Have a conversation with Lara Sullivan, CEO of Pyxis Oncology. Pyxis is a clinical-stage oncology company focusing on head and neck cancer and other advanced solid tumors. The company's lead candidate, micutorbopilidotin or MICO, is being investigated for monotherapy use for the treatment of recurrent and metastatic head and neck cancer. In addition, combination use with MICO and pembrolizumab is also being investigated in a separate study in advanced solid tumors. To talk about MICO, I welcome Lara to this fireside chat. Lara, glad to see you, and thanks for accepting our invitation and talking to our audience today. For those who are new to Pyxis, could you provide an overview of your business strategy?
Sure. Thank you very much for having us, RK. It's a pleasure to be here. We appreciate the time and the interest. As RK mentioned, Pyxis Oncology is focused on our lead asset, which is our ADC. We had licensed it in from Pfizer. It was originally developed by Pfizer, so it has a very strong history of construct development. The initial data set for this asset came out last November, which was the dose escalation readout across nine solid tumor types. I think it was 10 dose levels in escalation, of which the head and neck signal was the strongest. We have prioritized focusing on validating that signal in our programs that are underway right now. As RK mentioned, we have two programs underway. One is a monotherapy program with two different arms.
The other is a combination program in combo with pembrolizumab, which is provided through a supply agreement with Merck & Co. We have catalysts coming up out of both of those programs.
What are the major catalysts that we should expect, let's say, in the next 12 to 18 months?
The monotherapy program focused on head and neck has two arms. The first arm is addressing patients who are currently not responding to platinum and PD-1. This is the current standard of care. This is the patient population that Merus is going after. Many of you have awareness of what's going on in the head and neck space. That arm for us is the exact same population as Merus. The second arm we're looking at is for the EGFR/PD-1-resistant population. This population is the group that is currently not responding to cetuximab, as well as the Merus patients who are enrolled in those trials and not responding to Merus.
We designed this arm specifically because we believe the standard of care is moving to EGFR-based therapies, and we want to be sure that we have data in a population that shows our ability to come in as the line right behind the EGFRs. This development strategy allows us to play optimally in this head and neck market, both as competitors to Merus with the data coming out in our first arm, and then as the line immediately following them for the data that's coming out in our second arm. We are somewhat, I guess, you know, preventing some commercial market risk mitigation by looking at these two populations. There's a place for us regardless of what happens to Merus.
Before we start talking about the data and the clinical programs, what is micutorbopilidotin? Obviously, you're looking at a novel target. How was that drug designed?
Yeah, Pfizer had a very strong ADC effort in the 2010s, well before CGEN was in their sights for acquisition. They looked at a number of different targets. They looked at a number of different constructs. I was actually at Pfizer at the time. I saw this firsthand. One of the targets they had identified is EDB, extracellular domain B, which is our target. It's a novel target that's a splice variant of fibronectin. It's an extracellular target. It's part of the structural component of the tumor. It's ubiquitously expressed across a variety of tumor types. In terms of the construct, one of the benefits of ADCs that are built by big pharmas versus little biotechs is that Pfizer was able to empirically test all the different components of the ADC to create the best combination of all of them for the final construct for our ADC.
They optimized the payload. It's a modified form of orostatin. We have a site-specific conjugation chemistry. We have a specific binder. The whole construct has been optimized for stability and potency. It was empirically tested against a number of different constructs. The ADC that survived that empirical testing was kind of best of breed. That's what we have. In addition to the target being a novel non-cellular or extracellular target, the mechanism is novel as well. The ADC cleaves in the extracellular matrix. The canonical view of ADCs has been that the ADCs need to be internalized. They need to address a cell surface-based target, be internalized, cleaved inside the tumor cell, and then do their thing. In fact, what the Pfizer scientists showed as early as 2014 is that the proteases that are needed for ADC cleavage actually exist in the extracellular matrix.
The bystander effect, triggered by that extracellular presence of the payload, is a real component of the mechanism, not just of our asset, but what has recently been characterized in INHER2, that bystander effect and extracellular presence of payload is a meaningful component of ADC mechanisms. There's been a lot of work going on recently to characterize this. We feel that we are in a very privileged position from the fact that our mechanism has such a key component on this bystander effect, which is becoming better known to be an important component of how ADCs work overall.
Very good. Talking about the data expectations, you were saying that we should be seeing some data in the recurrent and metastatic head and neck squamous cell carcinoma. What sort of data would be considered as positive? Also, how is this data going to be different or expected to be different from the experienced patients, especially either with platinum or with other PD-1 therapies?
