All right, thanks for continuing to join our 2026 Virtual Target Oncology Forum. My name is Dara Azar. I'm a senior biotech analyst here at Stifel. It is my pleasure to introduce Dave Lennon, President and CEO of Whitehawk Therapeutics. Dave, good to see you, and thanks for being here.
Oh, thanks, Dara. I'm glad to be here. Thank you to Stifel for hosting the virtual event.
Yeah, of course. First, congrats on the recent financing amid ongoing dose escalation trials. Maybe we can start with an intro of the company and its platform technology assets and where the new balance sheet can take you guys.
Thank you, Dara. We were really pleased with the financing we did last week for another $87.5 million to add to our coffers. Whitehawk is an ADC company focused in oncology. We have two ADC assets that are currently in the clinic with a third one that we're filing later this year. We're really now a clinical stage company since the beginning of this year, in dose escalation with those first two assets. All three assets that we have are based on the same technology, which is a linker payload known as CPT-113, and a bioconjugation approach that we call carbon-bridge cysteine rebridging. We think this is a really unique approach that provides some of the most stable ADC constructs that we can benchmark within the industry.
We think that will convey to our assets a real differentiation in terms of our ability to dose higher, to dose with better tolerability, and achieve greater potency in the indications that we're looking to address with each of our assets. This new balance sheet takes us to over approximately $200 million in cash on hand and a runway that projects us now into the end of 2028.
Okay. As a reminder to investors on the call, if you have questions that you'd like to ask, feel free to use the chat box underneath the webcast, I'll try to give those questions visibility as well. What was the quality of evidence behind this CPT-113 construct or platform when you entered the licensing deal with your partner? Did you examine some of the alternative approaches as well at that time? Maybe give us an oral history into your thinking and how this idea came to fruition at Whitehawk.
Sure. Well, we were approaching the ADC field a bit de novo as a company. We had been working on a different technology in the small molecule space and had decided to pivot the company to ADCs. When we did that, we were looking at trying to identify what we thought was really unique technology in the space that could be differentiated. We came through kind of a lot of searching. We came upon the technology that was housed at this company, Hangzhou DAC, and in collaboration with WuXi on the antibody side, they were developing this portfolio that we ended up in-licensing at the end of 2024. Obviously, a year and a half ago, the quality of the data that existed was less.
We did really interrogate from a non-clinical perspective, what we thought this technology could do. It's really unique because it actually is a dual chain linker payload system. It has two arms to its linker that allows it to conjugate to two different payloads, or two payloads, I should say. It's a Topo1 inhibitor-based platform. That dual payload structure can add on to an antibody as a pair, and that actually induces a lot greater stability in the ADC overall. Ultimately, you know, our evaluation of this approach, we compared across the whole range that's out there of known programs, but also programs that were, you know, and platforms that were in development within China. We found this one to be really unique.
We also, you know, felt good about what we saw from the company's own work in terms of how they developed it. WuXi had gone out and kind of verified that this was the platform they wanted to work with in terms of putting together novel ADC combinations. At the time, Johnson & Johnson also had a collaboration on this linker-payload system that they've since disclosed for their amivantamab-based ADC at AACR this year. There were a lot of folks kind of, you know, coming together to really identify this through, you know, independent means as potentially a best-in-class linker-payload system. That's what we bought into very early with this platform.
Let's start with the PTK7 asset. Maybe remind us what the biological rationale for PTK is, and help us understand your reasoning behind its selection as the first pipeline target.
PTK7 is a really ideal ADC target. It's known as an oncofetal pseudokinase, highly expressed during embryonic development and then down-regulated in adult tissues. It has very low levels of expression in healthy tissues. Cancers actually co-opt PTK7 and overexpressed it in the vast majority of cancers. Something like 70% of all cancers will express PTK7 to very high levels. This makes it a very exciting ADC target cause one, it's expressed at very high levels two, it's expressed across many different cancer types, and it doesn't necessarily have a mechanistic rationale. It's also expressed very consistently across progression and not necessarily down-regulated due to exposure to different therapies. It makes a really excellent ADC target.
We knew that it makes a good ADC target because there had been a prior program against this. Pfizer and AbbVie had a collaboration for a program called cofetuzumab pelidotin that showed some initial efficacy signals, but that platform didn't move forward largely because of safety associated with MMAE-based payload that that program used. We knew that it had some initial very promising efficacy signals. We knew that moving to a Topo1-based inhibitor could potentially alleviate the MMAE class payload that that program had generated. You have a then an opportunity to go after many different potential cancers that express this target.
