumor constructs, it's very easy to find in lots of different cancers, but you don't find it in normal cells, so an ideal target for an ADC. The one that we've built, that we call MICVO, came out of the Pfizer lab called the FACT platform, so about a decade worth of work and investment to find novel ADCs that have multiple constructs that allow it to do things that other ADCs haven't. That's the work that we've been doing over the last few years to get this program ready to get in the clinic, which we've been able to successfully do, and we're quite excited to share some of those results. Okay. You've completed dose escalation. You've selected the 5.4 mg per kg dose to move into expansion. I look at that dose, it's much higher relative to what we've seen from other DAR4 auristatin payload ADCs. Yet you don't appear to be driving a lot of the classical DLTs that we've seen with those drugs, whether it be heme or ocular. What do you think is driving the difference here in terms of your ability to dose high, not see DLTs? Do you think it's engineering, or do you think it's the biology of the target that you just talked about itself? I think it could be both. I think the scientific rationale was really sound to look for something that could deliver really solid efficacy. I think we're at, to your point, at doses higher that you'd normally see with ADCs, and that's probably has to do with both the mechanism action and the target, which led us into that dose escalation that you're talking about. I think many were surprised that we could get all the way up to a 5.4 mg dose, which is where we did in dose escalation. Okay. In dose expansion, you've prioritized head and neck. I know that there was an efficacy signal that was observed in that tumor type within kind of a very limited number of patients, but I think it was fairly clear you were active there. Is there something about the biology of head and neck, about the tumor biology itself that makes this tumor specifically kind of a good proxy for validating MICVO in the clinic, just given the way that MICVO works? Yeah. There's no scientific reason that this drug should only work in head and neck cancer. Through all the preclinical work that we did, there were multiple tumors that we could've selected. When we went into our basket study and dose escalation, again, lots of different tumors to explore, and we saw efficacy across almost six of those tumors in the basket dose escalation study. Maybe just to take a step back, our focus in escalation, being a small nimble biotech, was to follow the signal. Let's find out where we could have the biggest impact, where the opportunity was the most significant for patients. When we were doing dose escalation, two things became clear. The range of dose for us is somewhere between 3.6 and 5.4. That's where we were seeing the efficacy in the basket study and dose escalation. What also became clear was that head and neck was a very strong signal. When we moved into dose expansion, we took 5.4 in head and neck cancer and have been exploring that analysis, that experiment for a while now. To your point, we've now released two data sets. November of 2024, where we showed a 50% response rate in head and neck cancer, and we recapitulated those extraordinary results in head and neck cancer again at 5.4 in December of last year. 46% response rate in head and neck at 5.4. The part that we'll talk about in 1 second is that we've now expanded that study, 5.4 mg in head and neck, but with a dose cap to see if we can maintain that extraordinary efficacy, but potentially improve the safety and tolerability of the drug. Okay. Maybe before we get into some of those specifics around dosing, you can just talk a bit more broadly about the design of the dose expansion effort that you're pursuing. I know you have a couple of different monotherapy cohorts. You've got a combination cohort. What informed the design of the trial itself? Yeah. Steve, I'm really, really pleased with the thinking that came out of Pyxis Oncology here, because we've got two arms that you mentioned that really are preparing us for not only where the market is today, what is the standard of care, but where the market might be moving to, and let me explain those two arms. We've got one arm that's post platinum plus PD-1, and the other arm is EGFR inhibitors plus PD-1. In each of those, we've been able to enroll around 20 patients in each arm, and we've been guiding to having that data in the mid part of this year. The novelty of that design is that we should be able to answer questions with a pretty substantial data set on how we perform post-EGFRs and how we perform post-platinum. I think that answers a really important question for patients and investigators and physicians as you think about how the treatment dynamics are likely going to change over the coming years in frontline head and neck cancer. We think we might be, if the data holds and we're able to do what we plan, to have an answer to the question about what do you do post-platinum, but what do you also do post-EGFR. Okay. I know you've recently announced that you've completed patient enrollment into each of these monotherapy cohorts, dose expansion. You're guiding to a midyear update. Can you just provide us with a framework of what we should expect