STIFEL 2026 HEALTHCARE CONFERENCE - PYXIS ONCOLOGY INC

I'm Stephen Woolley, one of the senior biotech analysts here at Stifel, and glad to have with us to wrap up day one of this Stifle Healthcare Conference, Tom Sivick, CEO of Pixis. Tom, thanks for joining us, and not sure if you want to make any opening statements before we jump into Q&A. Sure. Well, first off, thanks, Steve. Thanks for the invitation. Excited to be here, and big appreciation to you and the team and for all the folks dialing in. And, yeah, we've had a really exciting 2026 so far, really impressive data that we shared just a couple months ago, a couple fundraisings that have set us off on a path to stand up a pivotal trial in the middle part of 2027. So we're excited about the progress we're making on this novel first-in-concept ADC that I know we'll talk about and the work that the team's doing. I'm really privileged to be here representing our small but mighty PIXIS team. All right. So obviously there's a lot going on in the head and neck space right now, and we'll try to get to some or all of that, but maybe you can just kind of first give us a lay of the land with respect to Mikva, the data you've generated to date, and then maybe just kindof briefly highlight like what differentiates Mikva from other ADCs with respect to design mechanism and then how you settled on a head and neck as kind of this lead tumor type. Yeah. Well, let's start with maybe the middle part of your question around sort of what is MICBO. So it's a first-in-concept ADC. We set out to design a program that targeted the extracellular matrix, and the specific target is called EDBFN. Important because we find EDBN in almost every solid tumor around, but we don't find it in normal tissue. So the premise was, let's go out and pursue this target with a novel EDC with a payload that's been optimized for this specific place. We did a large basket study, and we were lucky enough to see strong signals for this ADC in multiple tumor types, but the strongest was head and neck cancer. And that led us to then take a look at where we thought we could have the biggest impact. And head and back at that time, second-line head and neck specifically, there weren't a lot of things being developed in second- line head and necks, and it was a really large patient population. I hope we can get there a little bit later, but we estimate that there's 20,000 patients that are going to be seeking treatment in second line head neck. And so those two things, we saw really nice clinical activity in head and head cancer. We saw an opportunity where we could become the standard of care in a patient population that was large enough to matter. And so we started pursuing MCFO in second-line head and neck cancer. All right. Maybe we can jump into the dose expansion data that you provided back in September. And before we do that, maybe just kind of remind us of the general trial design and some of the key questions that you were trying to answer within the context of this dose expansion effort specifically. Yeah, there were multiple questions we were trying to answer, but it started with we had two arms in the study. One of them was platinum plus PD-1, prior treatment of platinum and PD-2. So the current standard of care in frontline head and neck cancer. We wanted to see how MCFO would perform after the current standards of care. But we also had an arm that was EGFR inhibitor plus PD1 so that we could evaluate how MCVO performed after what we believed was going to be the future standard of care. We started enrolling patients in 2025 in that study, and we disclosed some data at the end of 2025 that showed two things. So an early look at the data, really impressive response rates up in the 40% range, but we had a limiting toxicity that was being driven by patients that were high body weight. So in December of last year, we decided to implement what's called a dose cap or a modified weight-based dosing for those patients. And from that moment on, end of December, moving forward, we saw an explosive enrollment in our study, I think mainly driven by the physicians were extraordinarily excited by the efficacy data and really comfortable with a modified weight-base dose approach that's often used for ADCs. And the data that we shared in September was more patients that were following the current standard of care as well as the the future standard of care, we were able to look at, because of the size of the study, patients, regardless of their HPV status, regardless of prior treatment, and showed all the activity for each one of those subgroups in the data. We were also looking to see what impact the dose cap would have on safety. And we were happy to see that we nearly cut the discontinuation rate in half as well for any grade 3 peripheral neuropathy. So we left the September data, and I'm happy to get into more of the details, but really confident that we have a profile that's ready to move into a pivotal trial. Okay. Yeah, maybe on those details, I thought, you know, the headline efficacy data read really well. It was pretty impressive. Maybe you can just kind of talk about, like, which of those efficacy data points really kind of stood out for you, and maybe talk about that in the context of what are some of the existing kind of second line efficacy benchmarks that you think are the most relevant? Well, I mean, I think it would be inappropriate for me to pick one because I think it's all of them together. And maybe for those people that aren't as familiar with the data, we