Maybe talk about the clinical development strategy as well too. Is the dose escalation still ongoing? If yes, how's the enrollment going there? How far do you think you are from the active dose range in dose escalation currently?
Well, it's really a great question, and I think one of the reasons we're so confident, and investors are confident in what we're doing is that we could look at our preclinical data and already know we had a very potent molecule. This program was active around 1 mg/kg in xenograft studies, and generally, those studies translate one to one when you think about the minimally active dose that you knew it to achieve in humans. We had this idea that we would be active above 1 mg/kg. When we looked at our monkey toxicology studies, we had a very high HNSTD, so the non most non-severe of highest dose. That allowed us to really think we might have quite a range in TI.
We could start very high in our clinical trials, and we have started in the range we think is already an active dose for this program. We're currently still enrolling dose escalation, but we anticipate that we will be quickly looking at the activity of this program in a very reasonable dose range for HWK-007.
Okay. What does clinically successful data disclosure from this trial look like in your opinion?
Yeah. We've taken a very stringent approach to how we've thought about the phase I development of this program. ADC is a hypercompetitive space. We believe that it's incumbent upon anybody new coming into the space to demonstrate the potential to be best in class as an asset itself. When we constructed our phase I trial, we only actually have targeted three indications, which is non-small cell lung cancer, particularly EGFR wild type, delineated non-small cell, endometrial cancer, and platinum-resistant ovarian cancer. We picked those, one, because they're high expressor, PTK7-expressing tumors. We also had some precedent data for non-small cell and ovarian cancer from the cofetuzumab program. These three indications also have very clear benchmarks for what good looks like in the ADC field overall.
We've established internal benchmark for efficacy from our dose escalation studies that for each of these indications, and we do believe that to be competitive in the space in gynecological tumors like ovarian and endometrial, we need to see at least a 50% ORR in our initial phase I dose escalation efficacy evaluable population at the relevant dose. In non-small cell, it's probably lower, like 35% or 40%, just given the benchmarks that exist in those places. We believe if we can achieve higher than that with our current program, then it's not gonna be differentiated, and this is not a program that we should be pursuing. We've set those very high bars, very explicit bars, in our execution and our choice of indication that we've gone after.
We believe by demonstrating that best-in-class profile on these indications, then we can expand into all of those places where PTK7 might be an effective therapy.
Okay. It sounds like those indications were selected on the basis of giving you the ability to learn the clinical profile of this drug and be able to benchmark it with where there's existing data. Beyond that, maybe paint the picture for us in terms of the opportunity landscape where this ADC in a, in a, in a scenario that is successful, what indications and opportunities can it go to?
Well, first we think this is a great potential lung cancer drug and where PTK7 is highly expressed across a whole range of cancer subtypes and consistently expressed, whether you're talking EGFR wild type or not, whether you're talking squamous or non-squamous, whether you're talking about individual AGA mutations, PTK7 is always riding along in that and our ability there for it to target the vast plethora of lung in sub-indications, we think is highly promising. That's clearly where we have this focus coming out of our those initial indications.
When we think about potential for exploring PTK7 in other indications, we're really interested in places, like head and neck cancer, like other squamous cell carcinomas, and as well as colorectal and the entire GI tract actually, which is quite high in PTK7 expression, and where ADCs yet have not yet really made their mark in terms of setting the standard for, you know, what we think these therapies can do. There's multiple opportunities to think about how we play in the big field of non-small cell lung cancer, but also picking off various indications where we can take a faster-to-market approach, where ADCs have not yet penetrated.
Okay. Maybe we can move on to the MUC16 ADC.
Could you please spend some time now on this target's biology, maybe advantages, opportunities, open questions that are around this target, for you?
Yeah. MUC16 is really a fascinating molecule. It's often overexpressed in gynecological tumors, and it has a couple of interesting parts of its biology. First is that it's very highly expressed, particularly in ovarian cancer. When you look at MUC16 expression, it's anywhere from 3 to 10-fold more highly expressed than any of your common targets that are out there for ADCs, including things like FR alpha or HER2, or CDH6 or claudin-6. We start with a target that's already much more highly expressed than other ADC targets out there, which should be an advantage in terms of our ability to deliver more ADC against the tumor.
The second component, though, that has made MUC16 difficult in its biology is that it actually is cleaved, and it's very commonly cleaved into a circulating antigen called CA125. CA125 actually originates from MUC16 overexpression, and it is one of the most common blood-based biomarkers that's utilized within gynecological oncology to measure tumor burden and progression and response to therapy. This is a blood-based biomarker that's well known within the gynecological community and gives an advantage in that we can identify, readily identify patients who may be overexpressing or highly overexpressing MUC16. But it also means that we actually have to think about how we target MUC16 such that we actually don't target the CA125 that's circulating in the blood, because that would mean that the ADC wouldn't get to the tumor. It would bind in the blood.
