Good morning, everyone. My name is Farzin Haque, one of the biotech analysts at Jefferies. It's my pleasure to introduce Thomas Civik, CEO of Pyxis Oncology. This is a fireside chat format. Thank you for joining us today, Tom. For those new to the story, can you provide a one-minute intro to Pyxis and explain essentially the main thing, the mechanistic rationale for targeting the tumor stroma versus the tumor cells directly? Farzin, thanks for having us, first off, and thanks for everyone on the webcast that's dialed in. One minute, huh? One minute to tell the whole story seems like that might be hard, but maybe three minutes, is that okay? Boston-based company, we've got a group of people that are deeply committed to having a really significant impact on hard-to-treat cancers. We've got a technology that we've invested a lot of time, energy in that is novel both in its mechanism and its target. We have been focusing on the extracellular matrix, and you'll hear me talk a lot about that because our target is actually in the extracellular matrix, and we deliver a novel antibody drug conjugate to that target. The exciting part about uncovering the role that the extracellular matrix played in tumor growth, cancer growth, was that we felt like we could develop something that would have a significant impact there. After doing all this great biologic and scientific work, we took our lead program into the clinic a few years ago. The program is called MICVO. We did dose escalation against multiple tumors, and what we were able to uncover during dose escalation is a range that we thought the drug would be efficacious, and a significant number of tumors that we were seeing efficacy in. We took that learning that we had early on in dose escalation and did a dose expansion study with a very specific dose at 5.4 milligrams and in head and neck cancer. You may ask, why head and neck cancer? It's a space that, one, mechanistically, it makes a lot of sense for our program. Two, we saw efficacy in the clinic in dose expansion or dose escalation, I should say. Three, it's a tumor that's quite hard to treat, and at this moment, there aren't a lot of available therapies there. During dose expansion at 5.4 milligrams, we saw some pretty extraordinary efficacy, and we released that data last December. At the same time, we saw some side effects that were coming from the drug that were being driven exclusively by heavy-weighted patients. We started to fine-tune the dose, and end of last year into early Q1, we were able to enroll a significant number of patients at 5.4 milligrams in head and neck cancer with a fine-tuned dose that was based upon modified weight-based dosing. That's the data that we hope to share with everyone at the mid-year update, is a very specific patient population in head and neck cancer in second-line at a 5.4-milligram dose at a dose cap. We're quite excited about the advancements that we've made there. Right after that, in the second half of the year, we also have been exploring MICVO in combination with pembrolizumab, that combination study we've guided to sharing those results in the second half of the year. That's fine We've been busy. It's a great team that's been doing a lot of work, and hard to do that in a minute. With the mid-year update coming up for the second-line monotherapy, so what can you tell us about the overall objective and the key messages that you intend to highlight? Yeah. This one's really clear for us. We want to be able to show at the mid-year update three things. One, that we've got a path to develop a drug, that the results that you'll see at mid-year should give us confidence, and you, that the activity that we're seeing gives us a path to saying this is something that's got both efficacy and safety in the patient population that we're studying it in. Two, we want to make sure that the profile that we reveal in the mid-year is something that would be potentially the standard of care in second-line head and neck cancers. Third, we want to make sure that it's clear the patient population that we're studying it in. All three of those things are going to be extremely important for us as we think about what the next step in development is for MICVO, which is, we hope, going into a pivotal trial. If that data is clear, our plan would be to move there quickly with those three things accomplished. Maybe double-clicking on the two cohorts that will have the data. You have the arm one, and then you have the arm one post-platinum, and then arm two is the post-EGFR cohort. Yeah. That one is more strategically important because of the EGFR therapies moving into the first line. Is there any reason to think that the post-EGFR cohort's efficacy and safety might differ from arm one? Yeah. Do you mind if I sort of describe arm one and arm two for those folks that maybe aren't as close to it? Please. This is, in my mind, extraordinarily good drug development as it is future-proofing this program for where we are today and where the market might be going in the future. There's two arms in our trial, in our dose expansion trial. The first arm is platinum plus PD-1, which is the standard of care today. The second arm is EGFR inhibitors plus PD-1s, and where we think the standard of care is likely moving to, and hopefully we'll get a chance to talk about ASCO, but there was a lot of exciting data that came out of ASCO, and I'm really excited about what the head and neck space might look like for patients as advancements continue to come. Those two arms are going to look at MICVO compared to the standard of care today and what we believe the standard of care is tomorrow, and each of those arms will have roughly about 20 patients in them. For our midyear update, we expect that the data set that we should be sharing should be 40 patients or so from the dose expansion, and there are still a handful of patients that we did in the earlier study. Those are the two arms. Our