GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - PYXIS ONCOLOGY INC

All right, so welcome to this next Fireside Chat. My name is Michael Schmidt, and I'm pleased to welcome the Pixis team with us today. We have Tom Civic, CEO. Tom, welcome. Thanks for joining us. Thank you for having us. So Pixis is at an interesting junction here, but before we go into the details, maybe just talk about a MiCMO Elite program, which targets the tumor stroma, a little different than what other ADCs are targeting, and why is it exciting, and why is head and neck cancer the right place to start? Yeah, it's such a great question, Michael, and really the reason I joined PIXIS was a completely novel, first-in-concept ADC gives me a lot of excitement to pursue something that hasn't been done before, and we started off with this thesis that targeting the extracellular matrix with an ADC could have really profound impact on many different cancers but a small biotech we have to focus on where the signal is the strongest and in a fairly large basket study we saw a really strong signal and head neck cancer and we decided to follow that not only because of the strong signal but because the the unmet need was significant the treatment options for patients and second-line head and neck cancer really not that great and so we felt like there was an opportunity there with a clinical signal, the unmet need, and a pretty significant size population of patients that were desperate for something better. What I will say is what we've learned through our first phase one study was the initial hypothesis was that you needed a lot of what's called EDBFN or extra domain B fibronectin that you find in the extracellular matrix, And you don't find it anywhere outside the tumor cell, which is an interesting component to it. We had this thesis that you needed a lot of it to be able to find where our drug would be effective. And in the phase one study we did in head and neck cancer, we did an EDVFN-H score and found that actually all you need is a little bit of EDVN to find efficacy with our drug. That's exciting for a couple of different reasons. One is that you probably don't need any sort of biomarker-driven therapy, but two, it opens up opportunities for significant life cycle options beyond head and neck cancer. And the way the extracellular matrix works, and EDBN specifically, is we find this in almost every solid tumor today. So while we're excited about the head and the neck opportunity and the data that we shared just a couple months ago, I think the life cycle option are quite significant for this program. Before we dive into the head and neck data, what other tumor types are on your radar? Yeah, we did, in our large basket study, we had nine tumors that showed activity, and they are the ones that you would expect, like breast cancer, lung cancer, pancreatic cancer, sarcoma. We use a pretty straightforward decision-making criteria to think about where we're going to invest our time and our resources, and it starts off with where do you see activity in the clinic. And it's followed by where can we become standard of care in a patient population that's large enough to matter. So we're gonna use those same two criteria as we think about where we're going to go next. But I don't want to dilute my message, which is we have a really significant opportunity in second line head and neck where the current treatment options are pretty poor. And a pivotal trial that we're already starting to set up to get this product program to the market as quickly as possible. Right. So the head and neck cancer landscape is changing. We've just seen top line data for new EGFR directed by specific antibodies announced a couple of weeks ago. Amivantamab just received a third approval a few days ago in second line. So where does Mikmo fit in and how do you expect the market to evolve longer term? Well, I mean, first off we should, I can say personally, I'm just, I'm celebrating the advancements that are being done in head and neck cancer. This was an area that did not receive a lot of investment for many, many years. And we have three fairly large programs focused on the frontline setting as we speak, and you mentioned a few of them. I think to answer your question about where does this position make vote today, it's clear that the standard of care is changing in the frontline setting. And we had consistently said that it was a matter of both if and when. I think it's probably a little bit more clear that it's not just a question of when the EGFRs move into the frontline. But what happens, like we see in other cancers, like endometrial cancer, small cell cancer, some different subgroups of lung cancer, is that when the frontline changes, it leaves the patients in second line and beyond with very few options. And this is where MCBO is really uniquely positioned in our study, which I know we'll talk a little bit more about later, we looked at patients following both the current standard of care in frontline, which is platinum plus PD-1s, but also those patients that get EGFR bispecifics or EGF-R inhibitors plus PD-2s. And we saw really universal efficacy regardless of what their prior treatment was. And this, I think, answers a really significantly large unmet need for patients in the second line and beyond. So today, what's nearest term for us is an opportunity to have a big impact for second-line head and neck cancer. So you had a very important data update just recently in September from your ongoing phase one study. So just remind us what the key takeaways were from that. Yeah, I think it's, thank you for that, and it's exciting to talk about the data that we disclosed a couple months ago. And I think there's two main takeaways from what we shared. One is in a heavily pretreated patient population, we saw three consecutive versions of efficacy. Really impressive response rate, 36% overall, regardless of HPV status or prior therapy. We saw over six months of progression-free survival, and we had a 79% 12-month OS probability. So all three of those efficacy signals, really important. response rate leading to survival benefit, PFS, and overall survival. And then secondarily, we saw a really manageable safety profile. We had implemented modified weight-based dosing at the end of last year to really see if we could have a positive impact on things like discontinuation and grade 3 peripheral neuropathy. And the