Conference Transcript - PYXS 2026-06-04

Farzin Hak, Analyst — Jefferies

Good morning, everyone. My name is Farzin Haak, one of the biotech analysts at Jefferies. It's my pleasure to introduce Tom Civic, CEO of Pixis Oncology. This is a fireside chat format. Thank you for joining us today, Tom. So for those new to the story, can you provide a one-minute intro to Pixis and explain essentially the main thing, the mechanistic rationale for targeting the tumor's trauma versus the tumor cells directly? Well, Farzin, thanks for having us

Thomas Civik, CEO

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? So 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. So 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 MICFO. 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. And 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. And 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. And three, it's a tumor that's quite hard to treat, and at this moment there aren't a lot of available therapies there. So during dose expansion at 5.4 milligrams, we saw some pretty extraordinary efficacy, and we released that data last December. But at the same time, we saw some side effects that were coming from the drug that were being driven exclusively by heavy-weighted patients. So we started to fine-tune the dose, and end of last year and 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. And that's the data that we hope to share with everyone at the mid-year update is a very specific patient population and had neck cancer in second line at a 5.4 milligram dose at a dose cap. And 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 PEMBRO. And that combination study we've guided to sharing those results in the second half of the year. So maybe not a minute, but 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.

Farzin Hak, Analyst — Jefferies

So 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?

Thomas Civik, CEO

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 midyear should give us confidence in 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 midyear is something that would be potentially the standard of care. and second-line head and neck cancers. And third, we want to make sure that it's clear the patient population that we're studying it in. And 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. And if that data is clear, our plan would be to move there quickly with those three things accomplished.

Farzin Hak, Analyst — Jefferies

So maybe double-clicking on the two cohorts that you'll have the data. So you have the ARM1, and then you have the ARM1 post-platinum, and then ARM2 is the post-EGFR cohort. So that one is more strategically important because of the EGFR therapies moving into the first line. But is there any reason to think that the post-EGFR cohort's efficacy and safety might differ from ARM1?

Thomas Civik, CEO

Yeah. Do you mind if I sort of describe ARM1 and ARM2 for those folks that maybe aren't as close to it? So 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. But so those two arms are going to look at MICFO 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. So for our mid-year 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. So 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 MICFO performs, regardless of HPV status, regardless of prior therapy, whether it's a platinum or an EGFR. And 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.

Farzin Hak, Analyst — Jefferies

And then also on the HPV status, that's another pre-differentiation. Do you think MECVO can show equi-importancy in both?

Thomas Civik, CEO

Yeah, I mean, I guess it's, there's what I believe and then what's true in the data, right? So the data that we shared last December showed that we have efficacy in both groups for both HPV positive and HPV unrelated. it. And 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 mid-year 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. And so our hope is with a really robust data that we should be able to share at the mid-year update, we'll be able to look at multiple different groups and evaluate how MICFO has performed against each one of them. Okay, great.

Farzin Hak, Analyst — Jefferies

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 3 treatment-related adverse events and a lot of discontinuation, high rate of discontinuation. But it's important to note that 100% of those discontinuations were in high body weight patients. And 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?

Thomas Civik, CEO

Yeah, this balance between finding efficacy and safety is one that I think any of us that are developing ADCs continue to look for. And I should say we've been able to show really extraordinary efficacy twice now. in the head and neck cancer population. But to your point, Farzan, in the second half of last year, our December update, we showed really significant efficacy for this second-line head and neck patient population, but an AEU revealed itself in those patients that were of high body weight that was leading to a discontinuation rate. And if I go back to the question you asked me before of what we're trying to strive for this mid-year 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 so 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 with micvo and we looked at sort of three different things one was the data that that you referenced which is that the aes were being driven by those patients that that had high body weight that was leading to a discontinuation. So 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. And what we found was the patients at high body weight were just clearly being overexposed to MYCFO. And 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. So we took those three learnings, sort of our clinical data, our PK analysis, and other ADCs in development, and said, how do we solve this problem for MICVO? And 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. And 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. So our plan is to share the mid-year updates. So there's no confusion, a significant number of patients in second-line head and neck cancer at a 5.4 milligram 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. So 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. But 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 AIVW as it relates to MICFO should produce almost identical results. So we feel like we've got a plan that has unlocked the potential for MICFO at 5.4 milligrams with the dose cap. and that's the data that we plan to share at the mid-year update.