expectation is based upon the mechanistic attributes of the program that there should be no difference in the way MICVO performs regardless of HPV status, regardless of prior therapy, whether it's a platinum or an EGFR. Yeah. We hope to have a database that's significant enough where we should be able to share both of those groups in a way that is easy to understand and make decisions on as we move forward. Also on the HPV status, that's another key differentiation. Do you think MICVO can show equipotency in both? Yeah, I guess it's, there's what I believe and then what's true in the data, right? The data that we shared last December showed that we have efficacy in both groups, for both HPV positive and HPV unrelated. I think that's an important signal. The opportunity to show that again in a larger data set is what we're striving for as the midyear update. There's no reason to believe mechanistically that this drug wouldn't work regardless of HPV status. There's no reason to think that the drug won't work based upon prior therapies, whether they're EGFR inhibitors, platinums, or even taxanes. Our hope is with a really robust data set that we should be able to share at the midyear update, we'll be able to look at multiple different groups and evaluate how MICVO has performed against each one of them. Okay, great. Switching to the safety profile, so that has been a lot of focus, and then you had the last update had a lot of grade three treatment-related adverse events and a lot of discontinuation, high rate of discontinuation. It's important to note that 100% of those discontinuations were in high body weight patients. Now you have recently noted plans to pursue dose capping over AIBW implementation. Can you walk us through the key factors that drove the decision, and how do you weigh the trade-offs between the two? Yeah, this balance between finding efficacy and safety is one that I think any of us that are developing ADCs continue to look for. I should say we've been able to show really extraordinary efficacy twice now in the head and neck cancer population. To your point, Farzin, is in the second half of last year in our December update, we showed really significant efficacy for this second-line head and neck patient population, but an AE revealed itself in those patients that were of high body weight that was leading to a discontinuation rate. If I go back to the question you asked me before of what we're trying to strive for at this midyear update, we're looking for a profile in this program that would give us confidence that if we were to go to a pivotal trial, we could beat the current standard of care. When we saw these AEs that were leading to discontinuations, the team got really busy on trying to figure out how we would solve it with MICVO. We looked at three different things. One was the data that you referenced, which is that the AEs were being driven by those patients that had high body weight that was leading to a discontinuation. Our clinical data was obviously a really important attribute to it. Two, we did a fair bit of PK analysis, and we looked at dose exposure based upon patients' weight. What we found was the patients at high body weight were just clearly being overexposed to MICVO. Then three, we looked at the marketplace and the ADC drug development, and what we found is that moving to some version of modified weight-based dosing for an ADC is very commonplace today. I believe it's the last four that have been approved either have a dose cap or AIBW, and the four that are closest to us in development all have similar plans to use some sort of modified weight-based dosing. We took those three learnings, our clinical data, our PK analysis, and other ADCs in development and said, "How do we solve this problem for MICVO?" What we did was we implemented a dose cap in December of last year. This was received extraordinarily well from our investigators as they're very comfortable with modified weight-based dosing of ADCs. I should say that's also when we saw explosive enrollment in our clinical trial, and it's not lost on me that you show great efficacy and you show a plan to improve safety, that the investigators get quite excited. Our plan is to share at the midyear update, so there's no confusion, a significant number of patients in second-line head and neck cancer at a 5.4 mg dose with a dose cap. We contemplated AIBW or adjusted ideal body weight as a solution. Frankly, it's just harder to implement. It requires a study protocol. We've done that. We've completed the protocol, and we will enroll some patients throughout this year as a backup plan in case dose cap is not sufficient. I should say all of our analysis and all the experts that we've talked to and our own internal instincts are that dose cap and AIBW as it relates to MICVO should produce almost identical results. We feel like we've got a plan that has unlocked the potential for MICVO at 5.4 milligrams with a dose cap, and that's the data that we plan to share at the midyear update. Great. Just out of curiosity, if you ultimately adopt the AIBW for the pivotal study, do you need to contact a bridging analysis then, or how are you going to basically transition if needed? Yeah. We are spending a lot of time making sure that we have a plan that is exciting, helpful for patients that have second-line head and neck cancer. Obviously, the regulatory agencies are a really important component to that to ensure that we're aligned. Our belief right now is that if the data that we hope to produce for the mid-year update has the ability to show similar efficacy to what we've already shown and a significantly improved safety profile with 5.4 milligrams at a dose cap, we think that that's likely the dose that we would move forward with. AIBW, I think, is another great option. If it reveals itself as better than dose cap, obviously, we're going to do what's right for patients to ensure that this drug has the best