implementation of that dose cap cut both of those nearly in half. One of the areas, based upon our payload, that we've been paying a lot of attention to is peripheral neuropathy. It is something that we have been working with the investigators across the globe on. And I think what we saw in this data, Michael, was that peripheral neuthropathy happens late. It often resolves, and patients receive a really significant benefit. And so this is a benefit-risk conversation for the physicians and patients that we think has been answered with the data that we shared in September. With peripheral neuropathy, I think physicians typically worry about the irreversible kind. So maybe how would you characterize the type of PN that you've seen and maybe how it compares to other approved ADCs that have this class effect? Yeah, I, I don't know. I think the easiest way for me to answer the question is that grade three peripheral neuthropathy, we've been paying very close attention to this. We only had six patients in the study that developed grade 3 peripheral neuropathy. The average time to onset was five and a half months. So it happens much, much later than when the patient has already seen if they're benefiting from the drug. So that's the first and probably most important part is that it happens late. But second is that if you do develop grade 3 temporal neuropathies, in our protocol, the patients go on a dose holiday. And in the case of the data that we shared in September, five of the six patients had either resolved or were resolving, and one we were still tracking. So it happens late. When the drug is stopped, those patients are either resolving or have resolved. And then third, we looked at both response rate and progression-free survival for that same patient population. And the response rate for those patients with grade 3 peripheral neuropathy is 67%. and their median PFS is over eight months. And again, it gets back to this benefit-risk is unfortunately the options for patients with second-line head and neck cancer are pretty limited and don't deliver significant benefit like we saw with MCFO. Right. And so I think you have a data update coming up at the triple meeting soon. So what should investors expect from that update? Yeah, we're really excited to be joining Dr. Johnson from MD Anderson who will be presenting the data in Barcelona in a couple weeks. So we will be there, anxious to get feedback on the data set that will be disclosed there. I think maybe intent is probably important to understand here. We have a pivotal trial that we are working hard to set up for a first patient, first dose in the middle part of next year. And we thought it was really important that the investigator community got a chance to see the data under the spotlight of a meeting like the triple meeting. And so our hope is to create even more investigator enthusiasm coming out of the triple meeting. We're under embargo, so there's not a lot much more I can say about the data and what you'll see there. But safe to say I'm going to be in Barcelona sitting in the front row and excited to hear what Dr. Johnson presents. Will it be longer term follow up on the September data with additional patients? Yeah, unfortunately, the triple meaning is very, very clear on what I can and can't say. And unfortunately, I'm not going to be able to say much more than I've already said. Sounds good. I had to ask. Thank you. And then as we think about the phase three study next year, may we talk about any FDA interactions you have had so far and how you approach dose selection and other design aspects of this study? Yeah, so we had a really collaborative meeting with both the FDA and the EMA at the end of 2025. And obviously, there's a really significant unmet need in second line head and neck. So that collaboration allowed us to design what we're calling the headliner trial, which is a pretty straightforward design for second-line head and neck cancer, primary endpoint, B response rate, and overall survival. We've designed it where the investigator choice is cetuximab, docetaxel, or methotrexate. Most of this is driven by it being a global trial and needing to have standard of care available globally. But we're quite excited about the conversations we've had with both agencies around the design. We've also guided that in the first quarter of next year, we'll provide an update on our end of phase two meeting as it relates to Project Optimist and dose optimization, or dose selection, I should say. We believe quite strongly that 5.4 with the dose cap, the data that you saw back in September is the dose we'll be moving forward with, but we're going to have that conversation with the agency rather soon, and hope to disclose that in the first part of next year. And obviously, so amivantamab was just approved based on a small single-arm phase 2 study. So is there an accelerated approval opportunity or an opportunity to stop the phase 3 early on response rate? Michael, this is a question our team talks about a lot, and I would just say we have three remits for 2027. One is to get the first patient dosed as quickly as possible in the headliner trial. We want to enroll this trial as quickly as possible, and we want to get the drug to patients as quickly as possible. We are going to be looking for partners like the agency to help us on this mission to deliver this drug to patients in second line as quickly as possible and I suspect that in early 2027 our full plan for the regulatory will be disclosed at that point and it will be in support of getting this drug to patients as quickly as possible. Okay, sounds good. And how should investors think about the size of that second line opportunity, which will be the initial market for the drug? Yeah, it's been really interesting to see people start to pay a lot more attention to head and neck cancer. And part of paying a lot of more attention is just really understanding patient flow and the impact to earlier lines of treatment as it relates to later lines. And I've seen things like DRG and SEER and Global Database as a good place to start. But those folks that have spent even more time understanding patient flow have found that there's probably about 30,000 patients that will be looking for treatment in the frontline setting. And that population likely will see a new standard of care in the very short term. What we've also seen in the data is that those patients that