That was the problem with one of the early attempts for an ADC against the MUC16 target. Genentech had a program that targeted MUC16, but they had chosen an epitope that was part of that CA125. While they're able to generate some really high response rates, they had to dose very high to overcome the circulating CA125 in the body, so overcome the so-called antigen sink issue that sometimes occurs with different ADCs. BCMA is another target which has some issues around cleavage and circulating antigen sync issues. While there were some really promising early efficacy signal, because of the very high dosing they had to go to, it generated a lot of side effects, and that program was discontinued.
With our approach, we've actually taken advantage of that biology in unique ways. We can identify these kind of highly expressed patients in a blood-based biomarker. We've also targeted an epitope that is below the cleavage site of CA125. That allows us to bind both intact and cleaved MUC16 at the surface of the tumor, not in the blood. Our ability to go around that, we've demonstrated that preclinically, allows us to make a really potent molecule against a very highly expressed target in this field. We think that that could be a clear differentiator for our ability to target MUC16, address, you know, the number one target within ovarian and endometrial cancers.
Okay. Now, from clinical translation perspective.
if you see activity with your HWK-016, relative to the Genentech experience.
how would you know that it is attributable to your antibody? How would you know that you have the right antibody here? There's also the linker payload.
Yeah
difference between your experience and also Genentech's.
Yeah. Well, we've shown preclinically that we can overcome the circulating CA125 or bypass circulating CA125. We'd wanna see that our PK and dose reflects that in humans, so that we maintain our ability to have a long half-life of this product, that we don't see, you know, and that we see similar dosing dynamics that we see with our HWK-007 program in terms of effectiveness. So that would tell us that it's behaving similarly, and we're not being impacted by the CA125, like Genentech's program. That would, you know, those parameters of PK will be important initially to demonstrate that, as well as kind of where we see efficacy in dose.
I think, you know, beyond that, we do think there's advantages of our linker payload system, which should add on to the Genentech or relative to the Genentech program, which was also an MMAE-based program. We typically have seen, you know, anywhere from 15 to 30 points of gain in overall response rate when you switch from MMAE to topo. Genentech was showing 40%. We think, you know, that potentially puts us in the high 50s to above 60% overall response rate, and that would be our expectation for the potential of what we might be able to achieve with this program.
Okay. How important do you think is seeing responses early in dose escalation with this HWK-016 program?
Yeah, we would expect, as I mentioned, we believe we're starting in an active dose range. We would expect to see responses early in the program. I think the question for us is how tolerable is the platform going to be. We have chosen a payload which actually is, we think is more heme-sparing, and hematological toxicities are a key issue for topoisomerase-based inhibitor programs, especially those that rely on XTCamp. As a XTCamp payload, you see typically Grade three neutropenia rates, 25%-40%, sometime leading to febrile neutropenia and Grade five events in some cases. We think we will avoid most of that issue and that tolerability, which should allow us to dose quite high.
While we may see, you know, responses early in our dose escalation, the question will be can we achieve even greater response, given the potential for the tolerability we think we can achieve with this molecule?
The scientific comparator here may be the Genentech program. From a clinical perspective, there will be a level of anchoring to 50%-60% plus ORRs of emerging folate receptor alpha ADCs. Would you think that that's ultimately a fair bar to expect from this program as well?
I do. I mean, I think that's where the competition is really those FR alpha ADCs that have been reading out over the last year or so, kind of have demonstrated that most of those are Topo1-based molecules, and so you do see that tolerability issue that I mentioned, whether it's, you know, [bryna house] or Lilly's FR alpha or others. It does establish an efficacy bar that we intend to, that we do think is the relevant bar for competitive profiling.
Maybe go back to some of the science and platform discussions that we had earlier. Could you please differentiate different Topo1 payload technologies and which category you guys fall into?
Yeah, sure.
What is the materiality of that?
It's interesting cause often, you know, we get this question a lot from investors, and I think that it can be hard for folks to separate out the class or lump the class together is probably the most common thing, that all Topo1s are the same. That's really not the case. There are really kind of two emerging major kind of categories of topoisomerase-based inhibitors, one that's really typified by DXd, and generic DXd is a molecule that's used about third of all programs, Topo1 programs that are out there today. It's quite common. You'll find it within many programs. DXd is a highly hydrophobic form of topoisomerase-based inhibitor. It's quite potent. It also has a lot of bystander effect 'cause it easily goes across the cell membrane.