Yeah, so with the two arms of the monotherapy trial and the combo trial we have going on in combo with pembrolizumab, we have three catalysts, one for each of the two arms in mono and for combo. For the two arms in mono, the first catalyst is expected this second half of the year, and that's in the PD-1 plus platinum-resistant population. The EGFR-resistant population, we're guiding that that data will be first half of next year. The reason for that is we are targeting the clinical trial sites where Merus and VYIRIA are at. We're giving ourselves a little more time to try to pick up actual trial participants. We can get the cetuximab EGFR patients easily. That's, you know, out there. It's been out there for 20 years. Those two catalysts, one will come second half this year, the other first half next year.
In terms of the combo trial, that's in dose escalation. We started that trial earlier this year. We guided to three dose levels in escalation, starting at 3.6 mg/kg, which was the low end of what we believe is the effective dose range for monotherapy. It's combined with 200 mg of fixed dose pembrolizumab. Three dose levels, 3.6, 4.4, 5.4. In that study, since it's a dose escalation, we are actually using multiple tumor types to escalate. That helps us speed through escalation. We're using the backfill for head and neck. The preliminary data that will come out of the combo escalation will have some other tumor types in it as well. All three of these catalysts, we're looking for roughly 20 patients each in them. We believe that Merus has essentially set the bar on what, you know, efficacy expectations should be.
Merus had in monotherapy a 36% ORR, in combo a 63% ORR. Early stage development, if you're a couple basis points here or there, you're essentially in the same place. We think from a monotherapy perspective, something in the 30s is very competitive in this space. Obviously, in combo, you really need to be in the 60s to be competitive in this space.
In addition to that, would we also see any durability data, or is it just too early to ask for durability?
Yeah, I know we all want it. We all want the durability data. The way we always think about this is that we can give some anecdotes. We can give some patient vignettes about the early enrollers. Unfortunately, if we really wanted durability data, we'd all have to hold our trials a few extra quarters to allow that to accumulate. Nobody wants that. We did share some durability anecdotes out of our November data set. Back with what we showed in November, we had a patient that I think at that time had 14 months on therapy. That patient had a very strong PR. We gave an update in February on that patient. They were up to 17 months on therapy. We need to sort of look at the emerging clues patient by patient to give some, you know, maybe insight into durability.
To your point, it will ultimately come at the next stage of development when you actually really have the time and test that type of endpoint.
The other big thing with ADCs is safety, right? In terms of looking at a new target plus an ADC, what sort of a safety profile have you seen with micutorbopilidotin (MICO) at this point? What are we hoping to see as these data come out?
Yeah, orostatin-based ADCs, and again, our payload is an optimized form of orostatin, tend to have a cluster of AEs that are sort of expected with that type of modality. Those include neutropenia, neuropathy, ocular tox. People also look a lot at skin, cutaneous lesions as well as pneumonitis. Some of the pneumonitis is more associated with certain tumor types like lung cancer, for example. We take all the AEs very seriously, but we spend a lot of time in particular keeping an eye on these. As we showed in our November data disclosure, which covered 77 patients, 39 of which were at 5.4 mg/kg dose, which is the expansion dose we're in now. We had 39 patients at that dose in the November data disclosure.
We showed we were either as good as or better on each of those five AEs to the approved ADCs that are in the market right now. We look to cohort expansion to hopefully validate and amplify the insights that we've seen out of dose escalation. Those are the major areas we keep an eye on.
As you're looking at these programs and also looking at EGFR-resistant population, how big is that EGFR-resistant population, and what's the real market opportunity there?
Yeah, so, we think it's a super exciting time for head and neck patients after 20 years of really nothing. For both Merus and VYIRIA to come along with very strong combination therapy activity in both of them, and in the case of Merus in particular, very strong monotherapy data. What we are hearing from investigators is that, as a patient, you kind of have one shot at an EGFR. If you go on Merus and you don't respond, you're not going to get put on VYIRIA. You're going to be put on a next line of therapy. What that tells us is that there are essentially two distinct markets here, right? Competing for that first opportunity to dose patients, whether it's Merus, whether it's VYIRIA, whether it's us, right, going after that platinum PD-1 resistant population. That's the same group.