receive treatment in the front line, about 70% of them seek treatment in a second line. So just simple math gets you to about over 20,000 patients that are in the United States will be looking for a second-line treatment option. We think, based upon the profile that we've shown just two months ago, that it's reasonable that MCFO could play a really important role for that patient population. So 20,000 patients with not a lot of other options available for those patients gives us a great deal of motivation to get this drug to patients as soon as possible. Makes sense. And I think you said earlier that the drug would like to be biomarker agnostic. There's been a lot discussion of HPV status as a possible selection biomarkers. How do you think about that in context of your profile? Yeah, I think as it relates to MICFO, I think our data has been very clear. work regardless of HPV status, and it's been borne out in multiple different data sets at this point. And so our plan remains to develop this drug regardless of the HPV status in the second line. Makes sense. Okay. Then you're also looking in first line, obviously, in combination with pembrolizumab. So update us on where you are with those studies. Yeah. So maybe for those people that the story might be new to, we disclosed some data at the end of 2025, where we had a small N, we had seven patients, but we showed a 71% response rate in combination with pembrolizumab. And that included both first-line, second-line and even third-line patients. And at that point, we were really trying to understand, is the drug efficacious and safe? And is it worthy of additional investigation? We've guided to just recently that in December of this year, you should expect an updated data set from us in combination with pembrolizumab that will be frontline focused and looking at doses of 3.6 and 4.4 and both HPV status groups. I think the frontline setting is likely to be evolving right in front of us right now. And so, I think, the opportunity for us in December is to really take an early look at what response rate and safety looks like to see if we're having the impact that we would hope, early, but it's likely, because it's a first-line patient population, durability is likely the most important avenue. We'll probably need a bit more time to evaluate the impact of the combination, so we've guided to the second half of 27. That same time, we should have access and a better understanding of some of the emerging data for EGFR bispecifics, and I think a great opportunity to compare our data both from an efficacy and safety standpoint to see where the opportunity lies. Right. And so in frontline, there are a bunch of subgroups, PD-L1 negatives and positives, and then some companies like J&J are focusing on HP negatives only, for example. How does your phase one cohort compare on some of those metrics? Yeah, I think it will be borne out in the data that we share in December. I think, again, we'll have 20 patients, multiple dose, 3.6 and 4.4 as a dose. cross-HPV status. I think it's a sample size that's large enough to figure out what is the patient population that's receiving the most benefit from that combination. But as I said before, I think this is likely a durability story. So the second half of next year, we'll have updated data at that point. And that's the point when we'd have to decide, is it worthy of additional investigation? And you said earlier that target expression is very broad in head and neck cancer, but will you look at biomarker levels and could a selection process be implemented in the frontline setting, for example? Yeah, I think we, you know, I spent a lot of time at companies like Genentech and Foundation Medicine where biomarkers-driven therapies were core to our thesis there, and I've been quite interested in seeing if there is a biomarkER strategy that we could unlock for MCFO, and at this point. There doesn't seem to be one, or at least it's not EDBN at FH score. So we'll continue to do the work. We think it's the right scientific questions to be asking. And if there is a patient population that would receive more benefit from MICFO, we'll be very interested in understanding that. And then we earlier touched on other opportunities beyond head and neck. So What are you doing there, and anything that you're prioritizing at this point? Yes, small selective investment there to ensure that we're following the same robust decision-making process. Where do we see clinical efficacy? Where is there an opportunity for us to become standard of care in a patient population that's large enough? We're focused on second-line head and neck cancer right now for those reasons. It's where we saw the signal and where we think we can have the biggest impact. We have to be judicious with the resources that we have. So the signals will have to Be strong. We're excited about some of the things we're seeing, but we also have to be patient to ensure that we can financially resource those activities as well. Right. This is a good segue to my next question. How do you think about partnering longer term? Is that something that you're considering for the program? We are quite excited about what we have in front of us to stand up the headliner trial in second line head and neck cancer. And my team is focused on first patient in, enroll those patients as quickly as possible to get this drug to patients as quick as possible. I've been doing this a long time. I know a lot of people across the industry. I think having discussions with others to inform your strategy to pressure test it is always helpful. helpful, but we have 100% rights to this program and are excited to push it forward. Great. So next up, triple meeting, then the final FDA meeting, phase three start, and then the frontline data next year. Is that right? Well, you even missed one. So yeah, you're right. So triple meeting. We're excited to share the second line head and neck data. We've got the December update that will be a robust review of our head and next strategy, combination data, optimist feedback in the first quarter, and don't forget our OS data that we've planned to share in the next half of next year, too, which we think completely de-risks the program moving forward. So a really exciting time for us over the next six to 12 months, and the team is doing some great work to get us there. Great, Tom. Thank you. Appreciate it. Thanks, Mike. Appreciate it Thank you