That is fine, except that what tends to happen with DXd that gets released into the blood is it will home to the bone marrow. In particular, neutrophils and the neutrophil compartment is very sensitive to topoisomerase-based inhibitors like DXd that can cross membranes easily because of the high division rate and the expression of topoisomerase in those cells. That's where you're generating that, you know, high rates of neutropenia is often because of free DXd that those programs are releasing into the blood. There's a second category now that, you know, is generally typified by more polar molecules or polar versions, still quite hydrophobic in nature, but often associated with some charge that has been used to modify the DXd core molecule itself a little bit.
Dato-DXd is part of this class, and CPT-11, which is part of our CPT-113 linker payload, is also similar in its construct. These molecules cross the membrane barrier a little less consistently, and so therefore don't generate the same hematological toxicity. Sometimes they can also be seen as less potent, potentially driven by efflux pump inhibitors. I think one of the core advantages of our platform within this subclass of topoisomerase-based inhibitors is it's not a substrate for most efflux pump inhibitors. It really retains its effectiveness in the cell and can kill cells quite effectively. That's how we achieve, you know, greater potency than you typically see in these more polar and Dato-DXd-like payload class.
Overall, you know, I think what we've tried to optimize on is the benefits of being in this more polar space. You have that less heme toxicity. You're often trading off some potency due to efflux pump. We've gotten around that by our design, and therefore, we think we're really best in class within this payload group.
Yep. Now could you spend some time on the SEZ6 program and how is this asset being positioned as a biparatopic ADC, and how are you thinking about differentiation versus AbbVie's program that I believe now is moving to phase III?
Yeah.
Some commentary would be helpful.
Yeah, for sure. Our third program, SEZ6 is against SEZ6. HWK-206 is a biparatopic antibody. Now, biparatopic antibodies bind to the two different epitopes on the same molecule. That allows actually for improved clustering and internalization of the ADC itself into the cell. That improvement internalization improves potency of the molecule, and we've demonstrated this against ABBV-706, which is a more standard monoclonal antibody, where we can generate two-three times greater potency on the antibody itself. This is really important because the ability to achieve kind of suppression and internalization is a key dynamic within the performance of ADCs. Now, ABBV-706 is a very potent molecule. It utilizes a payload that is of that DXd class that I described earlier.
A very highly potent molecule, but also highly toxic, so generates a lot of grade three neutropenia and grade three hematology in general and grade three AE events in general. Much, much less tolerable, but has shown some really promising efficacy in that 55+ 50%-60% range ORR in small cell lung cancer. We think we can improve upon that with this improved antibody. If you take our heme-sparing and just generally more tolerable payload that is still quite potent, we believe produces an overall better profile, both from an efficacy perspective and a safety perspective. We wanna see that translated into the clinic, of course, but that's where we think we can generate, differentiate and improve upon AbbVie's molecule.
Obviously, potency advantage, you know, we can talk about that improvement, but we think the tolerability advantage may be more important when you think about combination therapy down the road, and overlapping toxicities with chemotherapy or IO, which is what you're gonna wanna do to be in kind of first line setting with these molecules. HWK-206 really has the potential to be a best in class single agent asset, but more importantly really, we think really best in class combination agent for small cell and neuroendocrine tumors, of which SEZ6 is kind of the one of the best targets for.
Okay. How do you think about the cadence of internal and external disclosures as the kind of the catalyst path? Should we be paying attention to any disclosures at ASCO 2026, either from either one of competitors or partners or constituencies that may be helpful to make read-throughs?
It's an exciting time when ASCO comes up. There's always data to sort through, and it can be difficult sometimes to figure that out. For our internal programs, what we've said is we will communicate our phase I dose escalation in the first half of next year. You can really look for that at congresses in 2027. What we think is really interesting for ASCO next week or in the coming weeks, sorry, two weeks, is the fact that one of our partners, Hangzhou DAC, is actually releasing data on an internal program they have that utilizes the CPT-113 linker payload. This is the first clinical validation of that linker payload system against a target called CD56 that they've been developing in China.
Again, China data, it's being utilized in lung cancer, as well as neuroendocrine tumors. We'll see some data from that program coming up at ASCO. It's been accepted for an oral presentation in the coming weeks.
Great. Very good. Thanks for the discussion. I think this was helpful, at least for me, and hopefully it is for investors as well. Thanks everyone for your attendance.
Thank you, Dara.