chance of helping as many patients as possible. Great. Jumping ahead, regarding a development path, you have indicated previously that you have a regulatory alignment on a pivotal monotherapy trial in the second-line setting and second-line plus setting. Is this still the plan next step, and what can you share about how you're approaching the design and timing of that pivotal? Yeah. We've announced that we've had a regulatory meeting last year with the agencies to align on what the pivotal path forward would be. We're not going to share specifics today, but at the mid-year update, you can rest assured that that will be part of the disclosure of what the regulatory path forward is. I think the great news, and hopefully we'll get a chance to talk about some of the emerging data that's coming out of other manufacturers in the head and neck space. I think there's an opportunity for us to continue to learn of where the patients need the most support and where we can serve that with MICVO. The short answer to your question is mid-year update, we will provide more clarity on what our regulatory path forward is. Great. let's move on to the ASCO poster and dataset from Corbus and J&J specifically. What is your perspective on the data, and how does that influence your strategy for MICVO? I think we should take a second just to celebrate the advancements that are happening in head and neck cancer, long overdue. All I can do is celebrate the advancements that are happening right now for these patients who are desperate for more and better care. I don't mean this to be glib, but we're really focused on developing a program that could be the standard of care in second-line head and neck cancer. There's nothing that came out of ASCO that gives us any less confidence that we've got a program that could have a really significant impact there. I think the opportunity to ensure that patients and investigators are aware of the opportunity that exists in second-line head and neck is really important. If you don't mind, Farzin, I'd love to just spend a second there. Our estimations are that in 2030, there will be 31,000 patients who are seeking care for first-line head and neck cancer. Because of those advancements that we're seeing right now, like the next gen EGFRs in combination with KEYTRUDA, moving into the front line, that patient population is much more likely to move into second-line with a better performance status, better prepared to take on a second-line treatment. In our estimation, there's about 21,000 patients in 2030 that will be seeking some version or some type of second-line care. That patient group is split into two groups, HPV positive and HPV unrelated. Our estimations are that the HPV positive group is about a third of that, and the HPV unrelated group is about two-thirds of that. The way we're developing this drug and based upon its mechanism is that we believe that MICVO should be able to work regardless of status of HPV and regardless of prior therapy. That second-line patient population of 21,000 patients who are seeking and looking for an option in second-line, we're hopeful that at the mid-year update, MICVO can share the data that gives people confidence, including us, that there's a path forward there. Does the poster updates make your plans different, or it's just consistent with what you had expected? Our plans are to first off make sure that we have a drug that's efficacious and safe. We'll take that data that we produce at the mid-year and play it up against where are the opportunities for us to ensure that we can be the standard of care to provide something better for patients in second-line. We also want to make sure that there's a patient population that's large enough for us to help. I leave ASCO and think about the data that's coming from emerging therapies with nothing but enthusiasm for this space, and continued excitement about the program that we're developing called MICVO. There was a Biocare update too, but that is in the EGFR setting and also HPV unrelated. That's right. In front line maybe. In the front line, too. Moving on to the combo update. We should talk about that, right? Yeah. The front line options are changing, and that patient population who's been treated with an EGFR inhibitor in the front line, I think it's important to be able to show that our program works regardless of what their prior therapies are. Getting back to the question you asked me a few minutes ago, arm two of our trial is those patients who's received an EGFR inhibitor plus PD-1, and we will be able to share that data at the midyear update to see how MICVO performed in that patient population. Exactly. Moving to the frontline setting, you have the combo update coming up in second half with pembrolizumab. Where are you at with the enrollment, and what has been the feedback from the site investigators, and any challenges in recruiting both HPV positive and negative patients? Well, I can't update you on the numbers yet. That will come with the disclosure. Okay. Investigator enthusiasm is extraordinarily high for this program. We hear in multiple settings the need for an ADC in the second line, the data that you're referencing in the frontline, you may recall we shared an update in December of 2025 that looked at the combination of MICVO and pembrolizumab and saw a really impressive response rate of 71%, a disease control rate that was extraordinarily high, and a safety profile that's very, very clean. One question that we get asked a lot is this just because it's earlier in the disease and the patients are better performance status, or is there something about the combination? At this point, I think the experiment's not complete yet. We remain extraordinarily enthusiastic about the investigator enthusiasm for MICVO in combination with a PD-1 in the frontlines. We see there's a really significant opportunity to help a lot of patients there, too. For the combo, can you remind