showed a 36% response rate regardless of HPV status. We showed a 94% disease control rate, highest that I think anyone has ever produced before, followed by a 6.2-month medium PFS and a 79% OS probability. So I think the four of them together really matter. But what we heard from our physicians who were enrolling patients in the study is one of the things that they really like about what they saw in the MICFO data was that these responses were both fast and deep. So more than two-thirds of the patients saw their response at the first scan. So that's six weeks, and more than half the patients saw greater than a 50% reduction in their tumor. This matters for a head and neck cancer patient because it's really hard to eat or drink, sometimes even speak. So to have rapid and deep responses in this patient population means a lot. For us, as we think about is it worthy of continued investigation and getting ready for a pivotal trial, So seeing all three, response rate followed by PFS followed by overall survival, gives us a lot of confidence that the advocacy benefit for this drug is very clear. I know that there were some initial questions when the data was disclosed about this discrepancy in response rate that was observed as a function of prior EGFR inhibition. and again this is a patient population that's probably of the most interest to investors you know probably more so now post the gen map disclosure but what's your level of confidence that this delta that we saw was driven more by prior treatment intensity and not some kind of biological phenomenon yeah so maybe let's just start with going back to the trial design so we enrolled patients that got the combination of EGFR inhibitor plus PD-1s. And we had about 57% of the patients enrolled in the trial got an EGF-R or received an EFG-R in an earlier line. We also had about five patients that Got one of the EGIF-R bispecifics in the data prior to getting MCFO. I think what excites us, and it started when we started designing this trial, the KOLs told us, look at the future, is going to be EGFR bispecifics in the front line. And it's going to Be really important that you study this patient population. So we're excited about this innovative global trial that we designed. I think as far as we can tell, this is the best data set ever produced post an EGF-R in head and neck cancer. And so the discrepancy that you're talking about is the efficacy is really quite high. It's almost 50% in those patients that didn't get an EGFR, but it's almost 30% in those patients that got an EGR as a prior treatment. And we saw a 40% response rate for those patients. They got a novel EGR. So we have two things. One scientifically, there's no reason that, that MCFO shouldn't be really effective post EGF-R. And two, I think it's, I Think it's the most robust data set that's been produced post EGR in head and neck cancer today. So quite excited about what it means. Okay. And I think within that previously treated EGFR cohort too, it appeared that you had a minority of, I guess, what you would characterize as pure second line patients, correct? Steve, thanks for the question. So we actually, you can see it in the slides that are up on our corporate deck, but if you look at line of therapy and just response rate, our response rate for MCFO in second line alone is 45%. If you get MCFO on the third line, it drops to 35%. And this is sort of normal for many cancer treatments. You're right. In those patients that got an EGFR as a pretreatment, it's normally a third line MCFO use there. So we think a lot of it is just answered by line of therapy. Okay. I know you're guiding to an update of the OS data that you provided a snapshot of in the September disclosure. What's your confidence in the durability of that of that os signal right i know again it's a point estimate the lower bound confidence interval on that point estimate i think is still 60 which is a really good number but i guess when i look at the curve right there's there's i think two-thirds of patients are still censored at that 12-month landmark and there's only maybe like four patients at risk so as you think about the evolution of that curve over time going into this 2Q update, what's your level of confidence that there's not going to be some meaningful amount of deterioration off that 79% estimate? Yeah, I mean, I think the best way for me to describe the OS data is it's early, but very encouraging. I think there were only six events at the time of the data cut. We're going to continue to pay attention to how these patients perform. I think what gives me a lot of confidence that the data will mature well is what we talked about earlier. Response rate, DCR, followed by median PFS all look to be trending in the same direction. And the early data is very encouraging for OS. So I think it's a matter of time. We've guided towards an update in the first half of next year on OS. And we see this as a really important de-risking moment for the pivotal trial, as one of our primary item points in the trial will be overall survival. Okay. You talked about the dose capping strategy. I think that obviously had a favorable impact on safety, tolerability, dose intensity. You know, I guess you unsurprisingly saw like a few of these AEs that we know to be characteristic of an overstatin payload, right? You saw some neuropathy, a little bit of ocular, maybe a little bit of pneumonitis, or cutaneous, I should say. I know most of these patients, actually all of these patients, were platinum experienced. Do you know what proportion of these patients, if any, had low-grade neuropathies at time of enrollment? And was that even allowed in the trial? Yeah. So it was allowed. 