Farzin Hak, Analyst — Jefferies

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?

Thomas Civik, CEO

Yeah, you know, 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 and 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 of the dose cap, we think that that's likely the dose that we would move forward with. AIBW, I think, is another great option. And 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.

Farzin Hak, Analyst — Jefferies

Great. Jumping ahead, so 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. So is this still the planned next step, and what can you share about how you're approaching the design and timing of that pivotal?

Thomas Civik, CEO

Yeah, I mean, 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, and 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 MICPO. The short answer to your question is mid-year update, we will provide more clarity on what our regulatory path forward is.

Farzin Hak, Analyst — Jefferies

Great. So let's move on to the ASCO computer data set from Corbus and J&J specifically. And what is your perspective on the data, and how does that influence your strategy for MIGFO?

Thomas Civik, CEO

Well, I think we should take a second just to celebrate the advancements that are happening in head and neck cancer, and long overdue, and 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, and 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. And if you don't mind, Farzan, 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. And that patient group is split into two groups, HPV-positive and HPV-unrelated. And 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 and the way we're developing this drug and based upon its mechanism is that we believe that MCFO should be able to work regardless of status of HPV and regardless of prior therapy so 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 mcfo can can share the data that gives people confidence including us that there's a

Farzin Hak, Analyst — Jefferies

path forward there and does the computer updates make your plans different or it's just consistent

Thomas Civik, CEO

with what you had expected our plans are are to first off make sure that we have a drug that's efficacious and safe we'll take that 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. And we also want to make sure that there's a patient population that's large enough for us to help. And so I think the, I leave ASCO and the data 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 MICFO.

Farzin Hak, Analyst — Jefferies

There was a biker update, too, but that is in the EGFR setting, and also HPV unrelated.

Thomas Civik, CEO

That's right, and in the front line, maybe. And in the front line, too.

Farzin Hak, Analyst — Jefferies

So moving on to the combo update.

Thomas Civik, CEO

But we should talk about that, right? Like, 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 and getting back to the question you asked me a few minutes ago we have arm two of our of our trial is those patients who've received an egfr inhibitor plus pd1 and we we will be able to share that data at the mid-year update to see how micvo performed in that patient

Farzin Hak, Analyst — Jefferies

population exactly so moving to the frontline settings you have the combo update coming up in second half with pembro so where are you at where are you at with enrollment and what has been the feedback from the site investigators and any challenges in recruiting both hbb positive and

Thomas Civik, CEO

negative patients well i can't update you on the numbers yet that will come with the the disclosure investigator enthusiasm is extraordinarily high for this program we hear we hear in multiple settings the the need for an ADC in the second line and the data that you're referencing in the frontline we you may recall we shared an update in December of 2025 that looked at the combination of Mikvo and Pembro 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. And, you know, 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? And at this point, we just don't, I think the experiment's not complete yet, but we remain extraordinarily enthusiastic about the investigator enthusiasm for MICFO in combination with a PD-1 in the front lines. We see there's a really significant opportunity to help a lot of patients there, too.

Farzin Hak, Analyst — Jefferies

And for the combo, can you remind us what dose you're taking forward? Is it 5.4 as well?

Thomas Civik, CEO

In the December data, we shared both 3.6 and 4.4 doses, and we plan to update that data at the second half update.

Farzin Hak, Analyst — Jefferies

And then just to be clear, like, how are you defining the first line for this study? Is it truly treatment-naive, or does it include patients who record after adjuvant therapy as well or chemo-radiation?