to see in terms of incremental patient numbers, incremental follow-up, and then maybe if you can just, I don't know, either qualitatively or quantitatively speak to what a good outcome is for Pyxis. Yeah. Well, let me take a step back, Stephen, and just say how enormously proud I am of the team working here at Pyxis, because we were in a position in December of last year where we shared 13 efficacy-evaluable patients in that data set. That was the one that had 46% response rate. While we're thrilled with that response rate, we know we needed more patients to really answer this question. We've had an explosive enrollment in this study, and I think it's for two different reasons. One is we tightened up a lot of execution around how do we make sure that we've got the right sites, right engagement, right protocols in place, but we also have enormous investigator enthusiasm. I think that was driven, well, I know it was driven because we've had the conversations with them, by two things. One is the efficacy that they saw that we were sharing for our second-line head and neck cancer population was really, really exciting to them. When we announced that we'd be moving to a dose cap for these patients to see if we can improve the safety profile and tolerability, the enrollment, it was just explosive from that point forward. As we think about what the mid-year update is going to look like, keep in mind just to do some simple math, we shared 13 efficacy-evaluable patients in December of last year, and we've announced that we've completed enrollment in our dose expansion trial, which was roughly about 40 patients. Those 40 patients, plus some patients that were in dose escalation, is what we've been guiding to, that we should be able to share that data at the mid-year update. Okay. You talked about the dose cap that was instituted here, and I think that's obviously intended to mitigate some of the payload-related, treatment-related adverse events that we saw led to treatment discontinuation in some of these high body weight patients, right? I think a number of the responding patients that you referenced per the efficacy-evaluable patient population back in December, some of those patients had to drop off therapy because of AEs. That's right. Can you maybe just walk us through this notion of why use a dose cap? I understand that you've previously talked about this concept of adjusted ideal body weight dosing. There are ADC sponsors that are pursuing both of these approaches. A lot of the work with the auristatins has been done via dose cap. Maybe if you could just talk about what incentivized you to first pursue this dose cap strategy, and then maybe we can talk about the AIBW stuff afterwards. Sure. Our primary goal is to do the experiment to see if we have in MICVO a program that we think could beat the standard of care in a pivotal trial. One of the ways that is going to be really important to understand is can we keep people on drugs so they can receive the longest benefit as possible? When we looked at our analysis, you're right, we made a really important discovery that the patients, all the patients that discontinued in the December data that we shared last year were patients that had a high body weight. That learning sent us back to the shop to say, "Okay, how do we make sure that we're not overexposing the patients at high body weight?" There's a bunch of easy places to go learn, and you've mentioned one of them. Almost every ADC developer in the space right now is using some sort of modified weight-based dosing. The most recent four that are in late-stage development, like us, are using some form of modified weight-based dosing that comes in either one of two forms, either a simple dose cap or something called adjusted ideal body weight. We considered both of those. We also took a bunch of PK data that we were able to generate for our molecule specifically, and we saw very clearly that there's a nonlinear relationship to the exposure and clearance of MICVO in patients that are heavy-weighted. We went back to our investigators and chatted with them about what is the best way to implement a plan that could improve safety, improve durability, improve or make discontinuations far, far less. What we decided to do was implement a dose cap immediately, in the fourth quarter of last year. I mentioned that I think was one of the drivers behind the explosive enrollment. Dose capping is fairly easy to implement. You literally just call the sites and say, "Nobody gets more than this amount of drug." You can turn that very quickly, which we did. We also went through the process of writing an amendment, for adjusted ideal body weight or AIBW. That takes a little bit longer to get through all the different places that have to sign off on it. We did recently start dosing patients at AIBW, but I want to be super clear. The dataset that we plan to share later this year in the mid-year update will be patients that were dosed with a dose cap or at total body weight. That's where we're putting our focus right now. Okay. Have you said how many of these AIBW patients you're targeting for enrollment through this dose strategy? We haven't. We're doing it as a good experiment to ensure that we have the right dose. I think it's important that I say it out loud multiple