100% of the patients had platinum. Over 70% ofthe patients had a prior taxane. So these were, as is often the case in a phase one study, you're getting some patients that have seen some pretty serious therapies before they got to us. So we haven't disclosed what percentage of patients walked in with peripheral neuropathy, but I think it's a really important question that we need to answer and share publicly, likely a medical conference or a publication down the road. There's a lot of really interesting analysis that we can do on the data set that we have. But I think where maybe your question is leading is that when we think about the standard of care changing in the future with a non-chemo option in frontline, it should give us a lot of confidence that what we see with MCFO only gets better if you have less taxane or chemotherapy-exposed patients when they arrive at MCFO in the second line. Yeah, I guess that's the data point that would presumably be of the most interest, right? Because I know a lot of these patients are getting a platinum agent in either the adjuvant or neoadjuvant setting. But in terms of those patients who are getting frontline platinum as their most proximal therapy prior to enrollment, that would be kind of an interesting data point. and then do you implement any kind of supportive care at all for these patients to mitigate some of the cutaneous and ocular aes and i guess if not is there anything that you can do to bring those numbers down a little bit there's been no prophylactic treatment for any of those and we've talked to our investigators multiple times about this and they don't think we should they they think it's quite manageable the way that it is we have been quite excited about where the profile is. We've been focusing on making sure that the dose cap does exactly what we had hoped it would do. And I think we see that in the data. Okay. So I know we were just talking about lovely Barcelona. You're going to be going there to present this, or your investigators will be presenting this as a late-breaking abstract at the TRIPLA meeting. Can you say anything? I think I know the answer to this question, but can you say something about whether or not we should see anything incremental there relative to the prior disclosure? We are really excited that Dr. Faye Johnson from MD Anderson will be presenting the data. Not me. That would be a bad decision. We think this forum is really important for what our plan is for 2027. Primary goal for PICSIS right now is first patient dosed on MCFO in the pivotal trial. And we think bringing this data to a conference like the triple meeting, it gives us an opportunity to shine the light on the data and share it more broadly with that community. Unfortunately, I'm under embargo, so I can't say anything more, but I will tell you, I'll be in Barcelona sitting in the front row. Okay. So that initial dosing of a patient with MICVO in phase three, I think you've got it to that happening sometime around the middle part of next year. I know there's a few other kind of box checking things that you need to do between now and then maybe you can speak to that yep yeah I think we we plan to have an end of phase two meeting with the agency to lock in the dose project optimus we as we disclosed in September we've dosed more than 30 patients at 5-4 with the dose cap we've also disclosed that we've dosed More than 20 patients at 3.6 milligram we planed to bring that information to the agency and we think it should fulfill our commitment on Project Optimist, and that is the gate that moves us forward to standing up the trial. We also, and I mentioned this before, the OS data we're guiding to an update in the first half of next year and seeing that data and giving us confidence that, you know, the current standard of care or the control arm that's in our trial probably delivers somewhere between five and six months of OS. So we want to see what our data looks like to give us confidence that we've got the right trial design to be successful in second-line head and neck. Can you speak to your level of confidence that the 5.4 mg per kg dose is going to be the one that moves forward? Yeah, I've got a lot of confidence. I think the data that you saw from September is all 5.04 with the dose cap, and we think it clearly answers the benefit-risk question. The efficacy is extraordinarily regardless of HPV status, and And we think the safety profile is manageable and expected based upon prolonged or statin exposure. We've seen 3.6 data. We'll be sharing that with the agency. And we thank the benefit-risk profile clearly points to 5.4 with the dose cap. Okay. Maybe you can speak to some of the key design features of the Phase 3 trial that you're now at least have sketched out. I think it's called Headliner. maybe just walk through some of those key features and also if you can just speak to any of the variables that you're hoping to stratify for yeah yeah we have we it's a pretty standard second line head and neck trial so eligibility criteria as you would expect our plan and what we've disclosed in September is 500 patients randomized one-to-one from migbo versus an investigator choice of docetaxel, methotrexate, or cetuximab. Primary endpoints would be response rate and overall survival. I think until we finish up Project Optimist, I think I'm going to resist the urge to tell you about the