The EGFR resistant population will have some percentage of patients treated by Merus, VYIRIA, and cetuximab that don't respond and come. While the Merus, VYIRIA data is still getting characterized, we're keeping a close eye on that. We have not sort of gotten to the point yet where we're guiding on market sizes across any of these. I'm a little hesitant to quantify right now. That second market will be a subset of what that first market ultimately is. Of course, like with any other new therapy, you have sort of an initial catch-up of the incident patient population who are sitting there who don't have those alternatives. Then you start to get that steady flow once you get a sense of how responsive patients are to EGFR therapies overall.
Okay. Your strategy is very interesting in the sense you're trying to catch the market before it starts being a market. In that sense, when you presented the data last November, you looked at multiple indications besides head and neck that we are talking about.
Yeah.
What additional data do you need to make you go into those other indications that you outlined?
Yeah, going into the data last year, we had, as I mentioned, a strong hypothesis across multiple tumor types because the target is expressed across multiple tumor types. Biologically, there was no reason to believe going into the data set that any one tumor type might be superior to any other tumor type. We wanted to test all of them for early signals last year. In each of the tumor types at the effective dose level of 3.6 through 5.4, we had anywhere from three to six or seven data points. They're all small numbers, but in aggregate, we did see meaningful tumor regression across six different tumor types. The head and neck jumped out at us. That was a confirmed ORR of 50%. The N was six patients. There was one confirmed CR. There were two confirmed PRs.
In this time of macro uncertainty, resource constraints in biotech, we felt it was prudent to focus on head and neck signal first. I think as we see how this data comes back, as we see how the funding climate evolves, we're certainly hearing inquiries out there, not just from investigators, pharmas, but investors too, around, okay, you had these other signals. How are you thinking about them? I think in a mechanism like ours and a target like ours that has broad applicability, because remember, a lot of ADCs that are the cell surface targeting ADCs are restricted to where those targets exist. If the cell doesn't have that target, they can't go into that tumor type. We don't have that issue because our target is across multiple tumor types.
For us, this becomes a bit of an exercise around funding, gathering data that validates signal, and commercial opportunity as we think about what that could look like. I do think there's interesting potential future opportunities for this asset, but for now, we're squarely focused on characterizing the head and neck signal.
Okay. Considering your experience and also, if money was not a constraint, I know you just spoke about funding, how would you think about expanding your portfolio beyond MICO?
It's always an interesting question, right? Because at the end of the day, we're all trying to risk mitigate and yet use whether it's multiple shots on goal by indication or by assets to find the thing that people have most confidence in, right? Put your focused resources around it. Of course, there's asymmetry between where investors think you may have your thing and where management thinks they have their thing. We have very strong conviction in micutorbopilidotin (MICO). We've been a company with a broader portfolio in the past. We've had as many as three clinical assets and a handful of preclinical programs. Over the last two to three quarters, we've been through a concerted effort on focusing on MICO because we have such high conviction on it. We think the molecule itself, for the reasons we just described, gives those multiple shots on goal.
Right now, we are really solely focused on MICO. Obviously, there's a lot of exciting assets out there in distressed hands. I think for us, we really want to make sure that this asset gets all the attention it deserves, gets all the resources it deserves from a financial and an FTE perspective. For now, it's MICO all the way.
Okay, as a last question from me, on the balance sheet, you know, what's your current cash position and what sort of a runway can you get from that?
Yeah, in our last 10-Q, indicated about $90 million on the balance sheet, and our runway is through the second half of next year. We feel pretty good given the catalysts that are in the near term for us, two potentially coming up this second half of the year, one in the first half of next year. Those provide opportunities to add to the balance sheet, depending again on what's going on in the world, in the sector. We're not in a position where we need to raise the money to get to those catalysts. The catalysts are well funded, and we're able to deliver on our commitments with the cash that we have.
Okay, there's one more minute left, Lara.
Sure.
Let's see if the audience has any questions for you.
Yeah, this last paragraph is more about just presenting or at least getting what, how many people, but limited to the second line now, are getting cetuximab? I know that's going to change, but I'm just curious.
Yeah, it's actually interesting. The question was how many people are getting cetuximab right now as a standard of care. In the U.S. and the Western markets, you tend to see more of the platinum plus pembrolizumab as the first line, but in Europe, you actually still see a lot of cetuximab and other parts of the world. From a global perspective, and I don't know, Tom, I think it's fairly, like if you look globally, it's actually more equal when you consider some of these other markets than what we're used to here in the U.S. Sam Woxel will tell you it's 100% response rate in cetuximab, but we know nothing is 100%.
Thank you. Thanks for your attention.
Thank you.
Thank you, Lara.