Thomas Civik, CEO

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 experimenting or, I'm sorry, advancing the program in frontline with MICFO and combinational and Pembro.

Farzin Hak, Analyst — Jefferies

Great. This is the next question I get a lot from investors, too, and there is some confusion, like, you know, the EGFR targeting therapy should be used in frontline, but is there any rationale, like, why an ADC cannot be used first, followed by the EGFR targeting therapies?

Thomas Civik, CEO

Wow, that's a great question, and 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 Pembro. Now, remember that those are almost exclusively focused on the HPV-unrelated patients. And just to make sure I didn't communicate it not clearly, was our study in December looked at HPV-positive patients in combinational cumbrose. The sequence of therapies I think is fantastic that we're even talking about. Novel new developments in head and neck cancer and 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. So I think there's a long way to go from here to there on when we're talking to physicians with a commercial product and to what is the sequence of events for them.

Farzin Hak, Analyst — Jefferies

Makes sense. And then head and neck is known for rapid progression and resistance to therapy. So have you characterized mechanisms of primary or acquired resistance to MICFO that could potentially be problematic for second-line sequencing?

Thomas Civik, CEO

You know, 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, and the benefit of a program like MICFO 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.

Farzin Hak, Analyst — Jefferies

And just to double-click on it, like, when you mean the fast onset of action, do you see responses within the first cycle, and do you see any deepening of responses?

Thomas Civik, CEO

This will be a major focus of the mid-year update for 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 MICFO deliver responses in patients?

Farzin Hak, Analyst — Jefferies

Good. And then thinking more from a future perspective, can you potentially, the mechanism allows combination with other therapies. So is there something near term or something that will be afterwards that you'd consider?

Thomas Civik, CEO

Yeah, I mean, we spent all of our time today talking about head and neck cancers, but the work that we did preclinically, and we have an extraordinary translational team back in Boston that has been looking at the mechanistic reasons that this drug should work in cancer. And our preclinical work pointed to more than a half dozen cancer types that are clearly targets for us down the road. And then when we did the basket study to start the clinical investigation of this program, again, we saw, again, more than a dozen cancers that were responding to this. So the first part of the question is there's no reason that this is just a head and neck cancer. drug. And 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 MICFO in combination. There's many places that, many other cancers that we could explore with MICFO and other tumor types.

Farzin Hak, Analyst — Jefferies

And then quickly on the manufacturing side, do you have the scale to support for pivotal

Thomas Civik, CEO

trials and potential launch? Our CMC team has made sure that we are prepared for a successful outcome at the mid-year to ensure that we can pivot very quickly to a pivotal trial.

Farzin Hak, Analyst — Jefferies

And then would you consider a co-development partnership for a combo regimen like with Mark, for example, for the PD-1, or would you prefer to retain the full economics?

Thomas Civik, CEO

Thanks. It's a question you know that the easy way for me to answer is I can't answer that question. 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 to really help a lot of patients. and second-line head and neck cancer, first-line head and neck cancer in combination with Pembro, and then far beyond that. So 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

Farzin Hak, Analyst — Jefferies

And then can you remind us of the IP of the drug?

Thomas Civik, CEO

Yeah, it's a fascinating story. We actually acquired MICFO through Pfizer, and Pfizer had dedicated about a decade-long investment in ADC space. And so we have the benefit of all that investment that happened over many, many years in the hands of a very nimble organization. And so that's where we found MICFO.

Farzin Hak, Analyst — Jefferies

and to close out what is your cash position and the key catalyst and milestones that investors should focus in the next six months

Thomas Civik, CEO

cash until the fourth quarter of this year I think is as we've mentioned multiple times a mid-year update on second line head and neck cancer and and then a second half update on first line in combination with Pembro that's 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.

Farzin Hak, Analyst — Jefferies

Thank you so much for your time.

Thomas Civik, CEO

Thanks, Farza. Thank you.