full stats plan, but we expect that to be shared in early part of next year. Okay. But would you be stratifying patients at time of enrollment on the basis of things like HPV status, on the basis of thing like prior EGFRI and Frontline? Yeah, I think it is clear to us that we've got a drug that works regardless of HPV status. We want to make sure that there's a good sample size of those patients. We also know that the current standard of care today in the U.S. is likely to change, and it's probably different than what's going to be available in the rest of the world. So we needed to design a trial that could meet our global investigators and where those patients are. So I think a good mix of patients that have received platinum plus a PD-1, but also has room to accommodate those patients that had received an EGFR inhibitor in an earlier line. Okay. Presumably you will be executing this trial in a world where pitocemptomab and pembro are becoming frontline standard of care um i know one of the control arm investigator choice options has been specified as cetuximab i guess would you expect the institutionalization of pembro pito and frontline to translate to less cetuxumab utilization in your control arm? And given that the two remaining choices, if not cetuximab or docetaxel and methotrexate, does that then become kind of a tailwind for you guys? Yeah, I think we are trying to stand this trial up as fast as we can because we think the unmet need in second line has become even bigger with the EGFRs moving into frontline. I think timing matters here. So I think there's multiple tailwinds that are working to our advantage, Steve. So, if you think about potential approvals for EGFR biospecifics in the frontline, let's assume they happen sometime next year. Those patients probably get a PFS benefit of somewhere between six months and a year. Those patients would be enrolling in our trial, I would think, at the end of 2028. So we've got a long time between those patients are looking, those commercial patients are looking for a clinical trial, and we need to be available for those patients that are on the current standard of care, platinum plus PD-1. There's also a lot of infrastructure in place already for those phase three trials in frontline, head and neck, where there's been lots of enrollment of EGFR bispecifics plus PD1. We want to be able to accommodate those patients as well and be set up so that they can roll into our trial quickly and have an option there. So I think the structure of the trial will accommodate for all of that. Okay. How are you thinking about FDA's recent accelerated approval for AMI, for J&J's Amivaneb? And, you know, is there any concern that control arm patients post-progression in your study, if a U.S. site, are then subsequently receiving AMI and somehow that biases the KM curve on survival? Yeah, I think the question that you asked me just a minute ago probably plays into this, too. So if there is an EGFR bispecific in the front line, we're going to celebrate what looks like really good data for those patients. I think AMI's introduction into the commercial setting right now has really little impact on our pivotal setting. And then I think I fast forward to if we're fortunate enough to have a successful trial and be launching MICFO commercially, let's assume EGFRs are in the front line there needs to be a novel mechanism in the second line so I I think we're set up well both for the pivotal trial and for the commercial setting based upon the timing and the tailwinds for us okay maybe we could talk a little bit about the second line opportunity yeah that you see I know you just mentioned 20,000 patients I know a lot of the contemporary phase three studies that have been conducted would suggest you know that there's attrition rates right anywhere between 50 and 60 percent right depending upon the trial in terms of the proportion of patients who will just never see systemic um systemic therapy post-progression on a frontline regimen so how do you think about those stats do you that number changes over time as we improve frontline standard of care but that 20,000 patient estimate, how does that triangulate around some of that historical attrition data? We'd just be kind of curious to. Yeah, I think, so all we do right now is focus on head and neck cancer. So we've gotten really, really sophisticated in understanding what we think is happening in the frontline setting and the impacts as it relates to the second line setting. Whether you look at DRG, Global Data, or SEER, they all point you in different directions, but they have gaps in their data set. So we've been trying to triangulate those three data sources, but also leverage other research that's been done. And it starts at sort of, there's unfortunately a really big unmet need in frontline head and neck cancer, and we estimate it's about 30,000 patients. There's multiple data sources that say the movement from first line to second line is somewhere around 60% to 65% in today's environment. And we think with the evolution of the treatments in frontline that that number only gets better. The healthier patients are going to be coming off those therapies. So I think it's safe to assume 70% of those patients in the frontline setting move into the second line. So at the simple level, it's 30,000 patients, 70% progressing into the Second Line, which gives you 21,000 patience. When I look at the options for patients in Second Line you can sort of break it up into two groups. For HPV unrelated, there's not