us what dose you're taking forward? Is it 5.4 as well? In the December data, we shared both 3.6 and 4.4 doses. Right. We plan to update that data at the second half update. Got it. Just to be clear, how are you defining the first line for this study? Is it truly treatment naive, or does it include patients who recur after adjuvant therapy as well, or chemoradiation? Yeah, I think we'll be very specific in the second half update about all the therapies that those patients have received in prior lines and not, but think about first line as a true first-line experiment. You may recall that in the December data, we had a mix between frontline and second line, and it was only HPV positive patients in that group. We have been enrolling both HPV status patients and have focused our efforts on advancing the program in frontline with MICVO in combination with pembrolizumab. Great. This is the next question I get a lot from investors, too, and there is some confusion like now the EGFR targeting therapy should be used in frontline, but is there any rationale why an ADC cannot be used first, followed by the EGFR-targeting therapies? Wow. That's a great question. I would just say this is why we do the experiment. First off, I would say, let me just again celebrate the advances that are going on with the EGFR inhibitors in combination with pembrolizumab. Remember that those are almost exclusively focused on the HPV-unrelated patients. Yeah. Just to make sure I didn't communicate it not clearly was our study in December looked at HPV positive patients in combination with pembrolizumab. The sequence of therapies I think is fantastic that we're even talking about novel new developments in head and neck cancer. Right What is the right sequence of them, since many of these patients have been stuck with nothing but decade-old chemo for so long as their only option after a PD-1. I think there's a long way to go from here to there on when we're talking to physicians with a commercial product onto what is the sequence of events for them. Makes sense. Head and neck is known for rapid progression and resistance to therapy. Have you characterized mechanisms of primary or acquired resistance to MICVO that could potentially be problematic for second-line sequencing of patients? I think this is why the investigators are so excited about an ADC in this space, that it's a disease that unfortunately does move quite quickly. The benefit of a program like MICVO that delivers very rapid responses to patients is something that in the second line or the first line is a very attractive attribute of this program. Just to double-click on it, when you mean the fast onset of action, do you see responses within the first cycle? Do you see any deepening of responses? This will be a major focus of the midyear update. Okay the enhanced data set that we have coming, and I think this is a question that not only you have, but our investigators have, which is how quickly does MICVO deliver responses in patients? Good. Thinking more from a future perspective, can you potentially, the mechanism allows combination with other therapies. Is there something near term or something that'll be afterwards that you'd consider? Yeah. We spent all of our time today talking about head and neck cancers. Yeah The work that we did preclinically, we have an extraordinary translational team back in Boston that has been looking at the mechanistic reasons that this drug should work in cancer. Our preclinical work pointed to more than a half dozen cancer types that are clearly targets for us down the road. When we did the basket study to start the clinical investigation of this program, again, we saw more than a dozen cancers that were responding to this. The first part of the question is there's no reason that this is just a head and neck cancer drug. Right. Two, the data that we saw last December in combination with pembro, I think gives us a lot of confidence that there are many places that we could go with MICVO in combination. There's many other cancers that we could explore with MICVO and other tumor types. Quickly on the manufacturing side, do you have the scale to support for pivotal trials and potential launch? Our CMC team has made sure that we are prepared for. Okay a successful outcome at the midyear to ensure that we can pivot very quickly to a pivotal trial. Would you consider a co-development partnership for a combo regimen, like with Merck, for example, for the PD-1? Would you prefer to retain the full economics? It's a question you know that the easy way for me to answer is I can't answer that question. Sure. We are focused on one clear goal, which is to unlock the potential of this novel ADC in head and neck cancers, and we think that we've got a path forward there. That's fine really help a lot of patients currently in second-line head and neck cancer, first line head and neck cancer in combination with pembro, and then far beyond that. Our plans are not modest. We would like to develop this program to help a lot of patients, and we'll find a way to get there. Can you remind us of the IP of the drug? Yeah. It's a fascinating story. We actually acquired MICVO through Pfizer. Yeah Pfizer had dedicated about a decade-long investment in ADC space. We have the benefit of all that investment that happened over many, many years in the hands of a very nimble organization. That's where we found MICVO. To close out, what is your cash position and the key catalysts and milestones that investors should focus on in the next six months? Cash until the Q4 of this year. I think as we've mentioned multiple times, a midyear update on two-line head and neck cancer and then a second-half update on 1-line in combination with pembro. That's what we've guided to, and I would just say the execution of the team has been extraordinarily tight, and our plan is to deliver against those guidelines. Thank you so much for your time. Thanks, Farzin. Thank you.