times. We're very confident that 5.4 mg with a dose cap is going to hopefully answer the questions that we need to answer. All of the work we've done says that dose capping and AIBW are basically identical as it relates to MICVO. There should be no ambiguity on where we're putting our position. Okay. Maybe you can talk a little bit about the EGFR, the post-EGFR cohort. Can you just speak to the proportion of patients within that cohort who may have seen prior next-gen EGFR targeting therapy, right? I think a lot of the patients we saw from the first cut were post-cetuximab. I think there's a lot of investors who are interested in maybe trying to understand how this drug might work, like post-ficlatuzumab, post-Opdivo. Do you expect to see a meaningful amount of representation of those patients in this post-EGFR cohort at the next cut? Let's first say how exciting it is that there's this kind of development going on in head and neck cancer. We are thrilled and excited to be out at ASCO and hear updates from other people that are focused on head and neck cancer. We fundamentally believe that there will be a shift in standard of care as it relates to the HPV-unrelated and CPS greater than one patients. That patient population looks like there's obviously an opportunity to improve with the next-gen EGFRs plus PD-1s. Our dataset, that arm two that you were talking about when dose escalation, we'll have around 20 patients that we expect to be able to update in the mid-year. We haven't guided yet on what percentage of those patients will be next-gen EGFR. It's subject to sort of that of being available in the sites that we're using. Those sites that we're studying MICVO on are head and neck cancer sites at this point. I would suspect there will be some, but we haven't guided on what that specific number will be. Okay. Can you remind me what the scan frequency is that you're implementing in the monotherapy part of this? Sure. It's every six weeks. Every six weeks. At a later point, it moves out to be a little bit longer to be sort of patient-centered to make sure that we're doing it right for them as well. Okay. Connecting the dots on completing enrollment in March means that you're likely to have a second confirmatory scan in most, if not all, the patients that you present data for come mid-year. Sure. Let me be clear that we said that we completed enrollment in the first quarter. We didn't say March. Okay. Yes, 12 weeks from the first quarter would be the math that you just did from a calendar standpoint. I was under the impression this conversation would not involve math. Maybe we can talk about the combination cohort. I know you're guiding to having an update in the second half of the year. Obviously, the data we saw for this in December, I thought was quite encouraging. 70%+ response rate, 100% disease control. Could this update include some preliminary dose expansion data as well? I think the way that you've characterized it is that you're still in dose escalation. Should we anticipate that the update you give at the end of the year will include some number of expansion cohort patients at the selected dose? We haven't guided yet, Steve, on that. I would just say that the combo study, MICVO+KEYTRUDA, has been enrolling quite well. We're quite excited with the investigator enthusiasm. We haven't given much more specifics on what to expect in the second half of the year update. To say that this is in a very fast evolving marketplace in frontline, with clearly a lot of focus on the HPV unrelated and CPS greater than one. You may recall in our data in December, those were all HPV positive. Patients that we released. Just to put some numbers behind it, we had a 71% response rate in that patient group with 100% disease control rate and a very clean safety profile. Our plan is to go beyond just HPV-positive patients. We should have a data set that will include a much more diverse patient population than what you saw in December. Okay. Frontline head and neck, still competitively dynamic, but it maybe sounds like you think that there's some opportunity to carve out some differentiation within some certain patient subsets. Yeah. Look, I think there's a long way to go from here to commercialization for any of us that are studying drugs in head and neck cancer, and I'm thrilled with the advancements that are happening. I think the data's going to define sort of where the market goes and where we're going to play. I think there's a couple things that give us a lot of confidence that we're going to be able to help a lot of patients. If I just go back to the monotherapy data in second-line, when we analyze sort of how this market changes, there's a couple things that I think are worth noting. One is that the patient population that's going to show up in second-line is probably going to be quite a bit healthier because they're not getting hit with any of the chemos, or less of them, I should say. That patient population has changed. When we think about how many patients there will likely be seeking treatment in the second-line in, let's say, 2030 or something, we estimate that there's 21,000 patients in the U.S. that will be looking for better care than is available for them today. That gives us a lot of excitement to continue to want to do the experiment