much available for them assuming they get an EGFR bispecific in the front line. It's maybe Mycfo, Platinum, maybe Ataxane, docetaxel, as we talked about, the efficacy for those drugs isn't very good and the safety isn't much better. And so we think MCFO is a real significant opportunity to serve a lot of patients in that group. And then in the HPV positive group, I think there's us and one other emerging therapy that are studying patients there. And I think we've got a long way to go to helping try to solve for patient need in that Group. And, um, I'm wishing I'm rooting them on and hoping that we can get there as well because I think there's an opportunity for more therapies to be available for these patients. Okay. You also have some dose escalation work that's ongoing in combination with PEMBRO in the frontline setting. You are now guiding, I think, to an update occurring before the end of this year. Can you maybe just talk about what we should expect to learn at time of that update? Yeah. I think we'd like to be able to use the opportunity to have another look at our mono data, think about our combo data, and compare it against the entire competitive landscape at that point, hopefully knowing a little bit more. What we've guided to is that we've got 20 patients, more than 20 patients that we dosed in the front line. We've been looking at a dose of 3.6 and 4.4, so quite a bit lower than the monotherapy dose that we're using in the second line trial. And we've been dosing patients regardless of HPV status. So I think for me, what we'd be looking at in this early cut is what kind of response rates, what's the safety look like in combination. And more importantly, we think that the update at the end of 2027 will be really important. We'll have full clarity on what's going on in the frontline setting, specifically maybe with the EGFR bispecifics and how our data has matured over time. So in the next few weeks, we'll be updating. I would think about response rate and safety in a group of patients that's more than 20 at the dose of 3.6 and 4.4, and then second half of next year we'll be looking at durability. Okay. I think the first cut of the frontline data we saw was it was pretty limited in patient number seven. The response rate was fairly provocative, but it was all HPV positive patients. That's right. So have you tried to intentionally get a better balance of HPV subtypes within that front line? We have, yeah. And I think we'll have a really nice combination of both HPV positive and HPV unrelated patients in December. But you're right, the data we shared last year, December, seven patients, 71% response rate. We had four patients in the front line. And so I think there's some interesting learnings to be had from that data as well. Okay. So it kind of feels like you're obviously moving forward in second line, front line, kind of let's wait and see. And if it looks like maybe there's some competitive white space there, you could possibly take action? I think I'd say it in a different way. I think the data is, we're excited about sharing the combo data for multiple different reasons, but it would be far too early to be thinking about investing into a large pivotal trial as we think durability is really important. But I think there's also potentially a read-through on what's the combinability look like for MYCVO in combination with PEMBRO. And head and neck is obviously the place we're studying it right now, but opportunities for life cycle options also exist. Yeah. Any interest in locally advanced disease, where maybe you could come in with, on a backbone of PEMBRRO, come in maybe with fixed-duration dosing of MYCFO in a neoadjuvant or adjuvant and setting. Yeah. I love that we're having these conversations because my job for the last nine months is to keep the team focused on delivering monotherapy and second line head and neck to determine if we had an efficacious and safe drug. And your question implies that we've answered that question. And now it's like, where else can you explore MCFO? And I think from a mechanistic standpoint, there's no reason to believe that MCFO is only a head and back cancer drug. And I look forward to exploring those options, but right now we're focused on delivering headliner trial middle of next year. If you had to start a MCVO trial tomorrow in another tumor type, what would that tumor type be? I'm excited to share some data that gives more clarity as to how we decide where and when to go. And I think we're going to use the same process we've used for for quite some time now, which is where is their clinical activity and where is there an opportunity to be a standard of care in a marketplace that's large enough to matter? OK, maybe just lastly, how does the balance sheet look right now and kind of what does that allow you to execute on? Yeah, fortunately, we we did two fundraisings in 2026. We really thoughtful investors who know the health care space, who joined us on this journey and has put us in a position where we've got enough cash to get us into the first half of 2028, well beyond sort of the enrollment of headliner trial getting started. And we look forward to disclosing our OS data in the first Half of this year to unlock the full potential of this program. Right. Anything we didn't talk about that you'd like to cover before we wrap up? No, I appreciate the time and really the great opportunity for us to share the progress that PIXIS and our team is making on Mikvo. So appreciate the opportunity. All right. Thanks, Tom. Thanks everyone.