with MICVO in second-line head and neck. As you think or as you said, the frontline is dynamic. New data coming out fairly regularly from a handful of fully invested groups that are trying to better the standard of care. Whether there's a small subset of patients that we can serve or a full population, I think the data will drive that decision, and it's just too early to make a call yet. Yeah. No, I think you make a really good point, right? I think we often see this in other tumor types where upstream improvements in standard of care improve the performance status of those patients who flow down to second-line and later. I think in this instance too, right, it's maybe even more particularly relevant given if you're eliminating chemo out of frontline, you're then probably enrolling patients who have no baseline neuropathy, and are probably much better suited to tolerate MICVO. Whether we're enrolling them today or the patients that we hope to benefit years from now, I think they will be a healthier patient. I also want to go back to what I said earlier, Steve, is that the opportunity to help frontline patients with a next gen EGFR plus a PD-1 is fantastic, but it also eliminates an ability to use an EGFR in the second-line, or at least that's what our investigators are telling us, that an EGFR followed by an EGFR doesn't make sense. This novel mechanism of action that we started with is a real unique opportunity for MICVO to have a really significant impact on a large group of patients that desperately need a better care. Yeah. No, also a very good point. The monotherapy dose escalation data that you provided also hinted at MICVO efficacy in some additional tumor types like you referenced. How do you think about this combo data that you're establishing in frontline head and neck? Yes, it gives you a path to further development opportunities in this tumor type specifically, how do you think about it as a springboard for potentially evaluating MICVO with a PD-1 inhibitor as a combo in some of these other tumor types? Sure. As monotherapy in other tumor types as well. Yeah. Stephen, I think we've done it the right way. Let's prove that we have an active agent that works in monotherapy in a hard-to-treat cancer in later lines. That's the experiment we're doing in second-line head and neck. If we can show that, give us confidence that we have a drug that can help a lot of people, and then we think about combination. You think about other tumor types. Experiment 1 is the one that we've got blinders on. We're really focused on delivering for the patient group that's in second-line head and neck. If we can show that, I think it unlocks a lot of different opportunities because there's no mechanistic reason that this drug should only work in head and neck cancer. I would say that if you even go back and look at our escalation dose or you look at the preclinical work, there's a lot of reason to believe that there's other tumors and patients that have that cancer that could really benefit from a product like MICVO. Yeah. I would agree with that statement wholeheartedly. To me, I think it's interesting just given the fact that a lot of investors kind of learned about this concept of bystander effect through ENHERTU. That's right. We have seen ENHERTU obviously work across a number of different tumor types, and I think we now know that in ENHERTU, this bystander effect from ENHERTU is actually driven through this ECM-mediated effect, right? Yeah. It's not due to internalization. If you're kind of recapitulating the same thing here via MICVO, I think the ability to connect the dots on this working in other tumor types does not necessarily require a massive leap of faith. That's true. Yeah. The great part too is that the Translational Medicine and Research Group here at Pyxis is doing some really good work to connect all the dots. We recently had a poster at AACR where we looked at, in a mouse model, patients that are normally refractory to PD-1s. We saw two things. One is that MICVO had some really great efficacy signals as a monotherapy. The part that has caught a lot of people's attention is that the combination of a mouse version of PD-1 plus a mouse version of MICVO showed actually synergistic benefit. in a head and neck oral cavity cancer tumor that was resistant to PD-1. That, combined with we did the exact same experiment in TNBC a couple of years ago, I think there's reasons to believe that the scientific rationale is playing itself out in the clinic in a really interesting way. I would agree. Maybe just last question to finish up here. Can you just speak to the balance sheet and what that allows you to execute on here? Yeah Going forward? We have enough money in the bank to be able to get us to the opportunity to understand if MICVO is going to meet this profile that we think is required to move it into a pivotal trial, and that being the mid-year update for monotherapy and the combo update in the second half of the year. Should we be fortunate enough to have a program that we think is ready for a pivotal trial, I think we then have to get busy on building that plan. All right. Well, very good. That's all we have for time. Tom, really appreciate it. Looking forward to the update and thanks everyone for listening. Thanks, Steve. Thanks, everyone.